No

Biological Response Modulator

Hairy-cell leukemia in patients >18 years, condylomata acuminata, AIDS-related Kaposi's sarcoma in patients >18 years, chronic non-A/non-B/C hepatitis in patients >18 years, chronic hepatitis B in patients >18 years (indications and dosage are specific for a particular brand of interferon)

C

Known hypersensitivity to interferon alfa-2b or any components, patients with pre-existing thyroid disease uncontrolled by medication, coagulation disorders, diabetics prone to DKA, pulmonary disease

Use with caution in patients with seizure disorders, brain metastases, compromised CNS, multiple sclerosis, and patients with pre-existing cardiac disease, severe renal or hepatic impairment, or myelosuppression; safety and efficacy in children <18 years has not been established. Higher doses in the elderly or in malignancies other than hairy cell leukemia may result in severe obtundation. A baseline ocular exam is recommended in patients with diabetes or hypertension.

>10%:

Central nervous system: Dizziness, fatigue, malaise, fever (usually within 4-6 hours), chills

Dermatologic: Skin rash

Gastrointestinal: Xerostomia, nausea, vomiting, diarrhea, dizziness, abdominal cramps, weight loss, metallic taste, anorexia

Hematologic: Mildly myelosuppressive and well tolerated if used without adjunct antineoplastic agents; thrombocytosis has been reported, leukopenia (mainly neutropenia), anemia, thrombocytopenia, decreased hemoglobin, hematocrit, platelets

Myelosuppressive:

WBC: Mild

Platelets: Mild

Onset (days): 7-10

Nadir (days): 14

Recovery (days): 21

Neuromuscular & skeletal: Rigors, arthralgia

Miscellaneous: Flu-like syndrome, diaphoresis

1% to 10%:

Central nervous system: Neurotoxicity

Dermatologic: Dry skin, alopecia

Gastrointestinal: Stomatitis

Hepatic: Hepatotoxicity

Neuromuscular & skeletal: Peripheral neuropathy, leg cramps

Ocular: Blurred vision

Miscellaneous: Diaphoresis

<1%: Cardiotoxicity, tachycardia, arrhythmias, hypotension, SVT, arrhythmias, chest pain, edema, EEG abnormalities, confusion, sensory neuropathy, headache, psychiatric effects, delirium, somnolence, partial alopecia, increased uric acid level, hypothyroidism, change in taste, increased hepatic transaminase, increased ALT/AST, sensitivity to injection, myalgia, rigors, visual disturbances, proteinuria, increased creatinine, increased BUN, coughing, dyspnea, nasal congestion, neutralizing antibodies; usually patient can build up a tolerance to side effects

Symptoms of overdose include CNS depression, obtundation, flu-like symptoms, myelosuppression

Treatment is supportive

Increased effect: Cimetidine: May augment the antitumor effects of interferon in melanoma

Increased toxicity:

Theophylline: Clearance has been reported to be decreased in hepatitis patients receiving interferon

Vinblastine: Enhances interferon toxicity in several patients; increased incidence of paresthesia has also been noted

Zidovudine: Increased myelosuppression

Store intact vials at refrigeration (2°C to 8°C); powder and premixed solutions are stable at 95°F to 113°F for 7 days

Reconstitute vials with diluent; solution is stable for 30 days under refrigeration (2°C to 8°C)

Standard I.M./S.C. dilution: Dose/syringe or dispense vial to floor

Solution is stable for 7 days at room temperature and 30 days under refrigeration (2°C to 8°C)

Alpha interferons are a family of proteins, produced by nucleated cells, that have antiviral, antiproliferative, and immune-regulating activity. There are 16 known subtypes of alpha interferons. Interferons interact with cells through high affinity cell surface receptors. Following activation, multiple effects can be detected including induction of gene transcription. Inhibits cellular growth, alters the state of cellular differentiation, interferes with oncogene expression, alters cell surface antigen expression, increases phagocytic activity of macrophages, and augments cytotoxicity of lymphocytes for target cells

Absorption: Filtered and absorbed at the renal tubule

Distribution: The V_d of interferon is 31 L; but has been noted to be much greater (370-720 L) in leukemia patients receiving continuous infusion IFN; IFN does not penetrate the CSF

Metabolism: Majority of dose thought to be metabolized in the kidney

Bioavailability: I.M.: 83%; S.C.: 90%

Half-life: Elimination: I.M., I.V.: 2 hours; S.C.: 3 hours

Time to peak serum concentration: I.M., S.C.: ~6-8 hours

Adults (refer to individual protocols):

AIDS-related Kaposi's sarcoma: I.M., S.C. (use 50 million international unit vial): 30 million units/m² 3 times/week

Condylomata acuminata: Intralesionally (use 10 million international unit vial): 1 million units/lesion 3 times/week for 4-8 weeks; not to exceed 5 million units per treatment (maximum: 5 lesions at one time)

Chronic hepatitis C (non-A/non-B): I.M., S.C.: 3 million units 3 times/week for approximately a 6-month course

Chronic hepatitis B: I.M., S.C.: 5 million international units/day or 10 million international units 3 times/week for 16 weeks; if severe adverse reactions occur, reduce dosage 50% or temporarily discontinue therapy until adverse reactions abate; when platelet/granulocyte count returns to normal, reinstitute therapy

Hemodialysis: Supplemental dose is not necessary

Peritoneal dialysis: Supplemental dose is not necessary

Baseline chest x-ray, EKG, CBC with differential, liver function tests, electrolytes, thyroid function tests, platelets, weight; patients with pre-existing cardiac abnormalities, or in advanced stages of cancer should have EKGs taken before and during treatment

Dizziness and drowsiness are common; may rarely cause delirium or depression

May cause leukopenia; use caution with clozapine and carbamazepine; concurrent use with psychotropics may produce additive sedation and dry mouth

No information available to require special precautions

>10% of patients experience dry mouth and metallic taste

Use as directed; do not change dosage or schedule of administration without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience flu-like syndrome (acetaminophen may help); nausea, vomiting, dry mouth, or metallic taste (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help); drowsiness, dizziness, agitation, abnormal thinking (use caution when driving or engaging in tasks requiring alertness until response to drug is known). Report unusual bruising or bleeding; persistent abdominal disturbances; unusual fatigue; muscle pain or tremors; chest pain or palpitation; swelling of extremities or unusual weight gain; difficulty breathing; pain, swelling, or redness at injection site; or other unusual symptoms. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Use acetaminophen to prevent or partially alleviate headache and fever; do not use 3, 5, 18, and 25 million unit strengths intralesionally, solutions are hypertonic; 50 million unit strength is not for use in condylomata, hairy cell leukemia, or chronic hepatitis.

Injection, albumin free: 3 million units (0.5 mL); 5 million units (0.5 mL); 10 million units (1 mL); 25 million units

Powder for injection, lyophilized: 18 million units, 50 million units

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