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Ribavirin (oral inhalation): Drug information

Ribavirin (oral inhalation): Drug information
(For additional information see "Ribavirin (oral inhalation): Patient drug information" and see "Ribavirin (oral inhalation): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Appropriate use:

Use of ribavirin in patients requiring mechanical ventilator assistance should be undertaken only by health care providers and support staff familiar with this mode of administration and the specific ventilator being used. Strict attention must be paid to procedures that have been shown to minimize the accumulation of drug precipitate, which can result in mechanical ventilator dysfunction and associated increases in pulmonary pressures.

Sudden deterioration of respiratory function has been associated with the initiation of ribavirin use in infants. Carefully monitor respiratory function during treatment. If the initiation of ribavirin treatment appears to produce sudden deterioration of respiratory function, stop treatment and reinstitute only with extreme caution, continuous monitoring, and consideration of coadministration of bronchodilators.

Aerosolized ribavirin is not indicated for use in adults. Be aware that ribavirin has been shown to produce testicular lesions in rodents and to be teratogenic in all animal species in which adequate studies have been conducted (rodents and rabbits).

Brand Names: US
  • Virazole
Brand Names: Canada
  • Virazole
Pharmacologic Category
  • Antiviral Agent
Dosing: Adult
Respiratory syncytial virus infection in hematopoietic cell or heart/lung transplant recipients

Respiratory syncytial virus infection in hematopoietic cell or heart/lung transplant recipients (off-label use): Note: May use in combination with intravenous immune globulin (IGIV), methylprednisolone, and palivizumab. Dosage and protocol may be institution-specific (Boeckh 2007; Chemaly 2006; Liu 2010; Shah 2013; Whimbey 1995). Pretreatment with albuterol may be necessary (Hynicka 2012).

Oral inhalation:

Mechanically-ventilated patients: Continuous dosing: 6 g over 12 to 18 hours daily (Chemlay 2006; Ghosh 2000; Hynicka 2012; Shah 2013; Whimbey 1995)

Non-mechanically-ventilated patients: Intermittent dosing: 2 g (over 2 to 4 hours) every 8 hours (Boeckh 2007; Hynicka 2012; Liu 2010) or 6 g (over 2 to 6 hours) every 6 to 8 hours via a small particle aerosol generator (SPAG-2) nebulizer (mask or hood) (Chemlay 2006; Ghosh 2000; Shah 2013; Trang 2018)

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Ribavirin (oral inhalation): Pediatric drug information")

Respiratory syncytial virus infection

Respiratory syncytial virus (RSV) infection: Note: Due to lack of clinically significant effect on outcomes, the AAP recommends against routine use of ribavirin to treat RSV. Additionally, concerns exist regarding cost and potential toxicity in exposed health care personnel (Red Book [AAP 2018]).

Aerosol inhalation: Note: Dose actually delivered to the patient will depend on patient's minute ventilation.

Continuous aerosolization: Infants and Children: 6 g administered over 12 to 18 hours/day for 3 to 7 days using Bausch Health small particle aerosol generator (SPAG-2).

Intermittent aerosolization: Very limited data available: Infants, Children, and Adolescents: 2,000 mg over 2 to 3 hours 3 times daily for 2 to 10 days has been used to permit easier accessibility for patient care and limit environmental exposure of health care workers (Chemaly 2014; Dallas 2020; Englund 1994). Utilization of the SPAG-2 is the most common method of administration; however, use of a vibrating mesh micropump nebulizer (Aerogen Solo) has also been described (Dallas 2020; Walsh 2016).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Bigeminy, bradycardia, chest pain, hypotension, tachycardia

Dermatologic: Skin rash

Ophthalmic: Conjunctivitis

Respiratory: Apnea, atelectasis, bacterial pneumonia, bronchospasm, cyanosis, dyspnea, hypoventilation, pneumothorax, pulmonary complications (ventilator dependence), pulmonary edema, severe dyspnea (worsening of respiratory status)

<1%, postmarketing, and/or case reports: Anemia, hemolytic anemia, reticulocytosis

Contraindications

Hypersensitivity to ribavirin or any component of the formulation; women who are pregnant or may become pregnant

Warnings/Precautions

Concerns related to adverse effects:

• Respiratory deterioration: [US Boxed Warning]: Sudden respiratory deterioration has been observed during the initiation of aerosolized ribavirin in infants; carefully monitor during treatment. If deterioration of respiratory function occurs, stop treatment; reinstitute with extreme caution, continuous monitoring, and consider concomitant administration of bronchodilators.

