E.P.A.R s  Editing

Halaven

What is Halaven?

Halaven is a cancer medicine that contains the active substance eribulin. It is available as a solution for injection.

What is Halaven used for?

Halaven is used to treat locally advanced or metastatic breast cancer which has continued to spread after at least one previous treatment for advanced cancer. Previous treatment should have included cancer medicines of the types known as anthracyclines and taxanes, unless these treatments were not suitable. 'Metastatic' means that the cancer has spread to other parts of the body.Halaven is also used to treat adults with advanced or metastatic liposarcoma (a type of cancer of the soft tissues that develops from fat cells) that cannot be surgically removed. It is used in patients who have already been treated with anthracyclines (unless this treatment was not suitable).The medicine can only be obtained with a prescription.

How is Halaven used?

Halaven treatment should be given under the supervision of a doctor experienced in the use of cancer medicines.Halaven is given as intravenous (into a vein) injections over 21-day cycles. The dose to be given is calculated using the patient's height and weight. The calculated dose is given into a vein over two tofive minutes on days 1 and 8 of each cycle. Doctors should consider giving patients an antiemetic (a medicine that prevents nausea and vomiting) as Halaven may cause nausea or vomiting.Doses may be delayed or reduced if patients have very low levels of neutrophils (a type of white blood cell) and platelets (components that help the blood to clot) in their blood or if liver or kidney function is impaired. For more details on the use of Halaven including recommendations on dose reduction, see the summary of product characteristics (also part of the EPAR).

How does Halaven work?

The active substance in Halaven, eribulin, is similar to an anticancer substance called halichondrin B, which is found in the marine sponge Halichondria okadai. It attaches to a protein in cells called tubulin, which is important in the formation of the internal 'skeleton' that cells need to assemble when they divide. By attaching to tubulin in cancer cells, eribulin disrupts the formation of the skeleton, preventing the division and spread of the cancer cells.

How has Halaven been studied?

In breast cancer, Halaven was studied in two main studies involving a total of 1,864 patients. In the first study, Halaven was compared with other treatments in 762 women with advanced or metastatic breast cancer, who had previously undergone at least two other treatments, which included an anthracycline and a taxane. The women were given either Halaven or another approved cancer medicine chosen by their doctor. The main measure of effectiveness was overall survival (how long the patients lived).The second study involved 1,102 patients with advanced or metastatic breast cancer, with one or two previous treatments for advanced/metastatic cancer including an anthracycline and a taxane. The study compared Halaven with capecitabine (another cancer medicine). The main measures of effectiveness were overall survival and progression-free survival (how long the patients lived without their disease getting worse).Halaven was also studied in 143 patients with liposarcoma who had previously undergone at least two other treatments, which included an anthracycline. Halaven was compared with dacarbazine (another cancer medicine), and the main measure of effectiveness was overall survival.

What benefit has Halaven shown during the studies?

In the first study, when comparing Halaven with all the other treatments grouped together, Halaven was shown to be more effective at prolonging life. Women in the Halaven group lived for an average of 13.1 months, compared with 10.6 months in the group that received other treatments.In the second study, there was no significant difference in the average progression-free survival with Halaven (4.1 months) compared with capecitabine (4.2 months) or in the average overall survival with Halaven (15.9 months) compared with capecitabine (14.5 months).The third study showed that Halaven was effective at prolonging life in patients with liposarcoma: patients treated with Halaven lived for an average of 15.6 months, compared with 8.4 months for patients treated with dacarbazine.

What is the risk associated with Halaven?

The most common side effects with Halaven (seen in more than 1 patient in 10) are neutropenia (low levels of neutrophils, a type of white blood cell that fights infection), leucopenia (low white blood cell counts), anaemia (low red blood cell counts), reduced appetite, peripheral neuropathy (damage to the nerves in the extremities causing numbness, tingling and prickling sensations), headache, dyspnoea (difficulty breathing), cough, nausea (feeling sick), constipation, diarrhoea, vomiting, alopecia (hair loss), muscle and joint pain or pain in the back or limbs, fatigue (tiredness), pyrexia (fever) and weight loss. For the full list of all side effects reported with Halaven, see the package leaflet.Halaven must not be used in women who are breastfeeding. For the full list of restrictions, see the package leaflet.

Why has Halaven been approved?

The CHMP noted that, when Halaven was used as a third-line therapy for breast cancer (after at least two previous treatments with cancer medicines for advanced/metastatic disease), it prolonged the length of time that patients lived and the safety profile is within what is expected for chemotherapy medicines. When Halaven was used as breast cancer second-line therapy (after at least one previous cancer treatment for advanced/metastatic disease), Halaven was a valuable treatment option similar to capecitabine and with an acceptable safety profile. Additionally, Halaven prolonged the length of time that liposarcoma patients lived, and this was considered important as these patients have limited treatment options. Safety in this patient population was considered acceptable and similar to that in patients with breast cancer.The CHMP decided that Halaven's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Halaven?

A risk management plan has been developed to ensure that Halaven is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Halaven, including the appropriate precautions to be followed by healthcare professionals and patients.

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Harvoni

What is Harvoni and what is it used for?

Harvoni is an antiviral medicine used to treat adults and children from 3 years of age with chronic (long-term) hepatitis C, an infectious disease of the liver caused by the hepatitis C virus.Harvoni contains the active substances ledipasvir and sofosbuvir.

How is Harvoni used?

Harvoni can only be obtained with a prescription and treatment should be started and monitored by a doctor experienced in the management of patients with chronic hepatitis C.Harvoni is available as tablets and as granules in sachets. The granules are suitable for children and patients who cannot take tablets and they can be sprinkled on soft food, swallowed with water or swallowed dry without chewing.For adults the recommended dose of Harvoni is one tablet containing 90 mg ledipasvir and 400 mg sofosbuvir once a day. For children and young people aged up to 18 years the daily dose is based on their weight. There are several varieties (called genotypes) of hepatitis C virus and Harvoni is recommended for use in patients with virus of genotypes 1, 4, 5 and 6 and for some patients with genotype 3. The duration of treatment with Harvoni and whether it is used alone or in combination with another medicine called ribavirin depends on the genotype of the virus and the nature of the liver problems patients have, for example if they have liver cirrhosis (scarring) or their liver is not working properly.For more information about using Harvoni, see the package leaflet or contact your doctor or pharmacist.

How does Harvoni work?

The active substances in Harvoni, ledipasvir and sofosbuvir, block two proteins essential for the hepatitis C virus to multiply. Sofosbuvir blocks the action of a protein called NS5B RNA-dependent RNA polymerase, while ledipasvir targets a protein called NS5A. By blocking these proteins, Harvoni stops the hepatitis C virus from multiplying and infecting new cells.Sofosbuvir has been authorised as Sovaldi since January 2014.

What benefits of Harvoni have been shown in studies?

Harvoni has been investigated in three main studies involving a total of around 2,000 adults infected with hepatitis C virus of genotype 1 whose liver function was normal. In all three studies, the main measure of effectiveness was the number of patients whose blood tests did not show any sign of hepatitis C virus 12 weeks after the end of treatment.In these studies, patients were given Harvoni, with or without ribavirin, for 8, 12 or 24 weeks, depending on the characteristics of the patients. Around 94% to 99% of patients given Harvoni alone had no sign of the virus 12 weeks after treatment. Ribavirin was not needed for most patients.The studies also found that patients who have compensated cirrhosis (when the liver is scarred but it continues to work adequately) had a higher likelihood of clearing the virus when treatment was extended to 24 weeks. Patients whose infection was resistant to other antiviral medicines could also benefit from extending treatment to 24 weeks.Supportive data showed that Harvoni in combination with ribavirin would be of benefit for some patients with genotype 3 virus.Harvoni was also found effective in patients infected with virus of genotype 4, 5 and 6, those with decompensated cirrhosis (when the liver is scarred and does not work adequately) and those who had received a liver transplant.Harvoni was also investigated in children and young people aged 3 to 17 years infected with hepatitis C virus (mostly genotype 1). Results from 100 patients aged 12 to 17 years showed that 98% of them had no sign of the virus 12 weeks after the end of treatment. Similarly, there were no signs of the virus in 97% of children (33 out of 34) aged 3 to 5 years and in 99% of children (91 out of 92) aged 6 to 11 years.

What are the risks associated with Harvoni?

The most common side effects with Harvoni (which may affect more than 1 in 10 people) are tiredness and headache. Harvoni must not be used together with the cholesterol medicine rosuvastatin. It must also not be used together with the following medicines which can reduce the effects of Harvoni:• rifampicin and rifabutin (antibiotics);• carbamazepine, phenobarbital and phenytoin (medicines for epilepsy);• St John's wort (a herbal preparation used to treat depression and anxiety).For the full list of all side effects and restrictions of Harvoni, see the package leaflet.

Why is Harvoni authorised in the EU?

The European Medicines Agency decided that Harvoni's benefits are greater than its risks and it can be authorised for use in the EU.The Agency considered that treatment with Harvoni, with or without ribavirin, is highly effective for many patients with hepatitis C virus, including those who have had a liver transplant or who have compensated or decompensated cirrhosis. The side effects of Harvoni are manageable.

What measures are being taken to ensure the safe and effective use of Harvoni?

The company that markets Harvoni will carry out a study in patients who previously have had liver cancer to evaluate the risk of liver cancer returning after treatment with direct-acting antivirals such as Harvoni. This study is being carried out in light of data suggesting that patients treated with these medicines who have had liver cancer could be at risk of their cancer returning early.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Harvoni have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Harvoni are continuously monitored. Side effects reported with Harvoni are carefully evaluated and any necessary action taken to protect patients.

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Hbvaxpro

What is HBVaxPro?

HBVaxPro is a vaccine, which is available as a suspension for injection in vials and pre-filled syringes. It contains parts of the hepatitis B virus as the active substance. HBVaxPro is available in two strengths (10 and 40 micrograms/ml).

What is HBVaxPro used for?

HBVaxPro is used to vaccinate against hepatitis B in people who are at risk of exposure to the hepatitis B virus, as determined on the basis of official recommendations.The medicine can only be obtained with a prescription.

How is HBVaxPro used?

A course of vaccination should include at least three injections of HBVaxPro. The recommended dose for children from birth up to the age of 15 years is 0.5 ml of the lower strength (10 micrograms/ml) at each injection. For adults and adolescents aged 16 years of age and older, 1 ml of the lower strength is given at each injection. The higher strength (40 micrograms/ml) is used in patients who are undergoing or are about to undergo dialysis (a blood clearance technique).HBVaxPro is usually given as an injection into the muscle of the thigh in babies and infants, and of the shoulder in children, adolescents and adults.The timing of injections depends on the patient's age, strength of the immune system, response to vaccination and likelihood of exposure to the hepatitis B virus. For full details, see the summary of product characteristics (also part of the EPAR).

How does HBVaxPro work?

HBVaxPro is a vaccine. Vaccines work by 'teaching' the immune system (the body's natural defences) how to defend itself against a disease. HBVaxPro contains small amounts of 'surface antigens' (proteins from the surface) of the hepatitis B virus. When a person is given the vaccine, the immune system recognises the surface antigens as 'foreign' and makes antibodies against them. The immune system will then be able to produce antibodies more quickly when the person is naturally exposed to the viruses. This helps to protect against infection with the hepatitis B virus.The surface antigens in HBVaxPro are produced by a method known as 'recombinant DNA technology':they are made by a yeast that has received a gene (DNA), which makes it able to produce the proteins. The surface antigens are also 'adsorbed'. This means that they are fixed onto aluminium compounds to help stimulate a better response.HBVaxPro was specifically developed from a vaccine that was already in use in the European Union (EU), in order to produce a vaccine that does not contain the preservative thiomersal.

How has HBVaxPro been studied?

Because the active substance used in HBVaxPro was already authorised for use in the EU, there have been no formal studies with HBVaxPro. The company provided information comparing other vaccines with and without thiomersal, including studies of a vaccine that contains the same active substance as HBVaxPro.

What benefit has HBVaxPro shown during the studies?

The results of the studies presented showed that the thiomersal-free vaccines produced protective levels of antibodies against hepatitis B virus to a similar extent to the vaccines that contained thiomersal at the end of the vaccination course. This included the vaccines that contain the same active substance as HBVaxPro.

What is the risk associated with HBVaxPro?

The most common side effects with HBVaxPro (seen in between 1 and 10 patients in 100) are reactions at the injection site, including temporary soreness, erythema (redness) and induration (hardening). For the full list of all side effects reported with HBVaxPro, see the package leaflet.HBVaxPro should not be given to people who may be hypersensitive (allergic) to the active substance or any of the other ingredients including substances present at very low (trace) levels, such as formaldehyde and potassium thiocyanate, used in the manufacture of the vaccine. Vaccination should be postponed for people with a severe illness with fever.

Why has HBVaxPro been approved?

The CHMP concluded that the removal of thiomersal from vaccines did not reduce their effectiveness in protecting against hepatitis B virus infection, but reduced their risks. Therefore, the Committee decided that HBVaxPro's benefits are greater than its risks and recommended that it be given marketing authorisation.

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Hefiya

What is Hefiya and what is it used for?

Hefiya is a medicine that acts on the immune system and is used to treat the following conditions:• plaque psoriasis (a disease causing red, scaly patches on the skin);• psoriatic arthritis (a disease causing red, scaly patches on the skin with inflammation of the joints);• rheumatoid arthritis (a disease causing inflammation of the joints);• axial spondyloarthritis (inflammation of the spine causing back pain), including ankylosing spondylitis and when X-ray does not show disease but there are clear signs of inflammation;• polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis (both rare diseases causing inflammation in the joints);• Crohn's disease (a disease causing inflammation of the gut);• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);• hidradenitis suppurativa (acne inversa), a long-term skin disease that causes lumps, abscesses (collections of pus) and scarring on the skin;• non-infectious uveitis (inflammation of the layer beneath the white of the eyeball).Hefiya is mostly used in adults when their conditions are severe, moderately severe or getting worse, or when patients cannot use other treatments. For more information on the use of Hefiya in all conditions, including when it can be used in children, see the package leaflet or contact your doctor or pharmacist.Hefiya contains the active substance adalimumab and is a 'biosimilar medicine'. This means that Hefiya is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Hefiya is Humira. For more information on biosimilar medicines, see here.

