Ribavirin

Ribavirin is an antiviral medication used together with an interferon alfa product (such as Peg-Intro or Intron A) to treat chronic hepatitis C.

Ribavirin is available under the following different brand names: Rebetol, Ribasphere, RibaPak, Copegus, Virazole, and Moderiba.

Dosages of Ribavirin:

Adult and Pediatric Dosage Forms and Strengths

Tablet

• 200 mg
• 400 mg
• 600 mg

Inhalation solution

• 6 g/vial

Oral solution

• 40 mg/mL

Dosage Considerations – Should be Given as Follows:

Chronic Hepatitis C

Adult:

In combination with pegterferon alfa-2a (Pegasys)

Dose reductions/interruptions recommended if Hgb falls (see manufacturer's package insert for specifics)

Tablets (Copegus)

• In combination with peginterferon alfa-2a
• Genotype 1, 4; HIV-free (less than 75 kg): 1000 mg/day orally divided every 12 hours for 48 weeks
• Genotype 1, 4; HIV-free (75 kg or greater): 1200 mg/day orally divided every 12 hours for 48 weeks
• Genotype 2/3; HIV-free: 800 mg/day orally divided every 12 hours for 24 weeks
• Chronic hepatitis C co-infected with HIV: peginterferon alfa-2a 180 mcg SC once/week plus ribavirin 800 mg orally divided every 12 hours (regardless of genotype)

Rebetol capsule, oral solution, Ribasphere combo with peginterferon alfa 2b

• Less than 66 kg (145 lbs): 800 mg/day (400 mg AM and 400 PM) + peginterferon 1.5 mcg/kg/week subcutaneously (SC)
• 66-80 kg (145-177 lbs): 1000 mg/day (400 mg AM and 600 PM) + peginterferon 1.5 mcg/kg/week SC
• 81-105 kg (178-231 lbs): 1200 mg/day (600 mg AM and 600 PM) + peginterferon 1.5 mcg/kg/week SC
• Greater than 105 kg (231 lbs): 1400 mg/day (600 mg AM and 800 PM) + peginterferon 1.5 mcg/kg/week SC
• Recommended therapy duration
  • Genotype 1: 48 weeks
  • Genotype 2,3: 24 weeks
  • Patients who previously failed therapy: 48 weeks, regardless of genotype

Ribavirin (Rebetol capsule and solution; Ribasphere) with interferon alfa 2b

• Up to 75 kg: 400 mg orally every morning, 600mg orally every evening plus 3 million IU three times weekly subcutaneously (SC) for 24-48 weeks
• Greater than 75 kg: 600 mg orally every 12 hours plus 3 million IU three times weekly SC for 24-48 weeks
• Recommended therapy duration
  • Patients previously untreated with interferon: 24-48 weeks
  • Patients who relapse following inteferon monotherapy: 24 weeks

HIV/HCV co-infection: Copegus

• 800 mg/d orally divided every 12 hours for 48 weeks

RibaPak, Copegus, Ribasphere, and equivalents used with peginterferon alfa-2a (Pegasys)

• Coadministered dose of peginterferon alfa-2a: 180 mcg once/week

Pediatric:

Indicated in combination with peginterferon alfa-2a for treatment of chronic hepatitis C in patients with compensated liver disease and no prior history of interferon therapy

Patients who initiate treatment before their 18th birthday should maintain pediatric dosing through completion of therapy

Length of treatment determined by genotype; genotypes 2 or 3 administer for 24 weeks, for genotype 1 in 48 weeks

Rebetol capsule, oral solution

• Less than 47 kg (103 lbs): 15 mg/kg/day, plus peginterferon alfa-2b 60 mcg/m² subcutaneously (SC) once/week
• 47-59 kg (103-131 lbs): 400 mg orally every 12 hours, plus peginterferon alfa-2b 60 mcg/m² SC once/week
• 60-73 kg (132-162 lbs): 400 mg orally every morning, 600 mg orally every evening plus peginterferon alfa-2b 60 mcg/m² SC once/week
• Greater than 73 kg (162 lbs): 600 mg orally every 12 hours plus peginterferon alfa-2b 60 mcg/m² SC once/week

Copegus, Moderiba (tablets)

• Children under 5 years: Safety and efficacy not established
• 5-17 years: approximately 15 mg/kg/day orally divided every 12 hours with weekly subcutaneously (SC) peginterferon alfa-2a
• 23-33 kg: 200 mg orally every 12 hours
• 34-46 kg: 200 mg orally every morning and 400 mg orally every evening
• 47-59 kg: 400 mg orally every 12 hours
• 60-74 kg: 400 mg orally every morning and 600 mg orally every evening
• 75 kg or greater: 600 mg orally every 12 hours

