interferon alfa-2a

interferon alfa-2a, recombinant,

a parenteral antineoplastic drug.

indications It is administered in the treatment of AIDS-related Kaposi's sarcoma, hairy cell and chronic myelogenous leukemia, and chronic hepatitis C. It also has a variety of unlabeled or investigational uses.

contraindications Caution is recommended in prescribing this product for patients with severe cardiovascular disease.

adverse effects Among reported adverse effects are influenza-like symptoms, particularly at the beginning of therapy with the drug; confusion; dizziness; nervousness; depression; anorexia; nausea; vomiting; diarrhea; throat inflammation; dry and itching skin; alopecia; diaphoresis; blood pressure changes; and tachycardia.

---

interferon alfa-2a,

a synthetic form of interferon-α produced by recombinant technology that acts as a biologic response modifier, used as an antineoplastic in the treatment of hairy cell leukemia and AIDS-related Kaposi's sarcoma. It is administered intramuscularly or subcutaneously.

---

interferon alfa-2a, recombinant Warning - Hazardous drug!

Roferon-A

Pharmacologic class: Biological response modifier

Therapeutic class: Antineoplastic, antiviral

Pregnancy risk category C

FDA Boxed Warning

• Drug may cause or worsen fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor patient closely with periodic clinical and laboratory evaluations. Discontinue drug in patients with persistently severe or worsening signs or symptoms of these conditions. In many cases, these disorders resolve after withdrawal.

Action

Unknown. Antitumor and antiviral activity may stem from direct antiproliferative action against tumor or viral cells, inhibition of viral replication, and modulation of host immune response.

Availability

alfa-2a

Injection (single-use vials): 3 million, 6 million, 9 million, and 36 million international units

Injection (multidose vials): 9 million and 18 million international units

Sterile powder for injection: 18 million international units with diluent

alfa-2b

Injection: 3 million international units/0.5-ml vial, 5 million international units/0.5-ml vial, 10 million international units/1-ml vial; 18 million international units/3.2-ml vial, 25 million international units/3.2 ml vial

Powder for injection (vial with diluent): 3 million, 5 million, 10 million, 18 million, 25 million, and 50 million international units

⊘Indications and dosages

➣ Chronic hepatitis C

alfa-2a -

Adults: 3 million international units subcutaneously or I.M. three times weekly for 48 to 52 weeks. Alternatively, induction dose of 6 million international units subcutaneously or I.M. three times weekly for first 12 weeks; then 3 million international units three times weekly for 36 weeks. Poor response after 3 months warrants withdrawal. Prescriber may order 6 to 12 months of retreatment with either 3 or 6 million international units three times weekly.

alfa-2b -

Adults: 3 million international units subcutaneously or I.M. three times weekly. If patient tolerates therapy and alanine aminotransferase (ALT) level is normal after 16 weeks, continue for 18 to 24 weeks. If ALT doesn't normalize, drug may be withdrawn.

➣ Chronic hepatitis B

alfa-2b -

Adults: 30 to 35 million international units subcutaneously or I.M. weekly for 16 weeks, given as 5 million international units daily or 10 million international units three times weekly

➣ Hairy cell leukemia

alfa-2a -

Adults: 3 million international units subcutaneously or I.M. daily for 16 to 24 weeks. Maintenance dosage is 3 million international units subcutaneously or I.M. three times weekly.

alfa-2b -

Adults: 2 million international units/m² I.M. or subcutaneously three times weekly for 6 months or longer

➣ AIDS-related Kaposi's sarcoma

alfa-2a -

Adults: 36 million international units subcutaneously or I.M. daily for 10 to 12 weeks. Maintenance dosage is 36 million international units subcutaneously or I.M. three times weekly. May start at 3 million international units and increase q 3 days, up to daily dosage of 36 million international units.

alfa-2b -

Adults: 30 million international units/m² subcutaneously or I.M. three times weekly. Continue dosage unless intolerance occurs or disease advances rapidly.

➣ Chronic myelogenous leukemia (Philadelphia chromosome-positive)

alfa-2a -

Adults: Initially, 3 million international units subcutaneously or I.M. daily for 3 days; then 6 million international units for 3 days; then 9 million international units daily for duration of treatment

➣ Malignant melanoma (as adjunct to surgery)

alfa-2b -

Adults: 20 million international units/m² I.V. for 5 consecutive days per week for 4 weeks; then a maintenance dosage of 10 million international units/m² subcutaneously three times weekly for 48 weeks. Withhold drug if adverse reactions occur; when reactions ease, resume at half of previous dosage. Withdraw if reactions persist.

