Infergen

Action

Binds to membrane receptors on viral cells, inducing protein synthesis, inhibiting viral replication, and suppressing cell proliferation. Increases phagocytosis, enhances expression of human leukocyte antigen, and augments lymphocyte cytotoxicity.

Availability

Injection: 9-mcg/0.3-ml vials, 15-mcg/0.5-ml vials

Indications and dosages

➣ Chronic hepatitis C

Adults: Initially as monotherapy, 9 mcg subcutaneously as a single dose three times weekly for 24 weeks; for patients who tolerated previous interferon therapy and didn't respond or relapsed following its discontinuation, 15 mcg subcutaneously as a single injection three times weekly for up to 48 weeks. For combination therapy, 15 mcg subcutaneously daily as a single injection with weight-based ribavirin at 1,000 to 1,200 mg (less than 75 kg to 75 kg or more, respectively) P.O. daily in two divided doses for up to 48 weeks.

Dosage adjustment

• Hematologic toxicities

• Patients with depression

• Serious adverse reactions

Off-label uses

• Hairy cell leukemia

Contraindications

• Hypersensitivity to drug, its components, or ribavirin

• Hepatic decompensation (Child-Pugh score above 6), autoimmune hepatitis

• Patients with creatinine clearance below 50 ml/minute (combination therapy with ribavirin)

• Hemoglobinopathies, such as tha-lassemia major and sickle cell anemia (combination therapy with ribavirin)

• Pregnant patients and men whose female partners are pregnant (combination therapy with ribavirin)

Precautions

Use cautiously in:

• cardiac disease, severe psychiatric disorders, ischemic and hemorrhagic cerebrovascular events, pulmonary disorders, chronic hepatitis C infection with cirrhosis, renal insufficiency, colitis, pancreatitis, ophthalmologic disorders, endocrine disorders, any abnormal test values

• history of significant or unstable cardiac disease (avoid use)

• other autoimmune disorders

• abnormally low peripheral blood cell counts or concurrent use of agents known to cause myelosuppression

• combination therapy with ribavirin in patients with low baseline neutrophil count (less than 1,500/mm³)

• transplant patients or other chronically immunosuppressed patients

• combination of interferon alfacon-1 and ribavirin in treatment-naïve patients or in patients co-infected with hepatitis B virus or HIV-1 (safety and efficacy not established)

• breastfeeding patients

• children age 18 and younger.

Administration

• Give by subcutaneous route only.

• Give antiemetics for nausea and vomiting, as needed and prescribed.

• Be aware that female patients must have a negative pregnancy test before starting combination therapy with ribavirin.

• Be aware that patients who have preexisting cardiac abnormalities should have an ECG before starting treatment with interferon alfacon-1 and ribavirin combination.

• Be aware that laboratory tests are recommended for all patients before starting therapy. Entrance criteria that may be considered as a guideline to acceptable baseline values for initiation of treatment are shown below:

Adverse reactions

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

CV: chest pain, hypertension, palpitations, hypotension, tachycardia, angina pectoris, cardiomyopathy, myocardial infarction, arrhythmias

EENT: visual disturbances, stye, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema, retinal detachment, hearing disorders, nasal congestion, rhinitis, sinusitis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, flatulence, eructation, stomatitis, dry mouth, anorexia, intestinal obstruction, hemorrhagic and ischemic colitis, pancreatitis

GU: impaired fertility in women, gynecomastia, erectile dysfunction, renal failure

Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia, severe cytopenias, hemolytic anemia

Hepatic: hepatic decompensation

Metabolic: hyperglycemia, diabetes mellitus, hypothyroidism, hyperthyroidism

Musculoskeletal: joint pain, back pain, limb pain, neck pain, myalgia

Respiratory: cough, dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis, pulmonary hypertension, sarcoidosis

Skin: rash, dryness, pruritus, flushing, alopecia, candidiasis, dermatitis, diaphoresis

Other: gingivitis, flulike symptoms, edema, weight loss, fever, body pain, injection-site erythema, infections, hypersensitivity including urticaria, autoimmune disorders, angioedema, bronchoconstriction, anaphylaxis

Interactions

Drug-diagnostic tests. Alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, lactate dehydrogenase, neutralizing antibodies, serum creatinine, thyroid-stimulating hormone, triglycerides, uric acid: increased values

Granulocytes, hematocrit, hemoglobin, platelets, serum albumin, thyroxine white blood cells: decreased values

Patient monitoring

See Before and regularly during therapy, assess CBC with white cell differential and hepatitis C virus antibodies.

• Assess fluid intake and output. Keep patient well hydrated.

See Stay alert for depression, mental status changes, psychosis, and suicidal ideation (especially in patients with history of mental illness).

• Assess for bleeding and bruising.

• Institute infection-control measures. Monitor for signs and symptoms of infection.

• Watch for flulike symptoms.

See Monitor patient for hypersensitivity reactions; discontinue drug immediately and institute appropriate treatment if severe signs and symptoms (such as urticaria, angioedema, bronchoconstriction, or anaphylaxis) occur.

See Monitor patient for signs and symptoms of pancreatitis. Suspend treatment if signs and symptoms occur; discontinue treatment in patients diagnosed with pancreatitis.

See Closely watch for and discontinue treatment if patient develops persistent or unexplained pulmonary infiltrates or pulmonary function impairment. Be aware that respiratory failure has been observed with interferon rechallenge.

See Be aware that patients with chronic hepatitis C with cirrhosis may be at risk for hepatic decompensation when treated with this drug. Closely monitor hepatic function during treatment. Treatment should be immediately discontinued if signs and symptoms of hepatic decompensation, such as jaundice, ascites, coagulopathy, or decreased serum albumin, are observed.

• Monitor renal function (particularly increases in serum creatinine level) during therapy.

See Be aware that hemorrhagic and ischemic colitis, sometimes fatal, has been observed within 12 weeks of initiation of therapy. Discontinue drug immediately in patients who develop signs and symptoms of colitis.

See Be aware that development or exacerbation of autoimmune disorders (such as autoimmune thrombocytopenia, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, thyroiditis, interstitial nephritis, and systemic lupus erythematosus have occurred in patients receiving interferon alpha therapies.

• Monitor patients for vision impairment; be aware that patient who develop ocular signs and symptoms should receive a prompt and complete eye examination. Discontinue therapy in patients who develop new or worsening ophthalmologic disorders.

• For patients receiving combination therapy, discontinue ribavirin in patients who temporarily or permanently discontinue interferon alfacon-1.

Patient teaching

• Teach patient or caregiver how to administer drug subcutaneously, rotate injection sites, and track dosing schedule and injection sites on calendar.

• Advise patient to avoid sources of potential infection, such as crowds and people with known infections.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, and vision.

• Tell female patient that drug is linked to fetal abnormalities. Advise her not to get pregnant during therapy, and to use barrier contraception.

See Instruct patient to immediately report signs and symptoms of infection, unusual bleeding or bruising, mental status changes, dizziness, palpitations, vision impairment, diarrhea, abdominal pain, respiratory signs and symptoms, rash, hives, or new or worsening symptoms.

• 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.