Terbutaline (Terbutaline Sulfate) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Monoamine Oxidase Inhibitors and Tricyclic Antidepressants

Terbutaline sulfate should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, since the action of terbutaline sulfate on the vascular system may be potentiated.

Beta-Blockers

Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists, such as terbutaline sulfate, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

Diuretics

The ECG changes and/or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the co-administration of beta-agonists with non-potassium sparing diuretics.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year study in Sprague-Dawley rats, terbutaline sulfate caused a significant and dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 50 mg/kg, and above (approximately 25 times the maximum recommended daily oral dose for adults on a mg/m² basis). In a 21-month study in CD-1 mice, terbutaline sulfate showed no evidence of tumorigenicity at dietary doses up to 200 mg/kg (approximately 55 times the maximum recommended daily oral dose for adults on a mg/m² basis). The mutagenicity potential of terbutaline sulfate has not been determined.

Reproduction studies in rats using terbutaline sulfate demonstrated no impairment of fertility at oral doses up to 50 mg/kg (approximately 25 times the maximum recommended daily oral dose for adults on a mg/m² basis).

Pregnancy

Teratogenic Effects

Pregnancy Category B

A reproduction study in Sprague-Dawley rats revealed terbutaline sulfate was not teratogenic when administered at oral doses of 50 mg/kg (approximately 25 times the maximum recommended daily oral dose for adults on a mg/m² basis). A reproduction study in New Zealand white rabbits revealed terbutaline sulfate was not teratogenic when administered at oral doses up to 50 mg/kg (approximately 55 times the maximum recommended daily oral dose for adults on a mg/m² basis).

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (See PRECAUTIONS, Tocolysis).

OVERDOSAGE

The median subcutaneous lethal dose of terbutaline sulfate in mature rats is approximately 165 mg/kg (approximately 90 times the maximum recommended daily oral dose for adults on a mg/m² basis). The median subcutaneous lethal dose of terbutaline sulfate in young rats is approximately 2000 mg/kg (approximately 1100 times the maximum recommended daily oral dose for adults on a mg/m² basis).

The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS, e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Hypokalemia may also occur.

There is no specific antidote. Treatment consists of discontinuation of terbutaline sulfate together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of terbutaline sulfate.

In the alert patient who has taken excessive oral medication, the stomach should be emptied by induced emesis followed by lavage. In the unconscious patient, the airway should be secured with a cuffed endotracheal tube before lavage, and emesis should not be induced. Instillation of activated charcoal slurry may help reduce absorption of terbutaline. Adequate respiratory exchange should be maintained, and cardiac and respiratory support provided as needed. The patient should be monitored until signs and symptoms of overdosage have subsided.

CONTRAINDICATIONS

Terbutaline sulfate is contraindicated in patients known to be hypersensitive to sympathomimetic amines or any component of this drug product.