Interferon Alfacon-1

Pronunciation: IN-ter-FEER-on AL-fa-kon
Class: Immunomodulator

Trade Names

Infergen
- Injection 9 mcg per 0.3 mL
- Injection 15 mcg per 0.5 mL

Pharmacology

These small protein molecules bind to specific cell surface receptors and initiate complex sequences of intracellular events, including production of enzymes and other products with antiviral, antiproliferative, and immunomodulatory effects.

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Pharmacokinetics

Absorption

T _max is 24 to 36 h.

Special Populations

Renal Function Impairment

The safety and efficacy of interferon alfacon-1 in patients with renal impairment have not been studied. Do not administer interferon alfacon-1 plus ribavirin to patients with CrCl less than 50 mL/min.

Hepatic Function Impairment

The safety and efficacy of interferon alfacon-1 in patients with hepatic impairment have not been studied.

Indications and Usage

Treatment of chronic hepatitis C virus (HCV) infection in patients 18 y of age and older with compensated liver disease.

Contraindications

Allergy to alpha-interferons or any component of the product; hepatic decompensation (Child-Pugh score greater than 5 [class B and C]); autoimmune hepatitis.

Dosage and Administration

Combination therapy with ribavirin
Adults

Subcutaneous 15 mcg daily in combination with weight-based ribavirin at 1,000 to 1,200 mg (less than 75 kg and at least 75 kg) orally in 2 divided doses for up to 48 wk.

Monotherapy
Adults

Subcutaneous 9 mcg 3 times weekly for 24 wk.

Nonresponders/Relapse
Adults

Subcutaneous 15 mcg 3 times weekly for up to 48 wk.

Dose Adjustment
Adults Subcutaneous Combination therapy with ribavirin Anemia

If Hgb is less than 10 g/dL with a history of cardiac or cerebrovascular disease, reduce dose of interferon alfacon-1 and adjust the first dose reduction of ribavirin by 200 mg/day. The second dose reduction of ribavirin (if needed) is by an additional 200 mg/day. For adult patients with a history of stable cardiac disease receiving interferon alfacon-1 in combination with ribavirin, the interferon alfacon-1 dose should be reduced from 15 to 9 mcg or 9 to 6 mcg and the ribavirin dose reduced by 200 mg/day if a decrease of more than 2 g/dL in Hgb is observed during any 4-wk period. Both interferon alfacon-1 and ribavirin should be permanently discontinued if patients have Hgb levels less than 12 g/dL after this ribavirin dose reduction.

If Hgb is less than 8.5 g/dL, permanently discontinue interferon alfacon-1 and ribavirin.

Depression

For mild depression, no change to interferon alfacon-1 or ribavirin dose. For moderate depression, decrease interferon alfacon-1 dose from 15 to 9 mcg or from 9 to 6 mcg, with no change to ribavirin dose. For severe depression, discontinue interferon alfacon-1 and ribavirin permanently.

Hematologic toxicities

If absolute neutrophil count (ANC) is less than 0.75 × 10 ⁹ /L, reduce interferon alfacon-1 dose from 15 to 9 mcg or from 9 to 6 mcg; maintain ribavirin dose at 1,200 mg or 1,000 mg. If ANC is less than 50 × 10 ⁹ /L, suspend interferon alfacon-1 and ribavirin treatment until ANC values return to more than 1,000/mm ³ .

If platelet count is less than 50 × 10 ⁹ /L, reduce interferon alfacon-1 dose from 15 to 9 mcg or from 9 to 6 mcg; maintain ribavirin dose at 1,200 mg or 1,000 mg. If platelet count is less than 25 × 10 ⁹ /L, discontinue interferon alfacon-1 and ribavirin treatment.

Severe adverse reactions

Stepwise dose reduction from 15 to 9 mcg and from 9 to 6 mcg may be necessary for serious adverse reactions.

Monotherapy

Withhold dosage temporarily for patients who experience a severe adverse reaction. If reaction does not become tolerable, discontinue therapy. Dose reduction to 7.5 mcg may be necessary following an intolerable adverse reaction.