Special populations:

• Pregnancy: [US Boxed Warning]: Significant teratogenic and/or embryocidal effects have been observed in all animal species with adequate studies. Use is contraindicated in pregnant women.

Dosage form specific issues:

• Inhalation: [US Boxed Warning]: Use with caution in patients requiring assisted ventilation because precipitation of the drug in the respiratory equipment may interfere with safe and effective patient ventilation; sudden deterioration of respiratory function has been observed; monitor carefully in patients with COPD and asthma for deterioration of respiratory function.

Warnings: Additional Pediatric Considerations

Sudden respiratory deterioration has been observed during the initiation of aerosolized ribavirin in infants; carefully monitor infants. If deterioration of respiratory function occurs, stop treatment; reinstitute with extreme caution, continuous monitoring, and consider concomitant administration of bronchodilators.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Inhalation:

Generic: 6 g (1 ea)

Solution Reconstituted, Inhalation [preservative free]:

Virazole: 6 g (1 ea)

Generic: 6 g (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (reconstituted) (Ribavirin Inhalation)

6 g (per each): $24,000.00 - $27,600.00

Solution (reconstituted) (Virazole Inhalation)

6 g (per each): $29,953.50

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Inhalation:

Virazole: 6 g (1 ea)

Administration: Adult

Oral inhalation: Ribavirin should be administered in well-ventilated rooms (at least 6 air changes/hour). In mechanically ventilated patients, ribavirin can potentially be deposited in the ventilator delivery system depending on temperature, humidity, and electrostatic forces; this deposition and drug precipitation can lead to malfunction or obstruction of the expiratory valve, resulting in inadvertently high positive end-expiratory pressures. The use of one-way valves in the inspiratory lines, a breathing circuit filter in the expiratory line, and frequent monitoring and filter replacement have been effective in preventing these problems. Solutions in SPAG-2 unit should be discarded at least every 24 hours and when the liquid level is low before adding newly reconstituted solution. Should not be mixed with other aerosolized medications. Environmental services/infection control should be notified of ribavirin inhaled administration to any patient. The manufacturer recommends that pregnant health care workers take precautions to limit exposure to ribavirin aerosol.

Administration: Pediatric

Inhalation: Aerosolize with Bausch Health small particle aerosol generator (SPAG-2). Ribavirin should be administered in negative-pressure or other well-ventilated rooms (at least 6 air changes/hour). Additional precautions to limit exposure to health care personnel include the use of scavenging devices or respirator masks and turning off the aerosolizer for 5 to 10 minutes prior to prolonged patient contact. Solutions in SPAG-2 unit should be discarded at least every 24 hours and when the liquid level is low before adding newly reconstituted solution. Should not be mixed with other aerosolized medication.

The manufacturer recommends that pregnant health care workers take precautions to limit exposure to ribavirin aerosol.

Continuous inhalation:

Non-mechanically ventilated patients: Administer via an infant oxygen hood; if not available, may use an oxygen tent or face mask.

Mechanically ventilated patients: Ribavirin can potentially be deposited in the ventilator delivery system, which can lead to mechanical ventilator dysfunction and increased pulmonary pressures. To minimize accumulation of drug precipitate, use and frequently change (every 4 hours) filters in the expiratory line, use water column pressure release valves, frequently monitor devices, and verify that ribavirin crystals have not accumulated within circuit. Endotracheal tubes should be suctioned every 1 to 2 hours and pulmonary pressures should be monitored every 2 to 4 hours.

