Usual Adult Dose for Hairy Cell Leukemia

2 million international units/m2 IM or subcutaneously 3 times a week
Duration of therapy: Up to 6 months

Comments:

• This drug should be administered subcutaneously (and not IM) in patients with platelet counts below 50,000/mm3.
• Responding patients may benefit from continued treatment. A minimum effective dose has not yet been established.

Usual Adult Dose for Malignant Melanoma

Induction phase: 20 million international units/m2/day IV (via 20-minute infusion), 5 consecutive days per week
Duration of therapy: 4 weeks

Maintenance phase: 10 million international units/m2 subcutaneously 3 times a week
Duration of therapy: 48 weeks

Comments: Differential WBC count and liver function tests should be monitored weekly during induction phase and monthly during maintenance phase of therapy.

Use: As adjuvant to surgical treatment in malignant melanoma patients free of disease but at high risk for systemic recurrence, within 56 days of surgery

Usual Adult Dose for Follicular Lymphoma

5 million international units subcutaneously 3 times a week
Duration of therapy: Up to 18 months

Comments:

• This drug should be used in conjunction with anthracycline-containing chemotherapy regimen and after completion of the chemotherapy regimen.
• Doses of myelosuppressive drugs were reduced by 25% from a full-dose CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone), and cycle length increased by 33% (e.g., from 21 to 28 days) when alpha interferon was added to the regimen.
• Efficacy in patients with low-grade, low-tumor burden follicular non-Hodgkin's lymphoma has not been established.

Use: In conjunction with anthracycline-containing combination chemotherapy, for the initial treatment of clinically aggressive follicular non-Hodgkin's lymphoma

Usual Adult Dose for Condylomata Acuminata

1 million international units injected into each lesion (up to 5 lesions in a single course) 3 times a week on alternate days
Duration of therapy: 3 weeks

Comments:

• An additional course may be administered at 12 to 16 weeks.
• The injection should be administered intralesionally using a tuberculin (or similar) syringe and a 25- to 30-gauge needle.
• The needle should be directed at the center of the base of the wart and at an angle almost parallel to the plane of the skin (approximately that in the commonly used PPD test); this will deliver the interferon to the dermal core of the lesion, infiltrating the lesion and causing a small wheal.
• Care should be taken not to go beneath the lesion too deeply; subcutaneous injection should be avoided as this area is below the base of the lesion.
• This drug should not be injected too superficially since leakage may occur, infiltrating only the keratinized layer and not the dermal core.
• Should consider monitoring leukocytes and serum AST levels

Use: For intralesional treatment of selected patients with condylomata acuminata involving external surfaces of genital and perianal areas

Usual Adult Dose for Kaposi's Sarcoma

30 million international units/m2 IM or subcutaneously 3 times a week
Duration of therapy: Until disease progression or maximal response achieved after 16 weeks of therapy

Comments:

• Dose reduction is often required.
• Greater likelihood of response to therapy in patients without systemic symptoms, with limited lymphadenopathy, and with relatively intact immune system (indicated by total CD4 count).

Use: For the treatment of selected patients with AIDS-related Kaposi's sarcoma

Usual Adult Dose for Chronic Hepatitis C

3 million international units IM or subcutaneously 3 times a week

Duration of Therapy:
Combination therapy with ribavirin:

• Interferon alpha-naive patients: 24 to 48 weeks
• Retreatment in patients relapsing after nonpegylated interferon monotherapy: 24 weeks

Monotherapy: 72 to 96 weeks

Comments:

• In patients tolerating therapy with ALT normalization at 16 weeks of treatment, monotherapy should be extended to 18 to 24 months to improve sustained response rate.
• Patients whose ALTs have not normalized or high levels of HCV-RNA persist after 16 weeks of monotherapy rarely achieve sustained response with extended treatment; should consider discontinuing therapy in such patients
• When used with ribavirin, patients with renal dysfunction and/or those older than 50 years should be carefully monitored for anemia.
• The manufacturer product information for ribavirin capsules/oral solution should be consulted.
• Duration of combination therapy should be individualized for interferon alpha-naive patients depending on baseline disease characteristics, response to therapy, and tolerability of regimen.
• Virologic response should be assessed after 24 weeks of combination therapy; discontinuation of combination therapy should be considered in any interferon alpha-naive patient whose HCV-RNA levels remain detectable after 24 weeks of therapy.
• Studies established that this drug can have clinically meaningful effects on this disease, shown by serum ALT normalization and reduced liver necrosis and degeneration.
• Liver biopsy is recommended to establish diagnosis of chronic hepatitis; patients should be tested for antibody to HCV.
• Confirmation that the patient has compensated liver disease is recommended before starting this drug.
• The following should be considered before therapy (patient entrance criteria for compensated liver disease in clinical studies): No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation; bilirubin up to 2 mg/dL; albumin stable and within normal limits; prothrombin time prolonged less than 3 seconds; WBC at least 3000/mm3; platelets at least 70,000/mm3; serum creatinine normal/near normal
• Before starting therapy, CBC and platelet counts should be evaluated to establish baselines (for monitoring potential toxicity); these tests should be repeated at 1 and 2 weeks after starting therapy, and monthly thereafter.
• Serum ALT should be measured about every 3 months (to assess response to therapy).
• Thyroid-stimulating hormone (TSH) should be within normal limits when starting therapy; TSH testing should be repeated at 3 and 6 months.