Respiratory Syncytial Virus, Pediatric

• Virazole: Put 20 mg/mL solution (6 g drug reconstituted with 300 mL sterile water for injection) in SPAG-2 unit
• Continuous aerosolized administration for 12-18 hours/day for 3-7 days
• Delivers 190 mcg/L of air for 12 hours

Lassa Fever Prophylaxis, Pediatric

• Children over 9 years: As adult; Load 30 mg/kg IV (up to 2 g), THEN 16 mg/kg IV (up to 1 g) every 6 hours for 4 days, THEN 8 mg/kg intravenously (IV) (up to 500 mg) every 8 hours for 6 days
• Children years: 400 mg orally every 6 hours

Renal Impairment

Rebetol capsules/solution, Ribasphere capsules

• CrCl less than 50 mL/minute: Use contraindicated
• CRC l 50 mL/minute or greater: Dose adjustment not necessary

Ribasphere tablets

• CrCl less than 50 mL/minute: Use contraindicated
• CrC l 50 mL/minute or greater: Dose adjustment not necessary

Copegus tablets

• CrCl less than 30 mL/minute or hemodialysis: 200 mg orally once/day
• CrCl 30-50 mL/minute: Alternating doses, 200 mg and 400 mg orally every other day
• CrCl 50 mL/minute or greater: Dose adjustment not necessary

Administration

• Take with food
• Take 1 dose in the morning and one at night (may not be equal)

Common side effects of Ribavirin include:

• Fatigue
• Headache
• Hemolysis
• Muscle pain
• Nausea
• Rigors
• Fever
• Trouble sleeping (insomnia)
• Decreased Hgb
• Depression
• Hyperbilirubinemia
• Joint pain
• Hair loss
• Irritability
• Musculoskeletal pain
• Rash
• Loss of appetite
• Dizziness
• Itching
• Flu-like syndrome (e.g., fever, chills, sore throat, muscle aches, or pain)
• Shortness of breath
• Nasal congestion
• Indigestion/heartburn
• Impaired concentration
• Low blood platelets (thrombocytopenia)
• Sinus infection (sinusitis)
• Vomiting
• Mood swings
• Decreased white blood cells; ANC less than 500 /cu.mm
• Hemolytic anemia
• Weakness
• Chest pain
• Changes in taste
• Changes in hearing
• Nervousness
• Diarrhea
• Stomach pain or upset
• Tiredness
• Anxiety
• Blurred vision
• Cough
• Weight loss or gain
• Dry skin
• Dry mouth
• Tooth and gum problems
• Injection site reactions (pain, swelling, or irritation)

Serious side effects of ribavirin include:

• Unusual tiredness or weakness
• Fast/pounding/irregular heartbeat
• Trouble breathing
• Mental/mood changes (e.g., severe depression, suicidal thoughts)
• Vision changes
• Easy bruising or bleeding
• Dark urine
• Yellowing of eyes or skin (jaundice)

Postmarketing side effects of ribavirin reported include:

Combined with peginterferon alfa-2a:

• Dehydration
• Hearing impairment
• Hearing loss
• Retinal detachment
• Pure red cell aplasia (PRCA)
• Serious skin reactions
• Liver and renal graft rejection
• Homicidal ideation
• Growth inhibition in pediatric patients

This is not a complete list of side effects and other serious side effects may occur. Call your doctor for information and medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ribavirin has no known severe interactions with other drugs.
• Severe interactions of ribavirin include:
  • didanosine
• Serious interactions of ribavirin include:
  • abacavir
  • stavudine
  • zidovudine
• Moderate interactions of ribavirin include:
  • emtricitabine
  • lamivudine
  • tobramycin inhaled
• Mild interactions of ribavirin include:
  • warfarin

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Oral

• Monotherapy is not effective for the treatment of chronic hepatitis C virus (HCV) infection and should not be used alone for this indication
• Hemolytic anemia is the primary toxicity, which may result in worsening of cardiac disease and lead to fatal and nonfatal MI; do not use if the history of significant or unstable cardiac disease
• Significant teratogenic and/or embryocidal effects demonstrated in all animal species exposed to ribavirin
• Half-life is 12 days, and the drug may persist in non-plasma compartments for as long as 6 months
• Contraindicated during pregnancy and in the male partners of pregnant women
• Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both female patients and female partners of male patients taking ribavirin
• At least 2 reliable forms of effective contraception must be used during treatment and the 6-month post-treatment follow-up period

