Virazole

Vir·a·zole (vîr-zl)

A trademark for the drug ribavirin.

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ribavirin Warning - Hazardous drug!

Copegus, Rebetol, Ribasphere, Virazole

Pharmacologic class: Synthetic nucleoside analog

Therapeutic class: Antiviral

Pregnancy risk category X

FDA Boxed Warning

• Ribavirin monotherapy isn't effective in treating chronic hepatitis C infection and shouldn't be used alone for this indication.
• Drug's main clinical toxicity is hemolytic anemia, which may worsen cardiac disease and lead to fatal and nonfatal myocardial infarctions. Don't administer to patients with history of significant or unstable cardiac disease.
• Drug is contraindicated in pregnant women and their male partners. Caution female patients and female partners of male patients receiving ribavirin to use extreme care to avoid pregnancy during therapy and for 6 months afterward.

Action

Unknown. Thought to inhibit RNA and DNA synthesis by depleting nucleotides and blocking replication and maturation of viral cells.

Availability

Capsules: 200 mg

Powder to be reconstituted for inhalation (Virazole): 6 g in 100-ml glass vial

Tablets: 200 mg

⊘Indications and dosages

➣ Chronic hepatitis C infection

Note: Dosage calculated solely on basis of patient's weight.

Adults and children weighing 75 kg (165 lb) or more: 600 mg P.O. q morning and evening, given with interferon alfa-2b

Adults weighing less than 75 kg (165 lb) and children weighing more than 61 kg (134 lb): 400 mg P.O. q morning and 600 mg P.O. q evening, given with interferon alfa-2b

Children weighing 50 to 61 kg (110 to 134 lb): 400 mg P.O. b.i.d., given with interferon alfa-2b

Children weighing 37 to 49 kg (81 to 108 lb): 200 mg P.O. every morning and 400 mg P.O. every evening, given with interferon alfa-2b

Children weighing 25 to 36 kg (55 to 79 lb) : 200 mg P.O. b.i.d., given with interferon alfa-2b

➣ Hospitalized children with severe lower respiratory infection caused by respiratory syncytial virus

Infants and young children: 20 mg/ml by inhalation as a starting solution in Viratek Small Particle Aerosol Generator (SPAG-2) for 12 to 18 hours daily for 3 to 7 days. Give by oxygen hood from SPAG-2 unit to infant who isn't mechanically ventilated.

Dosage adjustment

• Cardiovascular disease
• Chronic obstructive pulmonary disease (COPD)
• Renal impairment
• Hemoglobin below 10 g/dl

Off-label uses

• Influenza A or B
• Pneumonia caused by adenovirus
• Severe lower respiratory tract infection in adults
• Genital herpes
• Hemorrhagic fever

Contraindications

• Hypersensitivity to drug or its components
• Autoimmune hepatitis (oral combination therapy)
• Creatinine clearance below 50 ml/minute
• Significant or unstable cardiac disease
• Hemoglobinopathy (such as sickle cell anemia, thalassemia major)
• Females of childbearing age (inhalation form)
• Pregnancy, pregnant partner of male patient (oral drug)
• Breastfeeding

Precautions

Use cautiously in:
• decompensated hepatic disease, coinfection with hepatitis B or human cdecompensated hepatic disease, coinfection with hepatitis B or human immunodeficiency virus, COPD
• liver or other transplant recipients
• patients who don't respond to interferon.

Administration

☞ Be aware that oral form must be given with interferon alfa-2b injection.
• Give aerosol by Viratek SPAG-2 only. Don't use other aerosol-generating equipment.
• Dilute powder in sterile water for injection. Don't use solutions with antimicrobial ingredients.
• Know that drug may be given by oral or nasal inhalation.
• Discard solution in SPAG-2 every 24 hours before adding new solution.
☞ Avoid prolonged contact with aerosol, which can cause headache or eye irritation.

Route	Onset	Peak	Duration
Oral	Unknown	Unknown	Unknown
Inhalation	Slow	60-90 min	Unknown

Adverse reactions

CNS: fatigue, headache, nervousness, depression, suicidal ideation

CV: hypotension, bradycardia (with inhalation form), cardiac arrest

EENT: conjunctivitis, eyelid erythema or rash

GI: nausea, dyspepsia, anorexia, pancreatitis

Hematologic: reticulocytosis , hemolytic anemia

Respiratory: bacterial pneumonia, pneumothorax, bronchospasm, pulmonary edema, apnea, worsening respiratory status (with inhalation form)

Skin: rash, pruritus

Interactions

Drug-drug. Abacavir, didanosine, lamivudine, stavudine, zalcitabine, zidovudine: potentially fatal lactic acidosis

Stavudine, zidovudine: decreased antiviral activity

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin: increased levels

Hemoglobin: decreased level

Reticulocytes: increased count

Patient monitoring

☞ Carefully monitor patient's respiratory status. Check ventilator often to ensure that drug precipitates don't impede function.
☞ Monitor ECG and vital signs. Watch for hypotension, bradycardia, and other signs of impending cardiac arrest or worsening respiratory condition.
☞ Assess neurologic status. Stay alert for depression and suicidal ideation.
• Monitor liver function tests and CBC with white cell differential.

Patient teaching

• Explain drug delivery system and precautions carefully to patient or to parents of children receiving inhalation form.
☞ Tell patient or parents that drug may cause depression or suicidal thoughts, which should be reported immediately.
☞ Instruct patient or parents to immediately report new or worsening respiratory symptoms.
• Counsel sexually active patients (both males and females) about appropriate birth control. Tell them to use extreme care to avoid pregnancy. Stress importance of using two forms of effective contraception during and for 6 months after treatment (when using oral ribavirin).
• Advise female patient not to breastfeed.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.