Avonex

/ Medison

Adults: The recommended dosage for the treatment of relapsing MS is 30 micrograms (1 ml solution), administered by intramuscular (IM) injection once a week. No additional benefit has been shown by administering a higher dose (60 micrograms) once a week.
Titration: To help patients reduce the incidence and severity of flu-like symptoms, titration can be performed at the initiation of treatment. Titration using the BIOSET or pre-filled syringe can be achieved by initiating therapy on ¼ dose increments per week reaching the full dose (30 micrograms/week) by the fourth week. An alternative titration schedule can be achieved by initiating therapy on approximately a ½ dose once a week before increasing to the full dose. In order to obtain adequate efficacy, a dose of 30mcg once a week should be reached and maintained after the initial titration period. Prior to injection and for an additional 24 hours after each injection, an antipyretic analgesic is advised to decrease flu-like symptoms associated with administration. These symptoms are usually present during the first few months of treatment.
Paediatric population: The safety and efficacy in adolescents aged 12 to 16 years have not yet been established. no recommendation on a posology can be made. The safety and efficacy in children below 12 years of age have not yet been established. No data are available.
Elderly: Clinical studies did not include a sufficient number of patients aged 65 and over to determine whether they respond differently than younger patients. However, based on the mode of clearance of the active substance there are no theoretical reasons for any requirement for dose adjustments in the elderly. The intramuscular injection site should be varied each week. Doctors may prescribe a 25 mm, 25 gauge needle to patients for whom such a needle is appropriate to administer an intramuscular injection. At the present time, it is not known for how long patients should be treated. Patients should be clinically evaluated after two years of treatment and longer-term treatment should be decided on an individual basis by the treating physician. Treatment should be discontinued if the patient develops chronic progressive MS.
For full details see prescribing information.

Avonex is indicated for the treatment of relapsing forms of multiple sclerosis to slow the accumulation of physical disability and to decrease the frequency of clinical exacerbations. Avonex is also indicated for the treatment of patients who have experienced a single demyelinating event with an active inflammatory process if it is severe enough to warrant treatment with intravenous corticosteroids if alternative diagnosis have been excluded, including the prescence of MRI abnormalities characteristic of MS and if they are determined to be at high risk of developing clinically definite multiple sclerosis. Safety and efficacy in patients with chronic progressive multiple sclerosis has not been evaluated.

Initiation of treatment in pregnancy, Patients with a history of hypersensitivity to natural or recombinant interferon -ß, human albumin or to any excipients, Patients with current severe depression and/or suicidal ideation.

This product should be administered with caution to patients with previous or current depressive disorders, in particular to those with antecedents of suicidal ideation. Depression and suicidal ideation are known to occur in increased frequency in the multiple 3 sclerosis population and in association with interferon use. Patients should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician. Patients exhibiting depression should be monitored closely during therapy and treated appropriately. Cessation of therapy should be considered. This product should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their epilepsy is not adequately controlled with anti-epileptics. Caution should be used and close monitoring considered when administering to patients with severe renal and hepatic failure and to patients with severe myelosuppression. Thrombotic microangiopathy (TMA): Cases of thrombotic microangiopathy, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation is recommended. Nephrotic Syndrome: Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative glomerulonephritis (MPGN) and membranous glomerulopathy (MGN) have been reported during treatment with interferon-beta products. Events were reported at various time points during treatment and may occur after several years of treatment with interferon-beta. Periodic monitoring of early signs or symptoms, e.g. oedema, proteinuria and impaired renal function is recommended, especially in patients at higher risk of renal disease. Prompt treatment of nephrotic syndrome is required and discontinuation of treatment with this product  should be considered. Hepatic injury including elevated serum hepatic enzyme levels, hepatitis, autoimmune hepatitis and hepatic failure has been reported with interferon beta in post-marketing. In some cases, these reactions have occurred in the presence of other medicinal products that have been associated with hepatic injury. The potential of additive effects from multiple medicinal products or other hepatotoxic agents (e.g. alcohol) has not been determined. Patients should be monitored for signs of hepatic injury and caution exercised when interferons are used concomitantly with other medicinal products associated with hepatic injury. Patients with cardiac disease, such as angina, congestive heart failure or arrhythmia, should be closely monitored for worsening of their clinical condition during treatment with this product . Flu-like symptoms associated with therapy may prove stressful to patients with underlying cardiac conditions. Laboratory abnormalities are associated with the use of interferons. Therefore, in addition to those laboratory tests normally required for monitoring patients with MS, complete and differential white blood cell counts, platelet counts, and blood chemistry, including liver function tests, are recommended during therapy. Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts. Patients may develop antibodies to this product . The antibodies of some of those patients reduce the activity of interferon beta-1a in vitro (neutralising antibodies). Neutralising antibodies are associated with a reduction in the in vivo biological effects of this product  and may potentially be associated with a reduction of clinical efficacy. It is estimated that the plateau for the incidence of neutralising antibody formation is reached after 12 months of treatment. Recent clinical studies with patients treated up to three years with this product  suggest that approximately 5% to 8% develop neutralising antibodies. The use of various assays to detect serum antibodies to interferons limits the ability to compare antigenicity among different products.
For full details see prescribing information.

