Adult Dosing
General Information:- Not all dosage forms and strengths are appropriate for some indications; please refer to detailed PI for the appropriate dosage form and strength for the indication being treated
- To increase the tolerability of the drug, injections should be administered in the evening when possible
- Allow the solution to come to room temperature before using
- As powder form of interferon alfa-2b does not contain a preservative, discard the vial after reconstitution and withdrawal of a single dose
Condylomata Acuminata
- Recommended dose: 1 MIU intra-lesionally three times a week (TIW) on alternate days x 3 weeks
- Maximum: 5 condylomata lesions/course
- Administer an additional course at 12-16 weeks
Note:
- Do not use 18 million or 50 million IU powder for injection, 18 MIU multidose solution for injection or the multidose pens for this indication as all dosage forms and strengths are not appropriate for some indications
Hairy Cell Leukemia
- Recommended dose: 2 MIU/m2 IM/SC 3 times a week x 6 months
Note:
- Reduce the dose by 50% if severe adverse reactions (AR) develop or withold therapy temporarily until the AR abate and then resume at 50% (1 MIU/mm2 TIW); discontinue permanently if severe AR persist or recur even after dose adjustment
- Discontinue therapy if disease progresses or if there is failure to respond after 6 months of Rx
- Do not administer interferon alpha-2b IM if platelet counts are less than 50,000/mm3
Chronic Hepatitis B
- Recommended dose: 30-35 million IU/week SC/IM x16 weeks either as 5 million IU qd or 10 million IU TIW
Note:
- Reduce the dose by 50% or discontinue therapy if severe AR or laboratory abnormalities develop, until AR abate. Discontinue permanently if intolerance persists even after dose adjustments
- For patients with decreases in WBC, granulocyte count or platelet count, reduce the interferon alfa-2b dose by 50% if the WBC count is <1.5 × 109/L, or if the granulocyte count is <0.75 × 109/L, or if the platelet count is <50 × 109/L. Permanently discontinue therapy if the WBC count is <1 × 109/L, or if the granulocyte count is <0.5 × 109/L, or if the platelet count is <25 × 109/L
Chronic Hepatitis C
Monotherapy
- Recommended dose: 3 MIU three times a week SC/IM x 18-24 months in patients tolerating therapy with normalization of ALT at 16 wks of treatment
Note:
- Discontinue therapy if ALTs do not normalize or there is persistent high levels of HCV RNA after 16 weeks of therapy
- Reduce the dose by 50% if severe AR occur or discontinue temporarily until AR abate. Discontinue permanently if AR persist even after dose adjustment
- Careful monitoring is advised when used in combination with ribavirin in patients with impaired renal function and/or those >50 yrs due to the potential risk of development of anemia
AIDS-associated Kaposi’s sarcoma
- Recommended dose: 30 MIU/m2/dose SC/IM three times a week until disease progression or maximal response has been achieved after 16 weeks of Rx
Note:
- Do not use solution for injection form either in vials or in multidose pens for this condition
- Reduce dose by 50% or withhold therapy for severe AR; resume at a reduced dose if severe AR abate with dose interruption. Discontinue permanently if severe AR persist or recur even after dose modification
Adjuvant therapy for Malignant Melanoma (Two-phase therapy)
Induction Therapy
- Recommended dose: 20 MIU/m2 as IV infusion over 20 minutes x5 consecutive days/wk for 4 wks
Maintenance therapy
- Recommended dose: 10 MIU/m2 SC three times a week x 48 wks
Note:
- Withhold therapy if severe AR occur, including granulocyte counts >250/mm3 but <500/mm3 or ALT/AST >5 to 10 times ULN, until adverse reactions subside. Restart treatment at 50% of the previous dose
- Discontinue therapy permanently if toxicity does not abate after withholding Rx, severe AR recur in patients receiving reduced doses, or granulocyte count <250 mm3 or ALT/AST greater than 10 times ULN
- Avoid solution for injection in vials or multidose pens for IV administration; do not use for induction phase of malignant melanoma
Follicular Non-Hodgkin's Lymphoma
- Recommended dose: 5 MIU SC three times a week x 18 months in combination with other antineoplastic therapy
Note:
- Myelosuppressive drug doses were reduced by 25% when alfa interferon was added to the regimen
- Delay chemotherapy cycle if neutrophil count was less than 1500/mm3 or platelet count was less than 75,000/mm3
- Permanently discontinue therapy if AST exceeds 5 times the ULN or serum creatinine >2 mg/dL
- Withhold therapy for a neutrophil count <1000/mm3 or a platelet count <50,000/mm3
- Reduce therapy dose by 50% for a neutrophil count >1000/m3, but <1500/mm3
- Re-escalate the interferon alfa-2b dose to the starting dose after resolution of hematologic toxicity