How is Hefiya used?

Hefiya is available as a solution for injection under the skin in a pre-filled syringe or pen and is usuallygiven every 2 weeks. The dose and frequency of injection depends on the condition to be treated and the dose for a child is usually calculated according to the child's weight; because Hefiya is only available in doses of 40 mg, it is not suitable for children who need less than a 40-mg dose. After training, patients or their carers may inject Hefiya if their doctor considers it appropriate.Hefiya can only be obtained by prescription and treatment must be started and supervised by a doctor who has experience in the treatment of the diseases for which Hefiya is used. Eye specialists treating uveitis should also take advice from doctors who have experience of using Hefiya.For more information about using Hefiya, see the package leaflet or contact your doctor or pharmacist.

How does Hefiya work?

The active substance in Hefiya, adalimumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a substance in the body called tumour necrosis factor (TNF).TNF is involved in causing inflammation and is found at high levels in patients with the diseases that Hefiya is used to treat. By attaching to TNF, adalimumab blocks its activity, thereby reducing inflammation and other symptoms of the diseases.

What benefits of Hefiya have been shown in studies?

Laboratory studies comparing Hefiya with Humira have shown that the active substance in Hefiya is highly similar to that in Humira in terms of structure, purity and biological activity. Studies have also shown that giving Hefiya produces similar levels of the active substance in the body to giving Humira.In addition Hefiya was as effective as Humira in a study involving 465 patients with moderate or severe plaque psoriasis. The proportion of patients who had at least a 75% reduction in symptoms after 16 weeks of treatment was 68% with Hefiya and 63% with Humira.Because Hefiya is a biosimilar medicine, the studies on effectiveness and safety of adalimumab carried out with Humira do not all need to be repeated for Hefiya.

What are the risks associated with Hefiya?

The most common side effects with adalimumab (seen in more than 1 patient in 10) are infections (including in the nose, throat and sinuses), injection site reactions (redness, itching, bleeding, pain or swelling), headache and muscle and bone pain.Like other medicines of its class, Hefiya may affect the ability of the immune system to fight off infections and cancer, and there have been some cases of serious infections and blood cancers in patients using adalimumab.Other rare serious side effects (which may affect up to 1 in 1,000 people) include failure of bone marrow to produce blood cells, disorder of the nerves, lupus and lupus-like conditions (where the immune system attacks the patient's own tissues, causing inflammation and organ damage), and Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and painful rash affecting the skin, mouth, eyes and genitals).Hefiya must not be used in patients with active tuberculosis or other severe infections, or in patients with moderate to severe heart failure (an inability of the heart to pump enough blood around the body).For the full list of side effects and restrictions with Hefiya, see the package leaflet.

Why is Hefiya authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Hefiya has a highly similar structure, purity and biological activity to Humira and is distributed in the body in the same way.In addition, a study in psoriasis has shown that the effects of the medicine are equivalent to those of Humira in this condition. All these data were considered sufficient to conclude that Hefiya will behave in the same way as Humira in terms of effectiveness and safety in its approved uses. Therefore, the Agency's view was that, as for Humira, the benefit of Hefiya outweighs the identified risk and it can be authorised.

What measures are being taken to ensure the safe and effective use of Hefiya?

Patients treated with Hefiya must be given a reminder card with information on the safety of the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hefiya have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hefiya are continuously monitored. Side effects reported with Hefiya are carefully evaluated and any necessary action taken to protect patients.

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Helicobacter Test Infai

What is Helicobacter Test INFAI?

Helicobacter Test INFAI is a diagnostic test. It is available as a jar containing a powder to be made up into a solution for drinking. The powder is the active substance 13C-urea (45 mg for children or 75 mg for adults).

What is Helicobacter Test INFAI used for?

Helicobacter Test INFAI is used to diagnose Helicobacter pylori infection in the stomach and duodenum (the part of the gut just below the stomach). H. pylori is a bacterium that is a factor in diseases such as dyspepsia (heartburn, bloating and nausea), gastritis (inflammation of the stomach), and peptic ulcer disease (ulcers in the stomach or the duodenum).Helicobacter Test INFAI can be used to test adults, adolescents who are likely to have peptic ulcer disease, and children aged three to 11 years. It can only be used in children when invasive tests (taking a sample from the stomach using a probe) cannot be carried out or have given questionable results, or to check that H. pylori has been eliminated after a specific treatment to clear up the infection. The medicine can only be obtained with a prescription.

How is Helicobacter Test INFAI used?

Helicobacter Test INFAI is a breath test: breath samples are collected, which are then sent out for analysis to a specialised laboratory.To carry out the test, the patient must collect four samples, two before taking Helicobacter Test INFAI and two thereafter. The patient should not eat for at least six hours, preferably overnight, before taking the test. Firstly, the patient collects two breath samples, using the tubes or bags supplied with Helicobacter Test INFAI. The patient then takes a 'test meal' (either 200 ml of pure orange juice or 1 g of citric acid dissolved in 200 ml water), followed by the solution of Helicobacter Test INFAI dissolved in water. Finally, 30 minutes after drinking the solution, the patient collects a further two breath samples. In children aged three to 11 years, the 'test meal' should be 100 ml of pure orange juice. For full information on how the test is carried out, see the Package Leaflet.

How does Helicobacter Test INFAI work?

The active substance in Helicobacter Test INFAI, 13C-urea, is the natural chemical urea that has been labelled with carbon-13 (13C). This means that it contains 13C, a rare form of the carbon atom, instead of carbon-12 (12C), the form that is the most common in nature.(c)EMEA 2007 Reproduction and/or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledgedH. pylori contain enzymes called ureases that make it able to break down urea into carbon dioxide, which is then removed in the breath. When the patient takes Helicobacter Test INFAI, the 13C-urea contained in the test is broken down by H Pylori into carbon dioxide that also contains 13C. This labelled carbon dioxide can be measured by specialised laboratories using a technique called mass spectrometry. If there is labelled carbon dioxide in the breath sample after 30 minutes (a positive test), this means that the patient is infected with H. pylori. If there is no labelled carbon dioxide in the breath, this means there are no bacteria in the stomach or duodenum.

How has Helicobacter Test INFAI been studied?

Helicobacter Test INFAI has been tested in four studies in adult patients involving a total of 561 patients and one study in 335 children and adolescents. All received 75 mg of 13C-urea, except 204 children under the age of 11 who received 45 mg. One of the studies in adults was carried out in patients after they had received antibiotics to treat their infection. In all studies, patients underwent an endoscopy and histology (when a probe is inserted in the stomach to take a sample and the sample is then analysed) as well as a breath test with Helicobacter Test INFAI, and the results of the two tests were compared.

What benefit has Helicobacter Test INFAI shown during the studies?

In all studies, the results of the test done using Helicobacter Test INFAI agreed with the results obtained with the endoscopy and histology in over 95% of cases.

What is the risk associated with Helicobacter Test INFAI?

There are no known side effects of the test. However, if the patient vomits during the test, the test will need to be done again, but not until at least the following day.Helicobacter Test INFAI should not be used in patients who have, or may have gastric (stomach) infection or atrophic gastritis (stomach inflammation that causes the breakdown of the stomach lining), as these might interfere with the breath test.

Why has Helicobacter Test INFAI been approved?

The Committee for Medicinal products for Human Use (CHMP) decided that Helicobacter Test INFAI's benefits are greater than its risks for the in vivo diagnosis of gastroduodenal H. pylori infection in adults, adolescents who are likely to have peptic ulcer disease, and children aged three to 11 years for the evaluation of the success of eradication treatment, or when invasive tests cannot be performed, or when there are discordant results arising from invasive tests. The Committee recommended that Helicobacter Test INFAI be given marketing authorisation.

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Hemangiol

What is Hemangiol and what is it used for?

Hemangiol is a medicine that contains the active substance propranolol. It is used to treat children with proliferating infantile haemangioma, which are benign tumours (abnormal non-cancerous growths) of blood vessels.Hemangiol is used in infants with serious complications, such as painful ulcers, scarring and breathing difficulties, who require systemic therapy (treatment which can have an effect on the whole body).Treatment with Hemangiol is started in babies aged five weeks to five months.

How is Hemangiol used?

Hemangiol can only be obtained with a prescription. Treatment should be started by a doctor who has experience in the diagnosis, treatment and management of infantile haemangioma. Treatment should be started in appropriate facilities in case serious side effects develop.Hemangiol is available as a solution to be taken by mouth. The recommended starting dose of Hemangiol is 0.5 mg per kilogram bodyweight (0.5 mg/kg), twice a day (at least 9 hours apart). The dose is progressively increased to a maintenance dose of 1.5 mg/kg twice a day. The dose is given to the baby during or immediately after a feed using the oral syringe provided. Treatment with Hemangiol should last for six months and the child should be monitored once a month, in particular for dose adjustments. For further information, see the package leaflet.

How does Hemangiol work?

The active substance in Hemangiol, propranolol, belongs to a group of medicines called beta-blockers, which have been widely used to treat several conditions in adults, including diseases of the heart and high blood pressure.Although it is not exactly known how Hemangiol works in proliferative infantile haemangioma, it is thought to do so by several mechanisms including narrowing the blood vessels and so decreasing blood supply to the haemangioma, blocking the formation of new blood vessels in the growth, triggering cell death of the abnormal blood vessel cells and blocking the effect of certain proteins (called VEGF and bFGF), which are important for the growth of blood vessels.

What benefits of Hemangiol have been shown in studies?

Hemangiol was investigated in one main study involving 460 children aged from five weeks to five months at the start of treatment and who had proliferative infantile haemangioma that required systemic therapy. The study compared different doses of propranolol with placebo (a dummy treatment) and the main measure of effectiveness was based on whether the haemangiomas disappeared completely or almost completely after 6 months of treatment.Hemangiol at a dose of 3 mg/kg per day (given as two separate doses of 1.5 mg/kg) given for 6 months was shown to be more effective than placebo. In around 60% (61 out of 101) of children treated with the most effective dose of Hemangiol (3 mg/kg/day for 6 months), haemangiomas disappeared completely or almost completely compared with around 4% (2 out of 55) in children who received placebo.

What are the risks associated with Hemangiol?

The most common side effects with Hemangiol (which may affect more than 1 in 10 children) are sleep disorders, respiratory tract infections such as bronchitis (inflammation of the airways in the lungs), diarrhoea and vomiting. Serious side effects observed with Hemangiol include bronchospasm (temporary narrowing of the airways) and low blood pressure. For the full list of all side effects reported with Hemangiol, see the package leaflet.Hemangiol must not be used in: premature babies who have not reached the corrected age of 5 weeks (the corrected age is the age a premature baby would be if he/she had been born on the due date); breastfed children if the mother is being treated with medicines that must not be used with propranolol; children with asthma or with a history of bronchospasm; children with certain diseases of the heart and blood vessels, such as low blood pressure; and children who tend to have low blood sugar levels. For the full list of restrictions, see the package leaflet.

Why is Hemangiol approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Hemangiol's benefits are greater than its risks and recommended that it be approved for use in the EU. The Committee concluded that Hemangiol was an effective treatment for haemangioma. Regarding safety, the CHMP considered that the safety profile is acceptable; the risks identified are those already known for propranolol and can be appropriately managed.

What measures are being taken to ensure the safe and effective use of Hemangiol?

A risk management plan has been developed to ensure that Hemangiol is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Hemangiol, including the appropriate precautions to be followed by healthcare professionals and patients.The Company will provide caregivers who will give Hemangiol to children with an educational pack to inform them of the need to monitor children for certain side effects and how to manage them. It will also provide instructions on how to give the medicine correctly, in order to avoid the risk of low blood sugar levels.Further information can be found in the summary of the risk management plan.

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Hemgenix

What is Hemgenix and what is it used for?

Hemgenix is a medicine used to treat adults with severe and moderately severe haemophilia B, an inherited bleeding disorder caused by the lack of factor IX (a protein needed to produce blood clots to stop bleeding). It is used in adults who have not developed inhibitors (proteins made by the body's natural defenses) against factor IX.Haemophilia B is rare, and Hemgenix was designated an 'orphan medicine' (a medicine used in rare diseases) on 21 March 2018. Further information on the orphan designation can be found here: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-18-1999.Hemgenix contains the active substance etranacogene dezaparvovec and is a type of advanced therapy medicine called a 'gene therapy product'. This is a type of medicine that works by delivering genes into the body.

How is Hemgenix used?

The medicine can only be obtained with a prescription. Treatment must be started under the supervision of a doctor experienced in the treatment of haemophilia and/or bleeding disorders, in a facility equipped to promptly treat infusion-related reactions.Hemgenix is given once, as a single infusion (drip) into a vein lasting one to two hours. The dose depends on the patient's body weight.Before receiving the infusion, the patient will have a number of tests, including tests to check their liver health and if they have factor IX inhibitors. As it will be several weeks before Hemgenix shows any effects, patients will be monitored closely for at least 3 months after the infusion to decide if they need additional treatment with factor IX replacement therapy.For more information about using Hemgenix, see the package leaflet or contact your doctor or pharmacist.

How does Hemgenix work?

Patients with haemophilia B have mutations (changes) in a gene which the body needs to make the clotting protein Factor IX, resulting in either a partial or complete lack of its activity.The active substance in Hemgenix, etranacogene dezaparvovec, is based on a virus that contains copies of the gene responsible for producing factor IX. When given to the patient, the virus will carry the factor IX gene to the liver cells, enabling them to produce the missing factor IX and thereby limit bleeding episodes.The type of virus used in this medicine (adeno-associated virus) does not cause disease in humans.

What benefits of Hemgenix have been shown in studies?

A study in 54 adult male patients with severe or moderately severe haemophilia B found that Hemgenix was more effective at reducing bleeding events than factor IX replacement therapy. The study compared the number of bleeding episodes patients had with factor IX replacement therapy during a 6-month period before receiving Hemgenix with the number experienced over a 1-year period after achieving stable factor IX levels with Hemgenix. Data from the study showed that Hemgenix reduced the yearly bleeding rate from 4.2 to 1.5 bleeds per year. The study also found that Hemgenix was effective at increasing factor IX levels, with 96% of patients (52 out of 54) no longer needing factor IX replacement therapy for up to 2 years after the infusion.

