RIBAVIRIN

RIBAVIRIN (rye-ba-vye'rin) Virazole, Rebetol, Copegus, Ribasphere Classifications: antiviral agent; Therapeutic: antiviral Prototype: Acyclovir Pregnancy Category: X

Availability

6 g/100 mL vial; 200 mg tablets; 200 mg capsules; 40 mg/mL oral solution

Action

Synthetic nucleoside with broad-spectrum antiviral activity against DNA and RNA viruses. Mode is believed to involve multiple mechanisms including selective interference with viral ribonucleic protein synthesis.

Therapeutic Effect

Active against many RNA and DNA viruses, including respiratory syncytial virus (RSV), influenza A and B, parainfluenza, measles, mumps, Lassa fever, enterovirus 72 (formerly called hepatitis A), yellow fever, HIV, herpes simplex virus (HSV-1 and HSV-2), and vaccinia.

Uses

Aerosol treatment of carefully selected hospitalized infants and young children with severe lower respiratory tract infection caused by respiratory syncytial virus (RSV). Oral used in combination with interferon-alfa to treat hepatitis C and in combination with peginterferon alpha for treatment of hepatitis C in patients coinfected with HIV.

Unlabeled Uses

Prophylaxis and treatment of influenza A and B, pneumonia caused by adenovirus; Lassa fever, measles, HSV-1, HSV-2, hepatitis A, herpes zoster, and for carefully selected patients with AIDS and AIDS-related complex (ARC).

Contraindications

Mild RSV infections of lower respiratory tract; infants requiring simultaneous assisted ventilation; severe cardiovascular disease, congestive heart failure, angina, unstable cardiac disease; pancreatitis, prolonged or multiple courses of ribavirin inhalation therapy; autoimmune hepatitis; renal failure, or Cl_cr <50 mL/min; hemoglobinopathy, thalassemia major, sickle cell disease; pregnancy (category X), lactation; tablet form for children <18 y.

Cautious Use

COPD, asthma; anemia; history of MI, cardiac arrhythmias; older adults, decreased renal, hepatic, or cardiac function; respiratory depression; history of depression or suicidal tendencies.

Route & Dosage

RSV Child: Inhalation 20 mg via SPAG nebulizer administered over 12–18 h/d for a minimum of 3 d (max: 7 d) Hepatitis C (in combination with interferon-alfa) Adult: PO >75 kg, 600 mg b.i.d. for 24–48 wk; <75 kg, 400 mg in a.m., 600 mg in p.m. for 24–48 wk Child: PO >3 y, >75 kg, 600 mg b.i.d.; 62–75 kg, 400 mg in a.m., 600 mg in p.m.; 50–61 kg, 400 mg b.i.d.; 37–49 kg, 200 mg in a.m. and 400 mg in p.m.; 25–36 kg, 200 mg b.i.d. for 24–48 wk Renal Impairment Clcr <50 mL/min: oral ribavirin should not be used

Administration

Note: Aerosol solution is prepared with either sterile water for injection or sterile water for inhalation, without preservatives or any other added substance. See manufacturer's package insert for preparation directions. Inspect solution for discoloration or presence of particulate matter. Discard discolored or cloudy solutions.

Inhalation

• Administer only by SPAG-2 aerosol generator, following manufacturer's directions.
• Caution: Ribavirin has demonstrated teratogenicity in animals. Advise pregnant health care personnel of the potential teratogenic risks associated with exposure during ribavirin administration to patients.
• Do not give other aerosol medication concomitantly with ribavirin.
• Discard solution in the SPAG-2 reservoir at least q24h and whenever liquid level is low before fresh reconstituted solution is added.
• Store unopened vial in a dry place at 15°–25° C (59°–78° F) unless otherwise directed.
• Following reconstitution, store solution at 20°–30° C (68°–86° F) for 24 h.

Adverse Effects (≥1%)

CV: Hypotension (faintness, light-headedness, unusual fatigue), MI, cardiac arrest. Special Senses: Conjunctivitis, erythema of eyelids. Hematologic: Reticulocytosis, hemolytic anemia (especially in combination with interferon alpha). Respiratory: Deterioration of respiratory function, dyspnea, apnea, chest soreness, bacterial pneumonia, ventilator dependence. GI: Transient increases in AST, ALT, bilirubin; abdominal cramps, jaundice.

Interactions

Drug: Ribavirin may antagonize the antiviral effects of zidovudine against HIV; increased risk of fetal defects with peginterferon.

Pharmacokinetics

Absorption: Rapidly absorbed orally (44%) and systemically from lungs. Peak: Inhaled 60–90 min. PO 1.7–3 h. Distribution: Crosses placenta; distributed into breast milk. Metabolism: In cells to an active metabolite. Elimination: 85% in urine, 15% in feces. Half-Life: 24 h in plasma, 16–40 d in RBCs.

Nursing Implications

Assessment & Drug Effects

• Obtain specimens for rapid diagnosis of RSV infection before therapy is initiated or at least during the first 24 h of ribavirin therapy. Do not continue therapy without laboratory confirmation of RSV infection.
• Treatment efficacy in RSV infections appears greatest if initiated within the first 3 d.
• Monitor respiratory function and fluid status closely during therapy. Note baseline rate and character of respirations and pulse. Observe for signs of labored breathing: dyspnea, apnea; rapid, shallow respirations, intercostal and substernal retraction, nasal flaring, limited excursion of lungs, cyanosis. Auscultate lungs for abnormal breath sounds.
• Observe patients requiring simultaneous assisted ventilation closely for S&S of worsening pulmonary function. Check equipment carefully every 2 h, including endotracheal tube, for malfunction. Precipitation of ribavirin and accumulation of fluid in tubing can obstruct the apparatus and cause inadequate ventilation and gas exchange.
• Consult physician about management of fluid and food intake and keep an accurate record of I&O.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug