Interferon alfa-2b/ribavirin Disease Interactions

Proteinuria (rare), not associated with a decrease in serum protein, is the most common renal toxicity observed with interferon- alfa therapy. Increased BUN and serum creatinine levels, hematuria, acute renal failure and nephrotic syndrome have also been reported. Therapy with interferon alfa should be administered cautiously to patients with severe renal dysfunction. Renal function should be evaluated in all patients before initiation of interferon- alfa therapy. In addition, patients with any degree of renal impairment should be carefully monitored for laboratory abnormalities and decreased creatinine clearance. A reduced dose of medication is recommended in patients with low CrCl (less than 50 mL/min - 30 mL/min).

Antiviral interferons may exacerbate autoimmune disorders such as myositis, thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, or autoimmune hepatitis. Therapy should be avoided or administered with extreme caution in patients with autoimmune disorders.

Hepatotoxicity, including fatal cases, has been reported in patients treated with interferon alpha. Additionally, the risk of hepatic decompensation and death is increased in patients with cirrhosis. Any patient developing liver function abnormalities during treatment should be monitored closely and treatment should be discontinued if appropriate. Interferon-alfa is contraindicated in patients with autoimmune hepatitis and decompensated liver disease.

Hypertension, arrhythmias, angina, myocardial infarction, cardiomyopathy, and congestive heart failure have been reported during interferon therapy. Therapy with interferons should be administered with caution in patients with compromised cardiac function.

Reversible CNS effects such as seizures, mental status changes, manic behavior or psychotic reactions, gait disturbances, and dizziness have occurred in patients receiving interferons. Therapy with interferons should be administered cautiously in patients with or predisposed to seizures, psychiatric disorders, or conditions affecting posture or gait.

Interferons (alfa or beta) can induce depression and suicidal behavior. Suicidal attempts and suicides have been reported. Therapy with interferons (alfa or beta) should be administered cautiously to patients with or predisposed to mental depression. Clinical monitoring of psychological status is recommended.

Thyroid abnormalities, hypothyroidism or hyperthyroidism, have been reported in patients administered interferons. Therapy with interferons should be administered cautiously to patients with thyroid dysfunction. If thyroid control cannot be maintained within normal limits with medication, interferon-alfa should be discontinued. Clinical monitoring of thyroid function is recommended.

Oral ribavirin may cause anemia. The decrease in hemoglobin generally occurs within 1 to 2 weeks after initiation of therapy and stabilizes by week 4. Because significant anemia may adversely affect cardiac function, oral ribavirin should not be used in patients with severe anemia of any etiology or a history of serious or unstable heart disease. It should also be avoided in patients with hemoglobinopathies such as thalassemia or sickle- cell anemia. Therapy with oral ribavirin may be administered cautiously in patients with stable heart conditions. Both the hemoglobin level and cardiovascular status must be closely monitored. A permanent dosage reduction is required in these patients if the hemoglobin decreases by >= 2 g/dL during any 4- week period. If, after 4 weeks on the reduced dosage, the hemoglobin remains < 12 g/dL, therapy should be discontinued. The drug should also be withdrawn if cardiovascular status deteriorates. For all patients, a dosage reduction is recommended when hemoglobin is < 10 g/dL. If hemoglobin falls below 8.5 g/dL, oral ribavirin should be permanently discontinued. In clinical trials, hemoglobin values generally returned to baseline 4 to 8 weeks after cessation of therapy.

The use of aerosolized ribavirin in patients requiring mechanical ventilation demands meticulous care by a trained staff in order to prevent complications associated with drug precipitation within the respiratory equipment. Close, continuous monitoring, as well as frequent cleaning and changes of line valves and ventilator tubings and filters, are conducive to favorable outcomes. Certain equipment implementations and settings are also essential, but specific details regarding equipment circuitry maintenance and modifications are beyond the scope of this application and should be obtained from the SPAG-2 Operator's Manual.

The use of aerosolized ribavirin has been associated with deterioration in pulmonary function, most significantly in patients with chronic obstructive pulmonary disease or asthma. Respiratory status should be monitored in all patients receiving aerosolized ribavirin, but in particular, patients with underlying respiratory disorders. Therapy should be stopped if sudden deterioration occurs, and reinstituted only with extreme caution and consideration of concomitant bronchodilator therapy.

Orally administered ribavirin is metabolized by the liver, and both parent drug and metabolites are eliminated by the kidney. In patients with creatinine clearance between 10 and 30 mL/min, the mean area under the concentration-time curve has been shown to be three times greater than that in patients with normal renal function, presumably due to decreased clearance of the drug. Therapy with oral ribavirin should be administered cautiously in patients with creatinine clearance below 50 mL/min. Dosage adjustments may be necessary. The drug is not recommended for use in patients with severe renal impairment.

Fatal and nonfatal ulcerative or hemorrhagic/ischemic colitis have been observed within 12 weeks of the start of alpha interferon treatment. Abdominal pain, bloody diarrhea, and fever are the typical manifestations. Treatment should be discontinued immediately in patients who develop these signs and symptoms. The colitis usually resolves within 1 to 3 weeks of discontinuation of alpha interferons.

Flu-like symptoms frequently associated with interferon-alfa therapy can precipitate ketoacidosis in diabetic patients. Therapy with interferon alfa should be administered cautiously in patients with diabetes mellitus. Clinical monitoring of blood glucose concentrations and anti-diabetic therapy is recommended.

Interferons (alfa and gamma) induce a dose-dependent, generally mild, myelosuppression. Leukopenia is the primary manifestation. Thrombocytopenia and anemia occur less frequently. Therapy with interferons (alfa and gamma) should be administered cautiously to patients with bone marrow suppression. Clinical monitoring of hematopoietic function is recommended.

Paresthesia and numbness have been reported during interferon therapy. Therapy with interferons should be administered cautiously in patients with or predisposed to peripheral neuropathy.