What are the risks associated with Hemgenix?

The most common side effects with Hemgenix (which may affect more than 1 in 10 people) are headache, increased levels of certain liver enzymes and flu-like symptoms.For the full list of side effects of Hemgenix, see the package leaflet.Hemgenix must not be given to people who are hypersensitive (allergic) to any of its ingredients, who have an active or chronic (long-term) infection that is not controlled by medicines, or who have advanced liver fibrosis or liver cirrhosis (scarring of the liver).

Why is Hemgenix authorised in the EU?

At the time of approval, patients with severe haemophilia B required lifelong treatment with factor IX replacement therapy. Hemgenix, given as a single infusion, was effective at preventing bleeding over a period of at least 2 years, thus enabling patients to discontinue treatment with factor IX replacement therapy, which reduces the burden caused by treating the disease. There are some uncertainties about how long the benefits of Hemgenix last, given that the main study evaluated the response in a small number of patients for up to 2 years. Although the long-term safety data were limited, the safety profile was considered acceptable.Hemgenix has been given 'conditional authorisation'. This means that the European Medicines Agency decided that the benefits of Hemgenix are greater than its risks, but the company will have to provide additional evidence after authorisation.Conditional authorisation is granted on the basis of less comprehensive data than are normally required. It is granted for medicines that fulfil an unmet medical need to treat serious diseases and when the benefits of having them available earlier outweigh any risks associated with using the medicines while waiting for further evidence. Every year, the European Medicines Agency will review any new information that becomes available until data become comprehensive and this overview will be updated as necessary.

What information is still awaited for Hemgenix?

Since Hemgenix has been given conditional authorisation, the company that markets this medicine will provide additional data from ongoing studies on the long-term safety and effectiveness of the medicine, including how long the response lasts, in patients with severe to moderately severe haemophilia B. The company will also provide data from a registry of patients treated with Hemgenix to study its long-term safety and effectiveness.

What measures are being taken to ensure the safe and effective use of Hemgenix?

The company that markets Hemgenix will provide educational materials to patients or their carers and to healthcare professionals, with information on the benefits, risks and uncertainties about the long-term effects and safety of the medicine. Patients must also be given a patient card to inform healthcare professionals that they have been treated with Hemgenix.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hemgenix have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hemgenix are continuously monitored. Suspected side effects reported with Hemgenix are carefully evaluated and any necessary action taken to protect patients.

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Hemlibra

What is Hemlibra and what is it used for?

Hemlibra is a medicine used to prevent or reduce bleeding in patients with haemophilia A (an inherited bleeding disorder caused by lack of factor VIII).The medicine is used in:- patients who have developed factor VIII inhibitors, which are antibodies in the blood that act against factor VIII medicines and prevent them from working properly;- patients without factor VIII inhibitors if their haemophilia A is severe or moderate (with severe bleeding phenotype).Hemlibra contains the active substance emicizumab.

How is Hemlibra used?

Hemlibra can only be obtained with a prescription and treatment should be started by a doctor experienced in the treatment of haemophilia or bleeding disorders.Hemlibra is available as a solution for injection under the skin in the belly, thigh or upper arm. Patients or their carers may inject Hemlibra at home once they have been trained appropriately. The arm injection should only be given by a caregiver or healthcare professional.The day before starting Hemlibra treatment, patients should stop treatment with bypassing agents (medicines used to prevent bleeding in patients with factor VIII inhibitors, such as activated prothrombin complex concentrate or recombinant factor VIIa).The dose of Hemlibra depends on the patient's bodyweight. The recommended dose is 3 mg per kg of bodyweight once every week for the first 4 weeks. Patients can then continue with either 1.5 mg/kg once every week, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks. Hemlibra is intended for longterm use.For more information about using Hemlibra, see the package leaflet or contact your doctor or pharmacist.

How does Hemlibra work?

Patients with haemophilia A lack factor VIII, a substance in the body that helps the blood to clot. The active substance in Hemlibra, emicizumab, is a monoclonal antibody which has been designed to do the work that factor VIII normally does - bringing together 2 clotting factors (IXa and X) as part of a chain of reactions needed for blood to clot.Because emicizumab has a different structure to factor VIII, it is not affected by factor VIII inhibitors. However, the development of anti-emicizumab antibodies leading to loss of efficacy has been uncommonly observed during clinical studies.

What benefits of Hemlibra have been shown in studies?

A study in 109 patients showed that Hemlibra is effective at preventing bleeding in patients with haemophilia A of any severity who have factor VIII inhibitors: patients given Hemlibra for prevention had fewer bleeds that needed to be treated (equivalent to 3 per year) than patients who received no preventive treatment (equivalent to 23 per year).The study also enrolled patients who were already taking preventive treatment with medicines known as bypassing agents. When these patients were switched to Hemlibra, the number of treated bleeds per patient fell from the equivalent of around 16 bleeds per year before the switch to the equivalent of around 3 bleeds per year afterwards. Patients receiving Hemlibra also had better quality of life scores than those who were not given Hemlibra.A study in 152 patients showed that Hemlibra is also effective at preventing bleeding in patients with severe haemophilia A without factor VIII inhibitors: patients given Hemlibra for prevention had around 1 bleed per year that needed to be treated, compared with 38 bleeds per year in patients who received no preventive treatment.A study in 51 patients showed that Hemlibra was effective at preventing bleeding in patients with moderate haemophilia A without factor VIII inhibitors who needed preventative treatment because of their severe bleeding phenotype. Patients given Hemlibra had, on average, around 1 bleed per year that required treatment.

What are the risks associated with Hemlibra?

The most common side effects with Hemlibra (which may affect 1 in 10 people or more) are itching or pain at the place where it is injected, joint pain and headache.The most serious side effects, which may affect up to 1 in 100 people, are thrombotic microangiopathy (clots in small blood vessels) and thrombosis (formation of blood clots in the vessels), including cavernous sinus thrombosis (clotting at the base of the brain) and superficial vein thrombosis (clotting in veins under the skin, usually in the arms or legs) with skin damage.For the full list of side effects and restrictions with Hemlibra, see the package leaflet.

Why is Hemlibra authorised in the EU?

Only a few medicines, called bypassing agents, are suitable for patients with haemophilia A who have developed factor VIII inhibitors. Hemlibra reduces bleeding episodes in these patients and improvestheir quality of life. Hemlibra also reduces bleeding in patients with moderate or severe haemophilia A without factor VIII inhibitors.The side effects with Hemlibra are tolerable and information on how to manage the risks of serious side effects is included in the prescribing information and educational materials.The European Medicines Agency therefore decided that Hemlibra's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Hemlibra?

The company that markets Hemlibra will issue educational materials for healthcare professionals, patients, carers and laboratory professionals about abnormal clotting side effects, the risk of taking Hemlibra at the same time as bypassing agents and how laboratory tests should be carried out for these patients. Materials will include product information, guides, and a patient alert card.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hemlibra have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hemlibra is continuously monitored. Side effects reported with Hemlibra are carefully evaluated and any necessary action taken to protect patients.

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Hepcludex

What is Hepcludex and what is it used for?

Hepcludex is an antiviral medicine used to treat chronic (long-term) hepatitis delta virus (HDV) infection in adults with compensated liver disease (when the liver is damaged but is still able to work), when the presence of viral RNA (genetic material) has been confirmed by blood tests.HDV is an 'incomplete' virus, because it cannot replicate in cells without the help of another virus, the hepatitis B virus. Because of this, patients infected with the virus always also have hepatitis B.HDV infection is rare, and Hepcludex was designated an 'orphan medicine' (a medicine used in rare diseases) on 19 June 2015. Further information on the orphan designation can be found on the EMA websiteHepcludex contains the active substance bulevirtide.

How is Hepcludex used?

Hepcludex can only be obtained with a prescription and treatment should be started only by a doctor experienced in the management of patients with HDV infection.The medicine is available as an injection to be given under the skin. It can be given on its own, or in combination with a 'nucleoside/nucleotide analogue' medicine for the treatment of the underlying hepatitis B infection. Treatment should continue for as long as the patient benefits from it.For more information about using Hepcludex, see the package leaflet or contact your doctor or pharmacist.

How does Hepcludex work?

The active substance in Hepcludex, bulevirtide, works by attaching to and blocking a receptor (target) through which the hepatitis delta and hepatitis B viruses enter liver cells. By blocking the entry of the virus into the cells, Hepcludex limits the ability of HDV to replicate, preventing the spread of the virus in the liver and thereby reducing inflammation.

What benefits of Hepcludex have been shown in studies?

Two main studies showed that Hepcludex was effective at clearing all or 99% of the HDV genetic material (RNA) from the blood.In the first study, 55 out of 90 patients treated with Hepcludex plus tenofovir (a medicine for hepatitis B) had substantial reductions in HDV replication after 6 months, compared with 1 out of 28 patients given tenofovir alone. Patients treated with Hepcludex also showed a reduction in the blood levels of the liver enzyme ALT, indicating an improvement of liver disease.Similar results were seen in the second study where 8 out of 15 patients given Hepcludex plus peginterferon alfa (another medicine for hepatitis B) for 48 weeks no longer had detectable levels of HDV RNA 6 months after their treatment. Of the 15 patients treated with Hepcludex alone, one no longer had detectable levels of HDV RNA. Of the 15 patients treated with peginterferon alfa alone, no patient achieved this result.In a larger, confirmatory study in 150 patients, 45% (22 out of 49) of patients given a low dose of Hepcludex and 48% (24 out of 50) of patients given a higher dose of Hepcludex had almost all of their HDV RNA cleared after 48 weeks, compared with 2% (1 out of 51) of untreated patients.

What are the risks associated with Hepcludex?

For the full list of side effects and restrictions of Hepcludex, see the package leaflet.The most common side effects with Hepcludex (which may affect more than 1 in 10 people) include raised levels of bile salts in the blood, headache, itching and reactions at the site of injection.The most common serious side effect is a flare-up of liver inflammation after stopping Hepcludex.

Why is Hepcludex authorised in the EU?

Available data have shown a beneficial effect of Hepcludex on viral replication and liver inflammation in patients with HDV infection. As for its safety, the side effects seen with Hepcludex were considered acceptable.The European Medicines Agency therefore decided that Hepcludex's benefits are greater than its risks and it can be authorised for use in the EU.Hepcludex was originally given 'conditional authorisation' because there was more evidence to come about the medicine. The company has since provided comprehensive information confirming the findings from earlier studies. As a result, the conditional authorisation has been switched to a standard one.

What measures are being taken to ensure the safe and effective use of Hepcludex?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hepcludex have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hepcludex are continuously monitored. Side effects reported with Hepcludex are carefully evaluated and any necessary action taken to protect patients.

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Heplisav B

What is Heplisav B and what is it used for?

Heplisav B is a vaccine for preventing hepatitis B virus infection in adults. It is also likely to prevent infection with the hepatitis D virus as this virus is only present in people with hepatitis B infection.Heplisav B is used in accordance with official recommendations. It contains a protein from the hepatitis B virus.

How is Heplisav B used?

Heplisav B is given as two injections into the muscle of the upper arm 1 month apart.For more information about using Heplisav B, see the package leaflet or contact your doctor or pharmacist.

How does Heplisav B work?

Heplisav B is a vaccine. Vaccines work by preparing the immune system (the body's natural defences) to defend the body against a specific disease.Heplisav B contains a protein found on the hepatitis B virus. When a person is given the vaccine, the immune system recognises the protein in the vaccine as foreign and makes antibodies against it. If the person then comes into contact with virus, these antibodies, together with other components of the immune system, will be able to fight off the virus more effectively and so help protect the person against the infection. The vaccine also contains an adjuvant to stimulate a better response.

What benefits of Heplisav B have been shown in studies?

Results from three main studies involving over 13,000 participants showed that Heplisav B was more effective than Engerix B (another hepatitis B vaccine) at stimulating an immune response against the virus. Taken together the studies found that around 96% of people given Heplisav B developed enough antibodies to kill off the virus and protect against the disease compared with 80% of those given Engerix B.People given Heplisav B also had higher levels of antibodies and sufficient levels developed earlier with Heplisav B than with Engerix B.

What are the risks associated with Heplisav B?

The most common side effects with Heplisav B (which may affect more than 1 in 10 people) are pain at the injection site, headache, feeling generally unwell, tiredness, muscle pain and fever.People who have a severe allergic reaction after the first dose should not have a second dose. The vaccine should also not be given to people allergic to yeast.For the full list of restrictions and side effects, see the package leaflet.

Why is Heplisav B authorised in the EU?

Studies have shown that Heplisav B provides protection against hepatis B infection in 96% of people given the vaccine. Side effects occurred slightly less frequently with this vaccine than with the comparator vaccine (Engerix B) and they are considered manageable.The European Medicines Agency therefore concluded that Heplisav B's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Heplisav B?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Heplisav B have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Heplisav B are continuously monitored. Side effects reported with Heplisav B are carefully evaluated and any necessary action taken to protect patients.

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Herceptin

What is Herceptin?

Herceptin is a medicine that contains the active substance trastuzumab. It is available as a powder to be made up into a solution for infusion (drip) into a vein or as a solution for injection under the skin.

What is Herceptin used for?

Herceptin is used to treat the following types of cancer:• early breast cancer (when the cancer has spread within the breast or to the glands under the arm but not to other parts of the body) after surgery, chemotherapy (medicines to treat cancer), and radiotherapy (treatment with radiation) if applicable. It can also be used earlier in treatment, in combination with chemotherapy. For tumours that are locally advanced (including those that are inflammatory) or more than 2 cm wide, Herceptin is used before surgery in combination with chemotherapy and then again after surgery on its own;• metastatic breast cancer (cancer that has spread to other parts of the body). It is used on its own in patients in whom previous treatments have failed. It is also used in combination with other anticancer medicines: with paclitaxel or docetaxel, or with an aromatase inhibitor; When used as an infusion into a vein, Herceptin can also be used for:• metastatic gastric (stomach) cancer, in combination with cisplatin and either capecitabine or 5-fluorouracil (other anticancer medicines).Herceptin can only be used when the cancer has been shown to 'overexpress HER2': this means that the cancer produces a protein called HER2 in large quantities on the surface of the tumour cells, which makes the tumour cells grow more quickly. HER2 is overexpressed in about a quarter of breast cancers and a fifth of gastric cancers.The medicine can only be obtained with a prescription.