General Advice

• For subcutaneous administration only. Not for intradermal, IM, IV, or intra-arterial administration.
• Administer undiluted. Avoid vigorous shaking.
• Do not administer if particulate matter, cloudiness, or discoloration is noted.
• Vials contain no preservative. Use only 1 dose per vial and do not re-enter the vial. Discard any unused portion. Do not save or combine unused portions for later use.
• Just prior to injection, interferon alfacon-1 may be allowed to reach room temperature.
• Patients who fail to achieve at least 2 log ₁₀ drop at wk 12 or undetectable HCV-RNA at wk 24 are highly unlikely to achieve sustained viral response; consider discontinuing therapy.

Storage/Stability

Store at 36° to 46°F. Do not freeze. Avoid exposure to sunlight.

Drug Interactions

Myelosuppressive agents

Use interferon alfacon-1 with caution.

Adverse Reactions

CNS

Headache (82%); fatigue (71%); insomnia (39%); nervousness (31%); depression (26%); dizziness (25%); abnormal thinking (20%); anxiety (19%); paresthesia (13%); emotional lability (12%); malaise (11%); amnesia, asthenia, hypoesthesia (10%); ataxia, convulsions, delusions, gait abnormal, hallucinations, loss of consciousness, memory impairment, speech disorder, tremors, visual field defect (postmarketing).

Dermatologic

Alopecia, pruritus (14%); increased sweating, rash (13%); bruising, pyoderma gangrenosum, TEN (postmarketing).

EENT

Pharyngitis (34%); hearing impairment, hearing loss (postmarketing).

GI

Abdominal pain (41%); nausea (40%); diarrhea (29%); anorexia (24%); dyspepsia (21%); vomiting (13%); abdominal distention, gastritis, GI bleeding (postmarketing).

Hepatic

Abnormal hepatic function, ascites, hepatic encephalopathy, hepatic enzyme elevations (including ALT and AST elevation), hyperbilirubinemia, jaundice (postmarketing).

Lab Tests

Decreased hematocrit (5%); decreased Hgb (4%); decreased platelets (3%); decreased ANC, decreased thyroxine, decreased WBC, increased triglycerides, increased TSH.

Local

Injection-site erythema (23%); injection-site reactions (including injection-site necrosis, ulcer, and bruising) (postmarketing).

Musculoskeletal

Rigors (66%); myalgia (58%); arthralgia (51%); back pain (42%); limb pain (26%); neck pain, skeletal pain (14%); arthritis, bone pain, rhabdomyolysis (postmarketing).

Respiratory

Cough (22%); sinusitis (17%); dyspnea.

Miscellaneous

Fever (61%); body pain (54%); flu-like symptoms (15%); chest pain, hot flushes (13%); dehydration, hemorrhage, sepsis (postmarketing).

Precautions

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

Monitor Monitor patient's clinical status closely. Laboratory tests (eg, hepatic function, renal function, CBC, lipid panel, thyroid function) are recommended for all patients prior to beginning treatment, 2 wk after initiation of therapy, and periodically thereafter during the 24 or 48 wk of therapy. Following completion of therapy, monitor any abnormal test values periodically. For patients who have preexisting cardiac abnormalities (eg, arrhythmic disorders, MI), perform ECG before treatment and periodically during treatment. Monitor all patients for evidence of depression and other psychiatric symptoms. If patients develop psychiatric problems, monitor carefully during treatment and during the 6-month follow-up period. Monitor all patients for signs and symptoms of colitis, pancreatitis, and/or hypersensitivity reactions. Ensure that all patients have an eye exam at baseline. Ensure that patients with preexisting ophthalmologic disorders (eg, diabetic or hypertensive retinopathy) receive periodic ophthalmologic exams.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy in children younger than 18 y of age not established.

Elderly

Use with caution.

Renal Function

Do not administer interferon alfacon-1 plus ribavirin to patients with CrCl less than 50 mL/min.