Uses: For the treatment of chronic hepatitis C in patients with compensated liver disease who have history of blood or blood-product exposure and/or are HCV antibody positive; in combination with ribavirin, for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon therapy and in patients who relapsed after alpha interferon therapy

Usual Adult Dose for Chronic Hepatitis B

30 million to 35 million international units per week IM or subcutaneously, either as 5 million international units once a day or as 10 million international units 3 times a week
Duration of therapy: 16 weeks

Comments:

• Therapy may be appropriate for patients who have been serum HBsAg positive for at least 6 months and have proof of HBV replication (serum HBeAg positive) with elevated serum ALT; studies in such patients showed virologic remission (loss of serum HBeAg) and normalization of serum aminotransferases with this drug; therapy lead to loss of serum HBsAg in some responding patients.
• Liver biopsy is recommended before starting therapy to confirm presence of chronic hepatitis and the extent of liver damage.
• Confirmation that the patient has compensated liver disease is recommended.
• The following should be considered before therapy (patient entrance criteria for compensated liver disease in clinical studies): No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation; bilirubin normal; albumin stable and within normal limits; prothrombin time prolonged less than 3 seconds; WBC at least 4000/mm3; platelets at least 100,000/mm3
• Before starting therapy, CBC and platelet counts should be evaluated to establish baselines (for monitoring potential toxicity).
• CBC, platelet counts, liver function tests including serum ALT, albumin, and bilirubin should be assessed at treatment weeks 1, 2, 4, 8, 12, and 16.
• Transient increase in ALT (at least 2 times baseline value) can occur during therapy; therapy should generally continue unless signs/symptoms of liver failure; clinical symptomatology and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin should be monitored about every 2 weeks during ALT flare.
• HBeAg, HBsAg, and ALT should be measured at the end of therapy and 3 and 6 months post-therapy.

Use: For the treatment of chronic hepatitis B in patients with compensated liver disease

Usual Adult Dose for Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma

Case Report - Conjunctival MALT Lymphoma
1 million international units via intralesional injection 3 times a week for 12 doses (total)

Usual Pediatric Dose for Chronic Hepatitis C

3 years or older:
25 to 61 kg: 3 million international units/m2 subcutaneously 3 times a week
Greater than 61 kg: 3 million international units subcutaneously 3 times a week

Duration of therapy:

• Genotype 1: 48 weeks
• Genotypes 2 and 3: 24 weeks

Comments:

• For use in combination with ribavirin (capsules or oral solution)
• The manufacturer product information for ribavirin capsules/oral solution should be consulted.
• Virologic response should be assessed after 24 weeks of therapy.
• Discontinuation of therapy should be considered in any patient whose HCV-RNA levels remain detectable after 24 weeks of therapy.

Use: In combination with ribavirin, for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon therapy

Usual Pediatric Dose for Chronic Hepatitis B

1 year or older:
First week: 3 million international units/m2 subcutaneously 3 times a week
Subsequent weeks: Dose escalation to 6 million international units/m2 subcutaneously 3 times a week
Maximum dose: 10 million international units 3 times a week
Duration of therapy: 16 to 24 weeks (total)

Comments:

• Therapy may be appropriate for patients who have been serum HBsAg positive for at least 6 months and have proof of HBV replication (serum HBeAg positive) with elevated serum ALT; studies in such patients showed virologic remission (loss of serum HBeAg) and normalization of serum aminotransferases with this drug; therapy lead to loss of serum HBsAg in some responding patients.
• Liver biopsy is recommended before starting therapy to confirm presence of chronic hepatitis and the extent of liver damage.
• Confirmation that the patient has compensated liver disease is recommended.
• The following should be considered before therapy (patient entrance criteria for compensated liver disease in clinical studies): No history of hepatic encephalopathy, variceal bleeding, ascites, or other clinical signs of decompensation; bilirubin normal; albumin stable and within normal limits; prothrombin time prolonged up to 2 seconds; WBC at least 4000/mm3; platelets at least 150,000/mm3
• Before starting therapy, CBC and platelet counts should be evaluated to establish baselines (for monitoring potential toxicity).
• CBC, platelet counts, liver function tests including serum ALT, albumin, and bilirubin should be assessed at treatment weeks 1, 2, 4, 8, 12, and 16.
• Transient increase in ALT (at least 2 times baseline value) can occur during therapy; therapy should generally continue unless signs/symptoms of liver failure; clinical symptomatology and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin should be monitored about every 2 weeks during ALT flare.
• HBeAg, HBsAg, and ALT should be measured at the end of therapy and 3 and 6 months post-therapy.

