Active Substance: interferon alfa-2b
Common Name: interferon alfa-2b
ATC Code: L03AB05
Marketing Authorisation Holder: Merck Sharp & Dohme Limited
Active Substance: interferon alfa-2b
Authorisation Date: 2000-03-09
Therapeutic Area: Multiple Myeloma Leukemia, Myelogenous, Chronic, BCR-ABL Positive Hepatitis B, Chronic Carcinoid Tumor Leukemia, Hairy Cell Lymphoma, Follicular Melanoma Hepatitis C, Chronic
Pharmacotherapeutic Group: Immunostimulants
Chronic hepatitis B
Treatment of adult patients with chronic hepatitis B associated with evidence of hepatitis-B viral replication (presence of DNA of hepatitis-B virus (HBV-DNA) and hepatitis-B antigen (HBeAg), elevated alanine aminotransferase (ALT) and histologically proven active liver inflammation and / or fibrosis.
Chronic hepatitis C
Before initiating treatment with IntronA, consideration should be given to the results from clinical trials comparing IntronA with pegylated interferon.
IntronA is indicated for the treatment of adult patients with chronic hepatitis C who have elevated transaminases without liver decompensation and who are positive for hepatitis-C virus-RNA (HCV-RNA).
The best way to use IntronA in this indication is in combination with ribavirin.
Children three years of age and older and adolescents
IntronA is indicated, in a combination regimen with ribavirin, for the treatment of children three years of age and older and adolescents, who have chronic hepatitis C, not previously treated, without liver decompensation, and who are positive for HCV-RNA. When deciding not to defer treatment until adulthood, it is important to consider that the combination therapy induced a growth inhibition that resulted in reduced final adult height in some patients.
The decision to treat should be made on a case-by-case basis.
Treatment of patients with hairy cell leukaemia.
Chronic myelogenous leukaemia
Treatment of adult patients with Philadelphia-chromosome- or bcr/abl-translocation-positive chronic myelogenous leukaemia.
Clinical experience indicates that a haematological and cytogenetic major / minor response is obtainable in the majority of patients treated. A major cytogenetic response is defined by < 34 % Ph+ leukaemic cells in the bone marrow, whereas a minor response is ≥ 34 %, but < 90 % Ph+ cells in the marrow.
The combination of interferon alfa-2b and cytarabine (Ara-C) administered during the first 12 months of treatment has been demonstrated to significantly increase the rate of major cytogenetic responses and to significantly prolong the overall survival at three years when compared to interferon alfa-2b monotherapy.
As maintenance therapy in patients who have achieved objective remission (more than 50% reduction in myeloma protein) following initial induction chemotherapy.
Current clinical experience indicates that maintenance therapy with interferon alfa-2b prolongs the plateau phase; however, effects on overall survival have not been conclusively demonstrated.
Treatment of high-tumour-burden follicular lymphoma as adjunct to appropriate combination induction chemotherapy such as a CHOP-like regimen. High tumour burden is defined as having at least one of the following: bulky tumour mass (> 7 cm), involvement of three or more nodal sites (each > 3 cm), systemic symptoms (weight loss > 10 %, pyrexia > 38°C for more than eight days, or nocturnal sweats), splenomegaly beyond the umbilicus, major organ obstruction or compression syndrome, orbital or epidural involvement, serous effusion, or leukaemia.
Treatment of carcinoid tumours with lymph node or liver metastases and with 'carcinoid syndrome'.
As adjuvant therapy in patients who are free of disease after surgery but are at high risk of systemic recurrence, e.g. patients with primary or recurrent (clinical or pathological) lymph-node.
What is IntronA?
IntronA is a medicine that contains the active substance interferon alfa-2b. It is available as a powder and solvent that are made up into a solution for injection or infusion (drip into a vein), and as a ready-to-use solution for injection in a vial or in a multidose pen. These contain between 1 and 50 million international units (IU) per millilitre.
What is IntronA used for?
IntronA is used for the treatment of the following diseases:
- long-term hepatitis B (a disease of the liver due to infection with the hepatitis-B virus) in adults (aged 18 years and older);
- long-term hepatitis C (a disease of the liver due to infection with the hepatitis-C virus) in patients aged three years and older. It is usually used in combination with ribavirin (an antiviral medicine);
- hairy-cell leukaemia (a cancer of the white blood cells);
- chronic myelogenous leukaemia (CML, a cancer of the white blood cells) in adults. IntronA can be used in combination with cytarabine (an anticancer medicine) in the first year;
- multiple myeloma (a cancer of the bone marrow). IntronA is used to maintain anticancer effects in patients who have responded to previous treatment with anticancer medicines;
- follicular lymphoma (a cancer of the lymph tissue). IntronA is used as an add-on to anticancer treatments;
- carcinoid tumour (a tumour of the endocrine system that produces hormones);
- malignant melanoma (a type of skin cancer affecting cells called melanocytes). IntronA is used after surgery in patients whose melanoma could come back.
