DrugindexOnline^{2nd edition}

Pronouncation: (IN-ter-FEER-ahn AL-fuh-2b)
Class: Immunomodulator

Trade Names:
Intron A
- Powder for Injection, lyophilized 3 million units/vial with 1 mL diluent vial or syringe
- Powder for Injection, lyophilized 5 million units/vial with 1 mL diluent vial
- Powder for Injection, lyophilized 10 million units/vial with 2 mL diluent vial
- Powder for Injection, lyophilized 25 million units/vial with 5 mL diluent vial
- Powder for Injection, lyophilized 18 million units multiple-dose vial with 1 mL diluent vial
- Powder for Injection, lyophilized 50 million units/vial with 1 mL diluent vial
- Solution for injection 3 million units/0.5 mL vial,
- Solution for injection 5 million units/0.5 mL vial,
- Solution for injection 10 million units/1 mL vial,
- Solution for injection 18 million units multiple-dose pen (actually contains 22.5 million units/1.5 mL pen),
- Solution for injection 18 million units multiple-dose vial (actually contains 22.8 million units/3.8 mL vial),
- Solution for injection 25 million units multiple-dose vial (actually contains 32 million units/3.2 mL vial),
- Solution for injection 30 million units multiple-dose pen (actually contains 37.5 million units/1.5 mL pen),
- Solution for injection 60 million units multiple-dose pen (actually contains 75 million units/1.5 mL pen).

Mechanism of Action

Pharmacology

Inhibition of virus replication in virus-infected cells, suppression of cell proliferation and such immunomodulating activities as enhancement of phagocytic activity of macrophages and augmentation of specific cytotoxicity of lymphocytes for target cells.

Pharmacokinetics

Absorption

The T _max is 3 to 12 h (IM and subcutaneous) and 30 min (IV). The C _max is approximately 18 to 116 units/mL (IM and subcutaneous) and 135 to 273 units/mL (IV).

Metabolism

The kidney may be the main site for catabolism.

Elimination

The elimination t _½ is approximately 2 to 3 h.

Indications and Usage

Hairy cell leukemia; condylomata acuminata; AIDS-related Kaposi sarcoma; chronic hepatitis B; chronic non-A/non-B hepatitis (hepatitis C); malignant melanoma; follicular non-Hodgkin lymphoma.

Unlabeled Uses

Bladder tumors; chronic myelogenous leukemia.

Contraindications

Standard considerations.

Dosage and Administration

Decreased Granulocyte or Platelet Counts

If granulocyte count is less than 750/mm ³ and the platelet count is less than 50,000/mm ³ , then reduce dose 50%. If granulocyte count is less than 500/mm ³ and the platelet count is less than 30,000/mm ³ , then interrupt dose. When platelet or granulocyte counts return to normal or baseline values, therapy can be reinstituted at up to 100% of initial dose.

Hairy Cell Leukemia
Adults

IM or Subcutaneous Induction dose 2 million units (MIU)/m ² , 3 times/wk. Treat patients for about 6 mo before determining whether to continue therapy.

Malignant Melanoma
Adults

IV infusion

Induction

20 MIU/m ² for 5 consecutive days each week for 4 wk.

Maintenance

10 MIU/m ² 3 times/wk for 48 wk by subcutaneous injection. Discontinue treatment if disease progression occurs.

Condylomata Acuminata
Adults

Intralesionally 1 MIU/lesion 3 times/wk for 3 wk.

Chronic Hepatitis B
Adults

Subcutaneous or IM 30 to 35 MIU/wk, either as 5 MIU/day or 10 MIU 3 times/wk for 16 wk.

Chronic Hepatitis C
Adults

Subcutaneous or IM 3 MIU 3 times/wk. At 16 wk treatment, extend therapy to 18 to 24 mo at 3 MIU 3 times/wk to improve the sustained response. Consider discontinuing therapy in nonresponders after 16 wk.

Follicular Lymphoma
Adults

Subcutaneous 5 MIU/m ² , 3 times/wk in combination with other antineoplastic agents. Continue therapy for up to 18 mo.

AIDS-Related Kaposi Sarcoma
Adults

IM , IV , or Subcutaneous 30 MIU/m ² 3 times/wk. Use the 50 MIU vial.

Drug Interactions

Melphalan

Coadministration of melphalan and interferon alfa-2a may decrease serum levels of melphalan.

Theophylline and possibly barbiturates

Alfa-interferon may inhibit hepatic metabolism of theophylline and possibly barbiturates, leading to increased theophylline or barbiturate serum concentrations.

Vidarabine

Alfa-interferon may potentiate neurotoxicity when administered with vidarabine.