Use: For the treatment of chronic hepatitis B in patients with compensated liver disease

Usual Pediatric Dose for Angioblastoma

Case Reports - Giant Cell Angioblastoma
Greater than 4 months: 3 million international units/m2 subcutaneously daily

Usual Pediatric Dose for Idiopathic (Immune) Thrombocytopenic Purpura

Study (n=14)
Greater than 4 years old: 3 million international units/m2 subcutaneously 3 times a week for 4 weeks

Comments: In patients with no increase or partial increase in platelets (less than 150 x 10[9]/L), therapy should continue for another 8 weeks.

Renal Dose Adjustments

Interferon alfa-2b: Data not available

Interferon alfa-2b/ribavirin combination therapy:

• CrCl less than 50 mL/min: Contraindicated

Liver Dose Adjustments

Autoimmune hepatitis, decompensated liver disease: Contraindicated

If severe (grade 3) hepatic injury or hepatic decompensation (Child-Pugh B and C [score greater than 6]) during therapy: Permanently discontinue this drug.

Dose Adjustments

HAIRY CELL LEUKEMIA:

• If severe side effects develop: Reduce dose 50% or temporarily discontinue therapy until the side effects abate and then resume at 50% (1 million international units/m2 IM or subcutaneously 3 times a week).
• If severe side effects persist or recur after dose adjustment: Permanently discontinue this drug.
• Progressive disease or failure to respond after 6 months of therapy: Discontinue this drug.

MALIGNANT MELANOMA:

• Regular laboratory testing recommended to monitor laboratory abnormalities for the purpose of dose modification.
• Severe side effects, including granulocyte counts greater than 250/mm3 but less than 500/mm3 or ALT/AST greater than 5 to 10 times the upper limit of normal (5 to 10 x ULN): Withhold drug until side effects subside; restart therapy at 50% of the previous dose.
• Granulocyte count less than 250/mm3 or ALT/AST greater than 10 x ULN, toxicity not subsiding after therapy withheld, or severe side effects recurring in patients using reduced doses: Permanently discontinue this drug.

FOLLICULAR LYMPHOMA:

• Neutrophil count less than 1500/mm3 or platelet count less than 75,000/mm3: Delay chemotherapy cycle.
• Neutrophil count greater than 1000/mm3 but less than 1500/mm3: Reduce dose of this drug by 50% (2.5 million international units subcutaneously 3 times a week); may re-escalate to the initial dose (5 million international units subcutaneously 3 times a week) after hematologic toxicity resolves (absolute neutrophil count greater than 1500/mm3)
• Neutrophil count less than 1000/mm3 or platelet count less than 50,000/mm3: Withhold this drug.
• AST exceeds 5 x ULN or serum creatinine greater than 2 mg/dL: Permanently discontinue this drug.

AIDS-RELATED KAPOSI'S SARCOMA:

• Severe side effects: Reduce dose by 50% or withhold therapy.
• If severe side effects abate with therapy interruption: May resume at a reduced dose
• If severe side effects persist or recur after dose reduced: Permanently discontinue this drug.

CHRONIC HEPATITIS C:
Combination Therapy with Ribavirin:

• The manufacturer product information for ribavirin capsules/oral solution should be consulted.
• If severe side effects/laboratory abnormalities develop during combination therapy, dose should be modified or discontinued (if appropriate) until side effects abate or decrease in severity; combination therapy should be discontinued if intolerance persists after dose adjustment.
• WBC 1 to less than 1.5 x 10(9)/L, neutrophils 0.5 to less than 0.75 x 10(9)/L, platelets 25 to less than 50 x 10(9)/L (adults) or 50 to less than 70 x 10(9)/L (pediatrics), or at least 2 g/dL decrease in hemoglobin (Hgb) during any 4-week period during therapy in adults with history of stable cardiac disease: Reduce dose of this drug by 50%.
• WBC less than 1 x 10(9)/L, neutrophils less than 0.5 x 10(9)/L, platelets less than 25 x 10(9)/L (adults) or less than 50 x 10(9)/L (pediatrics), creatinine greater than 2 mg/dL (pediatrics), Hgb less than 8.5 g/dL, or Hgb less than 12 g/dL after 4 weeks of dose reduction in adults with history of stable cardiac disease: Discontinue combination therapy.