How is Herceptin used?

Herceptin treatment should only be started by a doctor who has experience in the use of anticancer medicines.When given as an infusion into a vein, Herceptin is given over 90 minutes every week or every three weeks for breast cancer, and every three weeks for gastric cancer. For early breast cancer, treatment is given for a year or until the disease comes back, and for metastatic breast or gastric cancer, treatment is continued for as long as it remains effective. The recommended dose depends on the patient's body weight and depends on the condition to be treated and whether Herceptin is given weekly or three-weekly.The infusion can be associated with allergic reactions, so the patient should be monitored during and after the infusion. Patients who tolerate the first 90-minute infusion can receive subsequent infusions over 30 minutes.When given as an injection under the skin, the recommended dose of Herceptin does not depend on the patient's body weight and is 600 mg given over 2 to 5 minutes every three weeks.

How does Herceptin work?

The active substance in Herceptin, trastuzumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found on certain cells in the body. Trastuzumab has been designed to attach to HER2, which is overexpressed in about a quarter of breast cancers and a fifth of gastric cancers. By attaching to HER2, trastuzumab activates cells of the immune system, which then kill the tumour cells.Trastuzumab also stops HER2 producing signals that cause the tumour cells to grow.

How has Herceptin been studied?

In early breast cancer, Herceptin given by infusion into a vein has been studied in five main studies involving around 10,000 patients. The first study was in patients who had first been treated with surgery, chemotherapy and radiotherapy (if applicable). Half of the patients received Herceptin, while the other half did not receive it. Three studies looked at the effects of giving Herceptin earlier in treatment, in combination with chemotherapy. A fifth study, in patients with locally advanced or inflammatory breast cancer, looked at the effect of giving Herceptin before surgery in combination chemotherapy and then again after surgery on its own. The studies measured how many patients died or had their cancer reappear or worsen.In metastatic breast cancer, Herceptin given by infusion into a vein has been studied in four main studies: one looked at Herceptin on its own in 222 patients whose previous treatment had failed; two looked at Herceptin in combination with paclitaxel or docetaxel in a total of 657 patients; and one looked at the combination of Herceptin and anastrozole (an aromatase inhibitor) in 208 women who had been through the menopause. These studies measured how many patients responded to treatment, or how long they lived without their cancer getting worse.In metastatic gastric cancer, Herceptin given by infusion into a vein in combination with cisplatin and either capecitabine or 5-fluorouracil was compared with the same combination but without Herceptin in one main study involving 594 patients. The main measure of effectiveness was how long the patients survived.Herceptin given as an injection under the skin was compared with Herceptin given by infusion into a vein in an additional study involving 596 patients with early breast cancer. Herceptin was given before surgery and the main measure of effectiveness was response to treatment assessed by measuring the proportion of patients who had no cancerous cells found on examination of the breast removed by surgery. The study also compared the levels of the active substance in the blood for Herceptin given under the skin and into a vein to demonstrate that sufficient levels are obtained when given under the skin.All the above studies were in patients whose cancers expressed HER2.

What benefit has Herceptin shown during the studies?

In the first study in early breast cancer, 8% of the patients who received Herceptin by infusion into a vein after having completed surgery, chemotherapy and radiotherapy (if applicable) experienced a reappearance of their cancer in the first year of treatment (127 out of 1,693), compared with 13% of the patients who did not receive it (219 out of 1,693). The addition of Herceptin to chemotherapy resulted in fewer patients experiencing a reappearance of their cancer over three years. The difference was between 4.8 and 11.8% depending on the type of chemotherapy. For locally advanced breast cancer, giving Herceptin by infusion into a vein before surgery in combination with chemotherapy and then again after surgery on its own resulted in fewer patients dying or having their cancer worsen or reappear over three years: after three years, 65% of patients given Herceptin were still alive without having their cancer worsen or reappear as compared to 52% in patients not given Herceptin.In metastatic breast cancer, 15% of the patients whose previous treatment had failed responded to Herceptin given by infusion into a vein. When used in combination with paclitaxel or docetaxel, around half of the patients responded to Herceptin, compared with around a quarter of those receiving paclitaxel or docetaxel alone. Patients receiving Herceptin in combination with anastrozole also lived for longer without their cancer getting worse (4.8 months, on average) than those receiving anastrozole alone (2.4 months, on average).In metastatic gastric cancer, the patients with higher levels of HER2 expression who received Herceptin by infusion into a vein survived for an average of 16.0 months, compared with 11.8 months in those receiving cisplatin and either capecitabine or 5-fluorouracil alone.When given by injection under the skin, Herceptin had the same effectiveness as when given by infusion into a vein. The levels of the active substance were at least as high as when Herceptin is given by infusion into a vein.

What is the risk associated with Herceptin?

The most common or serious side effects with Herceptin are heart problems, infections, lung and blood problems, and reactions related to the way Herceptin is given. In the study comparing Herceptin given under the skin and by infusion into a vein, some side effects have been reported more frequently with Herceptin given under the skin: infections with or without neutropenia (low levels of neutrophils, a type of white blood cells), heart problems, reactions related to the way Herceptin is given and high blood pressure. For the full list of all side effects reported with Herceptin, see the package leaflet.Herceptin must not be used in people who are hypersensitive (allergic) to trastuzumab, mouse proteins or to any of the other ingredients. It must not be used in patients who have serious breathing problems when they are at rest because of advanced cancer, or who need oxygen therapy.Herceptin can cause cardiotoxicity (harm to the heart), including heart failure (when the heart does not work as well as it should). Care should be taken if it is given to patients who already have heart problems or high blood pressure, and all patients need to be monitored during and after treatment to check their heart.

Why has Herceptin been approved?

The CHMP decided that Herceptin's benefits are greater than its risks and recommended that it be given marketing authorisation.

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Herzuma

What is Herzuma and what is it used for?

Herzuma is a cancer medicine used to treat the following conditions:• early breast cancer (when the cancer has spread within the breast or to the glands under the arm but not to other parts of the body) after surgery, chemotherapy (medicines to treat cancer), and radiotherapy (treatment with radiation) if applicable. It can also be used earlier in treatment, in combination with chemotherapy. For tumours that are locally advanced (including those that are inflammatory) or more than 2 cm wide, Herzuma is used before surgery in combination with chemotherapy and then again after surgery on its own;• metastatic breast cancer (cancer that has spread to other parts of the body). It is used on its own in patients in whom previous treatments have failed. It is also used in combination with other cancer medicines: with paclitaxel or docetaxel, or with another class of medicines called aromatase inhibitors;• metastatic gastric (stomach) cancer, in combination with cisplatin and either capecitabine or fluorouracil (other cancer medicines).Herzuma can only be used when the cancer has been shown to 'overexpress HER2': this means that the cancer produces a protein called HER2 in large quantities on the surface of the tumour cells. HER2 is overexpressed in about a quarter of breast cancers and a fifth of gastric cancers.Herzuma is a 'biosimilar medicine'. This means that Herzuma is similar to another biological medicine (the 'reference medicine') that is already authorised in the European Union (EU). The reference medicine for Herzuma is Herceptin. For more information on biosimilar medicines, see here.Herzuma contains the active substance trastuzumab.

How is Herzuma used?

Herzuma can only be obtained with a prescription and treatment should be started by a doctor who has experience in the use of cancer medicines.It is available as a powder used to make up a solution for adding to an infusion (drip) into a vein. The infusion is given over 90 minutes every week or every three weeks for breast cancer, and every three weeks for gastric cancer. For early breast cancer, treatment is given for a year or until the disease comes back, and for metastatic breast or gastric cancer, treatment is continued for as long as it remains effective. The recommended dose depends on the patient's body weight, on the condition being treated and on whether Herzuma is given weekly or three-weekly.The infusion may be associated with allergic reactions, so the patient should be monitored during and after the infusion. Patients who tolerate the first 90-minute infusion can receive subsequent infusions over 30 minutes.For further information, see the package leaflet.

How does Herzuma work?

The active substance in Herzuma, trastuzumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to the HER2 protein. By attaching to HER2, trastuzumab activates cells of the immune system, which then kill the tumour cells. Trastuzumab also stops HER2 producing signals that cause the tumour cells to grow.

What benefits of Herzuma have been shown in studies?

Laboratory studies comparing Herzuma with Herceptin have shown that the active substance in Herzuma is highly similar to that in Herceptin in terms of structure, purity and biological activity. Studies have also shown that giving Herzuma produces similar levels of the active substance in the body to giving Herceptin.In addition, one main study involving 549 patients with early breast cancer that overexpressed HER2 showed that Herzuma was as effective as Herceptin. Patients were given either Herzuma or Herceptin with other cancer medicines before surgery to remove the cancer, and then the same medicine on its own every three weeks for 1 year. There were no relevant differences in the main measure of effectiveness (absence of invasive cancer cells in the breast or in linked tissues called lymph nodes) between the two products: this was seen in nearly 44% of those given Herzuma (118 of 271) and 47% of those given Herceptin (131 of 278).Because Herzuma is a biosimilar medicine, the studies on effectiveness and safety of trastuzumab carried out with Herceptin do not all need to be repeated for Herzuma.

What are the risks associated with Herzuma?

The most common or serious side effects with Herzuma are heart problems, reactions related to the Herzuma infusion, reduced levels of blood cells (especially white blood cells), infections and lung problems.Herzuma can cause cardiotoxicity (harm to the heart), including heart failure (when the heart does not work as well as it should). Care should be taken if it is given to patients who already have heart problems or high blood pressure, and all patients need to be monitored during and after treatment to check their heart.Herzuma must not be used in people who are hypersensitive (allergic) to trastuzumab, mouse proteins or to any of the other ingredients. It must not be used in patients who have serious breathing problems because of advanced cancer, even when resting, or who need oxygen therapy.For the full list of all side effects and restrictions with trastuzumab, see the package leaflet.

Why is Herzuma approved?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Herzuma has been shown to have a comparable quality, safety and effectiveness to Herceptin.Therefore, the Agency's view was that, as for Herceptin, the benefit outweighs the identified risk and Herzuma should be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Herzuma?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Herzuma have been included in the summary of product characteristics and the package leaflet.

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Hetlioz

What is Hetlioz and what is it used for?

Hetlioz is a medicine used to treat totally blind adults with non-24-hour sleep-wake disorder. Non-24hour sleep-wake disorder is a condition that occurs almost exclusively in people who are completely blind, where patients have sleep patterns that are not synchronised with day and night and often follow a cycle that is longer than the standard 24-hour clock. As a result, patients fall asleep and wake up at unusual times.Hetlioz contains the active substance tasimelteon.Because the number of patients with non-24-hour sleep-wake disorder is low, the disease is considered 'rare', and Hetlioz was designated an 'orphan medicine' (a medicine used in rare diseases) on 23 February 2011.

How is Hetlioz used?

Hetlioz is available as 20 mg capsules and can only be obtained with a prescription.Hetlioz is intended for long-term use. The recommended dose is one capsule per day, taken one hour before bedtime, at the same time every night. The medicine should be taken without food.

How does Hetlioz work?

A hormone called melatonin plays a key role in co-ordinating the body's sleep-wake cycle. In people with normal perception of light and dark, melatonin is produced in hours of darkness and promotes sleep by acting on melatonin receptors in specific areas of the brain. The active substance in Hetlioz, tasimelteon, acts on the same receptors as melatonin to promote sleep and regulate sleep patterns. By taking it at a suitable time each day it can help to reset the sleep-wake cycle to more standard timing.

What benefits of Hetlioz have been shown in studies?

Hetlioz has been shown to be effective at helping patients adjust to the standard 24-hour clock in 2 main studies.The first study, which involved a total of 84 totally blind patients with non-24-hour sleep-wake disorder, compared Hetlioz with placebo (a dummy treatment). The main measure of effectiveness was the percentage of patients who were able to adjust to the 24-hour clock, which was calculated by looking at how the amount of melatonin breakdown products changed in the patient's urine over time. 20% of patients who received Hetlioz (8 out of 40) were able to adjust to the 24-hour clock after 1 months of treatment, compared with around 3% of patients on placebo (1 out of 38). Improved results were seen in a subset of patients after 7 months of treatment, which indicate that patients may take weeks or months to respond.In the second study, 57 patients first received Hetlioz for around 11 weeks. Those patients who were able to adjust to the 24-hour clock (20 patients in total) were then given Hetlioz or placebo for a further 8 weeks to study how well the effect of Hetlioz was maintained. Of the 10 patients who remained on Hetlioz, 9 people remained adjusted to 24-hour clock at the end of the study, compared with 2 of the 10 patients who were switched to placebo.

What are the risks associated with Hetlioz?

The most common side effects with Hetlioz (which may affect more than 3 in 100 people) are headache, somnolence, nausea (feeling sick) and dizziness. These are usually mild or moderate in severity and temporary.For the full list of all side effects and restrictions with Hetlioz, see the package leaflet.

Why is Hetlioz approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Hetlioz's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted that only around 20% of patients would be able to benefit from treatment with Hetlioz, but in view of the lack of approved treatments for non-24-hour sleep-wake disorder, which is a debilitating condition, this modest response was still considered important. However, continued treatment would be necessary to maintain the beneficial effects. Regarding safety, Hetlioz was shown to be well tolerated, causing only few mild side effects.

What measures are being taken to ensure the safe and effective use of Hetlioz?

A risk management plan has been developed to ensure that Hetlioz is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and thepackage leaflet for Hetlioz, including the appropriate precautions to be followed by healthcare professionals and patients.Further information can be found in the summary of the risk management plan.

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Hexacima

What is Hexacima and what is it used for?

