Adult Dosing

Chronic hepatitis C

• Recommended dose: 1.5 mcg/kg/wk SC injection of interferon alpha 2b in combination with 800-1400 mg/day of ribavirin x 48 wks (patients with genotype 1) and 24 wks (patients with genotype 2 & 3)

Dosing based on body weight

• <40 kg: 50 mcg (interferon alpha-2b) SC + 800 mg/day (ribavirin) PO divided bid
• 40-50 kg: 64 mcg (interferon alpha-2b) SC + 800 mg/day (ribavirin) PO divided bid
• 51-60 kg: 80 mcg (interferon alpha-2b) SC + 800 mg/day (ribavirin) PO divided bid
• 61-65 kg: 96 mcg (interferon alpha-2b) SC + 800 mg/day (ribavirin) PO divided bid
• 66-75 kg: 96 mcg (interferon alpha-2b) SC + 1000 mg/day (ribavirin) PO divided bid
• 76-85 kg: 120 mcg (interferon alpha-2b) SC + 1000 mg/day (ribavirin) PO divided bid
• 86-105 kg: 150 mcg (interferon alpha-2b) SC + 1200 mg/day (ribavirin) PO divided bid
• >105 kg: 150 mcg (interferon alpha-2b) SC + 1400 mg/day (ribavirin) PO divided bid

Note:

• Treatment duration is 48 wks for patients with genotype 1 and 24 wks for patients with genotype 2 and 3
• Safety and efficacy have not been established for treatment lasting longer than one year
• Ribavirin should be taken with food
• Refer to package insert for toxicity related dose adjustments

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of chronic hepatitis C (CHC) in patients with compensated liver disease previously not treated with interferon alpha and who are 18 yrs of age

• Hypersensitivity to any of the ingredients of the product
• Pregnant women
• Men whose female partners are pregnant
• Patients with autoimmune hepatitis
• Patients with hepatic decompensation in cirrhotic CHC patients before or during treatment
• Patients with hemoglobinopathies
• Creatinine clearance <50 mL/min

• Marked teratogenic/embryocidal effects have been reported in all animal species exposed to ribavirin. Ribavirin has a multiple-dose half-life of 12 days; hence, it may persist in non-plasma compartments for as long as 6 months. This therapy is therefore contraindicated in pregnant women and their male partners. Avoid pregnancy during and for 6 months post-treatment in both female patients and in female partners of male patients receiving therapy; use at least 2 reliable forms of contraception during and for 6 months after therapy
• Hemolytic anemia is the primary clinical toxicity of ribavirin therapy. Therapy-associated anemia may worsen cardiac disease leading to fatal and nonfatal MI; avoid use in patients with a history of significant or unstable cardiac disease
• Fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders have been reported with alpha interferons, including peginterferon alfa-2b. Monitor patients carefully with periodic clinical and laboratory evaluations; withdraw therapy if patients experience persistently severe or worsening signs/symptoms of these conditions. In most cases, therapy discontinuation resolves these disorders

Renal impairment (Based on CrCl)

• <50 mL/min: Contraindicated
• Renal impairment and/or >50 yrs of age: Extreme caution advised; dose adjustments not defined

Hepatic impairment

• Hepatic decompensation (Child-Pugh class B and C) in cirrhotic CHC patients: Contraindicated
• Hepatic decompensation (Child-Pugh class B and C) in cirrhotic CHC patients coinfected with HIV: Contraindicated

