FDA label 0296d73b-b2e9-3d84-e063-6294a90aabf8

WARNINGS USE OF AEROSOLIZED RIBAVIRIN FOR INHALATION SOLUTION, USP IN PATIENTS REQUIRING MECHANICAL VENTILATOR ASSISTANCE SHOULD BE UNDERTAKEN ONLY BY PHYSICIANS AND SUPPORT STAFF FAMILIAR WITH THE SPECIFIC VENTILATOR BEING USED AND THIS MODE OF ADMINISTRATION OF THE DRUG. 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 INCREASED PULMONARY PRESSURES (SEE WARNINGS ). SUDDEN DETERIORATION OF RESPIRATORY FUNCTION HAS BEEN ASSOCIATED WITH INITIATION OF AEROSOLIZED RIBAVIRIN FOR INHALATION SOLUTION, USP USE IN INFANTS. RESPIRATORY FUNCTION SHOULD BE CAREFULLY MONITORED DURING TREATMENT. IF INITIATION OF AEROSOLIZED RIBAVIRIN FOR INHALATION SOLUTION, USP TREATMENT APPEARS TO PRODUCE SUDDEN DETERIORATION OF RESPIRATORY FUNCTION, TREATMENT SHOULD BE STOPPED AND REINSTITUTED ONLY WITH EXTREME CAUTION, CONTINUOUS MONITORING AND CONSIDERATION OF CONCOMITANT ADMINISTRATION OF BRONCHODILATORS (SEE WARNINGS ). RIBAVIRIN FOR INHALATION SOLUTION, USP IS NOT INDICATED FOR USE IN ADULTS. PHYSICIANS AND PATIENTS SHOULD 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) (SEE CONTRAINDICATIONS ).

WARNINGS SUDDEN DETERIORATION OF RESPIRATORY FUNCTION HAS BEEN ASSOCIATED WITH INITIATION OF AEROSOLIZED RIBAVIRIN FOR INHALATION SOLUTION, USP USE IN INFANTS. Respiratory function should be carefully monitored during treatment. If initiation of aerosolized Ribavirin for Inhalation Solution, USP treatment appears to produce sudden deterioration of respiratory function, treatment should be stopped and reinstituted only with extreme caution, continuous monitoring, and consideration of concomitant administration of bronchodilators. Use with Mechanical Ventilators USE OF AEROSOLIZED RIBAVIRIN FOR INHALATION SOLUTION, USP IN PATIENTS REQUIRING MECHANICAL VENTILATOR ASSISTANCE SHOULD BE UNDERTAKEN ONLY BY PHYSICIANS 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 increased pulmonary pressures. These procedures include the use of bacteria filters in series in the expiratory limb of the ventilator circuit with frequent changes (every 4 hours), water column pressure release valves to indicate elevated ventilator pressures, frequent monitoring of these devices and verification that ribavirin crystals have not accumulated within the ventilator circuitry, and frequent suctioning and monitoring of the patient (see Description of Studies ). Those administering aerosolized Ribavirin for Inhalation Solution, USP in conjunction with mechanical ventilator use should be thoroughly familiar with detailed descriptions of these procedures as outlined in the SPAG-2 Instructions for Use.

