LEVATOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVATOL (LEVATOL).
Labetalol is a nonselective beta-adrenergic antagonist with additional alpha1-adrenergic blocking activity. It competitively blocks beta1 and beta2 receptors and alpha1 receptors, leading to decreased heart rate, myocardial contractility, and systemic vascular resistance.
| Metabolism | Primarily hepatic via glucuronidation (direct conjugation) and by CYP2D6 (minor pathway). Active metabolite (4-hydroxy-labetalol) has weak beta-blocking activity. |
| Excretion | Renal excretion accounts for 55-60% as unchanged drug; biliary/fecal elimination accounts for 40-45% as metabolites and unchanged drug. |
| Half-life | Terminal elimination half-life is 6-8 hours; prolonged to 10-16 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 90-95% bound primarily to albumin. |
| Volume of Distribution | Vd is 1.5-2.0 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is 60-70% due to first-pass metabolism; intravenous bioavailability is 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 2-5 minutes. |
| Duration of Action | Oral: 6-12 hours; Intravenous: 2-6 hours. Duration correlates with dose and renal function. |
50 mg orally once daily, increasing to 100 mg once daily after 2 weeks if tolerated; maximum 200 mg once daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: reduce dose by 50%; GFR <30 mL/min: use with caution, 25 mg once daily; dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Not established; safety and efficacy not evaluated in pediatric patients. |
| Geriatric use | Start at 25 mg once daily; titrate slowly due to increased sensitivity and risk of hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVATOL (LEVATOL).
| Breastfeeding | LEVATOL is present in breast milk in low concentrations. The M/P ratio is approximately 0.5-1.0. Exogenous levothyroxine is not expected to cause adverse effects in the infant. However, monitoring of infant thyroid function may be considered if high maternal doses are used. |
| Teratogenic Risk | LEVATOL (levothyroxine) is generally considered safe in pregnancy. No increased risk of congenital malformations has been associated with therapeutic doses. Hypothyroidism itself may increase risk of miscarriage, preeclampsia, and neurocognitive deficits in offspring; therefore, maintaining euthyroid state is critical. Thyroid hormones do not readily cross the placenta in early pregnancy, but maternal levothyroxine requirements increase in the second and third trimesters. |
■ FDA Black Box Warning
None.
| Serious Effects |
Bronchial asthma, overt cardiac failure, cardiogenic shock, severe bradycardia, heart block (greater than first degree), severe hypotension.
| Precautions | May cause heart failure exacerbation, bronchospasm (especially in asthma/COPD), hypotension, bradycardia, masking of hypoglycemia signs, and rebound hypertension after abrupt withdrawal. Caution in hepatic impairment. |
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| Fetal Monitoring | Monitor maternal thyroid function tests (TSH, free T4, total T4) every 4-6 weeks during pregnancy. Adjust dose to maintain TSH within trimester-specific reference ranges. Fetal monitoring includes assessment of growth, heart rate, and potential goiter if maternal dose is excessive. |
| Fertility Effects | Untreated hypothyroidism may impair fertility due to anovulation and luteal phase defects. Treatment with LEVATOL restores euthyroid state and improves fertility outcomes. There is no known direct negative effect of levothyroxine on fertility. |