Symptoms of the flu-like syndrome, muscle ache, fever, chills, asthenia, headache, and nausea. Symptoms decrease in frequency with continued treatment. Anorexia, hypersensitivity reactions, weight loss, weight gain and severe allergic reactions, alopecia, pruritus, rash, urticaria and injection site reaction including pain, diarrhea, hepatitis, liver function test abnormalities, vomiting, chest pain, palpitations, tachycardia, vasodilation. Arrhythmia, cardiomyopathy and congestive heart failure can rarely occur. Anxiety, dizziness, insomnia, paresthesia. Seizures can rarely occur, depression and suicide have been reported. Arthralgia, pain, dyspnoea.
For full details see prescribing information.

No formal interaction studies have been performed in humans. The interaction with corticosteroids or adrenocorticotropic hormone (ACTH) has not been studied systematically. The clinical studies indicate that MS patients can receive this product and corticosteroids or ACTH during relapses. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. The effect of high-dose administration on P450- dependent metabolism in monkeys was evaluated and no changes in liver metabolising capabilities were observed. Caution should be exercised when this product is administered in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. antiepileptics and some classes of antidepressants.

Pregnancy: There is limited information on the use of this product in pregnancy. Available data indicates that there may be an increased risk of spontaneous abortion. Initiation of treatment is contraindicated during pregnancy. Women of child-bearing potential Women of child-bearing potential have to take appropriate contraceptive measures. If the patient becomes pregnant or plans to become pregnant while taking Pregnancy There is limited information on the use in pregnancy. Available data indicates that there may be an increased risk of spontaneous abortion. Initiation of treatment is contraindicated during pregnancy. Women of child-bearing potential Women of child-bearing potential have to take appropriate contraceptive measures. If the patient becomes pregnant or plans to become pregnant while taking Pregnancy There is limited information on the use in pregnancy. Available data indicates that there may be an increased risk of spontaneous abortion. Initiation of treatment is contraindicated during pregnancy. Women of child-bearing potential Women of child-bearing potential have to take appropriate contraceptive measures. If the patient becomes pregnant or plans to become pregnant while taking this product she should be informed of the potential hazards and discontinuation of therapy should be considered. In patients with a high relapse rate before treatment started, the risk of a severe relapse following discontinuation in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion. Lactation It is not known whether this product is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made either to discontinue breast-feeding or therapy.  she should be informed of the potential hazards and discontinuation of therapy should be considered. In patients with a high relapse rate before treatment started, the risk of a severe relapse following discontinuation in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion. Lactation It is not known whether this product is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made either to discontinue breast-feeding or therapy.  she should be informed of the potential hazards and discontinuation of therapy should be considered. In patients with a high relapse rate before treatment started, the risk of a severe relapse following discontinuation of Pregnancy There is limited information on the use of this product in pregnancy. Available data indicates that there may be an increased risk of spontaneous abortion. Initiation of treatment is contraindicated during pregnancy. Women of child-bearing potential Women of child-bearing potential have to take appropriate contraceptive measures. If the patient becomes pregnant or plans to become pregnant while taking Pregnancy There is limited information on the use of this product in pregnancy. Available data indicates that there may be an increased risk of spontaneous abortion. Initiation of treatment is contraindicated during pregnancy. Women of child-bearing potential Women of child-bearing potential have to take appropriate contraceptive measures. If the patient becomes pregnant or plans to become pregnant while taking this product she should be informed of the potential hazards and discontinuation of therapy should be considered. In patients with a high relapse rate before treatment started, the risk of a severe relapse following discontinuation of this product in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion. Lactation It is not known whether this product is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made either to discontinue breast-feeding or therapy.  she should be informed of the potential hazards and discontinuation of therapy should be considered. In patients with a high relapse rate before treatment started, the risk of a severe relapse following discontinuation in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion.
Lactation: It is not known whether this product is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made either to discontinue breast-feeding or this producttherapy.  in the event of pregnancy should be weighed against a possible increased risk of spontaneous abortion. Lactation It is not known whether this product is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made either to discontinue breast-feeding or therapy.
Fertility: Fertility and developmental studies in rhesus monkeys have been carried out with a related form of interferon beta 1a. At very high doses, anovulatory and abortifacient effects in test animals were observed. No information is available on the effects of interferon beta 1a on male fertility.

No case of overdose has been reported. However, in case of overdose, patients should be hospitalised for observation and appropriate supportive treatment given.