Interferon Alfa-2A Dosage

Usual Adult Dose for Chronic Hepatitis C

3 million intl units subcutaneously or IM three times a week for 48 to 52 weeks (12 months). Alternatively 6 million intl units three times a week for the first 12 weeks (3 months), followed by 3 million intl units three times a week for 36 weeks (9 months).

Usual Adult Dose for Chronic Myelogenous Leukemia

9 million intl units daily subcutaneously or IM.

Usual Adult Dose for Hairy Cell Leukemia

Induction dose: 3 million intl units daily subcutaneously or IM for 16 to 24 weeks.
Maintenance dose: 3 million intl units three times a week for up to 24 consecutive months.

Usual Adult Dose for Kaposi's Sarcoma

Induction dose: 36 million intl units daily subcutaneously or IM for 10 to 12 weeks.
Maintenance dose: 36 million intl units three times a week.

Usual Adult Dose for Lymphoma

Study (n=5) - Lymphomatoid Papulosis
3 to 15 million intl units three times per week subcutaneously for up to 13 months.

Usual Adult Dose for Renal Cell Carcinoma

Study (n=75) Metastatic Renal-Cell Carcinoma
subcutaneous injection three times weekly, 4.5 million units titrated upwards to 18 million units, as tolerated, during the first 4 weeks (weekly dose increases). The individual maintenance dose, based on tolerability of side effects, was continued for 3 weeks (out of a 4-week cycle), up to 2 years if the patient responds or has stable disease.

Usual Pediatric Dose for Chronic Myelogenous Leukemia

Study (n=15)
2.5 to 5 million intl units/m2/day IM

Study (n=12) Philadelphia Chromosome-Positive CML
5 million intl units/m2/day subcutaneously (combined with Cytarabine 20 mg/m2/day for 10 days monthly).

Renal Dose Adjustments

CrCl less than 50 mL/min: Use with caution and monitor for side effects.

Liver Dose Adjustments

Interferon alfa-2a is contraindicated in patients with autoimmune hepatitis and in patients with hepatic decompensation (Child-Pugh class B and C) before or during treatment.

Dose Adjustments

Reduce dose by 50% if patient experiences severe reaction, or discontinue therapy until reaction subsides.

In CML patients a gradual increase of the dose over the first week of treatment may improve tolerance, give 3 million intl units daily for 3 days, 6 million intl units daily for 3 days, to the target dose of 9 million intl units daily.

An escalating dosing schedule for AIDS-related Kaposi's sarcoma may decrease the incidence of acute toxicity in some patients, give each, 3, 9, and 18 million intl units, dose for 3 consecutive days, followed by 36 million intl units daily for the remaining of the 10 to 12 weeks.

Precautions

Alpha interferons, including interferon alfa-2a, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping interferon alfa-2a.

Use of interferon alfa-2a is not recommended in patients with a history of autoimmune disease or patients who are immunosuppressed transplant recipients. Interferon alfa-2a is contraindicated in patients with autoimmune hepatitis and in patients with hepatic decompensation (Child-Pugh class B and C) before or during treatment. Interferon alfa-2a should not be used in the treatment of patients with visceral AIDS-related Kaposi's Sarcoma associated with rapidly progressive or life threatening disease. Interferon alfa-2a (Roferon-A) is contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurologic and other complications in neonates and infants, which are sometimes fatal.

Interferon alfa-2a should be given under the guidance of a qualified physician. Approximate management of interferon alfa-2a therapy and its complications is possible only when adequate facilities are readily available.

Depression and suicidal behavior including suicidal ideation, suicide attempts and suicides have been reported in patients receiving interferon alfa-2a. Interferon alfa-2a should be used with extreme caution in patients who reported a history of depression. If a patient develops clinically significant depression, interruption of therapy with interferon alfa-2a should be considered. Depression has been reported to have sometimes continued after decreases in dosage or discontinuation of therapy. Therefore, even after discontinuation of interferon alfa-2a therapy, continued monitoring of the patient is recommended. The manufacturer recommends careful periodic neuropsychiatric monitoring of all patients receiving interferon alfa-2a. It should be used with extreme caution in patients who report a history of depression.

Central nervous system (CNS) adverse events have been reported in a number of patients. These events have included decreased mental status, dizziness, impaired memory, agitation, manic behavior, and psychotic reactions. More severe obtundation and coma have been rarely reported. Most of these abnormalities were mild and reversible within a few days to 3 weeks upon dose reduction or discontinuation of therapy. Careful periodic neuropsychiatric monitoring of all patients is advised. Interferon alfa-2a should be used with caution in patients with seizure disorder and/or compromised CNS function.

Interferon alfa-2a should be used with caution in patients with preexisting cardiac disease. Patients with preexisting cardiovascular conditions (angina, congestive heart failure, arrhythmia) should be monitored closely for worsening of their condition during initiation of interferon alfa-2a therapy. Symptoms of flu-like syndrome associated with interferon alfa-2a are potentially stressful to patients with severe cardiac disease. Patients with preexisting cardiac abnormalities should have electrocardiograms taken before and during the course of therapy.

Acute hypersensitivity adverse events and skin rashes have been observed during alpha interferon therapy, including interferon alfa-2a. The drug should be discontinued if a serious adverse event develops and appropriate treatment should be implemented immediately. Transient rashes do not necessitate interruption of therapy.