Intermittent inhalation: Utilization of the SPAG-2 as described above is the most common method of administration; however, use of a vibrating mesh micropump nebulizer (Aerogen Solo) has also been described (Dallas 2020; Walsh 2016).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 3]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.

NIOSH recommends double gloving, a protective gown, and ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator) for preparation; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if liquid that could splash) eye/face protection for administration of a powder or solution for inhalation or an aerosol treatment; if there is potential for inhalation, respiratory protections is recommended (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

Use: Labeled Indications

Respiratory syncytial virus: Treatment of hospitalized infants and young children with respiratory syncytial virus (RSV) infections with efficacy possibly increased in early course therapy; treatment of severe lower respiratory tract RSV infections in patients with an underlying compromising condition (prematurity, cardiopulmonary disease, or immunosuppression)

Use: Off-Label: Adult

Respiratory syncytial virus infection in hematopoietic cell or heart/lung transplant recipients

Medication Safety Issues
Sound-alike/look-alike issues:

Ribavirin may be confused with riboflavin, rifAMPin, Robaxin

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

AzaTHIOprine: Ribavirin (Oral Inhalation) may increase serum concentrations of the active metabolite(s) of AzaTHIOprine. Specifically, concentrations of potentially myelotoxic methylated metabolites may be increased, while concentrations of active 6-thioguanine nucleotides may be decreased. Management: Consider using alternative agent(s) when possible. When these drugs are used in combination, monitor patients extra closely for signs/symptoms of myelosuppression. Risk D: Consider therapy modification

Didanosine: Ribavirin (Oral Inhalation) may enhance the adverse/toxic effect of Didanosine. Ribavirin (Oral Inhalation) may increase serum concentrations of the active metabolite(s) of Didanosine. Risk X: Avoid combination

Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid administration of live influenza virus vaccine (LAIV) within 2 weeks before or 48 hours after administration of antiviral agents. Consider avoiding LAIV if peramivir was given within the last 5 days or baloxavir was given within the last 17 days. Risk D: Consider therapy modification

Interferons (Alfa): May enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Hemolytic anemia has been observed. Risk C: Monitor therapy

Zidovudine: May enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Risk D: Consider therapy modification

Reproductive Considerations

Use is contraindicated in females who may become pregnant.

Pregnancy Considerations

Use is contraindicated in females who are pregnant. [US Boxed Warning]: Aerosolized ribavirin is not indicated for use in adults. Be aware that ribavirin has been shown to produce testicular lesions in rodents and to be teratogenic in all animal species in which adequate studies have been conducted (rodents and rabbits). The manufacturer recommends that pregnant health care workers take precautions to limit exposure to ribavirin aerosol; potential occupational exposure may be greatest if administration is via oxygen tent or hood, and lower if administered via mechanical ventilation. The minimum interval following exposure to ribavirin inhalation prior to pregnancy is not known.

Breastfeeding Considerations

It is not known if ribavirin is excreted in breast milk.

Monitoring Parameters

Respiratory function, hemoglobin, reticulocyte count, CBC with differential

Mechanism of Action

Inhibits replication of RNA and DNA viruses; inhibits influenza virus RNA polymerase activity and inhibits the initiation and elongation of RNA fragments resulting in inhibition of viral protein synthesis

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Inhalation: Systemic; dependent upon respiratory factors and method of drug delivery; maximal absorption occurs with the use of aerosol generator via endotracheal tube; highest concentrations in respiratory tract and erythrocytes

Metabolism: Occurs intracellularly and may be necessary for drug action; metabolized hepatically to deribosylated ribavirin (active metabolite)

Bioavailability: Oral: 64%

Half-life elimination:

Respiratory tract secretions: Infants and Children 6 weeks to 7 years: ~2 hours (Englund 1990)

Plasma: Infants and Children: Inhalation: 9.5 hours

Time to peak, serum: Inhalation: At end of inhalation period

Excretion: Inhalation: Urine (40% as unchanged drug and metabolites)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (NL) Netherlands: Virazole
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.
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