The medicine can only be obtained with a prescription.
How is IntronA used?
Treatment with IntronA should be started by a doctor who has experience in the management of the disease it is being used for. IntronA is generally given three times per week but the injection can be given more frequently in CML and melanoma. It is generally given by injection under the skin, but in melanoma it can also be given by infusion. The dose and duration of treatment depend on the disease being treated and the response of the patient, with doses ranging from 2 to 20 million IU per square metre of body surface area (calculated using the patient’s height and weight). Patients can inject themselves once they have been trained appropriately. For more information, see the package leaflet.
How does IntronA work?
The active substance in IntronA, interferon alfa-2b, belongs to the group ‘interferons’. Interferons are natural substances produced by the body to help it fight against attacks such as infections caused by viruses. The exact way that they work in cancer and viral diseases is not fully understood, but it is thought that they act as immunomodulators (substances that modify how the immune system works).
They may also block the multiplication of viruses.
Interferon alfa-2b has been available in the European Union (EU) for the treatment of various diseases for a number of years. The interferon alfa-2b in IntronA is produced by a method known as ‘recombinant DNA technology’: it is made by a bacterium that has received a gene (DNA), which makes it able to produce interferon alfa-2b. The replacement interferon alfa-2b acts in same way as naturally produced interferon alpha.
How has IntronA been studied?
Because interferon alfa-2b has been used in the EU for a number of years, the company presented the results of studies from the published literature, as well as from studies of its use with cytarabine in CML and studies of IntronA used alone (in adults) or with ribavirin (in patients from three years of age) for the treatment of long-term hepatitis C. The main measures of effectiveness were the number of patients who responded to treatment in the hepatitis studies and how long the patients survived in the cancer studies.
What benefit has IntronA shown during the studies?
The studies showed that IntronA is effective in the diseases for which it can be used. In CML, more patients who received IntronA with cytarabine were still alive after three years than patients who only received IntronA. IntronA was also shown to be effective in treating hepatitis C in adults when it was used with or without ribavirin, and in younger patients when used with ribavirin.
What is the risk associated with IntronA?
In adults, the most common side effects with IntronA used with or without ribavirin (seen in more than 1 patient in 10) are pharyngitis (sore throat), viral infection, leucopenia (low white-blood-cell counts), loss of appetite, depression, insomnia (difficulty sleeping), anxiety, emotional lability (mood swings), agitation, nervousness, dizziness, headache, impaired concentration, dry mouth, blurred vision, dyspnoea (difficulty breathing), coughing, nausea (feeling sick) or vomiting, abdominal pain (stomach ache), diarrhoea, stomatitis (inflammation of the lining of the mouth), dyspepsia (heartburn), alopecia (hair loss), pruritus (itching), dry skin, rash, increased sweating, myalgia (muscle pain), arthralgia (joint pain), musculoskeletal pain (pain in the muscles and bones), reactions at the site of the injection including inflammation, fatigue (tiredness), rigors (shaking chills), pyrexia (fever), flu-like symptoms, asthenia (weakness), irritability, chest pain, malaise (feeling unwell) and weight loss. In children and adolescents receiving IntronA in combination with ribavirin, side effects were similar to adults, although anaemia (low red blood cell counts), neutropenia (low levels of neutrophils, a type of white blood cell), hypothyroidism (underactive thyroid gland) and reduced growth were also seen in more than 1 patient in 10. For the full list of all side effects reported with IntronA, see the package leaflet.
IntronA should not be used in people who may be hypersensitive (allergic) to interferon alfa-2b or any of the other ingredients. IntronA must not be used in patients with severe kidney or liver disease, epilepsy or other central-nervous-system problems, or thyroid disease that is not controlled. It must not be used in patients who have had severe heart disease or certain immune-system disorders, in patients who are taking medicines that suppress the immune system, in hepatitis patients who have liver cirrhosis (scarring) that is causing symptoms or who have recently received medicines that affect the immune system, or in children or adolescents with a history of severe mental illness, particularly severe depression, thoughts about committing suicide or suicide attempts. For a list of all restrictions with IntronA, see the package leaflet.
Because IntronA is linked to side effects such as depression, patients must be closely monitored during treatment. IntronA in combination with ribavirin is also linked to weight loss and reduced growth in children and adolescents. Doctors should take this risk into account when deciding whether to treat a patient before adulthood.
Why has IntronA been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that IntronA’s benefits are greater than its risks and recommended that it be given marketing authorisation.
Other information about IntronA
The European Commission granted a marketing authorisation valid throughout the EU for IntronA on 9 March 2000. The marketing authorisation is valid for an unlimited period.
For more information about treatment with IntronA, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
Source: European Medicines Agency
Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.