INTERFERONS, ALPHA (in-ter-feer-onz, al-fa)
interferon alpha-2b (recombinant)
peginterferon alpha-2b (pegylated)
interferon alpha-n3 (human)
Therapeutic: immune modifiers
Peginterferon alpha-2a: Treatment of: Chronic hepatitis C (alone or with ribavirin), Chronic hepatitis B. Interferon alpha-2b: Treatment of: Hairy cell leukemia, Malignant melanoma, AIDS-related Kaposi’s sarcoma, Condylomata acuminata (intralesional), Chronic hepatitis B, Chronic hepatitis C (with oral ribavirin) which has relapsed following previous treatment with interferon alone, Follicular non-Hodgkin’s lymphoma. Peginterferon alpha-2b: Chronic hepatitis C (alone or with ribavirin). Interferon alpha-n3: Treatment of condylomata acuminata (intralesional).
Interferons are proteins capable of modifying the immune response and have antiproliferative action against tumor cells. Interferon alpha-2b is produced by recombinant DNA techniques, peginterferon is a “pegylated” formulation of interferon alpha-2b formulated to have a longer duration of action; interferon alpha-n3 is from pooled human leukocytes. Interferons also have antiviral activity. Therapeutic Effects: Antineoplastic, antiviral, and antiproliferative activities. Decreased progression of hepatic damage (for patients with hepatitis).
Adverse Reactions/Side Effects
All are more prominent with SC, IV, or IM administration
CNS: NEUROPSYCHIATRIC DISORDERS, confusion, depression, dizziness, fatigue, headache, insomnia, irritability, anxiety. EENT: blurred vision, nose bleeds, rhinitis. CV: ISCHEMIC DISORDERS, arrhythmias, chest pain, edema. GI: COLITIS, PANCREATITIS, anorexia, abdominal pain, diarrhea, dry mouth, nausea, taste disorder, vomiting, weight loss, drug-induced hepatitis, flatulence. Derm: alopecia, dry skin, pruritus, rash, sweating. Endo: thyroid disorders. Hemat: LEUKOPENIA, THROMBOCYTOPENIA, anemia, hemolytic anemia (with ribavirin). MS: arthralgia, myalgia, leg cramps. Neuro: paresthesia. Resp: cough, dyspnea. Local: injection site reactions. Misc: AUTOIMMUNE DISORDERS, INFECTIOUS DISORDERS, allergic reactions, including anaphylaxis, chills, fever, flu-like syndrome.
PHYSICAL THERAPY IMPLICATIONS
Examination and Evaluation
Continually monitor for signs of ischemic disorders, including MI (sudden chest pain, pain radiating into the arm or jaw, shortness of breath, dizziness, sweating, anxiety, nausea), stroke (sudden severe headache, confusion, nausea, vomiting, paralysis, numbness, speech problems, visual disturbances), or peripheral ischemia (extreme coldness in the hands and feet, cyanosis, muscle cramping). Seek immediate medical assistance if patient develops these signs.
Be alert for signs of colitis (diarrhea, abdominal pain, cramps, nausea, fecal incontinence) and pancreatitis (upper abdominal pain especially after eating, indigestion, weight loss, oily stools). Notify physician immediately of these signs.
Monitor signs of leukopenia (fever, sore throat, signs of infection), thrombocytopenia (bruising, nose bleeds, bleeding gums), or unusual weakness and fatigue that might be due to anemias or other blood dyscrasias. Report these signs to the physician immediately.
Be alert for signs of autoimmune reactions and infectious disorders, including muscle and joint pain, weakness, fever, dyspnea, skin reactions (rash, itching), and other unexplained symptoms. Notify physician of these signs immediately.
Monitor signs of neuropsychiatric disorders such as confusion, anxiety, irritability, delirium, and hallucinations. Notify physician promptly if these signs occur.
Monitor signs of hypersensitivity reactions and anaphylaxis, including pulmonary symptoms (tightness in the throat and chest, wheezing, cough, dyspnea), or skin reactions (rash, pruritus, urticaria, dermatitis). Notify physician or nursing staff immediately if these reactions occur.