Hexacima is a vaccine containing active substances derived from diphtheria, tetanus, pertussis and Haemophilus influenzae type b bacteria, the hepatitis B virus, and inactivated polioviruses. It is used in babies and toddlers aged from six weeks to protect against the following infectious diseases:• diphtheria (a highly contagious disease that affects the throat and skin, and can cause damage to the heart and other organs);• tetanus (lockjaw, usually caused by infection of a wound);• pertussis (whooping cough);• hepatitis B (a viral liver infection);• poliomyelitis (polio, a disease that affects the nerves and can lead to muscle weakness or paralysis);• invasive diseases (such as meningitis) caused by H. influenzae type b bacteria.

How is Hexacima used?

Hexacima is available as a suspension for injection in vials and prefilled syringes. It can only be obtained with a prescription. Vaccination with Hexacima should be carried out according to official recommendations.The recommended initial vaccination schedule is either two doses, given two months apart or three doses, given at least one month apart. A booster dose should be given at least six months after the last of these initial doses. Hexacima or an appropriate combination of other vaccines can be used for the booster dose. Hexacima is given by deep injection into a muscle, normally in the upper thigh or the shoulder.For further information, see the package leaflet.

How does Hexacima work?

Hexacima is a vaccine. Vaccines work by 'teaching' the immune system (the body's natural defences) how to defend itself against diseases. Hexacima contains small amounts of materials derived from the bacteria and viruses it protects against. These materials have been inactivated where necessary so that they do not cause any disease.When a child is given the vaccine, the immune system recognises the parts of the bacteria and viruses as 'foreign' and makes antibodies against them. The immune system will then be able to produce antibodies quickly when the person is naturally exposed to the bacteria or viruses. This helps to protect against the diseases that these bacteria and viruses cause.The vaccine is 'adsorbed'. This means that some of the active substances are fixed onto aluminium compounds, to stimulate a better response.

What benefits of Hexacima have been shown in studies?

Hexacima has been studied in several countries worldwide in 12 main studies involving over 3,400 children between six weeks and two years of age who were given three doses of the vaccine during their first six months of life according to different local vaccination schedules. The effects were compared with a combination of separate vaccines designed to protect against the diseases included in Hexacima. The main measure of effectiveness was the production of antibody levels known to be protective against those diseases.Five of these studies examined the effect of giving a booster dose at least 6 months after the initial vaccination schedule in 1,511 children. The studies showed that protective antibody levels against the various diseases developed in between 90 and 100% of children after the first three doses of Hexacima; protection was maintained or improved when a booster dose was given.A subsequent study involving 455 children looked at the longer-term persistence of protective antibodies up to 3 years after a booster dose with Hexacima, and another study in 1,336 children evaluated the response to different lots of the vaccine and what happened when it was given with vaccines for infections caused by the bacterium Streptococcus pneumoniae (Prevenar) and rotavirus (Rotarix). These studies showed that Hexacima produces similar antibody profiles over time to comparable vaccines, and that the vaccine can be given at the same time as Prevenar and Rotarix.The two-dose vaccination schedule was investigated in an additional main study involving 554 children. In the study, children who received Hexacima produced a similar antibody response to those whoreceived a comparator vaccine (Infanrix hexa), when given as a two-dose schedule followed by a booster 6 months later.

What are the risks associated with Hexacima?

The most common side effects with Hexacima include pain and redness at the site of injection, irritability and crying. Reactions may be more likely after the first dose than later doses. For the full list of all side effects reported with Hexacima, see the package leaflet.Hexacima must not be used in children who have ever had an allergic reaction to Hexacima or a vaccine containing the same components, including substances used during the manufacture of the vaccine and which may be found at extremely low levels (such as the antibiotics neomycin or streptomycin). It must not be used in children who have ever had encephalopathy (a brain disease) of unknown cause within seven days of receiving a vaccine containing pertussis components in the past. It must not be used in children who have an uncontrolled or severe illness affecting the brain or nervous system, such as uncontrolled epilepsy, unless the condition has stabilised with treatment and the benefit clearly outweighs the risk. Vaccination with Hexacima should be postponed if a child has amoderate to severe fever. For the full list of restrictions, see the package leaflet.

Why is Hexacima approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Hexacima's benefits are greater than its risks and recommended that it be approved for use in the EU.The CHMP noted that Hexacima has been shown to produce protective antibody levels against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and H. influenzae type b infections in children between six weeks and two years of age regardless of ethnicity. Although no data are available in children older than 2 years, there is no indication that older children would respond differently.Regarding safety, the CHMP considered that Hexacima's overall safety profile is similar to other vaccines, although Hexacima is more likely than similar vaccines to cause reactions (mainly at the injection site).

What measures are being taken to ensure the safe and effective use of Hexacima?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hexacima have been included in the summary of product characteristics and the package leaflet.

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Hexyon

What is Hexyon and what is it used for?

Hexyon is a vaccine containing active substances derived from diphtheria, tetanus, pertussis and Haemophilus influenzae type b bacteria, the hepatitis B virus, and inactivated polioviruses. It is used in babies and toddlers aged from six weeks to protect against the following infectious diseases:• diphtheria (a highly contagious disease that affects the throat and skin, and can cause damage to the heart and other organs);• tetanus (lockjaw, usually caused by infection of a wound);• pertussis (whooping cough);• hepatitis B (a viral liver infection);• poliomyelitis (polio, a disease that affects the nerves and can lead to muscle weakness or paralysis);• invasive diseases (such as meningitis) caused by H. influenzae type b bacteria.

How is Hexyon used?

Hexyon is available as a suspension for injection in vials and prefilled syringes. It can only be obtained with a prescription. Vaccination with Hexyon should be carried out according to official recommendations. The recommended initial vaccination schedule is either two doses, given two months apart or three doses, given at least one month apart. A booster dose should be given at least six months after the last of these initial doses. Hexyon or an appropriate combination of other vaccines can be used for the booster dose. Hexyon is given by deep injection into a muscle, normally in the upper thigh or the shoulder.For further information, see the package leaflet.

How does Hexyon work?

Hexyon is a vaccine. Vaccines work by 'teaching' the immune system (the body's natural defences) how to defend itself against diseases. Hexyon contains small amounts of materials derived from the bacteria and viruses it protects against. These materials have been inactivated where necessary so that they do not cause any disease.When a child is given the vaccine, the immune system recognises the parts of the bacteria and viruses as 'foreign' and makes antibodies against them. The immune system will then be able to produce antibodies quickly when the person is naturally exposed to the bacteria or viruses. This helps to protect against the diseases that these bacteria and viruses cause.The vaccine is 'adsorbed'. This means that some of the active substances are fixed onto aluminium compounds, to stimulate a better response.

What benefits of Hexyon have been shown in studies?

Hexyon has been studied in several countries worldwide in 12 main studies involving over 3,400 children between six weeks and two years of age who were given three doses of the vaccine during their first six months of life according to different local vaccination schedules. The effects were compared with a combination of separate vaccines designed to protect against the diseases included in Hexyon. The main measure of effectiveness was the production of antibody levels known to be protective against those diseases.Five of these studies examined the effect of giving a booster dose at least 6 months after the initial vaccination schedule in 1,511 children. The studies showed that protective antibody levels against the various diseases developed in between 90 and 100% of children after the first three doses of Hexyon; protection was maintained or improved when a booster dose was given.A subsequent study involving 455 children looked at the longer-term persistence of protective antibodies up to 3 years after a booster dose with Hexyon, and another study in 1,336 children evaluated the response to different lots of the vaccine and what happened when it was given with vaccines for infections caused by the bacterium Streptococcus pneumoniae (Prevenar) and rotavirus (Rotarix). These studies showed that Hexyon produces similar antibody profiles over time to comparable vaccines, and that the vaccine can be given at the same time as Prevenar and Rotarix.The two-dose vaccination schedule was investigated in an additional main study involving 554 children. In the study, children who either received Hexyon produced a similar antibody response to those who received a comparator vaccine (Infanrix hexa), when given as a two-dose schedule followed by a booster 6 months later.

What are the risks associated with Hexyon?

The most common side effects with Hexyon include pain and redness at the site of injection, irritability and crying. Reactions may be more likely after the first dose than later doses. For the full list of all side effects reported with Hexyon, see the package leaflet.Hexyon must not be used in children who have ever had an allergic reaction to Hexyon or a vaccine containing the same components, including substances used during the manufacture of the vaccine and which may be found at extremely low levels (such as the antibiotics neomycin or streptomycin). It must not be used in children who have ever had encephalopathy (a brain disease) of unknown cause within seven days of receiving a vaccine containing pertussis components in the past. It must not be used in children who have an uncontrolled or severe illness affecting the brain or nervous system, such as uncontrolled epilepsy, unless the condition has stabilised with treatment and the benefit clearly outweighs the risk. Vaccination with Hexyon should be postponed if a child has a moderate to severe fever. For the full list of restrictions, see the package leaflet.

Why is Hexyon approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Hexyon's benefits are greater than its risks and recommended that it be approved for use in the EU.The CHMP noted that Hexyon has been shown to produce protective antibody levels against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and H. influenzae type b infections in children between six weeks and two years of age regardless of ethnicity. Although no data are available in children older than 2 years, there is no indication that older children would respond differently.Regarding safety, the CHMP considered that Hexyon's overall safety profile is similar to other vaccines, although vaccination with Hexyon is more likely than similar vaccines to cause reactions (mainly at the injection site).

What measures are being taken to ensure the safe and effective use of Hexyon?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hexyon have been included in the summary of product characteristics and the package leaflet.

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Hirobriz Breezhaler

What is Hirobriz Breezhaler and what is it used for?

Hirobriz Breezhaler is a medicine that is used to keep the airways open in adults with chronic obstructive pulmonary disease (COPD). COPD is a long-term disease in which the airways and air sacs inside the lungs become damaged or blocked, leading to difficulty breathing. Hirobriz Breezhaler is used for maintenance (regular) treatment.The medicine contains the active substance indacaterol.

How is Hirobriz Breezhaler used?

Hirobriz Breezhaler capsules, which contain a powder for inhalation, are only used with a Hirobriz Breezhaler inhaler and must not be swallowed. To receive a dose, the patient places a capsule into the inhaler and breathes the powder in through the mouth.The recommended dose is one 150 microgram capsule, once a day at the same time each day. The doctor may increase the dose to one 300 microgram capsule once a day in cases of severe COPD.Hirobriz Breezhaler can only be obtained with a prescription.

How does Hirobriz Breezhaler work?

The active substance in Hirobriz Breezhaler, indacaterol, is a beta-2 adrenergic receptor agonist. It works by attaching to beta-2 receptors that are found in the muscle cells of many organs and thatcause the muscles to relax. When Hirobriz Breezhaler is inhaled, indacaterol reaches the receptors in the airways and activates them. This causes the muscles of the airways to relax, helping to keep the airways open and allowing the patient to breathe more easily.

What benefits of Hirobriz Breezhaler have been shown in studies?

In three main studies involving over 4,000 patients with COPD, Hirobriz Breezhaler was compared with placebo (a dummy treatment), tiotropium or formoterol (other inhaled medicines used to treat COPD).The main measure of effectiveness was based on changes in the patients' forced expiratory volumes (FEV1, the maximum volume of air a person can breathe out in one second) after 12 weeks.Hirobriz Breezhaler was more effective than placebo at improving how well the lungs work in patients with COPD. On average, the increase in FEV1 in patients who received Hirobriz Breezhaler was between 150 to 190 ml, while for patients who received placebo the change in FEV1 ranged from a decrease of10 ml to an increase of 20 ml. Overall, the effects of the 150 and 300 microgram doses of Hirobriz Breezhaler were similar, but the results showed that the 300 microgram dose may provide better relief in patients with more severe disease. The increase in FEV1 was 130 ml with tiotropium, and 80 ml with formoterol.

What are the risks associated with Hirobriz Breezhaler?

The most common side effects with Hirobriz Breezhaler (which may affect more than 1 in 10 people) are nasopharyngitis (inflammation of the nose and throat) and upper respiratory tract infection (infection of the nose and throat). Other common side effects include chest pain, cough and muscle cramps.For the full list of all side effects and restrictions with Hirobriz Breezhaler, see the package leaflet.

Why is Hirobriz Breezhaler approved?

The European Medicines Agency concluded that Hirobriz Breezhaler was shown to be effective at improving lung function in COPD. The Agency also noted that there were no major safety concerns with Hirobriz Breezhaler, with side effects being manageable and similar to other beta-2 adrenergic receptor agonist medicines. Therefore, the Agency decided that Hirobriz Breezhaler's benefits are greater that its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Hirobriz Breezhaler?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hirobriz Breezhaler have been included in the summary of product characteristics and the package leaflet.

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Hizentra

What is Hizentra and what is it used for?

Hizentra is used in patients whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins. It is used to treat the following conditions:• primary immunodeficiency syndromes (PID, when people are born with an inability to produce enough antibodies);• secondary immunodeficiencies (SID) in people who have severe or recurrent infections that do not respond to treatments and who are unable to produce certain antibodies;• chronic inflammatory demyelinating polyneuropathy (CIDP). In this rare disease, the immune system (the body's defense system) works abnormally and destroys the protective covering over the nerves.Hizentra contains the active substance human normal immunoglobulin.

How is Hizentra used?

Hizentra can only be obtained with a prescription and treatment should be started by a doctor or nurse who is experienced in the treatment of patients with weakened immune systems or CIDP.Hizentra is available as a solution for injection. It is given by subcutaneous infusion (very slow injection under the skin) through a device that controls the speed of infusion. It is given in the abdomen (belly), thigh, upper arm or hip. Patients (or their carers) may inject Hizentra at home once they have been trained.The dose and how often Hizentra infusion is given depend on the disease being treated. The dose may need to be adjusted depending on how well the medicine is working.For more information about using Hizentra, see the package leaflet or contact a doctor or pharmacist.

How does Hizentra work?

The active substance in Hizentra, human normal immunoglobulin, is a highly purified protein extracted from donated human blood. It contains mainly immunoglobulin G (IgG), which is composed of a rangeof antibodies involved in fighting organisms that can cause infection. Hizentra works by restoring abnormally low IgG levels to their normal range in the patient's blood. It can also help to control the immune system when it is working abnormally such as in CIDP. Normal immunoglobulin has been used as a medicine since the 1980s.

