No

Biological Response Modulator

Patients >18 years of age: Hairy cell leukemia, AIDS-related Kaposi's sarcoma, chronic myelogenous leukemia (CML), chronic hepatitis C, adjuvant treatment to surgery for primary or recurrent malignant melanoma; multiple unlabeled uses; indications and dosage regimens are specific for a particular brand of interferon

C

Hypersensitivity to alfa-2a interferon or any component of the product

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 of age have not been established. Higher doses in the elderly or in malignancies other than hairy cell leukemia may result in severe obtundation.

>10%:

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

Dermatologic: Rash

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

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: Headache, delirium, somnolence, neurotoxicity

Dermatologic: Alopecia, dry skin

Gastrointestinal: Anorexia, stomatitis

Hepatic: Hepatotoxicity

Neuromuscular & skeletal: Peripheral neuropathy, leg cramps

Ocular: Blurred vision

Miscellaneous: Diaphoresis

<1%: Tachycardia, arrhythmias, chest pain, hypotension, SVT, edema, confusion, sensory neuropathy, psychiatric effects, EEG abnormalities, depression, hypothyroidism, increased uric acid level, change in taste, increased hepatic transaminase, myalgia, visual disturbances, proteinuria, increased BUN/creatinine, coughing, dyspnea, nasal congestion, neutralizing antibodies, local sensitivity to injection; 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

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

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

Refrigerate (2°C to 8°C/36°F to 46°F); do not freeze; do not shake; after reconstitution, the solution is stable for 24 hours at room temperature and for 1 month when refrigerated

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 after administration; S.C.: 3 hours

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

Refer to individual protocols

Adults >18 years: I.M., S.C.:

Hairy cell leukemia:

Induction: 3 million units/day for 16-24 weeks.

Maintenance: 3 million units 3 times/week (may be treated for up to 20 consecutive weeks)

AIDS-related Kaposi's sarcoma:

Induction: 36 million units/day for 10-12 weeks

Maintenance: 36 million units 3 times/week (may begin with dose escalation from 3-9-18 million units each day over 3 consecutive days followed by 36 million units/day for the remainder of the 10-12 weeks of induction)

If severe adverse reactions occur, modify dosage (50% reduction) or temporarily discontinue therapy until adverse reactions abate

Baseline chest x-ray, EKG, CBC with differential, liver function tests, electrolytes, 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 significant 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.

Do not freeze or shake solution; a flu-like syndrome (fever, chills) occurs in the majority of patients 2-6 hours after a dose; pretreatment with nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen can decrease fever and its severity and alleviate headache

Injection: 3 million units/mL (1 mL); 6 million units/mL (3 mL); 9 million units/mL (0.9 mL, 3 mL); 36 million units/mL (1 mL)

Powder for injection: 6 million units/mL when reconstituted

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