Adult Dosing

Chronic Hepatitis C

Copegus, Ribasphere, Ribasphere Ribapak

• <75 kgs, (genotype 1 or 4): 1,000 mg/day PO divided doses bid x 48 wks in combination with peginterferon alfa-2a 180 mcg SC once weekly
• 75 kgs,(genotype 1 or 4): 1,200/day PO divided doses bid x 48 wks in combination with peginterferon alfa-2a 180 mcg SC once weekly
• Genotype 2 or 3: 800 mg/day PO divided doses bid x 24 wks in combination with peginterferon alfa-2a180 mcg SC once weekly

Chronic Hepatitis C with HIV Coinfection

Copegus

• Regardless of HCV genotype: 800 mg/day PO qd x 48 wks in combination with peginterferon alfa-2a 180 mcg SC once weekly

Chronic Hepatitis C

Rebetol

• <66 kg: 800 mg PO divided bid (400 mg qam and 400 mg qpm) in combination with peginterferon alfa-2b 1.5 mcg/kg/week SC
• 66-80 kg: 1000 mg PO divided bid (400 mg qam and 600 mg qpm) in combination with peginterferon alfa-2b 1.5 mcg/kg/week SC
• 81-105 kg: 1200 mg PO divided bid (600 mg qam and 600 mg qpm) in combination with peginterferon alfa-2b 1.5 mcg/kg/week SC
• >105 kg: 1400 mg PO divided bid (600 mg qam and 800 mg qpm) in combination with peginterferon alfa-2b 1.5 mcg/kg/week SC

• Dose duration - Give for 48 wks if genotype 1 and 24 wks for genotype 2 or 3
• Patients who failed previous therapy, give for 48 wks, regardless of HCV genotype
• Refer package insert for dose modification related information

Pediatric Dosing

• Safety and efficacy of Ribasphere and Ribasphere Ribapak have not been established in pediatric patients

Chronic Hepatitis C

Copegus

• >5 yo, 23-33 kg: 200 mg PO qam and 200 mg PO qam in combination with peginterferon alfa-2a 180 mcg SC once weekly
• >5 yo, 34-46 kg: 200 mg PO qam and 400 mg PO qamin combination with peginterferon alfa-2a 180 mcg SC once weekly
• >5 yo, 47-59 kg: 400 mg PO qam and 400 mg PO qam in combination with peginterferon alfa-2a 180 mcg SC once weekly
• >5 yo, 60-74 kg: 400 mg PO qam and 600 mg PO qam in combination with peginterferon alfa-2a 180 mcg SC once weekly
• >5 yo, >75 kg: 600 mg PO qam and 600 mg PO qam in combination with peginterferon alfa-2a 180 mcg SC once weekly

Note:

• Dosing of peginterferon alfa-2a is based on BSA (180mcg/1.73 m2 x BSA once weekly). Max dose=180mcg with Copegus

Chronic Hepatitis C

Rebetol

• Child 3-17 yrs
• <47 kg: 15 mg/kg/day PO divided bid in combination with peginterferon alfa-2b 60 mcg/m²/week
• 47-59 kg: 800 mg PO divided bid (400 mg qam and 400 mg qpm) in combination with peginterferon alfa-2b 60 mcg/m²week
• 60-73 kg: 1000 mg PO divided bid (400 mg qam and 600 mg qpm)in combination with peginterferon alfa-2b 60 mcg/m²week
• >73kg: 1200 mg PO divided bid (600 mg qam and 600 mg qpm) in combination with peginterferon alfa-2b 60 mcg/m²week

Note:

• Dose duration - Give for 48 wks if genotype 1 and 24 wks for genotype 2 or 3
• Refer package insert for dose modification related information

[Outline]

• Adult Dosing
• Pediatric Dosing

Copegus

• Treatment of chronic hepatitis C (CHC) virus infection in combination with peginterferon alfa-2a in patients 5 yrs of age having compensated liver disease untreated with interferon alpha, and in adult CHC patients coinfected with HIV

