Professional Information

Peginterferon Alfa-2b

Pronunciation: (peg-IN-ter-FEER-on AL-fa)
Class: Immunomodulator

Trade Names:
PEG-Intron
- Injection, lyophilized, powder for solution 100 mcg/mL (reconstituted)
- Injection, lyophilized, powder for solution 160 mcg/mL (reconstituted)
- Injection, lyophilized, powder for solution 240 mcg/mL (reconstituted)
- Injection, lyophilized, powder for solution 300 mcg/mL (reconstituted)

Trade Names:
PEG-Intron Redipen
- Injection, lyophilized, powder for solution 100 mcg/mL (reconstituted)
- Injection, lyophilized, powder for solution 160 mcg/mL (reconstituted)
- Injection, lyophilized, powder for solution 240 mcg/mL (reconstituted)
- Injection, lyophilized, powder for solution 300 mcg/mL (reconstituted)

Unitron PEG (Canada)

Pharmacology

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Binds to specific membrane receptors on cell surface and initiates a complex sequence of intracellular events (eg, suppression of cell proliferation, enhancement of phagocytic activity of macrophages).

Pharmacokinetics

Absorption

T _max is 15 to 44 h (postdose). Bioavailability increases with multiple dosing. Both AUC and C _max increased 70% when administered with a high-fat meal.

Elimination

Renal excretion is 30%. The half-life absorption is 4.6 h (subcutaneous) and elimination is approximately 40 h. Apparent Cl is 22 mL/h•kg.

Duration

Duration is 48 to 72 h.

Special Populations

Renal Function Impairment

Cl decreases by 17% in moderate renal impairment (CrCl 30 to 49 mL/min) and by 44% in severe renal impairment (CrCl 10 to 29 mL/min).

Children

In children receiving peginterferon alfa-2b 60 mcg/m ² /wk, exposure may be approximately 50% higher than observed in adults receiving 1.5 mcg/kg/wk.

Indications and Usage

For use alone (in patients 18 yr of age and older) or in combination with ribavirin (in patients 3 yr of age and older) for the treatment of chronic hepatitis C in patients not previously treated with interferon alfa who have compensated liver disease. For use in combination with ribavirin, see ribavirin package insert.

Unlabeled Uses

Treatment of renal cell carcinoma, chronic myelogenous leukemia, metastatic carcinoma.

Contraindications

Autoimmune hepatitis; decompensated liver disease; hypersensitivity to the drug.

Dosage and Administration

Once Weekly (on Same Day of Week) for 1 Yr; Initial Dose Based on Weight
Adults and Children 3 yr of age and older

Subcutaneous For patients weighing 45 kg or less, administer 40 mcg; 46 to 56 kg, administer 50 mcg; 57 to 72 kg, administer 64 mcg; 73 to 88 kg, administer 80 mcg; 89 to 106 kg, administer 96 mcg; 107 to 136 kg, administer 120 mcg; 137 to 160 kg, administer 150 mcg.

Peginterferon Alfa-2b Dose in Combination Therapy With Ribavirin
Adults

Subcutaneous For patients weighing less than 40 kg, administer 50 mcg; 40 to 50 kg, administer 64 mcg; 51 to 60 kg, administer 80 mcg; 61 to 75 kg, administer 96 mcg; 76 to 85 kg, administer 120 mcg; greater than 86 kg, administer 150 mcg.

Children 3 to 17 yr of age

Subcutaneous 60 mcg/m ² /week.

Dose Reduction
Adults and Children 3 yr of age and older

Subcutaneous If a serious adverse reaction occurs during treatment, discontinue or modify the dosage until the adverse event abates or decreases in severity. If persistent or recurrent serious adverse events occur despite adequate dosage adjustments, discontinue treatment. See product information for guidelines for dosage modification or discontinuation in adults and children.

Renal Function Impairment
Adults and Children 3 yr of age and older

Subcutaneous

Moderate renal function impairment (CrCl 30 to 50 mL/min)

Decrease the peginterferon alfa-2b dose 25%.

Severe renal function impairment (CrCl 10 to 29 mL/min), including patients on hemodialysis

Decrease the peginterferon alfa-2b dose 50%.

If renal function decreases during treatment, discontinue peginterferon alfa-2b. Do not use peginterferon alfa-2b/ribavirin in patients with CrCl less than 50 mL/min.