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established for indications other than chronic hepatitis B and chronic hepatitis C
Chronic Hepatitis B (Children >1 yr)
- Recommended dose: 3 million IU/m2 TIW x 1 wk followed by 6 million IU/m2 TIW SC x 16-24 weeks
- Maximum: 10 million IU TIW
Notes:- Not all dosage forms and strengths are appropriate for some indications; please refer to detailed PI for the appropriate dosage form and strength for the indication being treated
- Reduce the dose by 50% or discontinue therapy if severe AR or laboratory abnormalities develop, until AR abate. Discontinue permanently if intolerance persists even after dose adjustments
- For patients with decreases in WBC, granulocyte count or platelet count, reduce the interferon alfa-2b dose by 50% if the WBC count is <1.5 × 109/L, or if the granulocyte count is <0.75 × 109/L, or if the platelet count is <50 × 109/L. Permanently discontinue therapy if the WBC count is <1 × 109/L, or if the granulocyte count is <0.5 × 109/L, or if the platelet count is <25 × 109/L
- To increase the tolerability of the drug, injections should be administered in the evening when possible
- Allow the solution to come to room temperature before using
- As powder form of interferon alfa-2b does not contain a preservative, discard the vial after reconstitution and withdrawal of a single dose
[Outline]
Renal Dose Adjustment (Based on CrCl)
- <50 mL/min: Contraindicated (chronic hepatitis C)
- Renal impairment and/or >50 yrs of age: Caution advised; dose adjustments not defined
Hepatic Dose Adjustment
- Decompensated hepatic disease/autoimmune hepatitis: Contraindicated
- Hepatic failure: Contraindicated
See Supplemental Patient Information
- Closely monitor patients with a history of MI and/or previous or current arrhythmic disorder requiring interferon alfa-2b therapy. Cardiovascular adverse events including hypotension, arrhythmia, or tachycardia of 150 beats/min or greater, and occasionally, cardiomyopathy and MI have been reported in certain patients receiving therapy, among whom some patients had no hx of CVD. Cases of hypotension have been reported during administration of this drug or up to 2 days post-therapy which may require supportive therapy including fluid replacement
- Therapy may cause ischemic and hemorrhagic cerebrovascular events
- Cases of depression and suicidal behavior including suicidal ideation, suicidal attempts, and completed suicides, homicidal ideation, and aggressive behavior sometimes directed towards others have been reported with alpha interferon therapy, including interferon alfa-2b recombinant. Careful monitoring is recommended during Rx and in the 6-month follow-up period in patients developing psychiatric problems, including clinical depression. Discontinue therapy in patients developing severe psychiatric disorders during treatment. Obtundation and coma have been reported in elderly patients treated at higher doses. These effects are rapidly reversible upon discontinuation of therapy and complete resolution may take up to 3 weeks in a few severe episodes
- Exercise caution during concomitant use of narcotics, hypnotics, or sedatives; closely monitor patients until the adverse effects have resolved
- Pediatric patients, particularly adolescents are more susceptible to suicidal ideation or attempts compared to adult patients during treatment and post-therapy follow-up. Encephalopathy has been reported in certain elderly patients treated at higher doses of this drug
- Therapy may be associated with exacerbated symptoms of psychiatric disorders in patients with co-occurring psychiatric and substance use disorders. Early intervention is recommended for re-emergence or development of neuropsychiatric symptoms and substance use
- Therapy may cause bone marrow suppression, resulting in severe cytopenias including aplastic anemia. Obtain complete blood counts pretreatment and routinely during therapy; discontinue therapy in patients who develop significant reductions in neutrophil (<0.5 × 109/L) or platelet counts (<25 × 109/L)
- Treatment with interferon alfa-2b may induce or aggravate retinopathy, decrease or loss of vision including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots; optic neuritis, papilledema, and serous retinal detachment. Perform eye examination at baseline and periodically during therapy in patients with preexisting ophthalmologic disorders. Permanently discontinue therapy, if patients develop new or worsening ophthalmologic disorders
- Patients receiving therapy may rarely develop thyroid abnormalities, either hypothyroid or hyperthyroid; diabetes mellitus may occur during treatment with alpha interferons. Evaluate thyroid function and initiate appropriate medical therapy if patients develop symptoms consistent with possible thyroid dysfunction during therapy. Do not start therapy in patients with these conditions who cannot be maintained in the normal range by medications