Special Risk Patients

Use with caution in patients with abnormally low peripheral blood cell counts, patients with a history of endocrine disorders, and transplantation patients or other chronically immunosuppressed patients.

Autoimmune disease

Development or exacerbation of autoimmune disorders has been reported. Do not use interferon alfacon-I in patients with autoimmune hepatitis, and use with caution in patients with other autoimmune disorders.

Bone marrow toxicity

May suppress bone marrow function and result in severe cytopenias, including aplastic anemia.

Cerebrovascular disorders

Ischemic and hemorrhagic cerebrovascular events have been observed.

CNS effects

Depression, homicidal ideation, suicidal ideation, and suicide may occur. Use with caution in patients with history of depression. Discontinue use in patients developing severe depression, suicidal ideation, or other severe psychiatric disorders.

Colitis

Hemorrhagic/ischemic colitis, sometimes fatal, may occur.

CV disease

Use with caution. Angina pectoris, arrhythmia, cardiomyopathy, hypotension, MI, and tachycardia have been associated with interferon therapies.

Endocrine disorders

Occurrence or aggravation of hyperthyroidism or hypothyroidism may occur. Hyperglycemia and diabetes mellitus have also been observed.

Hepatic failure

Do not use in patients with decompensated hepatic disease. Discontinue use in patients who develop symptoms of hepatic decompensation (eg, ascites, coagulopathy, decreased serum albumin, jaundice).

Ophthalmologic disorders

Decrease or loss of vision; retinopathy, including macular edema; retinal hemorrhages; cotton wool spots; retinal artery or vein thrombosis; optic neuritis; papilledema; and serious retinal detachments are induced or aggravated by treatment with alpha-interferons.

Pancreatitis

May occur with fatal outcomes.

Peripheral neuropathy

Has been observed when alpha-interferon was given in combination with telbivudine.

Pulmonary effects

Bronchiolitis obliterans, dyspnea, interstitial pneumonitis, pneumonia, pulmonary hypertension and sarcoidosis, and pulmonary infiltrates, some resulting in respiratory failure and/or death, may be induced or aggravated. Discontinue in patients who develop persistent or unexplained pulmonary infiltrates or pulmonary impairment.

Renal effects

Increases in serum creatinine levels, including renal failure, have been observed.

Severe acute hypersensitivity

Discontinue drug immediately if hypersensitivity reactions occur (eg, anaphylaxis, angioedema, bronchoconstriction, urticaria).

Overdosage

Symptoms

Anorexia, chills, fever, increased ALT, increased AST, increased LDH, myalgia.

Patient Information

• Review Medication Guide if patient or caregiver will be administering at home. Ensure patient or caregiver understands how to store, prepare, and administer the dose, and how to dispose of used equipment and supplies. If possible, perform first injection under supervision of a qualified health care provider.
• Review dosing schedule with patient or caregiver. Advise patient or caregiver to administer prescribed dose at bedtime to minimize flu-like adverse reactions.
• Advise patient not to change the dose, stop taking, or change the brand of drug unless advised by health care provider.
• Advise patient that if a dose is missed to take it as soon as possible, and to schedule the next dose about 48 h later.
• Instruct patient to rotate injection sites as described in the Medication Guide to minimize likelihood of severe injection-site reactions.
• Advise patient that flu-like symptoms are common and nonnarcotic analgesics (eg, acetaminophen, ibuprofen) can be used to prevent or relieve fever, headache, and muscle and joint pain.
• Advise patient to notify health care provider immediately of any of the following: changes in thinking or behavior, depressed mood, hives, intolerable injection-site reaction, persistent fever, shortness of breath or difficult breathing, sore throat, suicidal ideation, unusual bleeding or bruising, vision changes.
• Advise patient to contact health care provider if experiencing bothersome adverse reactions or any unusual problems.
• Advise men and women of childbearing potential to use effective contraception during treatment.
• Advise patient that drug may cause drowsiness or dizziness, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Advise patients to be well hydrated, especially during the initial stages of treatment.

Copyright © 2009 Wolters Kluwer Health.