Rebetol


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Related to Rebetol: ribavirin, Ribasphere, Copegus, PegIntron

ribavirin

(rye-ba-vye-rin) ,

Copegus

(trade name),

Rebetol

(trade name),

Virazole

(trade name)

Classification

Therapeutic: antivirals
Pharmacologic: nucleoside analogues
Pregnancy Category: X

Indications

Inhalation: Treatment of severe lower respiratory tract infections caused by the respiratory syncytial virus (RSV) in infants and young children. Oral: Rebetol—with interferon alfa-2b (Intron A) or peginterferon alfa-2b (PegIntron) in the treatment of chronic hepatitis C in patients with compensated liver disease. Oral: Copegus—with peginterferon alfa-2a (Pegasys) in the treatment of chronic hepatitis C in patients with compensated liver disease who have not previously been treated with interferon alfa.Early (within 24 hr of symptoms) secondary treatment of influenza A or B in young adults.

Action

Inhibits viral DNA and RNA synthesis and subsequent replication.
Must be phosphorylated intracellularly to be active.

Therapeutic effects

Inhalation: Virustatic action.
Oral: Decreased progression and sequelae of chronic hepatitis C.

Pharmacokinetics

Absorption: Systemic absorption occurs following nasal and oral inhalation. Rapidly and extensively absorbed following oral administration, but undergoes first-pass hepatic metabolism (64% bioavailability).
Distribution: 70% of inhaled drug is deposited in the respiratory tract. Appears to concentrate in the respiratory tract and red blood cells. Enters breast milk.
Metabolism and Excretion: Eliminated from the respiratory tract by distribution across membranes, macrophages, and ciliary motion. Metabolized primarily by the liver; metabolites are renally excreted.
Half-life: Inhaln—9.5 hr (40 days in RBCs); oral—43.6 hr (single dose); 12 days (multiple dose).

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
Inhalnunknownend of inhalnunknown
POunknown1.7–3 hr12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Patients receiving mechanically assisted ventilation; Obstetric / Lactation: Pregnancy or lactation; Obstetric: Male partners of pregnant patients;CCr <50 mL/min;Significant/unstable cardiovascular disease;Hemoglobinopathies;Autoimmune hepatitis or hepatic decompensation before/during treatment (for combined therapy with interferon alfa-2b or peginterferon alfa-2a);Concurrent use of didanosine, stavudine, or zidovudine.
Use Cautiously in: Sarcoidosis (may exacerbate condition);Anemia (dose reduction/discontinuation may be required);Any pre-existing cardiac disease; Obstetric: Patients with childbearing potential. Pediatric: May result in ↓ growth.

Adverse Reactions/Side Effects

Inhalation

Central nervous system

  • dizziness
  • faintness

Ear, Eye, Nose, Throat

  • blurred vision
  • conjunctivitis
  • erythema of the eyelids
  • ocular irritation
  • photosensitivity

Cardiovascular

  • cardiac arrest (life-threatening)
  • hypotension

Dermatologic

  • rash

Hematologic

  • hemolytic anemia (with interferon alpha 2b) (most frequent)
  • reticulocytosis
Oral (may reflect combination with interferon)

Central nervous system

  • emotional lability (↑ in children)
  • fatigue (↓ in children)
  • impaired concentration (↓ in children)
  • insomnia (↓ in children)
  • irritability (↓ in children)

Ear, Eye, Nose, Throat

  • dry mouth
  • optic neuritis
  • papilledema
  • retinal artery/vein thrombosis
  • retinal detachment
  • retinal hemorrhage
  • retinopathy (with macular edema)
  • visual abnormalities

Respiratory

  • dyspnea (↓ in children)

Gastrointestinal

  • anorexia (↑ in children)
  • dyspepsia (↓ in children)
  • vomiting (↑ in children)

Hematologic

  • hemolytic anemia (most frequent)

Dermatologic

  • stevens-johnson syndrome (life-threatening)
  • pruritus (↓ in children)

Musculoskeletal

  • arthralgia (↓ in children)

Miscellaneous

  • fever (↑ in children)

Interactions

Drug-Drug interaction

Oral: May ↓ the antiretroviral action of stavudine and zidovudine.May ↑ hematologic toxicity of zidovudine.May ↑ risk of pancytopenia when used with azathioprine.May ↑ blood levels and risk of toxicity of didanosine.Although used together in the management of hepatitis, concurrent use with interferon alpha 2b ↑ risk of hemolytic anemia.