Assess heart rate, ECG, and heart sounds, especially during exercise (See Appendices G, H). Report any rhythm disturbances or symptoms of increased arrhythmias, including palpitations, chest discomfort, shortness of breath, fainting, and fatigue/weakness.
Assess peripheral edema using girth measurements, volume displacement, and measurement of pitting edema (See Appendix N). Report increased swelling in feet and ankles or a sudden increase in body weight due to fluid retention.
Assess any joint pain, muscle pain, or leg cramps to rule out musculoskeletal pathology; that is, try to determine if pain is drug induced rather than caused by anatomic or biomechanical problems.
Monitor signs of paresthesia (numbness, tingling). Perform objective tests (nerve conduction, monofilaments) to document any neuropathic changes.
Monitor and report any increase or decrease in metabolism that might indicate thyroid disorders. Signs of hyperthyroidism include tachycardia, nervousness, heat intolerance, weight loss, and muscle wasting. Hypothyroidism is typically indicated by bradycardia, lethargy, cold intolerance, weight gain, and muscle weakness.
Assess dizziness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.
Assess injection site for pain, swelling, and irritation. Report prolonged or excessive injection site reactions to the physician.
Implement resistive exercises and other therapeutic exercises as tolerated to maintain muscle strength and function and prevent muscle wasting associated with cancer, chronic hepatitis, and HIV infections.
Because of the risk of ischemic disorders and arrhythmias, use extreme caution during aerobic exercise and other forms of therapeutic exercise. Assess exercise tolerance frequently (blood pressure, heart rate, fatigue levels), and terminate exercise immediately if any untoward responses occur (See Appendix L).
Advise patient about the likelihood of GI reactions (nausea, vomiting, diarrhea, flatulence, loss of appetite). Instruct patient to report severe or prolonged GI problems, or signs of drug-induced hepatitis (yellow skin or eyes, abdominal pain, severe nausea and vomiting, fever, sore throat, malaise, weakness, facial edema).
Instruct patient to report other troublesome side effects such as prolonged or severe headache, sleep loss, blurred vision, nose bleeds, flu-like symptoms, or skin problems (rash, itching, hair loss, increased sweating)
Absorption: Not absorbed orally. Well absorbed (>80%) following IM and SC administration. Minimal systemic absorption follows intralesional administration.
Metabolism and Excretion: Filtered by the kidneys and subsequently degraded in the renal tubule; peginterferon alpha-2b—30% renally excreted.
Half-life: Peginterferon alpha-2a—50–160 hr; interferon alpha-2b—2–3 hr; peginterferon alpha- 2b—40 hr.
TIME/ACTION PROFILE (clinical effects)
|ROUTE ||ONSET ||PEAK ||DURATION |
|interferon alpha-2b IM, SC ||1–3 mo ||unknown ||unknown (CR) |
|interferon alpha-2b IM, SC ||unknown ||3–5 days ||3–5 days (BC) |
|interferon alpha-2b IM, SC ||2 wk ||unknown ||unknown (LFT) |
|interferons alpha-2b IM, SC and alpha-n3 SC ||unknown ||4–8 wk ||unknown (IL) |
|peginterferon alpha-2b SC ||unknown ||6 mos or more ||unknown |
Contraindicated in: Hypersensitivity to alpha interferons or human serum albumin; Autoimmune hepatitis; Hepatic decompensation (Child-Pugh classes B and C) before or during therapy; Pedi: Products containing benzyl alcohol should not be used in neonates.
Use Cautiously in: Severe cardiovascular, pulmonary, renal, or hepatic disease; Active infections; Underlying CNS pathology or psychiatric history; Decreased bone marrow reserve or underlying immunosuppression; Current history of chickenpox, herpes zoster, or herpes labialis (may reactivate or disseminate disease); Previous or concurrent radiation therapy; Autoimmune disorders (may ↑ risk of exacerbation); Geri: ↑ risk of adverse reactions; OB/Pedi: Childbearing potential, pregnancy, lactation and children <3 yr (safety not established).