Rebetol

• Treatment of chronic hepatitis C (CHC) virus infection in combination with peginterferon alfa-2a in patients 3yrs of age having compensated liver disease

Ribasphere, Ribasphere Ribapak

• Treatment of chronic hepatitis C (CHC) virus infection in combination with peginterferon alfa-2a in patients having compensated liver disease untreated with interferon alpha, and in adult CHC patients coinfected with HIV

• Hypersensitivity to any of the ingredients of the product
• Pregnancy
• Males whose female partners are pregnant
• Significant or unstable cardiac disease
• Hemoglobinopathies
• CrCl <50
• Autoimmune hepatitis
• Hepatic impairment, Child-Pugh Class B or C
• Coadministration with didanosine

• Ribavirin is not effective as monotherapy for chronic hepatitis C
• Primary clinical toxicity of ribavirin therapy is hemolytic anemia. It may worsen cardiac disease and lead to fatal and nonfatal MI, avoid use in patients with significant or unstable cardiac disease
• Teratogenic/Embryocidal effects have been demonstrated in all animal species. Multiple dose half-life is 12 days; ribavirin may persist in non-plasma compartments for as long as 6 months. Use is contraindicated in pregnant women and their male partners. Avoid pregnancy during and for 6 months after therapy in female patients and female partners of male patients, use 2 forms of reliable contraception during and for 6 months after therapy

Renal Dose Adjustment (Based on CrCl)

• <50 mL/min: Contraindicated

Hepatic Dose Adjustment

• Autoimmune hepatitis: Contraindicated
• Child-Pugh Class B/C: Contraindicated

Dose modifications due to adverse reactions or lab abnormalities

• Refer package insert for complete information on dose modifications due to severe adverse reactions or abnormal laboratory findings

Discontinuation of Therapy

• The treatment duration for patients with genotype 1 is 48 weeks. Discontinuation of therapy should be considered in patients who do not achieve at least a 2 log10 drop or loss of HCV-RNA at 12 weeks, or if HCV-RNA remains detectable after 24 weeks of therapy. Patients with genotype 2 and 3 should be treated for 24 weeks

• Not effective as monotherapy for chronic hepatitis C [US Black Box Warnings]
• Risk of hemolytic anemia; may worsen cardiac disease and lead to fatal and nonfatal MI, avoid use in patients with significant or unstable cardiac disease [US Black Box Warnings]
• Hemoglobin or hematocrit should be obtained pretreatment and at week 2 and week 4 of therapy, or more frequently if there is initial drop in hemoglobin
• Fatal and nonfatal myocardial infarctions have been reported in patients with anemia caused. Assess for underlying cardiac disease before initiation of therapy, appropriately monitor for ECG
• Suspend or discontinue therapy if any cardiovascular deterioration occurs
• Suspend therapy in patients with signs and symptoms of pancreatitis or discontinue in patients with confirmed pancreatitis
• Obtain an eye examination at baseline as the combination therapy may lead to various opthalmic disorders. Perform periodic ophthalmologic tests in patients with pre-existing ophthalmologic disorders
• Obtain hematology and blood chemistry testing before the start of treatment and then periodically thereafter as therapy may cause severe decreases in neutrophil and platelet counts, and hematologic, endocrine and hepatic abnormalities
• Dental and periodontal disorders have been reported. Patients should brush their teeth thoroughly twice daily and have regular dental examinations. If vomiting occurs, they should be advised to rinse out their mouth thoroughly afterwards
• Concomitant administration of pegylated interferon/ribavirin and azathioprine may lead to pancytopenia and bone marrow suppression.
• Use is contraindicated in pregnant women and their male partners. Avoid pregnancy during and for 6 months after therapy in female patients and female partners of male patients, use 2 forms of reliable contraception during and for 6mo after therapy. Due to significant teratogenic and embryocidal effects, obtain pregnancy test immediately prior to therapy, per month during and 6 months after discontinuation of therapy
• Weight loss and growth inhibition reported with combination therapy in pediatric patients
• Hypersensitivity reactions like urticaria, angioedema, bronchoconstriction, and anaphylaxis have been reported during the therapy.Discontinue the treatment if patient develops severe skin reactions
• Pulmonary disorders have been reported during the therapy, closely monitor and discontinue therapy if pulmonary function impairment develops