In chronic hepatitis C, initiation of alpha interferon treatment, including interferon alfa-2a, has been reported to cause transient liver abnormalities, which in patients with poorly compensated liver disease can result in increased ascites, hepatic failure or death. Caution is recommended in patients with severe hepatic disease. For patients being treated for chronic hepatitis C, serum ALT should be evaluated before therapy to establish baselines and repeated at week 2 and monthly thereafter following initiation of treatment for monitoring clinical response. Patients developing liver function abnormalities during interferon alfa-2a treatment should be monitored closely and if necessary treatment should be discontinued. Use of alpha interferons has been rarely associated with liver failure and severe hepatic dysfunction.

Severe or fatal gastrointestinal hemorrhage has been reported in association with alpha interferon therapy. Ulcerative and hemorrhagic/ischemic colitis, sometimes resulting in death, have been observed within 12 weeks of starting alpha interferon therapy. The drug should be discontinued immediately if these symptoms develop. The colitis usually resolves within 1 to 3 weeks of discontinuation of alpha interferon.

While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, other causes of high or persistent fever should be ruled out, particularly in patients with neutropenia. Serious and severe infections (bacterial, viral, fungal), sometimes fatal, have been reported during treatment with alpha interferons including interferon alfa-2a. Appropriate anti-infective treatment should be started immediately and discontinuation of therapy should be considered.

Caution is recommended if interferon alfa-2a is to be used in patients with myelosuppression or in patients receiving other therapies known to cause myelosuppression. Alpha interferons suppress bone marrow function and may result in severe cytopenias and anemias including rarely aplastic anemia. Cytopenias can lead to an increased risk of infections or hemorrhage. It is recommended that complete blood counts be obtained pretreatment and monitored routinely during treatment. Alpha interferon therapy should be discontinued in patients who develop severe decrease in neutrophil (less than 0.5 x 10(9)/L) or platelet counts (less than 25 x 10(9)/L).

Interferon alfa-2a causes or aggravates hypothyroidism and hyperthyroidism. Patients with preexisting thyroid abnormalities may be treated if normal thyroid stimulating hormone (TSH) levels can be maintained by treatment. Testing of TSH levels in these patients is recommended at baseline and every 3 months following initiation of interferon alfa-2a therapy.

Hyperglycemia has been observed in patients treated with interferon alfa-2a. Close monitoring of blood glucose with appropriate therapy is recommended. Patients with diabetes mellitus may require adjustments of their antidiabetic therapies.

Alpha interferons may induce or aggravate dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis, some resulting in respiratory failure and/or patients' deaths. Interferon alfa-2a should be discontinued if patient develops persistent or unexplained pulmonary infiltrates or pulmonary function impairment.

Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhage and cotton wool spots, optic neuritis, and papilledema are induced or aggravated by treatment with interferon alfa-2a or other alpha interferons. All patients should receive an eye examination prior to the start of treatment. Patients with preexisting ophthalmological disorders should receive periodic eye exams during interferon alpha treatment. The drug should be discontinued if patient develops new or worsening ophthalmologic disorders.

Elevated triglyceride levels have been observed in patients treated with interferons, including interferon alfa-2a. Triglyceride levels should be monitored during treatment and should be managed appropriately. Hypertriglyceridemia may result in pancreatitis. Interferon alfa-2a should be discontinued in patients with persistently elevated triglycerides (e.g., greater than 1000 mg/dL) associated with symptoms of potential pancreatitis, such as abdominal pain, nausea, or vomiting.

In all instances where the use of interferon alfa-2a is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risk of adverse events. Most adverse events are reversible if detected early. If severe events occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgement of the physician. Reinstitution of interferon alfa-2a for treatment of hairy cell leukemia and chronic myelogenous leukemia have not been determined. Patients with advanced stages of cancer should have electrocardiograms taken before and during the course of therapy.

Variations in dosage and adverse reactions exist among different brands of interferon. Therefore, do not use different brands of interferon in a single treatment regimen.

The efficacy and safety of interferon alfa-2a have not been established in organ transplant recipients.

Dose-limiting renal toxicities have been reported infrequently. Severe renal toxicities, sometimes requiring renal dialysis, have been reported infrequently with alpha interferon therapy alone or in combination with IL-2. In patients with impaired renal function, signs and symptoms of interferon toxicity should be monitored closely. Interferon alfa-2a should be used with caution in patients with creatinine clearance less than 50 mL/min.

Development or exacerbation of autoimmune diseases including idiopathic thrombocytopenic purpura, vasculitis, Raynaud's phenomenon, rheumatoid arthritis, psoriasis, interstitial nephritis, thyroiditis, lupus erythematosus, hepatitis, myositis and rhabdomyolysis have been reported in patients treated with alpha interferons. Any patient developing an autoimmune disorder during therapy should be closely monitored and, if appropriate, treatment should be discontinued. Use of interferon alfa-2a is not recommended in patients with a history of autoimmune disease or patients who are immunosuppressed transplant recipients.

Complete blood counts with differential platelet counts and clinical chemistry tests should be performed before initiation of interferon alfa-2a therapy and at appropriate periods during the course of therapy.

Dialysis

Data not available

Other Comments

Patients diagnosed with chronic hepatitis C who do not respond to Roferon-A therapy within the first 3 months are not likely to respond to continued treatment. In responders, normalization of serum ALT generally occurs within a few weeks after initiation of treatment (90% of responders do so within the first 3 months).

The manufacturer suggests that the subcutaneous route of administration be used for, but not limited to, patients with thrombocytopenia (platelet count less than 50,000) or for patients at risk of bleeding.

Further information

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