ADVERSE REACTIONS The description of adverse reactions is based on events from clinical studies (approximately 200 patients) conducted prior to 1986, and the controlled trial of aerosolized Ribavirin for Inhalation Solution, USP conducted in 1989-1990. Additional data from spontaneous post-marketing reports of adverse events in individual patients have been available since 1986. Deaths Deaths during or shortly after treatment with aerosolized Ribavirin for Inhalation Solution, USP have been reported in 20 cases of patients treated with Ribavirin for Inhalation Solution, USP (12 of these patients were being treated for RSV infections). Several cases have been characterized as "possibly related" to Ribavirin for Inhalation Solution, USP by the treating physician; these were in infants who experienced worsening respiratory status related to bronchospasm while being treated with the drug. Several other cases have been attributed to mechanical ventilator malfunction in which Ribavirin for Inhalation Solution, USP precipitation within the ventilator apparatus led to excessively high pulmonary pressures and diminished oxygenation. In these cases the monitoring procedures described in the current package insert were not employed (see Description of Studies , WARNINGS , and DOSAGE AND ADMINISTRATION ). Pulmonary and Cardiovascular Pulmonary function significantly deteriorated during aerosolized Ribavirin for Inhalation Solution, USP treatment in six of six adults with chronic obstructive lung disease and in four of six asthmatic adults. Dyspnea and chest soreness were also reported in the latter group. Minor abnormalities in pulmonary function were also seen in healthy adult volunteers. In the original study population of approximately 200 infants who received aerosolized Ribavirin for Inhalation Solution, USP, several serious adverse events occurred in severely ill infants with lifethreatening underlying diseases, many of whom required assisted ventilation. The role of Ribavirin for Inhalation Solution, USP in these events is indeterminate. Since the drug's approval in 1986, additional reports of similar serious, though non-fatal, events have been filed infrequently. Events associated with aerosolized Ribavirin for Inhalation Solution, USP use have included the following: Pulmonary Worsening of respiratory status, bronchospasm, pulmonary edema, hypoventilation, cyanosis, dyspnea, bacterial pneumonia, pneumothorax, apnea, atelectasis and ventilator dependence. Cardiovascular Cardiac arrest, hypotension, bradycardia and digitalis toxicity. Bigeminy, bradycardia and tachycardia have been described in patients with underlying congenital heart disease. Some subjects requiring assisted ventilation experienced serious difficulties, due to inadequate ventilation and gas exchange. Precipitation of drug within the ventilatory apparatus, including the endotracheal tube, has resulted in increased positive end expiratory pressure and increased positive inspiratory pressure. Accumulation of fluid in tubing ("rain out") has also been noted. Measures to avoid these complications should be followed carefully (see DOSAGE AND ADMINISTRATION ). Hematologic Although anemia was not reported with use of aerosolized Ribavirin for Inhalation Solution, USP in controlled clinical trials, most infants treated with the aerosol have not been evaluated 1 to 2 weeks post-treatment when anemia is likely to occur. Anemia has been shown to occur frequently with experimental oral and intravenous Ribavirin for Inhalation Solution, USP in humans. Also, cases of anemia (type unspecified), reticulocytosis and hemolytic anemia associated with aerosolized Ribavirin for Inhalation Solution, USP use have been reported through post-marketing reporting systems. All have been reversible with discontinuation of the drug. Other Rash and conjunctivitis have been associated with the use of aerosolized Ribavirin for Inhalation Solution, USP. These usually resolve within hours of discontinuing therapy. Seizures and asthenia associated with experimental intravenous Ribavirin for Inhalation Solution, USP therapy have also been reported. Adverse Events in Health Care Workers Studies of environmental exposure to aerosolized Ribavirin for Inhalation Solution, USP in health care workers administering care to patients receiving the drug have not detected adverse signs or symptoms related to exposure. However, 152 health care workers have reported experiencing adverse events through post-marketing surveillance. Nearly all were in individuals providing direct care to infants receiving aerosolized Ribavirin for Inhalation Solution, USP. Of 358 events from these 152 individual health care worker reports, the most common signs and symptoms were headache (51% of reports), conjunctivitis (32%), and rhinitis, nausea, rash, dizziness, pharyngitis, or lacrimation (10-20% each). Several cases of bronchospasm and/or chest pain were also reported, usually in individuals with known underlying reactive airway disease. Several case reports of damage to contact lenses after prolonged close exposure to aerosolized Ribavirin for Inhalation Solution, USP have also been reported. Most signs and symptoms reported as having occurred in exposed health care workers resolved within minutes to hours of discontinuing close exposure to aerosolized Ribavirin for Inhalation Solution, USP (also see Information for Health Care Personnel ). The symptoms of RSV in adults can include headache, conjunctivitis, sore throat and/or cough, fever, hoarseness, nasal congestion and wheezing, although RSV infections in adults are typically mild and transient. Such infections represent a potential hazard to uninfected hospital patients. It is unknown whether certain symptoms cited in reports from health care workers were due to exposure to the drug or infection with RSV. Hospitals should implement appropriate infection control procedures. To report SUSPECTED ADVERSE REACTIONS, contact Cameron Pharmaceuticals at 1-888-767-7913 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.