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• Cardiac disease
• Myelosuppression
• Elderly patients
• Concomitant use with Nucleoside analogues

Copegus, Rebetol, Ribasphere, Ribasphere Ribapak interacts with :

	Azasan
	Azathioprine
	Imuran
	Mercaptopurine
	Purinethol
	Purixan

Pregnancy Category:X

Breastfeeding: Possibly unsafe; due to the potential for possible serious adverse reactions in nursing infants a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• CNS: Fatigue, fatigue/asthenia, headache, rigors, anxiety/emotional lability/irritability, insomnia, depression, dizziness, impaired concentration, emotional lability, asthenia, agitation, impaired memory, mood alteration, nervousness
• HEMA: Hemolytic anemia, neutropenia, anemia, lymphopenia, leukopenia, thrombocytopenia
• DERM: Alopecia, pruritus, rash, dry skin, dermatitis, increased sweating, eczema, flushing
• EENT: Pharyngitis, taste perversion, rhinitis, blurred vision, conjunctivitis
• ENDO: Hypothyroidism
• GI: Nausea, anorexia, diarrhea, dyspepsia, dry mouth, vomiting, abdominal pain, constipation
• GU: Menstrual disorder
• HEPA: Hepatomegaly
• LABTEST: Hyperuricemia, decreased hemoglobin, hyperbilirubinemia
• LOCAL: Injection-site reaction, injection-site inflammation
• METABOLIC: Decreased weight
• MUSC: Myalgia, arthralgia, musculoskeletal pain, back pain
• RESP: Dyspnea, cough, sinusitis
• MISC: Pyrexia, flu-like symptoms, resistance mechanism disorders, right upper quadrant pain, viral infection, pain, chest pain, fungal infection, malaise

• Antiviral agent (nucleoside analogue); exact mechanism of action unknown; may inhibit activity of the enzyme RNA dependent RNA polymerase by incorporating into the viral genome causing lethal mutagenesis and a subsequent decrease in specific viral infectivity
• 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 mediated metabolism
• Renally excreted: 61%; feces: 12%
• Half-Life: 120-170 hrs

US Trade Name(s)

• Copegus
• Rebetol
• Ribasphere
• Ribasphere Ribapak

US Availability

ribavirin (generic)

• TABS: 200, 400, 500, 600 mg
• CAPS: 200 mg

Copegus

• TABS: 200 mg

Rebetol

• CAPS: 200 mg
• SOLN: 40 mg/mL

Ribasphere

• TABS: 200, 400, 600 mg
• CAPS: 200 mg

Ribasphere Ribapak

• 800 Dose Pack: 14 x 400 mg tabs
• 1000 Dose Pack: 7 x 400 mg tabs and 7 x 600 mg tabs
• 1200 Dose Pack: 14 x 600 mg tabs

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• Copegus
• Rebetol

UK Availability

Copegus

• TABS: 200, 400 mg

Rebetol

• CAPS: 200 mg
• SOLN: 40 mg/mL

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Antimicrobials

Antiviral Agents

Nucleoside Analogues

Pricing data from www.DrugStore.com in U.S.A.

• Rebetol 40 MG/ML SOLN [Bottle] (SCHERING)
  100 ml = $223.98
  300 ml = $614.94
• Rebetol 200 MG CAPS [Bottle] (SCHERING)
  60 mg = $554.02
  180 mg = $1633.06
• Ribasphere 200 MG CAPS [Bottle] (KADMON PHARMACEUTICALS)
  30 mg = $135.61
  90 mg = $360.96

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

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