Route/Dosage

Inhalation (Infants and Young Children) 300 mL of 20 mg/mL solution delivered via mist for 12–18 hr/day.

Rebetol (with peginterferon alfa-2b [PegIntron])

If retreatment is necessary, duration of therapy is 48 wk, regardless of viral genotype
Oral (Adults >105 kg) 600 mg in the morning, then 800 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Adults 81–105 kg) 600 mg in the morning, then 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Adults 66–80 kg) 400 mg in the morning, then 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Adults ≤65 kg) 400 mg in the morning, then 400 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and >73 kg) 600 mg in the morning and 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and 60–73 kg) 400 mg in the morning and 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and 47–59 kg) 400 mg in the morning and 400 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and <47 kg) 15 mg/kg/day in 2 divided doses (as oral solution) for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).

Rebetol (with interferon alfa-2b [Intron A])

If retreatment is necessary, duration of therapy is 24 wk
Oral (Adults >75 kg) 600 mg in the morning, then 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Adults ≤75 kg) 400 mg in the morning, then 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and >73 kg) 600 mg in the morning and 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and 60–73 kg) 400 mg in the morning and 600 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and 47–59 kg) 400 mg in the morning and 400 mg in the evening for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).
Oral (Children 3–17 yr and <47 kg) 15 mg/kg/day in 2 divided doses (as oral solution) for 48 wk (viral genotype 1) or 24 wk (viral genotypes 2 and 3).

Copegus—viral genotype 1 or 4 (with peginterferon alfa-2a)

Oral (Adults ≥75 kg) 600 mg twice daily for 48 wk.
Oral (Adults <75 kg) 500 mg twice daily for 48 wk.
Oral (Children ≥5 yr and ≥75 kg) 600 mg in the morning, then 600 mg in the evening for 48 wk
Oral (Children ≥5 yr and 60–74 kg) 400 mg in the morning, then 600 mg in the evening for 48 wk
Oral (Children ≥5 yr and 47–59 kg) 400 mg in the morning, then 400 mg in the evening for 48 wk
Oral (Children ≥5 yr and 34–46 kg) 200 mg in the morning, then 400 mg in the evening for 48 wk
Oral (Children ≥5 yr and 23–33 kg) 200 mg in the morning, then 200 mg in the evening for 48 wk

Renal Impairment

Oral (Adults) CCr 30–50 mL/min—200 mg/day alternating with 400 mg/day every other day for 48 wk; CCr <30 mL/min or Hemodialysis—200 mg once daily for 48 wk

Copegus—viral genotype 2 or 3 (with peginterferon alfa-2a)

Oral (Adults) 400 mg twice daily for 24 wk.
Oral (Children ≥5 yr and ≥75 kg) 600 mg in the morning, then 600 mg in the evening for 24 wk
Oral (Children ≥5 yr and 60–74 kg) 400 mg in the morning, then 600 mg in the evening for 24 wk
Oral (Children ≥5 yr and 47–59 kg) 400 mg in the morning, then 400 mg in the evening for 24 wk
Oral (Children ≥5 yr and 34–46 kg) 200 mg in the morning, then 400 mg in the evening for 24 wk
Oral (Children ≥5 yr and 23–33 kg) 200 mg in the morning, then 200 mg in the evening for 24 wk

Renal Impairment

Oral (Adults) CCr 30–50 mL/min—200 mg/day alternating with 400 mg/day every other day for 24 wk; CCr <30 mL/min or Hemodialysis—200 mg once daily for 24 wk

Copegus—with HIV coinfection (regardless of viral genotype) (with peginterferon alfa-2a)

Oral (Adults) 800 mg daily for 48 wk.

