PRECAUTIONS General Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias and hypertension, in patients with convulsive disorders, hyperthyroidism or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines. Large doses of intravenous albuterol have been reported to aggravate pre-existing diabetes mellitus and ketoacidosis. As with other beta-agonists, inhaled and intravenous albuterol may produce a significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation. Repeated dosing with 0.15 mg/kg of albuterol inhalation solution in children aged 5 to 17 years who were initially normokalemic has been associated with an asymptomatic decline of 20% to 25% in serum potassium levels. Information for Patients The action of albuterol sulfate inhalation solution may last up to six hours, and therefore it should not be used more frequently than recommended. Do not increase the dose or frequency of medication without medical consultation. If symptoms get worse, medical consultation should be sought promptly. While taking albuterol sulfate inhalation solution, other anti-asthma medicines should not be used unless prescribed. Drug compatibility (physical and chemical), efficacy, and safety of albuterol inhalation solution when mixed with other drugs in a nebulizer have not been established. See illustrated Patient's Instructions for Use . Drug Interactions Other sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol. Albuterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of albuterol on the vascular system may be potentiated. Beta-receptor blocking agents and albuterol inhibit the effect of each other. Carcinogenesis, Mutagenesis, Impairment of Fertility Albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium in a 2-year study in the rat, at oral doses of 2, 10, and 50 mg/kg, corresponding to 10, 50, and 250 times, respectively, the maximum nebulization dose for a 50 kg human. In another study, this effect was blocked by the coadministration of propranolol. The relevance of these findings to humans is not known. An 18-month study in mice and a lifetime study in hamsters revealed no evidence of tumorigenicity. Studies with albuterol revealed no evidence of mutagenesis. Reproduction studies in rats revealed no evidence of impaired fertility. Pregnancy Teratogenic Effects Pregnancy Category C Albuterol has been shown to be teratogenic in mice when given subcutaneously in doses corresponding to 1.25 times the human nebulization dose (based on a 50 kg human). There are no adequate and well-controlled studies in pregnant women. Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. A reproduction study in CD-1 mice with albuterol (0.025, 0.25, and 2.5 mg/kg subcutaneously, corresponding to 0.125, 1.25, and 12.5 times the maximum human nebulization dose, respectively) showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg. None were observed at 0.025 mg/kg. Cleft palate also occurred in 22 of 72 (30.5%) fetuses treated with 2.5 mg/kg isoproterenol (positive control). A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses at 50 mg/kg, corresponding to 250 times the maximum nebulization dose for a 50-kg human. During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been rarely reported in the offspring of patients being treated with albuterol. Some of the mothers were taking multiple medications during their pregnancies. No consistent pattern of defects can be discerned, and a relationship between albuterol use and congenital anomalies has not been established. Labor and Delivery Oral albuterol has been shown to delay preterm labor in some reports. There are presently no well-controlled studies that demonstrate that it will stop preterm labor or prevent labor at term. Therefore, cautious use of albuterol sulfate inhalation solution is required in pregnant patients when given for relief of bronchospasm so as to avoid interference with uterine contractibility. Nursing Mothers It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and effectiveness of albuterol sulfate inhalation solution have been established in children 2 years of age or older. Use of albuterol sulfate inhalation solution in these age groups is supported by evidence from adequate and well-controlled studies of albuterol sulfate inhalation solution in adults; the likelihood that the disease course, pathophysiology, and the drug's effect in pediatric and adult patients are substantially similar; and published reports of trials in pediatric patients 3 years of age or older. The recommended dose for the pediatric population is based upon three published dose comparison studies of efficacy and safety in children 5 to 17 years, and on the safety profile in both adults and pediatric patients at doses equal to or higher than the recommended doses. The safety and effectiveness of albuterol sulfate inhalation solution in children below 2 years of age have not been established.