Inhalation

• Aerosolized ribavirin in patients requiring mechanical ventilator assistance should be administered only by health care providers and support staff familiar with this mode of administration and the specific ventilator being used
• Strictly follow procedures that minimize drug precipitate accumulation to avoid mechanical ventilator dysfunction
• Sudden respiratory function deterioration in infants may occur during initiation of aerosolized ribavirin
• Carefully monitor respiratory function during treatment
• If sudden deterioration of respiratory function occurs, stop treatment and reinstitute only with extreme caution, continuous monitoring, and possibly bronchodilator coadministration
• Aerosolized ribavirin is not indicated for adults
• Produces testicular lesions in rodents and is teratogenic in all animal species in which adequate studies have been conducted (rodents and rabbits)

This medication contains ribavirin. Do not take Rebetol, Ribasphere, RibaPak, Copegus, Virazole, or Moderiba if you are allergic to ribavirin or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Women who are or may become pregnant
• Men whose female partners are pregnant
• Known hypersensitivity reactions to ribavirin (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)
• Autoimmune hepatitis
• Hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia)
• CrCl less than 50 mL/min
• Coadministration with didanosine; exposure to the active metabolite of didanosine (dideoxyadenosine 5'-triphosphate) is increased; fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis, have been reported with this combination

Effects of Drug Abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Ribavirin?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Ribavirin?"

Cautions

• Mechanically ventilated patients.
• Preexisting cardiac disease.
• May need interruption if cardiovascular status deteriorates.
• Risk of hemolytic anemia.
• Do NOT use for influenza.
• Only Copegus was studied in HCV/HIV coinfectees, however, the modified dose is CDC recommended.
• Ribavirin may cause birth defects and/or the death of an unborn child (see Warnings and Contraindications).
• There are significant adverse reactions caused by ribavirin/ interferon alfa therapy, including severe depression and suicidal or homicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes; suicidal ideation may occur more frequently among pediatric patients, primarily adolescents, compared to adult patients (2.4% versus 1%) during treatment and off-therapy follow-up.
• Suspend ribavirin and alfa interferon combination therapy in patients with signs and symptoms of pancreatitis and discontinue in patients with confirmed pancreatitis.
• Pulmonary symptoms, including shortness of breath (dyspnea), pulmonary infiltrates, pneumonitis, pulmonary high blood pressure (hypertension), and pneumonia, reported during therapy with ribavirin with alpha-interferon combination therapy; occasional cases of fatal pneumonia have occurred; sarcoidosis or the exacerbation of sarcoidosis reported; closely monitor a patient or if necessary discontinue therapy if pulmonary infiltrates or pulmonary function impairment observed.
• Dental and periodontal disorders reported in patients receiving ribavirin and interferon alfa combination therapy; dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with a combination of ribavirin and interferon alfa; patients should brush teeth thoroughly twice daily and have regular dental examinations; if vomiting occurs, they should be advised to rinse out their mouth thoroughly afterward.
• Take extreme care to avoid pregnancy.
• Risk of hemolytic anemia.
• Anemia associated with treatment may result in worsening cardiac disease.
• Genotoxic and mutagenic: Potential carcinogen.
• Ocular disorders are reported when ribavirin is used in combination therapy with alpha interferons (e.g., decrease or loss of vision, retinopathy including macular edema, retinal artery or vein, thrombosis, retinal hemorrhages; cotton wool spots, optic neuritis, papilledema, serous retinal detachment).
• A study in boys showed growth rate inhibited (i.e., height percentile decreases) with peginterferon alfa-2b plus ribavirin.
• Pancytopenia and bone marrow suppression was reported when coadministered with pegylated interferon and azathioprine.
• Hepatic decompensation:
  • Patients with chronic hepatitis C (CHC) and cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS
  • Cirrhotic CHC patients coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to patients not receiving HAART

Pregnancy and Lactation

Do not use ribavirin in pregnancy. The risks involved outweigh the potential benefits. Safer alternatives exist.

• Contraindicated during pregnancy and in the male partners of pregnant women
• Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both female patients and female partners of male patients taking ribavirin
• At least 2 reliable forms of effective contraception must be used during treatment and the 6-month post-treatment follow-up period

It is unknown if ribavirin passes into breast milk or if it would affect a nursing infant. Consult your doctor before breastfeeding.