What benefits of Hizentra have been shown in studies?

As human normal immunoglobulin has been used to treat these diseases for many years, in accordance with current guidelines, two small studies and an analysis of scientific literature were needed to establish the effectiveness and safety of Hizentra in patients.In the first study, Hizentra was investigated in 51 patients with PID who had already received human immunoglobulin into a vein for at least six months. The patients received Hizentra for 28 weeks and the lowest IgG levels during treatment with Hizentra (average level of 8.1 g per litre) were comparable to those seen during previous immunoglobulin treatment. IN addition, no infections occurred during the study period.In the second study Hizentra was studied in 172 patients with CIDP who had previously received human immunoglobulin treatment by injection into a vein. Patients received Hizentra or placebo (a dummy treatment) for 13 weeks and the study measured the proportion of patients in whom the disease came back within 13 weeks. For patients on placebo, the disease came back in about 63% of patients, for patients on Hizentra, the disease came back in 33 and 39% of patients; depending on the dose used.The scientific literature analysis involved seven studies comparing the use of Hizentra in patients with SID with other subcutaneous infusion or intravenous (injected directly into a vein) immunoglobulin treatments. All studies showed increases in antibody levels and/or a reduction in infection rates after receiving Hizentra or another subcutaneous immunoglobulin treatment; the effects were comparable to those seen with intravenous immunoglobulin treatment.

What are the risks associated with Hizentra?

The most common side effects with Hizentra (which may affect more than 1 in 10 people) are headache, rash, muscle and joint pain (including muscle spasm and weakness), reactions around the injection area (swelling, soreness, redness, pitting, warmth, itching, bruising and rash) and flu-like illness. Rarely patients may have a sudden drop in blood pressure or an anaphylactic shock (sudden, severe allergic reaction).Hizentra must not be used in patients with hyperprolinaemia (a genetic disorder causing high levels of the amino acid proline in the blood). It must not be injected into a blood vessel.For the full list of side effects and restrictions with Hizentra, see the package leaflet.

Why is Hizentra authorised in the EU?

The European Medicines Agency decided that Hizentra's benefits are greater than its risks and it can be authorised for use in the EU. Hizentra was shown to prevent serious bacterial infections in patients with PID or SID and reduce the chance of CIDP coming back. It may be given at home, with manageable side effects.

What measures are being taken to ensure the safe and effective use of Hizentra?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hizentra have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hizentra is continuously monitored. Side effects reported with Hizentra are carefully evaluated and any necessary action taken to protect patients.

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Holoclar

What is Holoclar and what is it used for?

Holoclar is a stem-cell treatment used in the eye to replace damaged cells on surface (epithelium) of the cornea, the transparent layer in front of the eye covering the iris (the coloured part).It is used in adult patients with moderate to severe limbal stem-cell deficiency caused by burns, including chemical burns, to the eyes. Patients with this condition do not have enough limbal stem cells which normally act as a regeneration system, replenishing the outer corneal cells when they get damaged and when they age.Holoclar is a type of advanced therapy product called a 'tissue engineered product'. It consists of cells taken from the patient's limbus (at the edge of the cornea) and then grown in a laboratory so that they can be used to repair the damaged corneal surface.Because the number of patients with limbal stem-cell deficiency due to burns to the eyes is low, the disease is considered 'rare', and Holoclar was designated an 'orphan medicine' (a medicine used in rare diseases) on 7 November 2008.

How is Holoclar used?

Holoclar must only be used by an appropriately trained and qualified eye surgeon in a hospital, and must only be given to the patient whose limbal cells were used to manufacture the medicine. In the first stage of treatment, a small part of healthy limbal tissue (1-2 mm2 in size) is taken from the patient in hospital and sent to the manufacturer on the same day. Next, the cells in the tissue are grown in a laboratory and frozen until the date of surgery is confirmed. Thawed cells are used to make Holoclar by growing them on a membrane made of a protein called fibrin. Holoclar, comprising the cells and the membrane, is then sent back to the hospital, where it is immediately surgically implanted in the patient's eye. Antibiotics to prevent eye infection should be given to patients after limbal tissue has been taken from them. Following the surgery, the patient should receive antibiotics and an appropriate antiinflammatory medicine.Holoclar is intended for a single treatment, although treatment can be repeated if the doctor considers it necessary. For further information, see the summary of product characteristics (also part of the EPAR).

How does Holoclar work?

The active substance in Holoclar is the patient's own limbal cells, which include cells from the surface of the cornea and limbal stem cells grown in a laboratory. Before Holoclar is used, the damaged corneal surface tissue of the affected eye is removed. Once implanted in the eye, the corneal cells of Holoclar help to replace the corneal surface, while the limbal stem cells serve as a reservoir of new cells that continuously replenish the cornea.

What benefits of Holoclar have been shown in studies?

Holoclar was shown to be effective in restoring a stable corneal surface in patients with moderate or severe limbal stem-cell deficiency caused by burns in a retrospective study using patients' past medical records. One year after Holoclar implantation, 75 out of 104 patients studied (72%) were judged to have had successful implants based on the presence of stable corneal surface with no surface defects and little or no ingrown blood vessels (a common feature of limbal stem-cell deficiency). There were also reductions in patients' symptoms, such as pain and inflammation, and improvements in vision.

What are the risks associated with Holoclar?

The most common side effect with Holoclar (seen in more than 1 patient in 10) is blepharitis(inflammation of the eye lid). For the full list of all side effects and restrictions, see the package leaflet.

Why is Holoclar approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that Holoclar treatment was effective in restoring healthy corneal surfaces in patients with moderate or severe limbal stem-cell deficiency caused by burns as well as in improving their symptoms and vision. The Committee noted that that moderate to severe forms of limbal stem-cell deficiency are serious conditions which, if untreated, can lead to severe reduction or complete loss of vision. As the side effects of Holoclar treatment are generally manageable, the CHMP concluded that Holoclar's benefits outweigh its risks and recommended that it be approved for use in the EU.The conclusion on the benefit-risk balance of Holoclar is based on results of two retrospective studies (using past medical records), and the company is to provide further data from a prospective study (that records outcomes during the course of the study).Holoclar has therefore been given 'conditional approval'. This means that there is more evidence to come about the medicine, which the company is required to provide. Every year, the European Medicines Agency will review any new information that becomes available and this summary will be updated as necessary.

What information is still awaited for Holoclar?

Since Holoclar has been granted a conditional approval, the company that markets Holoclar will provide further data on Holoclar. The company is to provide data on the benefits and risks of Holoclar from a prospective clinical study.

What measures are being taken to ensure the safe and effective use of Holoclar?

A risk management plan has been developed to ensure that Holoclar is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Holoclar, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company that makes Holoclar will provide healthcare professionals with educational material on the safe use of this treatment, including on the selection and follow-up of patients and on reporting side effects. Educational material will also be provided to patients undergoing treatment.Further information can be found in the summary of the risk management plan.

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Hukyndra

What is Hukyndra and what is it used for?

Hukyndra is a medicine that acts on the immune system (the body's natural defences) and is used to treat the following conditions:• plaque psoriasis (a disease causing red, scaly patches on the skin);• psoriatic arthritis (a disease causing red, scaly patches on the skin with inflammation of the joints);• rheumatoid arthritis (a disease causing inflammation of the joints);• polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis (both rare diseases causing inflammation in the joints);• axial spondyloarthritis (inflammation of the spine causing back pain), including ankylosing spondylitis and when there are clear signs of inflammation, but X-ray does not show disease;• Crohn's disease (a disease causing inflammation of the gut);• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);• hidradenitis suppurativa (acne inversa), a chronic skin disease that causes lumps, abscesses (collections of pus) and scarring on the skin;• non-infectious uveitis (inflammation of the layer beneath the white of the eyeball).Hukyndra is mostly used in adults when their condition is severe, moderately severe or getting worse, or when patients cannot use other treatments. For more information on the use of Hukyndra in all conditions, including when it can be used in children, see the package leaflet or contact your doctor or pharmacist.Hukyndra is a 'biosimilar medicine'. This means that Hukyndra is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Hukyndra is Humira. For more information on biosimilar medicines, see here.Hukyndra contains the active substance adalimumab.

How is Hukyndra used?

Hukyndra is available for injection under the skin in a pre-filled syringe or pen and is usually given every 2 weeks. The dose and frequency of injection depend on the condition to be treated and the dose for a child is usually calculated according to the child's weight; because Hukyndra is only available in doses of 40 or 80 mg, it is not suitable for children who need less than a 40-mg dose. After training, patients or their carers may inject Hukyndra if their doctor considers it appropriate.Hukyndra can only be obtained with a prescription and treatment must be started and supervised by a doctor who has experience in the treatment of the diseases for which Hukyndra is used. Eye specialists treating uveitis should also take advice from doctors who have experience of using adalimumab.For more information about using Hukyndra, see the package leaflet or contact your doctor or pharmacist.

How does Hukyndra work?

The active substance in Hukyndra, adalimumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a substance in the body called tumour necrosis factor (TNF).TNF is involved in causing inflammation and is found at high levels in patients with the diseases that Hukyndra is used to treat. By attaching to TNF, adalimumab blocks its activity, thereby reducing inflammation and other symptoms of the diseases.

What benefits of Hukyndra have been shown in studies?

Laboratory studies comparing Hukyndra with Humira have shown that the active substance inHukyndra is highly similar to that in Humira in terms of structure, purity and biological activity. Studies have also shown that giving Hukyndra produces similar levels of the active substance in the body to giving Humira.In addition, a study involving 412 adult patients with plaque psoriasis has shown that Hukyndra was as effective as Humira in controlling the disease; average scores measuring the extent and severity of the condition improved by 91% after 16 weeks of treatment with either medicine.Because Hukyndra is a biosimilar medicine, the studies on effectiveness and safety of adalimumab carried out with Humira do not all need to be repeated for Hukyndra.

What are the risks associated with Hukyndra?

The safety of Hukyndra has been evaluated and, on the basis of all the studies carried out, the side effects of the medicine are considered to be comparable to those of the reference medicine Humira.The most common side effects with adalimumab (which may affect more than 1 in 10 people) are infections (including in the nose, throat and sinuses), injection site reactions (redness, itching, bleeding, pain or swelling), headache and muscle and bone pain. Like other medicines of its class, Hukyndra may affect the ability of the immune system to fight off infections and cancer, and there have been some cases of serious infections and blood cancers in patients using adalimumab.Other rare serious side effects of adalimumab (which may affect up to 1 in 1,000 people) include failure of bone marrow to produce blood cells, disorder of the nerves, lupus and lupus-like conditions (where the immune system attacks the patient's own tissues, causing inflammation and organ damage), and Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and painful rash affecting the skin, mouth, eyes and genitals).Hukyndra must not be used in patients with active tuberculosis or other severe infections, or in patients with moderate to severe heart failure (an inability of the heart to pump enough blood around the body).For the full list of side effects and restrictions with Hukyndra, see the package leaflet.

Why is Hukyndra authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Hukyndra has a highly similar structure, purity and biological activity to Humira and is distributed in the body in the same way. In addition, studies in adults with plaque psoriasis have shown that the safety and effectiveness of Hukyndra is equivalent to that of Humira in this group.All these data were considered sufficient to conclude that Hukyndra will behave in the same way as Humira in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for Humira, the benefits of Hukyndra outweigh the identified risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Hukyndra?

Patients treated with Hukyndra must be given a reminder card with information on the safety of the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hukyndra have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hukyndra are continuously monitored. Suspected side effects reported with Hukyndra are carefully evaluated and any necessary action taken to protect patients.

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Hulio

What is Hulio and what is it used for?

Hulio is a medicine that acts on the immune system and is used to treat the following conditions:• plaque psoriasis (a disease causing red, scaly patches on the skin);• psoriatic arthritis (a disease causing red, scaly patches on the skin with inflammation of the joints);• rheumatoid arthritis (a disease causing inflammation of the joints);• axial spondyloarthritis (inflammation of the spine causing back pain), including ankylosing spondylitis and when X-ray does not show disease but there are clear signs of inflammation;• polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis (both rare diseases causing inflammation in the joints);• Crohn's disease (a disease causing inflammation of the gut);• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);• hidradenitis suppurativa (acne inversa), a long-term skin disease that causes lumps, abscesses (collections of pus) and scarring on the skin;• non-infectious uveitis (inflammation of the layer beneath the white of the eyeball).Hulio is mostly used in adults when their condition is severe, moderately severe or getting worse, or when patients cannot use other treatments. For more information on the use of Hulio in all conditions, including when it can be used in children, see the package leaflet or contact your doctor or pharmacist.Hulio contains the active substance adalimumab and is a 'biosimilar medicine'. This means that Hulio is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Hulio is Humira. For more information on biosimilar medicines, see here.

How is Hulio used?

Hulio is available as a solution for injection under the skin in a vial or pre-filled syringe or pen and is usually given every 2 weeks. The dose and frequency of injection depends on the condition to be treated and the dose for a child is usually calculated according to the child's weight. After training, patients or their carers may inject Hulio if their doctor considers it appropriate.Hulio can only be obtained with a prescription and treatment must be started and supervised by a doctor who has experience in the treatment of the diseases for which Hulio is used. Eye specialists treating uveitis should also take advice from doctors who have experience of using adalimumab.For more information about using Hulio, see the package leaflet or contact your doctor or pharmacist.

How does Hulio work?

The active substance in Hulio, adalimumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a substance in the body called tumour necrosis factor (TNF). TNF is involved in causing inflammation and is found at high levels in patients with the diseases that Hulio is used to treat. By attaching to TNF, adalimumab blocks its activity, thereby reducing inflammation and other symptoms of the diseases.

What benefits of Hulio have been shown in studies?