Availability

Powder for reconstitution for aerosol use (Virazole): 6 g/vial
Capsules (Rebetol): 200 mg
Oral solution (Rebetol): 40 mg/mL
Tablets (Copegus): 200 mg
In combination with: Rebetrol with interferon alfa-2b (Intron A) as combination therapy for chronic hepatitis C (Rebetron). See combination drugs.

Nursing implications

Nursing assessment

  • RSV: Assess patient for infection (vital signs, sputum, WBC) at beginning and during therapy.
    • Obtain specimens for culture and sensitivity prior to initiating therapy. First dose may be given before receiving results.
    • Assess respiratory (lung sounds, quality and rate of respirations) and fluid status prior to and frequently throughout therapy.
  • Chronic Hepatitis C: Monitor symptoms of hepatitis during therapy.
  • Assess patient for signs of depression during therapy. Monitor closely for neuropsychiatric changes, including suicidal thoughts.
    • Obtain ECG prior to therapy in patients with pre-existing cardiac disease. Assess patient for cardiovascular disorders (pulse, BP, chest pain). Reduce dose or discontinue therapy if cardiac disorders occur. May cause myocardial infarction.
    • Assess for signs of colitis (abdominal pain, bloody diarrhea, fever) and pancreatitis (nausea, vomiting, abdominal pain) during therapy. Discontinue therapy if these occur; may be fatal.
    • Assess pulmonary status (lung sounds, respirations) periodically during therapy. May require discontinuation.
    • Monitor for hypersensitivity reactions (urticaria, angioedema, bronchoconstriction, anaphylaxis). Discontinue immediately and institute supportive therapy.
  • Lab Test Considerations: Chronic Hepatitis C: Monitor CBC with differential and platelet count prior to initiation, at week 2, and week 4, and regularly during therapy. If hemoglobin <10 g/dL in patients with no history of cardiac disease or ↓ more than 2 g/dL in any 4-wk treatment period in patients with history of stable cardiac disease, ↓ ribavirin dose to 600 mg (200 mg in AM and 400 mg in PM). If hemoglobin <8.5 g/dL in patients with no history of cardiac disease or <12 g/dL despite dose reduction in patients with history of stable cardiac disease, discontinue combination therapy permanently. If dose withheld in children, may restart with 1/2 original dose.
    • Monitor biochemical tests and electrolytes prior to, after 4 wk, and periodically during therapy.
    • Monitor liver function tests and thyroid stimulating hormone prior to and periodically during therapy.
    • Monitor pregnancy tests prior to, monthly during, and for 6 mo following discontinuation of therapy in women of childbearing age. Ribavarin should be started following a negative pregnancy test.
    • May cause ↑ serum bilirubin and uric acid levels.

Potential Nursing Diagnoses

Risk for infection (Indications,  Side Effects)
Impaired gas exchange (Indications)

Implementation

  • Inhalation: Infants requiring assisted ventilation should be suctioned every 1–2 hr and pulmonary pressures monitored every 2–4 hr.
    • Ribavirin treatment should begin within the first 3 days of RSV infection to be effective.
    • Ribavirin aerosol should be administered using the Viratek SPAG model SPAG-2 only. Do not administer via other aerosol-generating devices. Usually administered using an infant oxygen hood attached to the SPAG-2 aerosol generator. Administration by face mask may be used if the oxygen hood cannot be used.
    • Reconstitute ribavirin 6-g vial with preservative-free sterile water for injection or inhalation. Transfer to clean, sterilized Erlenmeyer flask of the SPAG-2 reservoir and dilute to a final volume of 300 mL. This recommended concentration (20 mg/mL) in the reservoir provides a concentration of aerosol ribavirin of 190 mcg/L of air over a 12-hr period. Solution should be discarded and replaced every 24 hr.
    • Aerosol treatments should be administered continuously 12–18 hr/day for 3–7 days.
  • Oral: Administer with food. Capsules should be swallowed whole; do not open, crush, or chew.
    • For children, determine if child is able to swallow 200-mg tablet.