Monotherapy:

• If severe side effects develop during therapy: Reduce dose 50% or temporarily discontinue therapy until the side effects subside.
• If intolerance persists after dose adjustment: Discontinue this drug.

CHRONIC HEPATITIS B:

• If severe side effects/laboratory abnormalities develop during therapy, dose should be reduced 50% or discontinued (if appropriate) until side effects subside; this drug should be discontinued if intolerance persists after dose adjustment.
• WBC count less than 1.5 x 10(9)/L, granulocyte count less than 0.75 x 10(9)/L, or platelet count less than 50 x 10(9)/L: Reduce dose 50%; therapy was resumed at up to 100% of the initial dose when WBC, granulocyte, and/or platelet counts returned to normal/baseline values.
• WBC count less than 1 x 10(9)/L, granulocyte count less than 0.5 x 10(9)/L, or platelet count less than 25 x 10(9)/L: Permanently discontinue this drug.

Precautions

US BOXED WARNINGS:

• RISK OF SERIOUS DISORDERS: This drug causes/aggravates fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Close monitoring with periodic clinical and laboratory evaluations is recommended. Patients with persistently severe or worsening signs/symptoms of these disorders should be withdrawn from therapy. In many (but not all) cases, these disorders resolve after this drug is stopped.

Safety and efficacy for the treatment of chronic hepatitis B have not been established in patients younger than 1 year. Safety and efficacy of interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C have not been established in patients younger than 3 years. Safety and efficacy for the treatment of chronic hepatitis C (without ribavirin), hairy cell leukemia, malignant melanoma, follicular non-Hodgkin's lymphoma, condylomata acuminata, and AIDS-related Kaposi's sarcoma have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• At physician discretion, the patient may self-administer the medication.
• To enhance tolerability, administer injections in the evening, when possible.
• May administer acetaminophen at time of injection to reduce incidence of certain side effects
• Before use, allow the solution to come to room temperature.
• Consult the manufacturer product information to ensure the appropriate dose form and strength is used for the indication being treated; not all dose forms and strengths are appropriate for some indications.
• Solution for injection: Do not use IV; do not use for the induction phase of malignant melanoma; do not use for AIDS-related Kaposi's sarcoma (concentrations are inappropriate).
• Do not use the 18 million or 50 million international units/vial (powder for injection/reconstitution) or the 18 million international units/multidose vial (solution for injection) for condylomata acuminata.

Storage requirements:

• Powder for injection/reconstitution: Store in refrigerator at 2C to 8C (36F to 46F); after reconstitution, should use the solution immediately, but may store up to 24 hours at 2C to 8C (36F to 46F); discard solution remaining in vial after 1 dose has been withdrawn.
• Solution for injection in vials: Store in refrigerator at 2C to 8C (36F to 46F); do not freeze; keep away from heat; discard unused solution remaining in vial after 1 month.

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

General:

• This drug should not be used in patients with chronic hepatitis caused by anything other than chronic HBV or chronic HCV (e.g., autoimmune hepatitis).
• The powder formulations of this agent contain albumin (a derivative of human blood); based on effective donor screening and product manufacturing processes, risk for transmission of viral diseases is extremely low; theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also considered extremely low; no cases of transmission of viral disease or CJD ever reported for albumin.

Monitoring:

• Cardiovascular: ECG for patients with preexisting cardiac abnormalities and/or for those in advanced stages of cancer (before starting and during therapy)
• Endocrine: TSH (before starting therapy and periodically thereafter)
• Hematologic: Standard hematologic tests including CBC, Hgb, complete and differential WBC counts, platelet counts (before starting therapy and periodically thereafter)
• Hepatic: Hepatic function with serum bilirubin, ALT, AST, alkaline phosphatase, and LDH (at 2, 8, and 12 weeks after starting therapy, then every 6 months during therapy); liver function tests (before starting therapy and periodically thereafter)
• Metabolic: Electrolytes (before starting therapy and periodically thereafter)
• Ocular: Eye examination in all patients (at baseline); ophthalmologic exams in patients with preexisting ophthalmologic disorders (periodically during therapy)
• Psychiatric: Signs/symptoms of depression and other psychiatric symptoms (during therapy and for at least 6 months after last dose)
• Respiratory: Chest X-ray (at baseline and repeated as clinically indicated)

Patient advice:

• Keep well hydrated, especially during initial stages of therapy.