Zidovudine, acyclovir

There are synergistic antiviral effects with alfa-interferon and zidovudine and acyclovir.

Laboratory Test Interactions

A transient increase in ALT can occur and is more frequent in responders. Other abnormal lab values include the following: hemoglobin; WBC count; platelet count; serum creatinine; alkaline phosphatase; lactate dehydrogenase; serum urea nitrogen; AST; granulocyte count.

Adverse Reactions

Cardiovascular

Edema; hypotension.

CNS

Perioral tingling; dizziness; depression; paresthesia; sleep disturbances; confusion; hallucination; seizures; encephalopathy; gait disturbance; ataxia; tremor.

Dermatologic

Rash; transient alopecia or thinning of the hair; excessive sweating; night sweats.

Endocrine

Hypothyroidism; hyperthyroidism.

GI

Nausea; vomiting; dysgeusia; diarrhea; dry mouth; gingivitis; anorexia; weight loss; elevated LFTs.

Hematologic

Neutropenia, reversible and dose-related; thrombocytopenia, reversible and dose-limiting.

Hypersensitivity

Antinuclear antibodies; anaphylaxis; antibody formation.

Musculoskeletal

Severe lower extremities myalgias.

Renal

Proteinuria; acute renal failure; nephrotic syndrome.

Respiratory

Dyspnea; cough; pharyngitis; sinusitis; drying of the oropharynx.

Special Senses

Visual disturbance; ocular pain.

Miscellaneous

Flu-like syndrome.

Precautions

Warnings Neuropsychiatric, autoimmune, ischemic, and infectious disorders Interferons may cause or aggravate fatal or life-threatening disorders of this nature. Persistent severe or worsening signs or symptoms may necessitate discontinuation of therapy. Closely monitor patients with periodic clinical and laboratory evaluations.

Pregnancy

Category C .

Lactation

Discontinue breast-feeding or discontinue the drug.

Hypersensitivity

Acute serious hypersensitivity reactions (eg, urticaria, angioedema, bronchoconstriction, anaphylaxis) have been observed in treated patients; if an acute reaction develops, discontinue the drug immediately, and institute appropriate medical therapy.

Hepatic Function

Do not treat patients with decompensated liver disease, autoimmune hepatitis, history of autoimmune disease, or immunosuppressed transplant recipients. Worsening liver disease, including jaundice, hepatic encephalopathy, hepatic failure, and death have occurred following therapy. Discontinue therapy for any patient developing signs and symptoms of liver failure.

Special Risk Patients

Administer with caution in patients with severe renal or hepatic disease, cardiac disease, seizure disorders, or compromised CNS function.

AIDS-related Kaposi sarcoma

Use only the 50 MIU vial size.

Dosage reduction

Dosage reduction by 50% or withholding therapy may be needed when severe adverse reactions occur.

Fever/“Flu-like” symptoms

Because of fever and other “flu-like” symptoms associated with this drug, use cautiously in debilitating medical conditions, such as those with a history of pulmonary disease (eg, COPD) or diabetes mellitus prone to ketoacidosis. Observe caution in coagulation disorders (eg, thrombophlebitis, pulmonary embolism) or severe myelosuppression.

Malignant melanoma

Interferon solution for injection is not recommended for the IV treatment of malignant melanoma.

Neutralizing antibodies

May contribute to therapeutic failure in some patients.

Preexisting psychiatric condition/History of severe psychiatric disorder

Do not treat; discontinue therapy in any patient developing severe depression.

Thyroid abnormalities

Do not treat patients with preexisting thyroid abnormalities whose thyroid function cannot be maintained in the normal range by medication. Prior to initiation of therapy, evaluate serum TSH.

Patient Information

• Photosensitivity may occur; therefore, caution patients to take protective measures (eg, sunscreens, protective clothing) against exposure to ultraviolet light or sunlight until tolerance is determined.
• May cause drowsiness or dizziness.
• Notify health care provider if hives, itching, tightness in the chest, cough, difficulty breathing, visual problems, wheezing, low blood pressure, or lightheadedness occurs.
• Contraceptive measures are recommended during therapy with interferon alfa-2b. Notify health care provider immediately if suspecting pregnancy.
• Store in the refrigerator at 2° to 8°C (36° to 46°F). Do not freeze or shake.
• Do not change brands of interferon; changes in dosage may be necessary.
• The most common adverse reactions are “flu-like” symptoms, such as fever, headache, fatigue, anorexia, nausea, and vomiting. These appear to decrease in severity as treatment continues. Some of these “flu-like” symptoms may be minimized by bedtime doses. Use antipyretics to prevent or partially alleviate fever and headache.
• Hydrate patients well, especially during the initial stages of treatment.