Patient/Family Teaching

  • RSV: Explain the purpose and route of treatment to the patient and parents.
  • Inform patient and parents that ribavirin may cause blurred vision and photosensitivity.
  • Chronic Hepatitis C: Instruct patient to take ribavirin at the same time each day for the full course of therapy. Take missed doses as soon as remembered. If total day dose is missed, notify health care professional; do not double doses. Emphasize the importance of routine lab test to monitor for side effects.
    • Advise patient to brush teeth twice daily, have regular dental examinations, and rinse mouth thoroughly after vomiting to prevent dental and periodontal disorders.
    • May cause dizziness, confusion, fatigue, and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
    • Inform patient that ribavirin may not reduce the risk of transmission of HCV to others or prevent cirrhosis, liver failure, or liver cancer.
    • Advise patient to consult health care professional before taking any other Rx, OTC, or herbal products.
    • Advise patient to stop taking ribavirin and notify health care professional immediately if rash with fever; blisters or sores in mouth, nose, or eyes; or conjunctivitis occurs and to notify health care professional if trouble breathing, hives or swelling, chest pain, severe stomach pain or low back pain, bloody diarrhea or bloody or black stools, bruising or unusual bleeding, change in vision, fever >100.5°F, worsening psoriasis, worsening depression, or suicidal thoughts occur.
    • Inform patient about teratogenic effects of ribavirin. Instruct women with childbearing potential, and men, to use 2 forms of effective contraception during and for at least 6 mo following conclusion of therapy. Men must use a condom. Avoid breast feeding during use.

Evaluation/Desired Outcomes

  • Resolution of the signs and symptoms of RSV.
  • Decreased progression and sequelae of chronic hepatitis C. Therapy with peginterferon alfa-2a and ribavirin should be discontinued if at least a 2-log 10 reduction from baseline in HCV RNA by 12 wk of therapy, or undetectable HCV RNA levels after 24 wk of therapy.

Rebetol®

Ribavirin, see there.
References in periodicals archive ?
The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with REBETOL is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, REBETOL.
Based on the results of these studies, the CHMP recommended duration of dosing with PEGINTRON and REBETOL combination therapy for HCV/HIV coinfected patients is 48 weeks, regardless of HCV genotype.
Recommended Dosage: One subcutaneous injection of PEG-Intron per week, with Rebetol capsules every morning and afternoon.
Schering-Plough expects REBETOL Capsules, available by prescription only, to be available nationwide sometime this fall.
The incidence of skin adverse events (rash or pruritus) observed in the boceprevir arms was similar to that seen in the PEGINTRON and REBETOL control arm.
Schering-Plough also is conducting a large Phase II study evaluating the safety and efficacy of boceprevir 800 mg TID in combination with PEGINTRON and REBETOL in patients chronically infected with HCV genotype 1 who were nonresponders to previous peginterferon and ribavirin combination therapy.
The standard of care for treating hepatitis C is alpha interferon and oral Rebetol, which evokes a response in about 40% of patients, according to the FDA.
With the FDA approval of PEGINTRON and REBETOL combination therapy for this new indication, U.
The results of this study demonstrate that retreatment with PEGINTRON and REBETOL combination therapy may help address this unmet medical need in this difficult-to-treat patient population.
REBETOL is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity.
The response rate with Peg-Intron and Rebetol was 46% among patients infected with the genotype 1 form of hepatitis C virus, the most difficult strain to eliminate (INTERNAL MEDICINE NEWS, July 15, 2001, p.
PEG-INTRON and REBETOL combination therapy is the first and only pegylated interferon-based combination therapy approved in Japan.