Exercise Extreme Caution in: History of depression/suicide attempt.
Drug-Drug: Additive myelosuppression with other antineoplastic agents or radiation therapy. ↑ CNS depression may occur with CNS depressants, including alcohol, antihistamines, sedative/hypnotics, and opioids. May ↓ metabolism and ↑ blood levels and toxicity of theophylline and methadone. ↑ risk of adverse reactions with zidovudine. Ribavirin ↑ risk of hemolytic anemia, especially if CCr <50 mL/min (avoid if possible). May ↓ effects of immunosuppressant agents.
SC (Adults): Chronic hepatitis C180 mcg once weekly for 48 wk for genotypes 1, 4 (24 wk for genotypes 2, 3). Patients with chronic hepatitis C coinfected with HIV—180 mcg once weekly for 48 wk.
IV (Adults): Malignant melanoma (induction)—20 million units/m2 for 5 days of each week for 4 wk initially, followed by SC maintenance dosing. IM, SC (Adults): Hairy cell leukemia—2 million units/m2 IM or SC 3 times weekly for up to 6 mo. Malignant melanoma (maintenance)—10 million units/m2 SC 3 times weekly for 48 wk, following initial IV dosing. AIDS-related Kaposi's sarcoma—30 million units/m2 IM or SC 3 times weekly until disease progression or maximum response has been achieved after 16 wk. Chronic hepatitis C—3 million units IM or SC 3 times weekly. If normalization of ALT occurs after 16 wk of therapy, continue treatment for total of 18–24 mo. If normalization of ALT does not occur after 16 wk of therapy, may consider discontinuing treatment. Chronic hepatitis B—5 million units/day IM or SC or 10 million units IM or SC 3 times weekly for 16 wk. Follicular non-Hodgkin's lymphoma—5 million units SC 3 times weekly for up to 18 mo (to be used following completion of anthracycline-containing chemotherapy). SC (Children> 3 yr): Chronic hepatitis B—3 million units/m2 3 times weekly for the first week of therapy, then increase to 6 million units/m2 3 times weekly (not to exceed 10 million units/dose) for 16–24 wk. IL (Adults): Condylomata acuminata—1 million units/lesion 3 times weekly for 3 wk; treat only 5 lesions per course. An additional course of treatment may be initiated at 12–16 wk.
Peginterferon alpha-2b Monotherapy
SC (Adults): 137–160 kg—150 mcg once weekly for 1 yr. 107–136 kg—120 mcg once weekly for 1 yr. 89–106 kg—96 mcg once weekly for 1 yr. 73–88 kg—80 mcg once weekly for 1 year. 57–72 kg—64 mcg once weekly for 1 yr. 46–56 kg—50 mcg once weekly for 1 yr. 37–45 kg—40 mcg once weekly for 1 yr.
In Combination with Ribavirin (Rebetol)
SC (Adults): >85 kg—150 mcg once weekly. 76–85 kg—120 mcg once weekly. 61–75 kg—96 mcg once weekly. 51–60 kg—80 mcg once weekly. 40–50 kg—64 mcg once weekly. <40 kg—50 mcg once weekly.
IL (Adults): 250,000 units/lesion twice weekly for up to 8 wk; for large lesions, divide dose and inject at several sites.
Solution for injection: 180 mcg/mL in single-use vials. Prefilled syringes: 180 mcg/0.5 mL.
Powder for injection: 10-million unit single-use vial, 18-million unit single-use vial, 50-million unit single-use vial. Solution for injection: 10-million unit single-use vial, 18-million unit single-use vial, 18-million unit multidose pen, 25-million unit multidose vial, 30-million unit multidose pen, 60-million unit multi-dose pen. In combination with: oral ribavirin (Rebetol) as a combination package (Rebetron). See Appendix B (in various dosage packages).
Powder for injection (Redipen system or vials): 50 mcg/0.5 mL, 80 mcg/0.5 mL, 120 mcg/0.5 mL, 150 mcg/0.5 mL.
Solution for injection: 5-million units/mL.