BRETHINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BRETHINE (BRETHINE).
Beta-2 adrenergic receptor agonist; stimulates adenylate cyclase, increasing intracellular cAMP, leading to relaxation of bronchial smooth muscle and inhibition of mast cell mediator release.
| Metabolism | Primarily hepatic via sulfation; also undergoes some catechol-O-methyltransferase (COMT) metabolism; renal excretion of metabolites and unchanged drug. |
| Excretion | Renal: 50-60% as unchanged drug and metabolites; biliary/fecal: 20-30% |
| Half-life | 3-8 hours (terminal); shorter in children and smokers; prolonged in hepatic impairment |
| Protein binding | ~60-70% (albumin) |
| Volume of Distribution | 1.5-2.0 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 15-25% (extensive first-pass metabolism); subcutaneous: 100% |
| Onset of Action | Oral: 30-60 min; subcutaneous: 5-15 min; inhalation: 5-15 min |
| Duration of Action | Oral: 4-8 hours; subcutaneous: 3-6 hours; inhalation: 3-4 hours |
5 mg orally three times daily; may increase to 10 mg if needed; maximum 20 mg daily. Subcutaneous: 0.25 mg, may repeat once in 15-30 minutes (not to exceed 0.5 mg in 4 hours).
| Dosage form | TABLET |
| Renal impairment | GFR <10 mL/min: reduce dose by 50% or extend interval to every 12-18 hours; GFR 10-50 mL/min: use with caution, consider dose reduction; GFR >50 mL/min: no adjustment needed. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50% or extend interval; Child-Pugh Class C: avoid use or use with extreme caution (no specific dosing guidelines available). |
| Pediatric use | Oral: 0.5 mg/kg/day in 3-4 divided doses (max 5 mg/day for ≤20 kg, 10 mg/day for >20 kg). Subcutaneous: 0.01 mg/kg/dose (max 0.25 mg) every 15-30 min as needed. |
| Geriatric use | Initiate at lower end of dosing (e.g., 2.5 mg orally 3 times daily) due to increased sensitivity; monitor for tachycardia, tremor, and hypertension; adjust based on tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BRETHINE (BRETHINE).
| Breastfeeding | Terbutaline is excreted into human breast milk with an M/P ratio of approximately 1.4. Limited data suggest low concentrations (mean milk concentration 2.8 ng/mL after oral dosing). However, beta-agonists may cause adverse effects in nursing infants such as tachycardia and irritability. Caution is advised; consider alternative therapies or temporarily discontinue breastfeeding. |
| Teratogenic Risk | Pregnancy Category C. In animal studies, terbutaline (the active ingredient in Brethine) has been shown to be teratogenic in mice and rabbits at doses 3-10 times the human dose, causing skeletal malformations and delayed ossification. In humans, no adequate well-controlled studies exist. Due to beta-adrenergic effects, use during pregnancy, especially near term, may cause maternal tachycardia, pulmonary edema, and hyperglycemia. Fetal effects include tachycardia, hypoglycemia, and hypokalemia. Risk of fetal harm cannot be ruled out; use only if potential benefit justifies risk. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to terbutaline or any component of the formulation; tocolysis in patients with antepartum hemorrhage, eclampsia, severe preeclampsia, intrauterine infection, or fetal distress.
| Precautions | Hypersensitivity reactions, paradoxical bronchospasm, cardiovascular effects (tachycardia, arrhythmia, hypertension, myocardial ischemia), hypokalemia, hyperglycemia, use with caution in patients with cardiovascular disorders, seizure disorders, hyperthyroidism, diabetes, and those sensitive to sympathomimetics. |
| Food/Dietary | No significant food interactions. Avoid excessive caffeine intake as it may increase cardiac side effects. |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, blood glucose, and serum potassium. Fetal heart rate monitoring is recommended. Assess for signs of pulmonary edema, especially with prolonged use. During tocolysis, monitor for pulmonary edema, chest pain, or dyspnea. Perform fetal ultrasound for growth and development if used chronically. |
| Fertility Effects | No specific human studies on fertility. In animal studies, no adverse effects on fertility were observed at doses up to 50 mg/kg/day in rats. Beta-agonists may theoretically affect uterine contractility, but no evidence of impaired fertility in humans. |
| Clinical Pearls |
| Brethine (terbutaline) is a beta-2 agonist used for bronchospasm in COPD and asthma, and as a tocolytic for preterm labor. Monitor for hypoxia due to ventilation-perfusion mismatch. Avoid in patients with tachyarrhythmias. Coadministration with beta-blockers may reduce efficacy. Use with caution in diabetics as it can increase blood glucose. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · Notify your doctor if you experience chest pain, rapid heart rate, or worsening breathing. · If used for asthma, use as a rescue inhaler; seek medical help if symptoms do not improve. · Avoid use with other sympathomimetics (e.g., ephedrine) without consulting your doctor. · If pregnant or planning pregnancy, discuss risks and benefits with your healthcare provider. |