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

• Respiratory syncytial virus:

  • It is used in the treatment of hospitalized infants and young children with respiratory syncytial virus (RSV) infections
  • It is specially indicated for the treatment of severe lower respiratory tract RSV infections in patients with an underlying compromising condition (prematurity, cardiopulmonary disease, or immunosuppression)

• Off Label Usage of Ribavirin in Adults:

  • It is used in the treatment of RSV in adult hematopoietic stem cell or heart/lung transplant recipients

Ribavirin Dose in Adults

Off Label dosage of Virazole in the treatment of RSV infection in hematopoietic cell or heart/lung transplant recipients :

• Aerosol inhalation:

  • It is sued for RSV infection in hematopoietic cell or heart/lung transplant recipients
  • It is given as 2 g (over 2 hours) every 8 hours

Ribavirin Dose in Childrens

Virazole dosage in the treatment of RSV infection:

• Due to toxic effects of exposed healthcare workers and variable efficacy results in trials, the AAP recommends against routine use of ribavirin to treat RSV
• Its use should be reserved for patients with documented, potentially life-threatening disease.

• Infants and Children:

  • Aerosol inhalation:
    • It should be used with Viratek small particle aerosol generator (SPAG-2).
    • The dose is actually delivered to the patient will depend on the patient's minute ventilation.

• Continuous aerosolization:

  • 6 g is administered over 12 to 18 hours/day for 3 to 7 days

• Intermittent aerosolization:

  • 2,000 mg is given over 2 hours 3 times daily in nonmechanically ventilated patients for 3 to 7 days
  • It has been used to permit easier accessibility for patient care and limit the environmental exposure of health care workers.
  • Because of the apparent increased potential for crystallization of the high-dose 60 mg/mL solution around areas of turbulent flow such as bends in tubing or connector pieces, use of high-dose therapy in individuals with an endotracheal tube in place is not recommended.

Pregnancy Risk Factor: X

• Females who might become pregnant or are currently pregnant should not use this medication.
• Adults should not use aerosolized ribavirin.
• Ribavirin has been shown to cause testicular lesions and be teratogenic in rodents.
• The manufacturer recommends pregnant health care workers to take precautions to reduce their exposure to ribavirin aerosol.
• Potential occupational exposure is greatest when administered via an oxygen tent or hood. It can also be lower if administered using mechanical ventilation.
• It is unknown what the minimum time interval after ribavirin inhalation prior to pregnancy is.

Ribavirin use during breastfeeding:

• It is unknown if ribavirin excreted in breastmilk or not.

Ribavirin Dose in Kidney Disease:

• There are no dosage adjustments given in the manufacturer's labeling

Ribavirin Dose in Liver Disease:

• There are no dosage adjustments given in the manufacturer's labeling

Side effects of Inhalational Ribavirin (Virazole):

• 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)

Contraindication to Ribavirin Include:

• Hypersensitivity to ribavirin and any component of the formulation
• Women who may be pregnant or are currently pregnant with a baby

Warnings and Precautions

• Respiratory deterioration
  • Sudden respiratory deterioration was observed in infants who received aerosolized Ribavirin. Be sure to monitor your child during treatment.
  • Stop treatment if your respiratory function is declining
  • Reintroduce with extreme caution and continuous monitoring. Consider concomitant administrations of bronchodilators.

Ribavirin (oral inhalation): Drug Interaction

Monitor:

• Respiratory function
• hemoglobin
• reticulocyte count
• CBC with differential
• I & O

How to administer Ribavirin?

Inhalation:

• Ribavirin should be given in well-ventilated rooms (at least 6 air changes/hour).
• In mechanically-ventilated patients, ribavirin can potentially  deposit in the ventilator delivery system depending on temperature, humidity, and electrostatic forces
• this deposition can cause 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 useful in preventing these problems.
• Solutions in the SPAG-2 unit should be discarded at least every day and when the liquid level is low before adding the newly reconstituted solution.
• It should not be mixed with other aerosolized medication.

Mechanism of action of Ribavirin:

• It prevents the replication of RNA viruses and DNA viruses
• It also inhibits influenza virus' RNA polymerase activity, and inhibits initiation and extension of RNA fragments. This results in inhibition of viral protein production

Absorption:

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

Metabolism:

• It occurs intracellularly and may be necessary for drug action
• It is metabolized hepatically to deribosylated ribavirin (active metabolite)

Bioavailability:

• Orally is 64%

Half-life elimination:

• Respiratory tract secretions:
• in Infants and Children (6 weeks to 7 years) it takes almost 2 hours
• Plasma:
• In Infants and Children,  Inhalation takes 9.5 hours

Time to peak, serum:

• Inhalation: At the end of the inhalation period

Excretion:

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

International Brands of Ribavirin:

• Virazole
• Viramid
• Virazide
• Virazol
• Virazole

Ribavirin Brands in Pakistan:

Inhalational ribavirin is not available in Pakistan.