➣ Condyloma acuminatum (genital or venereal warts)

alfa-2b -

Adults: 1 million international units/lesion given intralesionally three times weekly for 3 weeks

➣ Aggressive follicular non-Hodgkin's lymphoma

alfa-2b -

Adults: 5 million international units subcutaneously three times weekly for up to 18 months (given with chemotherapy regimen containing anthracycline)

Off-label uses

• Adjuvant treatment of malignant melanoma
• Hepatitis D

Contraindications

• Hypersensitivity to drug or its components
• Autoimmune disorders
• Female partners of males receiving drug

Precautions

Use cautiously in:
• cardiac or pulmonary disease; bone marrow, autoimmune, seizure, or psychiatric disorders
• diabetic patients prone to ketoacidosis
• pregnant or breastfeeding patients
• children.

Administration

• Give alfa-2a by subcutaneous or I.M. route. Reconstitute with 3 ml of diluent provided; swirl gently to dissolve.
• Administer alfa-2b by subcutaneous, I.M., or I.V. route. For I.V. use, reconstitute with diluent provided (bacteriostatic water for injection), according to chart provided. Mix gently, draw drug up into sterile syringe, and inject into 100 ml of normal saline solution. Infuse slowly over 20 minutes.
• Give antiemetics, as needed and prescribed, for nausea and vomiting.

Route	Onset	Peak	Duration
I.V. (alfa-2b)	Unknown	15-60 min	4 hr
I.M.	Unknown	2-12 hr	Unknown
Subcut.	Unknown	3-12 hr	Unknown
Intrales.	Unknown	Unknown	Unknown

Adverse reactions

CNS: dizziness, confusion, paresthesia, rigors, lethargy, depression, difficulty thinking or concentrating, insomnia, anxiety, fatigue, asthenia, amnesia, malaise, nervousness, drowsiness, suicidal ideation

CV: chest pain, hypertension, palpitations, arrhythmias

EENT: visual disturbances, stye, hearing disorders, nasal congestion, sinusitis, rhinitis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, flatulence, eructation, stomatitis, dry mouth, intestinal obstruction

GU: gynecomastia, impaired fertility in women, transient erectile dysfunction

Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia

Metabolic: hyperglycemia, hypocalcemia

Musculoskeletal: joint pain, back pain, myalgia

Respiratory: cough, dyspnea

Skin: flushing, rash, dry skin, pruritus, alopecia, dermatitis, diaphoresis

Other: gingivitis, flulike symptoms, candidiasis, edema, weight loss

Interactions

Drug-drug. Aminophylline, theophylline: reduced clearance of these drugs

CNS depressants: additive CNS effects

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Zidovudine: synergistic effects

Drug-diagnostic tests. Alkaline phosphatase, ALT, aspartate aminotransferase, bilirubin, blood urea nitrogen, calcium, creatinine, fasting glucose, lactate dehydrogenase, neutralizing antibodies, phosphate, uric acid: increased levels

Hemoglobin, platelets, white blood cells: decreased values

International Normalized Ratio, partial thromboplastin time, prothrombin time: increased values

Patient monitoring

☞ Before therapy and monthly during therapy, assess CBC with white cell differential, bone marrow hairy cells, glucose and electrolyte levels, and liver and kidney function tests.
• Discontinue therapy if neutrophil count drops below 500 cells/mm².
• Monitor fluid intake and output. Keep patient well hydrated.
• Assess for GI upset. Provide small, frequent meals and antiemetics to ease severe nausea and vomiting.
☞ Monitor for mental status changes, depression, and suicidal ideation.
• Assess for bleeding and bruising.
• Institute infection-control measures. Monitor for signs and symptoms of infection.

Patient teaching

• Teach patient or caregiver how to prepare and give drug subcutaneously or I.M., rotate injection sites, and track dosing schedule and injection sites on calendar.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, and vision.
• Inform female patient that drug is linked to fetal abnormalities. Advise her not to get pregnant during therapy, and to use barrier contraception.
• Tell female patient not to breastfeed.
• Advise patient to avoid potential infection sources, such as crowds and people with known infections.
• Tell patient to eat small, frequent meals to combat nausea, vomiting, and loss of appetite.
• Inform male patient that drug may cause transient erectile dysfunction.
☞ Instruct patient to immediately report depression, suicidal thoughts, mental status changes, signs or symptoms of infection (such as fever, chills, sore throat), unusual bleeding or bruising, dizziness, palpitations, or chest pain.
• Tell patient he'll need regular follow-up examinations and blood tests to gauge drug effects.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.