See Supplemental Patient Information

• Therapy is contraindicated in pregnant women and their male partners. Avoid pregnancy during and for 6 months after therapy in both female patients and in female partners of male patients receiving therapy; use at least 2 reliable forms of contraception during and for 6 months post-treatment. Because of the potential for significant teratogenic and embryocidal effects, perform pregnancy test immediately prior to therapy initiation, every month during therapy, and for 6 months after discontinuation of therapy [US Black Box Warning]
• Hemolytic anemia has been reported in 10% of the patients within 1-4 wks of therapy initiation. Obtain complete blood counts pretreatment and at week 2 and week 4 of therapy or more frequently if indicated
• Hemolytic anemia may worsen cardiac disease and lead to fatal and nonfatal MI; avoid use in patients with a history of significant or unstable cardiac disease [US Black Box Warnings]
• Assess patients for underlying cardiac disease prior to therapy initiation and perform pre-treatment ECGs in patients with pre-existing cardiac disease. Suspend or discontinue therapy if any deterioration of cardiovascular status occurs. Do not use in patients with a history of significant or unstable cardiac disease
• Life-threatening or fatal neuropsychiatric reactions including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior have been reported in patients with and without a previous psychiatric disorder during peginterferon alfa-2b therapy. Use with extreme caution in patients with a history of psychiatric disorders; discontinue treatment if psychiatric symptoms persist or worsen, or suicidal ideation or aggressive behavior towards others is observed
• Higher doses of peginterferon alfa-2b may cause encephalopathy, particularly in elderly patients
• Therapy may cause bone marrow suppression, resulting in severe cytopenias; discontinue therapy in patients who develop significant reductions in neutrophil or platelet counts. Ribavirin may potentiate neutropenia induced by interferon alpha
• Increased risk of hepatic decompensation and death has been reported in CHC patients with cirrhosis and also in those co-infected with HIV receiving highly active antiretroviral therapy (HAART) and alpha interferons with/without ribavirin. Closely monitor hepatic function at baseline and at regular intervals following therapy initiation. Permanently discontinue therapy at any evidence of severe hepatic injury or hepatic decompensation
• Therapy may cause new onset or worsening of hypothyroidism and hyperthyroidism; hyperglycemia and diabetes mellitus may occur. Do not start therapy in patients with these conditions who cannot be treated by medications
• Therapy may cause cardiovascular adverse reactions, including hypotension, arrhythmia, tachycardia, cardiomyopathy, angina pectoris, and MI. Do not use in patients with a history of significant or unstable cardiac disease
• Interferon alfa-based therapies may cause ischemic and hemorrhagic cerebrovascular events
• Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis, interstitial pneumonitis and sarcoidosis, some resulting in respiratory failure and/or patient deaths have been reported during therapy. Suspend the combination treatment in patients who develop pulmonary infiltrates or pulmonary function impairment
• Fatal and nonfatal ulcerative or hemorrhagic/ischemic colitis manifested as abdominal pain, bloody diarrhea, and fever have been reported within 12 wks of therapy initiation; colitis usually resolves within 1-3 wks of therapy discontinuation
• Therapy may cause fatal and nonfatal pancreatitis; discontinue therapy in patients diagnosed with pancreatitis
• Development or exacerbation of autoimmune disorders such as thyroiditis, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, rheumatoid arthritis, interstitial nephritis, systemic lupus erythematosus, and psoriasis have been associated with this therapy; use cautiously in patients with autoimmune disorders
• Peginterferon alfa-2b may induce or aggravate retinal and ocular changes including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, and papilledema. Perform eye examination at baseline and anytime during the therapy; permanently discontinue therapy, if patients develop new or worsening ophthalmologic disorders
• Serious, acute hypersensitivity reactions and cutaneous eruptions may occur during alpha interferon therapy; discontinue treatment and promptly initiate appropriate therapy
• Therapy has not been studied in patients who have failed other alpha interferon treatments
• Safety and efficacy of peginterferon alfa-2b injection/ribavirin combo therapy has not been established for the treatment of patients with HCV co-infected with HIV or HBV
• Elevated triglyceride levels resulting in pancreatitis have been reported during therapy; manage hypertriglyceridemia as clinically appropriate. Consider therapy discontinuation for patients with symptoms of potential pancreatitis
• Therapy may increase serum creatinine levels in patients with renal insufficiency; closely monitor these patients for signs and symptoms of interferon toxicity
• Therapy may cause dental and periodontal disorders during therapy; dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term therapy with this combination drug

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• Cardiac diseases
• Psychiatric disorders

Supplemental Patient Information

• Inform patients of the benefits and risks associated with this combination drug before starting therapy
• Advise women of childbearing potential and also male patients whose partners are of childbearing age to use effective contraception to avoid pregnancy during therapy and for 6 months post therapy
• Instruct patients to notify their physician immediately in the event of a pregnancy
• Instruct patients of the importance of proper disposal of the used injection
• Advise patients to remain well hydrated, especially during the initial stages of treatment

Pregnancy Category:X

Breastfeeding: Interferon alpha is poorly excreted into breastmilk and is unlikely to adversely affect the breastfed infant. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/ht mlgen?LACT last accessed 7 December 2011). Because of the potential for possible serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, analyzing the importance of the drug to the mother.