- Cases of hepatotoxicity (including fatal) have been reported in patients treated with interferon alfa-2b recombinant. Closely monitor patients developing liver function abnormalities during treatment and discontinue therapy if appropriate
- Therapy may induce or aggravate dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, and sarcoidosis, some resulting in respiratory failure and/or deaths. Interferon rechallenge may cause recurrence of respiratory failure. Obtain chest X-ray in patients presenting with fever, cough, dyspnea, or other respiratory symptoms. Closely monitor patients if the chest X-ray indicates pulmonary infiltrates or there is evidence of pulmonary function impairment and consider therapy discontinuation, if appropriate
- Autoimmune diseases including thrombocytopenia, vasculitis, Raynaud's phenomenon, rheumatoid arthritis, lupus erythematosus, and rhabdomyolysis have been rarely reported in patients receiving interferon alfa-2b recombinant. Discontinue treatment if patients develop autoimmune disorder during treatment
- Avoid therapy in patients with rapidly progressive visceral disease. Also, there may be synergistic adverse effects between interferon alfa-2b recombinant and zidovudine
- Therapy should not be used for patients with decompensated liver disease, autoimmune hepatitis or a history of autoimmune disease, and patients who are immunosuppressed transplant recipients
- Peripheral neuropathy may occur when administered in combination with telbivudine; caution advised
- Concomitant use with ribavarin may cause birth defects and/or death of the unborn child. Do not start ribavarin therapy until a report of negative pregnancy test has been obtained immediately prior to therapy initiation. Advise patients to use at least two reliable forms of contraception and have monthly pregnancy tests
- Rare cases of acute serious hypersensitivity reactions have been reported during therapy; discontinue therapy immediately if such an acute reaction develops and initiate appropriate medical therapy
- Therapy may cause exacerbation of preexisting psoriasis and sarcoidosis as well as development of new sarcoidosis; hence, should be used in such patients only if the potential benefit justifies the potential risk
- Variations in dosage, routes of administration, and adverse reactions exist among different brands of interferon. Exercise caution not to use different brands of interferon in any single treatment regimen
- Increased triglyceride levels have been reported in patients treated with interferon alfa-2b recombinant; advised appropiate clinical management. Hypertriglyceridemia may result in pancreatitis. Discontinue therapy in patients with persistently elevated triglycerides (e.g., triglycerides >1000 mg/dL) associated with symptoms of potential pancreatitis, such as abdominal pain, nausea, or vomiting
Cautions: Use cautiously in
- Severe renal impairment
- Hx of pulmonary disease (e.g.,COPD)
- Diabetes mellitus (prone to ketoacidosis)
- Coagulation disorders (eg, thrombophlebitis, pulmonary embolism)
- Myelosuppression
- Concomitant myelosuppressive agents
- Concurrent nephrotoxic agents
- Seizure disorder
- Hx of cardiovascular disorders
- Prior cardiotoxic agents
- Hx of cerebrovascular disease
- Hx of psychiatric disorders
- Elderly patients
- Thyroid disorder
- Autoimmune disorders
- Concomitant ribavirin
Supplemental Patient Information
- Inform patient of the benefits and risks associated with this combination drug before starting therapy
- Advise women of childbearing potential and also male patients whose partners are of childbearing age to use effective contraception to avoid pregnancy during therapy and for 6 months post therapy with combined interferon alfa-2b recombinant and ribavarin
- Advise patients to remain well hydrated, especially during the initial stages of treatment
- Instruct patients on the importance of site selection for self-administering the injection, as well as the importance on rotating the injection sites
- Instruct patients of the importance of proper disposal of the used injection
Pregnancy Category:C (Category: X, for combination treatment with ribavarin)
Breastfeeding: Due to low levels in milk and poor oral absorption by infant, it is unlikely that use of interferon in nursing mothers presents any serious risk to the breastfed infant. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 18 August 2011). As per manufacturer's data, it is not known whether this drug is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue therapy, depending on the importance of the drug to mother.