General Advice

For subcutaneous administration only. Not for intradermal, IM, IV, or intra-arterial administration.
Administer dose at bedtime to minimize flu-like symptoms.
Administer antipyretics as ordered as pretreatment to minimize flu-like symptoms.
Reconstitute powder for injection in vials or Redipen following manufacturer's instructions.
Do not reconstitute with any solution other than that provided with the powder for injection or add any other medications to reconstituted solution.
Do not shake solution during reconstitution process. Gently invert Redipen or gently swirl contents in vial to obtain a clear, colorless solution.
Do not administer if solution is discolored or cloudy, or if particulate matter is noted.
Use only 1 dose/vial or pen. Do not re-enter vial. Discard any unused portions. Do not save unused solution for later administration.
In patients with genotype 1, the duration of combination therapy is 48 wk; in patients with genotype 2 or 3, the duration of combination therapy is 24 wk.

Storage/Stability

Store unopened vials at controlled room temperature (59° to 86°F). Store Redipen in refrigerator (36° to 46°F). Administer reconstituted solution immediately or store for up to 24 h in refrigerator. Do not freeze.

Drug Interactions

Drugs metabolized by CYP2C8/9 (eg, phenytoin, warfarin) or CYP2D6 (eg, flecainide)

The therapeutic effects of these agents may be decreased by peginterferon alfa-2b.

Methadone

Methadone plasma concentrations may be elevated, increasing the narcotic effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions

The incidences stated for the following adverse reactions were reported with peginterferon alfa-2b monotherapy

CNS

Adults

Headache (56%); asthenia/fatigue (52%); depression (29%); anxiety/emotional lability/irritability (28%); insomnia (23%); dizziness (12%); impaired concentration (10%); malaise (7%); nervousness (4%); agitation (2%).

Children

Pyrexia (80%); headache (62%); fatigue (30%); decreased appetite (22%); asthenia (15%); dizziness, irritability (14%).

Postmarketing

Memory loss; migraine headache; peripheral neuropathy; seizures.

Dermatologic

Adults

Alopecia (22%); pruritus (12%); dry skin (11%); flushing, increased sweating, rash (6%).

Children

Alopecia (17%).

Postmarketing

Erythema multiforme; Stevens-Johnson syndrome; toxic epidermal necrolysis.

EENT

Adults

Pharyngitis (10%); conjunctivitis (4%); blurred vision, rhinitis (2%).

Postmarketing

Hearing loss; impaired hearing; vertigo.

GI

Adults

Nausea (26%); anorexia (20%); diarrhea (18%); abdominal pain (16%); vomiting (7%); dry mouth, dyspepsia (6%); constipation (1%).

Children

Anorexia (29%); vomiting (27%); abdominal pain (21%); nausea (18%); upper abdominal pain (12%).

Postmarketing

Aphthous stomatitis.

Genitourinary

Adults

Menstrual disorder (4%).

Postmarketing

Renal failure; renal insufficiency.

Hematologic-Lymphatic

Adults

Decreased neutrophils (70%); decreased platelets (20%); thrombocytopenia (7%); neutropenia (6%).

Children

Neutropenia (33%); anemia (11%); leukopenia (10%).

Postmarketing

Pure red cell aplasia; thrombotic thrombocytopenic purpura.

Hepatic

Adults

Hepatomegaly (6%).

Local

Adults

Injection-site inflammation/reaction (47%).

Children

Injection-site erythema (29%).

Metabolic-Nutritional

Adults

Weight loss (11%); hypothyroidism (5%).

Children

Decreased weight (19%).

Musculoskeletal

Adults

Myalgia (54%); musculoskeletal pain (28%); arthralgia, rigors (23%).

Children

Arthralgia, myalgia (17%).

Postmarketing

Rhabdomyolysis; myositis.

Respiratory

Adults

Coughing (8%); sinusitis (7%); dyspnea (4%).

Miscellaneous

Adults

Fever (22%); viral infection (11%); right upper quadrant pain (8%); chest pain (6%).

Children

Chills (21%).

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.

Use with ribavirin

Ribavirin may cause birth defects and fetal death. Extreme care must be taken to avoid pregnancy. Ribavirin causes hemolytic anemia, which may result in worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.

Monitor

Closely monitor clinical status and hepatic function. Closely monitor patients with renal function impairment for peginterferon toxicity, including increases in serum creatinine. Hematology and blood chemistry should be evaluated before treatment and periodically thereafter. Patients with preexisting cardiac abnormalities should have ECG before treatment. Patients should have regular dental checkups.