• CNS: Headache, dizziness
• PSYCHIATRY: Insomnia, depression, anxiety/emotional lability/irritability, impaired concentration, agitation, nervousness, suicidal behavior
• CV: Chest pain, arrhythmias, myocardial infarction
• GI: Nausea, anorexia, diarrhea, dyspepsia, dry mouth, vomiting, abdominal pain, constipation
• HEPA: Hepatomegaly
• HEMA: Hemolytic anemia, neutropenia, anemia, lymphopenia, leukopenia, thrombocytopenia
• ENDO: Hypothyroidism
• RESP: Dyspnea, cough, sinusitis, pharyngitis, rhinitis
• MUSC: Myalgia, arthralgia, musculoskeletal pain
• EENT: Blurred vision, conjunctivitis
• LOCAL: Injection site reaction, injection site inflammation
• REPRODUCTIVE: Menstrual disorder
• DERM: Alopecia, pruritus, rash, dry skin, increased sweating
• LABTEST: Hyperuricemia, decreased hemoglobin, hyperbilirubinemia, elevated triglycerides
• MISC: Fatigue/asthenia, pyrexia, rigors, weight loss, chest pain, malaise, RUQ pain, flushing, infection

Peginterferon alfa-2b

• Immunomodulator; binds to type I interferon receptors on cell surface initiating a complex sequence of intracellular events such as induction of certain enzymes, suppression of cell proliferation, and enhancement of phagocytic activity; also, inhibits viral replication in virus-infected cells
• Metabolism: Unknown
• Excretion: Urine 30%
• Half-life: 40 hrs

Ribavirin

• Antiviral agent (nucleoside analogue); exact mechanism of action unknown; may inhibit activity of viral RNA polymerase and messenger RNA guanylyltransferase, thereby resulting in a marked reduction of intracellular guanosine triphosphate (GTP) pools and inhibition of viral RNA and protein synthesis. Also, may be incorporated into the viral genome causing lethal mutagenesis and a subsequent decrease in specific viral infectivity
• Rapidly and extensively absorbed following oral administration
• Metabolized by two pathways: a reversible phosphorylation pathway in nucleated cells and a degradative pathway involving deribosylation and amide hydrolysis to yield a triazole carboxylic acid metabolite. No cytochrome P450 enzyme-mediated metabolism
• Excretion: Urine 61%; feces 12%
• Half-Life: 43.6 hrs (single dose); 298 hrs (multiple dose)

US Trade Name(s)

• Pegintron/Rebetol Combo Pack

US Availability

Pegintron/Rebetol Combo Pack (peginterferon alfa-2b injection; ribavirin)

• Redipen INJ: 50 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 80 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 120 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 150 mcg/0.5 mL; CAPS: 200 mg

Canadian Trade Name(s)

• Pegetron

Canadian Availability

Pegetron (peginterferon alfa-2b injection; ribavirin)

• PWDR for INJ: 50 mcg/0.5 mL; CAPS: 200 mg
• PWDR for INJ: 80 mcg/0.5 mL; CAPS: 200 mg
• PWDR for INJ: 100 mcg/0.5 mL; CAPS: 200 mg
• PWDR for INJ: 120 mcg/0.5 mL; CAPS: 200 mg
• PWDR for INJ: 150 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 50 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 80 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 100 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 120 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 150 mcg/0.5 mL; CAPS: 200 mg

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• Pegatron Combination Therapy

Australian Availability

Pegatron Combination Therapy (peginterferon alfa-2b injection; ribavirin)

• Redipen INJ: 50 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 80 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 100 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 120 mcg/0.5 mL; CAPS: 200 mg
• Redipen INJ: 150 mcg/0.5 mL; CAPS: 200 mg

[Outline]

Antimicrobials

Hepatitis, Antivirals