rye-ba-VYE-rin

Therapeutic Classification: antivirals

Pharmacologic Classification: nucleoside analogues

• Inhaln: Treatment of severe lower respiratory tract infections caused by the respiratory syncytial virus (RSV) in infants and young children.
• PO: Treatment of chronic hepatitis C in patients with compensated liver disease who have not previously been treated with interferon alfa.

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

• Inhaln: Virustatic action.
• PO: Decreased progression and sequelae of chronic hepatitis C.

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/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).

(blood levels)

Contraindicated in:

• Hypersensitivity
• Patients receiving mechanically assisted ventilation
• CCr <50 mL/min
• Significant/unstable cardiovascular disease
• Hemoglobinopathies
• Autoimmune hepatitis or hepatic decompensation before/during treatment
• Concurrent use of didanosine, stavudine, or zidovudine
• OB: Pregnancy (may cause fetal harm)
• OB: Male partners of pregnant patients.

Use Cautiously in:

• Sarcoidosis (may exacerbate condition)
• Anemia (dose reduction/discontinuation may be required)
• Any pre-existing cardiac disease
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Women of reproductive potential and men with female partners of reproductive potential
• Pedi: May result in ↓ growth in children.

Inhalation

CV: CARDIAC ARREST, hypotension.

Derm: rash.

EENT: blurred vision, conjunctivitis, erythema of the eyelids, ocular irritation, photosensitivity.

Hemat: hemolytic anemia, reticulocytosis.

Oral

CNS: HOMICIDAL IDEATION, SUICIDAL IDEATION/ATTEMPTS, depression, aggressive behavior, emotional lability (↑ in children), fatigue (↓ in children), impaired concentration (↓ in children), insomnia (↓ in children), irritability (↓ in children).

Derm: pruritus (↓ in children).

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

GI: anorexia (↑ in children), dyspepsia (↓ in children), vomiting (↑ in children).

GU: ↓fertility (males).

Hemat: hemolytic anemia.

MS: arthralgia (↓ in children).

Neuro: dizziness, faintness.

Resp: dyspnea (↓ in children).
Misc: fever (↑ in children).

Drug-Drug:

• 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.

RSV Infection

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

Chronic Hepatitis C

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

(Generic available)

• Capsules: 200 mg;
• Powder for reconstitution for aerosol use (Virazole): 6 g/vial;
• Tablets: 200 mg; 400 mg; 600 mg;

• 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 for signs of neuropsychiatric disorders (irritability, anxiety, depression, suicidal ideation, aggressive behavior). May require discontinuation of ribavirin.
  • 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 and symptoms of 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.

• Chronic Hepatitis C:Verify negative pregnancy test before starting therapy, periodically during therapy and for 6 mo after final dose.
  • Monitor CBC with differential and platelet count prior to initiation, at wk 2, and wk 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.
  • May cause ↑ serum bilirubin and uric acid levels.

• Inhaln: 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.
• PO: Administer with food.
  • For children, determine if child is able to swallow 200-mg tablet.

• 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. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
  • 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.
  • Discuss with patient the possibility of hair loss. Explore methods of coping.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • 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 of reproductive potential, and men with female partners of reproductive potential, 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 therapy.
  • Emphasize the importance of routine lab test to monitor for side effects.

• 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.

Copegus, Rebetol, Virazole

Ibavyr

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