Laboratory studies comparing Hulio with the reference medicine Humira have shown that the active substance in Hulio is highly similar to that in Humira in terms of structure, purity and biological activity. Studies have also shown that giving Hulio produces similar levels of the active substance in the body to giving Humira.In addition, Hulio was as effective as Humira in a study involving 730 patients with rheumatoid arthritis that was not adequately controlled with the medicine methotrexate. After 24 weeks, a 20% improvement in symptoms was seen in 74% of Hulio-treated patients (270 of 363) and 76% of Humira treated patients (271 of 358).Because Hulio is a biosimilar medicine, the studies on effectiveness and safety of adalimumab carried out with Humira do not all need to be repeated for Hulio.

What are the risks associated with Hulio?

The most common side effects with adalimumab (seen in more than 1 patient in 10) are infections (including in the nose, throat and sinuses), injection site reactions (redness, itching, bleeding, pain or swelling), headache and muscle and bone pain.Like other medicines of its class, Hulio may affect the ability of the immune system to fight off infections and cancer, and there have been some cases of serious infections and blood cancers in patients using adalimumab.Other rare serious side effects (which may affect up to 1 in 1,000 people) include failure of bone marrow to produce blood cells, disorder of the nerves, lupus and lupus-like conditions (where the immune system attacks the patient's own tissues, causing inflammation and organ damage), and Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and painful rash affecting the skin, mouth, eyes and genitals).Hulio must not be used in patients with active tuberculosis or other severe infections, or in patients with moderate to severe heart failure (an inability of the heart to pump enough blood around the body).For the full list of side effects and restrictions with Hulio, see the package leaflet.

Why is Hulio authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Hulio has a highly similar structure, purity and biological activity to Humira and is distributed in the body in the same way.In addition, a study in patients with rheumatoid arthritis has shown that the effects of the medicine are equivalent to those of Humira in this condition. All these data were considered sufficient to conclude that Hulio will behave in the same way as Humira in terms of effectiveness and safety in its approved uses. Therefore, the Agency's view was that, as for Humira, the benefit of Hulio outweighs the identified risk and it can be authorised.

What measures are being taken to ensure the safe and effective use of Hulio?

The company that markets Hulio must provide educational packs for doctors who prescribe the medicine. These packs will include information on the safety of the medicine. An alert card will also be given to patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hulio have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hulio are continuously monitored. Side effects reported with Hulio are carefully evaluated and any necessary action taken to protect patients.

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Humalog

What is Humalog and what is it used for?

Humalog is a range of insulin medicines used to treat patients who have diabetes and need insulin to keep their blood glucose (sugar) level controlled, including patients whose diabetes has just been diagnosed.Humalog medicines contain the active substance insulin lispro on its own or combined with protamine to make it longer acting:• Humalog (100 units/ml): standard-strength insulin lispro (fast-acting);• Humalog (200 units/ml): high-strength insulin lispro (fast-acting);• Humalog Mix25 (100 units/ml): 25% insulin lispro (fast-acting) and 75% insulin lispro protamine (longer-acting);• Humalog Mix50 (100 units/ml): 50% insulin lispro (fast-acting) and 50% insulin lispro protamine (longer-acting).

How is Humalog used?

Humalog medicines are available as solutions or suspensions for injection in vials, cartridges or prefilled pens.The medicines are given by injection under the skin of the upper arm, thigh, buttock or abdomen (belly). Humalog 100 units/ml may also be given by continuous infusion under the skin using an insulin pump or by injection into a vein. Humalog 200 units/ml, Humalog Mix25 and Humalog Mix50 should never be given into a vein.The dose depends on the individual patient's needs and may be reduced in patients with reduced kidney or liver function. The medicines are normally given shortly before a meal, but can be given just after a meal if necessary.Humalog (100 or 200 units/ml) can be used with a longer-acting insulin or with sulphonylureas (a group of diabetes medicines that are taken by mouth).Patients can inject themselves with this medicine if they have been trained appropriately.Humalog can only be obtained with a prescription. For more information about using Humalog, see the package leaflet or contact your doctor or pharmacist.

How does Humalog work?

Diabetes is a disease in which the body does not produce enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. Humalog is a replacement insulin which is very similar to the insulin made by the body.The active substance in Humalog, insulin lispro, is produced by a method known as 'recombinant DNA technology': it is made by bacteria into which a gene (DNA) has been introduced, which makes them able to produce insulin lispro.Insulin lispro has a small difference from human insulin that allows it to be absorbed faster by the body so it can act shortly after injection. Humalog Mix25 and Humalog Mix50 contain both insulin lispro and a longer-acting form called insulin lispro protamine, which is absorbed more slowly so that it works for longer.Humalog works in the same way as naturally produced insulin and helps glucose from the blood to enter cells. By controlling the level of blood glucose, the symptoms and complications of diabetes are reduced.

What benefits of Humalog have been shown in studies?

Humalog was originally studied in eight clinical trials including 2,951 patients with type 1 diabetes (when the body cannot produce insulin) or type 2 diabetes (when the body is unable to use insulin effectively). The effectiveness of Humalog was compared with that of Humulin R (a soluble recombinant DNA human insulin), when added to long-acting insulins given once or twice a day.The studies measured the level of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled, and 'fasting' blood glucose levels (measured when the patient had not eaten for at least eight hours). Humalog and Humulin R had a similar effect on the control of diabetes, as measured by HbA1c and fasting glucose levels.Studies also looked at the use of Humalog in 542 patients aged between two and 19 years. The medicine's effects in the body were similar in both adults and children.Studies on the use of Humalog in combination with sulphonylureas showed that these medicines used together reduce HbA1c more than sulphonylureas used alone.

What are the risks associated with Humalog?

Humalog may cause hypoglycaemia (low blood glucose levels) and must not be given to patients whose blood glucose is already low.For the full list of side effects and restrictions with Humalog, see the package leaflet.

Why is Humalog authorised in the EU?

Humalog has been shown to effectively reduce glucose levels and is comparable to human insulin. The European Medicines Agency decided that Humalog's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Humalog?

When first marketing the high-strength Humalog (200 units/ml), the company provided information for patients and healthcare professionals to advise them of the 2 strengths and on how to use them safely to avoid medication errors.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Humalog have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Humalog are continuously monitored. Side effects reported with Humalog are carefully evaluated and any necessary action taken to protect patients.

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Humira

What is Humira and what is it used for?

Humira is a medicine that acts on the immune system and is used to treat the following conditions:• plaque psoriasis, a disease causing red, scaly patches on the skin• psoriatic arthritis (red, scaly patches on the skin with inflammation of the joints)• rheumatoid arthritis (a disease causing inflammation of the joints)• axial spondyloarthritis (inflammation of spine causing back pain), including ankylosing spondylitis and when X-ray does not show disease but there are clear signs of inflammation• Crohn's disease (a disease causing inflammation of the gut)• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut)• polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis (both rare diseases causing inflammation in the joints)• hidradenitis suppurativa (acne inversa), a chronic skin disease that causes lumps, abscesses (collections of pus) and scarring on the skin• non-infectious uveitis (inflammation of the layer beneath the white of the eyeball).Humira is mostly used in adults when their conditions are severe, moderately severe or getting worse, or when patients cannot use other treatments. For detailed information on the use of Humira in all conditions, including when it can be used in children, see package leaflet or contact your doctor or pharmacist.Humira contains the active substance adalimumab.

How is Humira used?

Humira is given as an injection under the skin, usually every 2 weeks. The dose and frequency of injection depends on the condition to be treated and the dose for a child is calculated according to the child's weight.Treatment with Humira must be started and supervised by a doctor who has experience in the treatment of the diseases that Humira is used for. Doctors treating uveitis should also take advice from doctors who have experience of using Humira. Patients or their carers can inject Humira once they have been trained.Humira can only be obtained with a prescription. For more information about using Humira, see the package leaflet or contact your doctor or pharmacist.

How does Humira work?

The active substance in Humira, adalimumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a substance in the body called tumour necrosis factor (TNF). This substance is involved in causing inflammation and is found at high levels in patients with the diseases that Humira is used to treat. By attaching to TNF, adalimumab blocks its activity, thereby reducing inflammation and other symptoms of the diseases.

What benefits of Humira have been shown in studies?

More than twenty main studies involving over 9,500 patients have looked at the effects of Humira in reducing symptoms of inflammatory conditions. The studies included adult patients for the most part, but included children in studies for Crohn's disease, ulcerative colitis, plaque psoriasis, polyarticular juvenile idiopathic arthritis, non-infectious anterior uveitis and enthesitis-related arthritis.Humira, when used as directed, has been shown in clinical trials to be effective at reducing important symptoms of each of the conditions for which it is approved. Below is a brief description of the studies and their results:• In studies in adults and children with plaque psoriasis, including psoriasis of the nail, a higher proportion of patients receiving Humira had improvements in symptoms compared with patients receiving methotrexate or placebo (a dummy treatment).• Humira produced a greater improvement in symptoms than placebo in studies of psoriatic arthritis, ankylosing spondylitis, axial spondyloarthritis without evidence in the X-ray of ankylosing spondylitis but with clear signs of inflammation, Crohn's disease and psoriasis.• In studies in adults with ulcerative colitis, Humira produced a greater improvement in symptoms and healing of the mucosa (the lining of the gut) than placebo. Humira improved symptoms and mucosal healing in children aged 6 to 17 years with paediatric ulcerative colitis.• In rheumatoid arthritis, the greatest reductions in symptoms were seen in the studies on Humira as an add-on to methotrexate: around two-thirds of the patients adding Humira had at least a 20% reduction in symptoms after six months, compared with a quarter of those adding placebo. Patients adding Humira also had less joint damage and less reduction in physical function after a year. In patients who had not taken methotrexate in the past, the combination of Humira and methotrexate was also more effective than methotrexate alone.• In polyarticular juvenile idiopathic arthritis, around 40% of patients aged between 4 and 17 years receiving Humira, either alone or in combination with methotrexate, had a flare-up of arthritis, compared with around 69% of those receiving placebo. Fewer patients receiving Humira with methotrexate developed antibodies against Humira (which can reduce its effects), so the results found that the use of Humira with methotrexate was more effective than Humira used alone. The study in younger children (aged 2 to 4 years) showed that the majority of children responded well to Humira treatment and this response was maintained after 24 weeks. For enthesitis-relatedarthritis, treatment with Humira resulted in fewer swollen and tender joints compared with placebo.• In hidradenitis suppurativa, 59% of patients receiving Humira in one main study and 42% of patients in another achieved at least a 50% reduction in abscesses and nodules after 12 weeks, without any increase in abscess count or fistulas. The proportions of patients taking placebo who achieved this goal were 28% in the first study and 26% in the second.• In non-infectious uveitis, Humira was found effective in 3 studies. The first study involved adults whose disease was not controlled with high doses of corticosteroids. In this study treatment failed in about 79% of patients receiving placebo compared with about 55% given Humira. The second study involved adults whose uveitis was under control with a corticosteroid but the corticosteroid dose was then reduced or stopped and Humira or placebo introduced. In this study, treatment failure occurred in about 55% of patients receiving placebo compared with 39% receiving Humira. In the third study in children aged 2 to 18 years with non-infectious anterior uveitis, in whom methotrexate alone did not work, treatment failed in about 60% of patients receiving placebo with methotrexate compared with about 27% of patients given Humira with methotrexate.

What are the risks associated with Humira?

The most common side effects with Humira (which may affect more than 1 in 10 people) are infections (including in the nose, throat and sinuses), injection site reactions (redness, itching, bleeding, pain or swelling), headache and muscle and bone pain.Humira and other medicines of its class may also affect the ability of the immune system to fight off infections and cancer, and there have been some cases of serious infections and blood cancers in patients using Humira.Other rare serious side effects (which may affect up to 1 in 1,000 people) include failure of bone marrow to produce blood cells, nerve damage caused by breakdown of the covering around the nerve fibres, lupus and lupus-like conditions (where the immune system attacks the patient's own tissues, causing inflammation and organ damage), and Stevens-Johnson syndrome (a life-threatening reaction with flu-like symptoms and painful rash affecting the skin, mouth, eyes and genitals). For the full list of side effects of Humira, see the package leaflet.Humira must not be used in patients with active tuberculosis or other severe infections, or in patients with moderate to severe heart failure (an inability of the heart to pump enough blood around the body). For the full list of restrictions with Humira, see the package leaflet.

Why is Humira authorised in the EU?

Humira has been studied extensively and has been shown to be effective at reducing symptoms in patients with inflammatory conditions.Some rare but serious side effects have been reported, including serious infections. However, these are considered to be manageable and specific recommendations are given to help doctors manage these risks.The European Medicines Agency therefore decided that Humira's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Humira?

Patients treated with Humira must be given a reminder card with information on the safety of the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Humira have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Humira are continuously monitored. Side effects reported with Humira are carefully evaluated and any necessary action taken to protect patients.

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Hycamtin

What is Hycamtin?

Hycamtin is a cancer medicine that contains the active substance topotecan. It is available as a powder to be made up into a solution for infusion (drip) into a vein and as capsules (0.25 and 1 mg).

What is Hycamtin used for?

Hycamtin is used on its own to treat patients with:• metastatic cancer of the ovary (when the cancer has spread to other parts of the body). It is used after at least one other treatment has failed;• small cell lung cancer, when the cancer has relapsed (come back). It is used when giving the original treatment again is not recommended.It is also used together with cisplatin (another cancer medicine) to treat women with cancer of the cervix, when the cancer has come back after radiotherapy, or when the disease is at an advanced stage (has spread beyond the cervix).The medicine can only be obtained with a prescription.

How is Hycamtin used?

Treatment with Hycamtin should only be given under the supervision of a doctor experienced in the use of chemotherapy. Infusions should be carried out in a specialised cancer ward.The dose of Hycamtin to be used depends on the type of cancer that it is being used to treat and the patient's weight and height. When Hycamtin is used on its own for ovarian cancer, it is given by intravenous infusion over 30 minutes. For lung cancer, Hycamtin can be given as an infusion or, for adults, as capsules. For both ovarian and lung cancer, Hycamtin is given every day for five days with a three-week interval between the start of each course. Treatment may continue until the disease gets worse.When used with cisplatin in cervical cancer, Hycamtin is given as an infusion on days 1, 2 and 3 (with cisplatin given on day 1). This is repeated every 21 days for six courses or until the disease gets worse.Doses of Hycamtin may need to be adjusted or treatment delayed, depending on side effects. For full details, see the summary of product characteristics, also part of the EPAR.

