Labetalol Hcl (labetalol HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Labetalol hydrochloride is a selective alpha1- and nonselective beta-adrenergic blocking agent (beta-blocker).
Labetalol is a nonselective beta-adrenergic blocking agent and a selective alpha1-adrenergic blocking agent. The pharmacology of labetalol is complex and in some ways resembles that of other beta-adrenergic blocking agents and that of postsynaptic alpha1-adrenergic blocking agents such as prazosin; however, the overall pharmacologic profile of labetalol differs from that of these other drugs. The beta-adrenergic blocking activity of labetalol is approximately 3 or 7 times greater than the alpha-adrenergic blocking activity following oral or IV administration, respectively; it has not been clearly established whether the ratio changes with dosage of the drug or following long-term administration.
The principal physiologic action of labetalol is to competitively block adrenergic stimulation of beta-receptors within the myocardium (beta1-receptors) and within bronchial and vascular smooth muscle (beta2-receptors) and alpha1-receptors within vascular smooth muscle. In addition to inhibiting access of endogenous or exogenous catecholamines to beta-adrenergic receptors, labetalol has been shown to exhibit some intrinsic beta2-agonist activity in animals; however, the drug exerts little, if any, intrinsic beta1-agonist activity. Labetalol does not exhibit intrinsic alpha-adrenergic agonist activity.
There is some evidence from animal studies suggesting that the drug may have a vasodilating effect.
The hemodynamic effects of labetalol are variable following oral or IV administration. Labetalol, unlike pure beta-adrenergic blocking agents, produces a dose-dependent (at usual doses) decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined alpha- and beta-adrenergic blocking activity. Labetalol effectively reduces blood pressure in the standing or supine position, but because of the drug's alpha1-adrenergic blocking activity, the effect on blood pressure is position dependent; labetalol-induced decreases in blood pressure are greater in the standing than in the supine position, and orthostatic hypotension can occur.
Labetalol hydrochloride is a lipophilic agent that is commercially available as a racemic mixture of its 4 stereoisomers. The RR-isomer, dilevalol, makes up 25% of the racemic mixture. Most of the alpha1-adrenergic blocking activity of labetalol hydrochloride is attributable to the SR-isomer.
Following IV administration of labetalol in normotensive patients with coronary artery disease, blood pressure, heart rate, systemic vascular resistance, and coronary vascular resistance are generally decreased; cardiac index, left ventricular end-diastolic pressure (LVEDP), and pulmonary artery wedge pressure are generally unchanged; and coronary sinus blood flow may be increased. The electrophysiologic effects of labetalol are variable and appear to be mediated via the drug's myocardial beta1-adrenergic blocking activity. Labetalol may decrease conduction velocity through the atrioventricular (AV) node and increase the atrial effective refractory period (ERP), but the drug appears to have inconsistent effects on sinoatrial (SA) conduction time and the AV nodal refractory period.
In healthy individuals and in patients with cardiac disease (e.g., coronary artery disease), labetalol generally has little effect on sinus rate, intraventricular conduction, the His-Purkinje system, or duration of the QRS complex.
Labetalol hydrochloride is rapidly and approximately 90-100% absorbed from the GI tract following oral administration. The drug undergoes extensive first-pass metabolism in the liver and/or GI mucosa. Only about 25% of an oral dose reaches systemic circulation unchanged in fasted adults.
Food delays GI absorption, but increases absolute bioavailability of the drug. Following oral administration of a single 200-mg dose in healthy adults, the absolute bioavailability of labetalol averaged 26 and 36% in the fasted and nonfasted state, respectively. First-pass metabolism may be reduced and bioavailability substantially increased in geriatric patients.
Following multiple-dose oral administration of labetalol hydrochloride, peak plasma concentrations are generally achieved within 40 minutes to 2 hours. Peak plasma concentrations reportedly increase proportionately with oral dosages ranging from 100 mg to 3 g daily. Following oral administration of labetalol, the hypotensive effect of the drug is generally apparent within 20 minutes to 2 hours, maximal within 1-4 hours, and persists in a dose-dependent manner for about 8-12 or 12-24 hours after a single 200- or 300-mg dose, respectively.
Steady-state plasma levels following repetitive oral dosing are expected by the third day. Following slow, direct IV injection of the drug, the hypotensive effect is apparent within 2-5 minutes, is usually maximal within 5-15 minutes, and generally persists for about 2-4 hours, although a longer duration of effect (i.e., up to 24 hours) has been reported in some patients. Steady-state plasma levels following repetitive IV dosing are reached following 22-28 hours of continuous infusion.
Following IV administration, labetalol is rapidly and widely distributed into the extravascular space. In vitro, labetalol is approximately 50% bound to plasma proteins. Labetalol crosses the placenta and is distributed into human milk.
Following oral administration, the drug is extensively metabolized in the liver and possibly in the GI mucosa principally by conjugation with glucuronic acid. Plasma concentrations of labetalol appear to decline in a biphasic, or possibly triphasic manner. In healthy adults and adults with hypertension, the half-life in the distribution phase (t1/2alpha) has been reported to average 6-44 minutes and the half-life in the terminal elimination phase (t1/2beta) has been reported to average 2.5-8 hours The manufacturers state that the drug has a plasma elimination half-life of 5.5 or 6-8 hours following IV or oral administration, respectively.