Hepatitis C virus levels

Determine hepatitis C virus levels before starting therapy and after 6 mo of therapy. Be prepared to discontinue therapy if viral levels remain high after 6 mo of therapy.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 3 yr of age.

Elderly

Use with caution.

Renal Function

Use with caution and monitor for signs and symptoms of interferon toxicity. Reduce dose in patients with moderate or severe renal function impairment.

Autoimmune disorders

Because interferon alfa may cause or exacerbate autoimmune disorders (eg, thyroiditis, SLE), use with caution in patients with history of autoimmune disorders. Discontinue use in patients with persistently severe or worsening signs or symptoms.

Bone marrow toxicity

Bone marrow function may be suppressed.

CV events

Use with caution in patients with CV disease, including hypotension, arrhythmia, tachycardia, cardiomyopathy, and MI.

Cerebrovascular disorders

Ischemic and hemorrhagic cerebrovascular events have been reported. Events have occurred in patients with few or no reported risk factors.

Colitis

Fatal and nonfatal ulcerative and hemorrhagic colitis have been observed. Discontinue use immediately in patients who develop symptoms.

Dental and periodontal disorders

Dental and periodontal disorders have been reported.

Endocrine disorders

Hypo- and hyperthyroidism may occur or be aggravated. Diabetes mellitus has been observed in treated patients.

Hepatic failure

Chronic hepatitis C patients with cirrhosis may be at risk of hepatic decompensation and death. Immediately discontinue treatment if decompensation occurs.

Hypersensitivity

Serious, acute hypersensitivity reactions (eg, angioedema, anaphylaxis) may occur with alfa interferon therapy.

Infectious disorders

Because life-threatening infectious disorders may occur, use with caution and monitor with periodic clinical and laboratory evaluations. Discontinue use in patients with persistently severe or worsening signs or symptoms.

Neuropsychiatric events

Because life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction, and aggressive behavior have occurred, use with caution, especially in patients with history of psychiatric disorder. Discontinue use in patients with persistently severe or worsening signs or symptoms.

Ophthalmic disorders

Decrease in or loss of vision, retinal hemorrhages, cotton wool spots, and retinal artery or vein obstruction have been observed. Ensure that all patients have an ophthalmic examination prior to beginning therapy and that patients with preexisting ophthalmic disorders (eg, diabetic, hypertensive retinopathy) receive periodic ophthalmic examinations during therapy.

Pancreatitis

Fatal and nonfatal pancreatitis has been observed. Discontinue use in patients who develop symptoms.

Patients with renal insufficiency

Increases in serum creatinine have occurred in patients with renal insufficiency.

Pediatric growth

Weight and height gain in children treated with peginterferon alfa-2b plus ribavirin lags behind that compared with normative population data. After about 6 mo posttreatment, subjects have weight gain rebounds and regain their weight to the 53rd percentile. After about 6 mo posttreatment, height gain stabilizes and children have an average height percentile of 44th percentile, which is less than the average normative population.

Pulmonary disorders

Dyspnea, pulmonary infiltrates, pneumonia, pneumonitis, and sarcoidosis, some resulting in respiratory failure and/or patient deaths, have been associated with use.

Triglycerides

Elevated triglyceride levels may occur.

Overdosage

Symptoms

Experience is limited. No serious reactions have been attributed to overdosage (ie, 10.5 times the intended dose).

Patient Information

If patient will be self-administering at home, review Medication Guide with the patient. Ensure that the patient understands how to store, prepare, and administer the dose, and dispose of used equipment and supplies.
Remind patient that prescribed dose is administered once weekly and should be administered on the same day of the week.
Caution patient not to change the dose or stop taking unless advised by health care provider.
Advise patient that dose may be reduced or the medication stopped if it causes depression or significant changes in blood cell counts.
Teach patient infection control and bleeding precautions.
Advise patient that it is not known if this drug will prevent transmission of hepatitis C to others, nor is it known if it can prevent cirrhosis, liver failure, or liver cancer that may develop as a result of hepatitis C infection.
Instruct patient to immediately report any of the following to health care provider: signs or feelings of depression and/or suicidal ideation; fever; sore throat; unusual bleeding or bruising; stomach pain; bloody diarrhea; rapid or irregular pulse; difficulty breathing or unexplained shortness of breath.
Advise women of childbearing potential to use effective contraception during treatment.
Advise patients to brush their teeth thoroughly twice daily and to have regular dental examinations.