How does Hycamtin work?

The active substance in Hycamtin, topotecan, is a cancer medicine that belongs to the group'topoisomerase inhibitors'. It blocks an enzyme called topoisomerase I, which is involved in the division of DNA. When the enzyme is blocked, the DNA strands break. This prevents the cancer cells from dividing and they eventually die. Hycamtin also affects non-cancer cells, which causes side effects.

How has Hycamtin been studied?

Hycamtin as an infusion has been studied in more than 480 women with ovarian cancer who had failed one treatment with platinum-containing cancer medicines. Three studies were 'open', meaning that the medicine was not compared to any other treatment and the patients knew that they were receiving Hycamtin. The fourth study involved 226 women, and compared Hycamtin with paclitaxel (another cancer medicine). The main measure of effectiveness was the number of patients whose tumours responded to treatment.Hycamtin has also been studied in three main studies in 656 patients with relapsed small cell lung cancer. One study compared Hycamtin capsules with symptom control alone and another compared Hycamtin as an infusion with cyclophosphamide, doxorubicin and vincristine (a standard combination of chemotherapy). The third study compared Hycamtin given as an infusion and as capsules. The effectiveness was measured by looking at survival or response rates.Hycamtin as an infusion has been studied in 293 women with advanced cervical cancer, where the effectiveness of a combination of Hycamtin and cisplatin was compared with that of cisplatin alone. The effectiveness was measured by looking at overall survival.

What benefit has Hycamtin shown during the studies?

In ovarian cancer, the studies showed the effectiveness of Hycamtin, with an overall response rate of about 16%. In the main study, 21% of the patients who received Hycamtin (23 out of 112) responded to treatment, compared with 14% of the paclitaxel patients (16 out of 114).In lung cancer, looking at the results obtained in all three studies, the response rate was 20% (480 patients received Hycamtin). Compared with symptom control alone, Hycamtin prolonged survival by12 weeks. It was as effective as the standard combination chemotherapy. Hycamtin given as capsules was as effective as Hycamtin given as an infusion.In cervical cancer, patients receiving the combination of Hycamtin and cisplatin survived an average of 9.4 months, compared with 6.5 months for the patients who received cisplatin only.

What is the risk associated with Hycamtin?

The most common side effects with Hycamtin (seen in more than 1 patient in 10) are neutropenia (low white blood cell counts), febrile neutropenia (neutropenia with fever), thrombocytopenia (low platelet counts), anaemia (low red blood cell counts), leucopenia (low white blood cell counts), nausea (feeling sick), vomiting and diarrhoea (all of which may be severe), constipation, abdominal (tummy) pain, mucositis (mouth sores), alopecia (hair loss), loss of appetite (which may be severe), infections, pyrexia (fever), asthenia (weakness) and fatigue (tiredness).Hycamtin must not be used in patients who are breast-feeding, or in patients who have severe bone marrow depression (low white blood cell and platelet counts) before treatment. For the full list of all side effects and restrictions with Hycamtin, see the package leaflet.

Why has Hycamtin been approved?

The CHMP decided that Hycamtin's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Hycamtin?

A risk management plan has been developed to ensure that Hycamtin is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Hycamtin, including the appropriate precautions to be followed by healthcare professionals and patients.

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Hyftor

What is Hyftor and what is it used for?

Hyftor is a medicine used to treat benign (non-cancerous) skin tumours on the face (facial angiofibroma) that are caused by a genetic disease called tuberous sclerosis complex. It is used in adults and children aged 6 years and older.Tuberous sclerosis complex is rare, and Hyftor was designated an 'orphan medicine' (a medicine used in rare diseases) on 23 August 2017. Further information on the orphan designation can be found on the EMA website.Hyftor is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substance, but Hyftor is given in a different way. While the reference medicine, Rapamune, is given by mouth (tablets or a liquid to be drunk), Hyftor is available as a gel to be applied to the skin.Hyftor contains the active substance sirolimus.

How is Hyftor used?

Hyftor can only be obtained with a prescription and is available as a gel that is applied twice a day to the areas of the face affected by angiofibroma. Treatment should be stopped after 12 weeks if there is no effect.For more information about using Hyftor, see the package leaflet or contact your doctor or pharmacist.

How does Hyftor work?

The way in which Hyftor works in facial angiofibroma due to tuberous sclerosis complex is not fully understood. The active substance of Hyftor, sirolimus, works by blocking an enzyme called'mammalian target of rapamycin' (mTOR). This enzyme is involved in the control of cell division and has increased activity in tumour cells in patients with tuberous sclerosis complex. By blocking mTOR, sirolimus stops tumour cells dividing, which is expected to reduce the growth of skin tumours associated with the disease.

What benefits of Hyftor have been shown in studies?

A main study involving adults and children aged 6 years and above with facial angiofibroma due to tuberous sclerosis complex has shown Hyftor to be effective at improving facial angiofibroma. After 12 weeks, facial angiofibroma size and redness improved or greatly improved in 18 out of 30 patients (60%) who used Hyftor compared with none of the 32 patients (0%) who used a placebo gel (dummy treatment).

What are the risks associated with Hyftor?

For the full list of side effects and restrictions with Hyftor, see the package leaflet.The most common side effects with Hyftor (which may affect more than 1 in 10 people) include irritation at the application site, dry skin, acne and pruritus (itching).

Why is Hyftor authorised in the EU?

Hyftor has been shown to improve the size and redness of facial angiofibroma due to tuberous sclerosis complex in adults and children aged 6 years and older, which are considered relevant benefits. The medicine's safety profile is considered acceptable. The European Medicines Agency therefore decided that Hyftor's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Hyftor?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hyftor have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hyftor are continuously monitored. Suspected side effects reported with Hyftor are carefully evaluated and any necessary action taken to protect patients.

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Hyqvia

What is HyQvia and what is it used for?

HyQvia is used in patients with immunodeficiency syndromes. These are patients whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins. HyQvia is used as 'replacement therapy' to treat:• primary immunodeficiency syndromes (PID, when patients are born with an inability to produce enough antibodies);• low levels of antibodies in the blood in patients who have chronic lymphocytic leukaemia or myeloma (two cancers affecting different types of white blood cell) and who have frequent infections.The product also contains recombinant human hyaluronidase, which is an enzyme used to help deliver the human normal immunoglobulin under the skin and improve its absorption into the body.HyQvia contains the active substance human normal immunoglobulin.

How is HyQvia used?

HyQvia can only be obtained with a prescription and treatment should be started and monitored by a doctor or nurse experienced in treating immunodeficiency syndromes.HyQvia is available as two solutions for infusion (drip) under the skin. A solution containing recombinant human hyaluronidase is given first and a solution containing human normal immunoglobulin (100 mg/ml) is then given by infusion in the same place. Detailed information about using HyQvia is provided in the package leaflet.Patients or their carers may be able to give HyQvia themselves once they have been trained appropriately. The dose and frequency of infusions (how often it is given) depend on the individual patient and may need to be adjusted depending on their response.

How does HyQvia work?

The active substance in HyQvia, human normal immunoglobulin, is a highly purified protein extracted from the blood. It contains immunoglobulin G (IgG), which is a type of antibody. IgG has been used as a medicine since the 1950s and has a wide range of activity against organisms that can cause infection. HyQvia works by restoring abnormally low IgG levels to their normal range in the blood.HyQvia also contains recombinant human hyaluronidase. This is a form of the natural human enzyme, hyaluronidase, which breaks down a substance called hyaluronic acid that is present in the tissues in the tiny spaces between cells and so makes the area between cells temporarily more liquid. When given under the skin before the normal human immunoglobulin, it helps to deliver the active substance under the skin, and assists its absorption into the body.

What benefits of HyQvia have been shown in studies?

Human normal immunoglobulin has been used to treat these diseases for many years. In accordance with current guidelines for these medicines, HyQvia was investigated in one main study lasting over a year and involving 89 patients with PID who had already had treatment with human normal immunoglobulin for at least three months. The main measure of effectiveness was the number of serious bacterial infections that developed over one year of treatment.The study showed that HyQvia was able to reduce this number to 0.03 per year. This was below the predefined number needed to show effectiveness (which is one infection per year), and was similar to that seen with other licensed human normal immunoglobulin products.This study was extended to almost 4 years and confirmed the long-term benefits and safety of HyQvia.

What are the risks associated with HyQvia?

The most common side effects with HyQvia (which may affect more than 1 in 10 people) are local reactions such as swelling and discomfort at the site of the infusion. For the full list of all side effects reported with HyQvia, see the package leaflet.HyQvia must not be used in people who are hypersensitive (allergic) to normal human immunoglobulin or hyaluronidase or any of the other ingredients, or in patients who are allergic to other types of immunoglobulins, especially where they have deficiency (very low levels) of immunoglobulin A (IgA) and they have antibodies against IgA. HyQvia must not be given into a blood vessel or a muscle.

Why is HyQvia approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) noted that HyQvia produces a similar reduction in the number of serious bacterial infections to that seen with other immunoglobulin products, and using recombinant hyaluronidase allows subcutaneous infusions to be given at much longer intervals, although local reactions are slightly more common. The possibility of patients or their carers giving the medicine themselves at home may also improve the convenience of the product. Although there had been concerns that antibodies that develop against recombinant hyaluronidase could cause side effects by affecting the natural version of the enzyme, the results of studies werereassuring. The Committee therefore decided that HyQvia's benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of HyQvia?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of HyQvia have been included in the summary of product characteristics and the package leaflet.

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Hyrimoz

What is Hyrimoz and what is it used for?

Hyrimoz is a medicine that acts on the immune system and is used to treat the following conditions:• plaque psoriasis (a disease causing red, scaly patches on the skin);• psoriatic arthritis (a disease causing red, scaly patches on the skin with inflammation of the joints);• rheumatoid arthritis (a disease causing inflammation of the joints);• axial spondyloarthritis (inflammation of the spine causing back pain), including ankylosing spondylitis and when X-ray does not show disease but there are clear signs of inflammation;• polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis (both rare diseases causing inflammation in the joints);• Crohn's disease (a disease causing inflammation of the gut);• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);• hidradenitis suppurativa (acne inversa), a long-term skin disease that causes lumps, abscesses (collections of pus) and scarring on the skin;• non-infectious uveitis (inflammation of the layer beneath the white of the eyeball).Hyrimoz is mostly used in adults when their conditions are severe, moderately severe or getting worse, or when patients cannot use other treatments. For more information on the use of Hyrimoz in all conditions, including when it can be used in children, see the package leaflet or contact your doctor or pharmacist.Hyrimoz contains the active substance adalimumab and is a 'biosimilar medicine'. This means that Hyrimoz is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Hyrimoz is Humira. For more information on biosimilar medicines, see here.

How is Hyrimoz used?

Hyrimoz is available as a solution for injection under the skin,usually given every 2 weeks. The dose and frequency of injection depends on the condition to be treated and the dose for a child is calculated according to the child's weight. After training, patients or their carers may inject Hyrimoz if their doctor considers it appropriate.Hyrimoz can only be obtained by prescription and treatment must be started and supervised by a doctor who has experience in the treatment of the diseases for which Hyrimoz is used. Eye specialists treating uveitis should also take advice from doctors who have experience of using Hyrimoz.For more information about using Hyrimoz, see the package leaflet or contact your doctor or pharmacist.

How does Hyrimoz work?

The active substance in Hyrimoz, adalimumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a substance in the body called tumour necrosis factor (TNF).TNF is involved in causing inflammation and is found at high levels in patients with the diseases that Hyrimoz is used to treat. By attaching to TNF, adalimumab blocks its activity, thereby reducing inflammation and other symptoms of the diseases.

What benefits of Hyrimoz have been shown in studies?

Laboratory studies comparing Hyrimoz with Humira have shown that the active substance in Hyrimoz is highly similar to that in Humira in terms of structure, purity and biological activity. Studies have also shown that giving Hyrimoz produces similar levels of the active substance in the body to giving Humira.In addition, Hyrimoz was as effective as Humira in a study involving 465 patients with moderate or severe plaque psoriasis. The proportion of patients who had at least a 75% reduction in symptoms after 16 weeks of treatment was 68% with Hyrimoz and 63% with Humira.Because Hyrimoz is a biosimilar medicine, the studies on effectiveness and safety of adalimumab carried out with Humira do not all need to be repeated for Hyrimoz.

What are the risks associated with Hyrimoz?

The most common side effects with adalimumab (seen in more than 1 patient in 10) are infections (including in the nose, throat and sinuses), injection-site reactions (redness, itching, bleeding, pain or swelling), headache and muscle and bone pain.Like other medicines of its class, Hyrimoz may affect the ability of the immune system to fight off infections and cancer, and there have been some cases of serious infections and blood cancers in patients using adalimumab.Other rare serious side effects (which may affect up to 1 in 1,000 people) include failure of bone marrow to produce blood cells, disorder of the nerves, lupus and lupus-like conditions (where the immune system attacks the patient's own tissues, causing inflammation and organ damage), and Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and painful rash affecting the skin, mouth, eyes and genitals).Hyrimoz must not be used in patients with active tuberculosis or other severe infections, or in patients with moderate to severe heart failure (inability of the heart to pump enough blood around the body).For the full list of side effects and restrictions with Hyrimoz, see the package leaflet.

Why is Hyrimoz authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Hyrimoz has a highly similar structure, purity and biological activity to Humira and is distributed in the body in the same way.In addition, a study in psoriasis has shown that the effects of the medicine are equivalent to those of Humira in this condition. All these data were considered sufficient to conclude that Hyrimoz will behave in the same way as Humira in terms of effectiveness and safety in its approved uses. Therefore, the Agency's view was that, as for Humira, the benefits of Hyrimoz outweigh the identified risks and it can be authorised.

What measures are being taken to ensure the safe and effective use of Hyrimoz?

Patients treated with Hyrimoz must be given a reminder card with information on the safety of the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Hyrimoz have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Hyrimoz are continuously monitored. Side effects reported with Hyrimoz are carefully evaluated and any necessary action taken to protect patients.

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