Labetalol and its metabolites are excreted in feces via biliary elimination and in urine. About 55-60% of a dose is excreted in urine, mainly as glucuronide conjugates, within 24 hours, and about 30% is excreted in feces within 4 days. Less than 5% of a dose is excreted unchanged in urine.
Labetalol is not appreciably removed (<1% of a dose) by hemodialysis, or peritoneal dialysis.
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Labetalol belongs to a class of drugs known as alpha and beta blockers.
It works by blocking the action of certain natural substances in your body, such as epinephrine, on the heart and blood vessels. This effect lowers heart rate, blood pressure, and strain on the heart.
Generic name: labetalol HCl
Pronunciation: (luh-BET-uh-lol)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Labetalol Hcl
Indications
The following indications are listed for Labetalol Hcl:
- Hypertension
Also known as: Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Systemic Arterial Hypertension.
Dosing
No dosing information is available for this tab.
Labetalol hydrochloride is usually administered orally, but may be administered by slow direct IV injection, or by slow continuous IV infusion.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Obstructive airway disease or bronchial asthma.
*Overt cardiac failure.
*Heart block greater than first degree.
*Cardiogenic shock.
*Severe bradycardia.
*Other conditions associated with severe and prolonged hypotension.
*Concomitant IV nondihydropyridine calcium-channel antagonist (e.g., verapamil) therapy.
*Known hypersensitivity, including anaphylaxis, to labetalol or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Most common adverse effects reported with oral therapy: dizziness, nausea, dyspepsia, and fatigue.
Most common adverse effects reported with IV therapy: symptomatic postural hypotension (58%), nausea (13%), and dizziness (9%).
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Although safety and efficacy remain to be fully established in children; some experts have recommended pediatric dosages for acute severe hypertension based on clinical experience.
Reproduction studies in rats and rabbits using oral labetalol hydrochloride dosages up to about 6 and 4 times the maximum recommended human dosage, respectively, have not revealed reproducible evidence of fetal malformation; however, oral dosages approximating the maximum recommended human dosage were associated with an increased incidence of fetal resorption in both species. There was no evidence of drug-related fetotoxicity in rabbits receiving IV dosages of the drug up to 1.7 times the maximum recommended human dosage. In rats, oral administration of labetalol hydrochloride at dosages 2-4 times the maximum recommended human dosage during the period of late gestation through weaning was associated with decreased neonatal survival. Labetalol crosses the placenta in humans. An association between major congenital malformations and the use of labetalol in pregnancy has not been demonstrated in published interventional and observational studies; however, most studies reported the maternal use of IV labetalol occurring after 20 weeks gestation. Inconsistent findings of intrauterine growth retardation, preterm birth, and perinatal mortality with maternal use of labetalol during pregnancy has been reported in the published literature. The manufacturer states these studies have methodological limitations hindering interpretation and the studies cannot definitively establish the absence of risk during pregnancy.
Use of labetalol in pregnant women with hypertension does not appear to affect the usual course of labor and delivery. Infants of mothers who received labetalol for the management of hypertension during pregnancy have experienced and may be at risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Published data and extensive experience from interventional and observational studies with use of labetalol in pregnant women have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pregnant women with hypertension are at risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, post-partum hemorrhage). Hypertension also increases the fetal risk for intrauterine growth restriction and intrauterine death.
Experts recommend oral labetalol for the management of hypertension in pregnancy; in patients requiring immediate blood pressure lowering (i.e., eclampsia, HELLP), IV labetalol may be used. Pregnant women with hypertension should be carefully monitored and managed accordingly. Neonates should be monitored for symptoms of hypotension, bradycardia, hypoglycemia, and respiratory depression and managed accordingly.
Small amounts (about 0.004% of the maternal dose) of labetalol are distributed into human milk. There are no data on the effects on the breastfed infant and milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for labetalol and any potential adverse effects on the breast-fed infant or from the underlying maternal condition.
Some geriatric individuals eliminate labetalol more slowly than younger adults. The manufacturer states that some elderly patients (>=60 years of age) have experienced orthostatic hypotension, dizziness, or lightheadedness during treatment with labetalol. Oral labetalol may be initiated and titrated upwards at the same dosage recommended for the general patient population (100 mg twice daily; titrate in increments of 100 mg twice daily). The manufacturer states that adequate control of blood pressure may be achieved at a lower maintenance dosage compared to the general population; the majority of elderly patients will require between 100 mg and 200 mg twice daily.
In geriatric patients, IV labetalol may be initiated at 2 mg/minute by continuous IV infusion; however, the manufacturer states lower maintenance dosages are generally required for elderly patients than nonelderly patients.
Orthostatic hypotension, dizziness, or lightheadedness, similar to that reported in younger adults, have been reported in geriatric patients (i.e., >=60 years of age) receiving labetalol. Geriatric individuals are generally more likely than younger adults to experience orthostatic symptoms and these individuals should be cautioned about the possibility of these adverse effects during therapy with the drug.
Elimination may be reduced and half-life may be slightly increased in geriatric individuals.
Because elimination of labetalol may be decreased in some geriatric patients, the usual maintenance dosage of the drug is slightly lower in geriatric individuals than in younger adults.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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