Labetalol is used for the management of hypertension. The drug is used for hypertension associated with angina or pheochromocytoma and during pregnancy. IV labetalol is used for hypertension associated with myocardial infarction and to control blood pressure in patients with severe hypertension or in hypertensive crises.
In addition, IV labetalol has been used to produce controlled hypotension during anesthesia and to control blood pressure in preeclampsia. The drug also has been used in the management of sympathetic overactivity syndrome with severe tetanus and in angina.
Labetalol hydrochloride is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Although β-blockers were previously considered a drug of choice for the initial management of hypertension, most current guidelines no longer recommend these drugs as first-line therapy because of the lack of established superiority over other recommended drug classes and at least one study demonstrating that they may be less effective than angiotensin II receptor antagonists in preventing cardiovascular death, myocardial infarction, or stroke. However, β-blockers may still be considered in hypertensive patients who have a compelling indication (e.g., prior myocardial infarction, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics). (See and )
In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blocking agents than to monotherapy with β-blockers. Although β-blockers have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients; however, this population difference in response does not appear to occur during combined therapy with a β-blocker and a thiazide diuretic. (See and in .)
Labetalol is at least as effective as pure β-blockers, thiazide diuretics, methyldopa, or clonidine.
For additional information on the role of β-blockers in the management of hypertension, see Uses in and .
Hypertension Associated with Angina or Myocardial Infarction
Oral labetalol has been used effectively for the management of hypertension in patients with coexisting angina pectoris, and IV labetalol has been used effectively for the management of hypertension associated with acute myocardial infarction. In patients with hypertension and ischemic heart disease, oral labetalol therapy reduced blood pressure and heart rate and was associated with elimination or reduction of anginal pain, improvement in exercise tolerance, and decreased consumption of nitroglycerin. In the management of hypertension associated with acute myocardial infarction, IV infusions of labetalol decreased blood pressure and heart rate and generally decreased cardiac index and pulmonary artery wedge pressure, without producing adverse hemodynamic effects.
Hypertension during Pregnancy
Labetalol has been used for the management of hypertension in pregnant women. The drug has been effective in controlling blood pressure in pregnant women with moderate to severe hypertension, in those with severe pregnancy-induced hypertension, and in those with hypertension and superimposed pregnancy-induced hypertension. In addition, in hypertensive pregnant women with proteinuria, labetalol therapy has resulted in substantially less proteinuria.
The goal of antihypertensive treatment in pregnant women with hypertension is to minimize the acute complications of maternal hypertension while avoiding therapy that would compromise fetal well-being. Antihypertensive therapy is recommended in pregnant women with chronic hypertension who have persistent, severely elevated blood pressure (e.g., systolic blood pressure of 160 mm Hg or higher or diastolic blood pressure of 105 mm Hg or higher); it is less clear whether antihypertensive therapy should be initiated in women with mild to moderate chronic hypertension. If initiation of antihypertensive therapy is considered necessary in a pregnant woman, use of labetalol, nifedipine, or methyldopa is recommended by the American College of Obstetricians and Gynecologists (ACOG) and other experts. In women who are already receiving antihypertensive therapy prior to pregnancy, ACOG states there are insufficient data to make recommendations regarding the continuance or discontinuance of such therapy; treatment decisions should be individualized in these situations. Antihypertensive therapy can reduce the risk of severe hypertension but has not been shown to prevent the development of preeclampsia. Use of labetalol in association with careful prenatal management during pregnancy does not appear to adversely affect the fetus.
(See Cautions: Pregnancy, Fertility, and Lactation.)
Labetalol also has been used parenterally in the hospital setting for urgent lowering of blood pressure in severely hypertensive pregnant women, including those with preeclampsia. Recommendations for the management of such patients are based principally on experience in women with preeclampsia or gestational hypertension in the third trimester. Delivery is the preferred method of management for women with severe preeclampsia; however, use of antihypertensive drugs is recommended in such women who have severely elevated blood pressures (sustained systolic blood pressure of at least 160 mm Hg or diastolic blood pressure of at least 110 mm Hg) to prevent potentially life-threatening cardiovascular, renal, and cerebrovascular complications. Results of several randomized clinical trials evaluating antihypertensive therapy in women with severe hypertension during pregnancy suggest that IV labetalol, IV hydralazine, or oral nifedipine are appropriate antihypertensives for urgently lowering blood pressure in such patients; choice of therapy should be based on clinician experience and preference as well as patient-specific factors (e.g., concomitant medical conditions or therapies) and drug-related factors (e.g., route of administration, adverse effects, contraindications, local availability, cost). Although hydralazine historically has been considered the agent of choice for management of hypertensive emergencies associated with pregnancy, some clinicians now prefer IV labetalol for its more rapid onset and shorter duration of action and its more predictable hypotensive effect. If antihypertensive therapy is considered for the management of preeclampsia, it should be recognized that such therapy is employed solely for maternal benefit; it does not improve perinatal outcomes and may adversely affect uteroplacental flow.
Hypertension Associated with Pheochromocytoma
Because of labetalol's α- and β-adrenergic blocking activity, the drug has been used alone to control hypertension and symptoms resulting from excessive β-receptor stimulation in patients with pheochromocytoma. Labetalol generally appears to be effective in these patients; some evidence suggests that the drug may be more effective in patients whose tumors predominantly secrete epinephrine rather than norepinephrine and in patients with sustained rather than paroxysmal hypertension. Since there have been reports that oral labetalol may induce a paradoxical hypertensive crisis in some patients with pheochromocytoma (possibly because the drug's predominant β-adrenergic blockade leaves α-adrenergic stimulation relatively unopposed), the manufacturers recommend that the drug be used with caution in patients with this tumor. Although labetalol has some α-adrenergic blocking activity, some clinicians caution that the drug, like other β-adrenergic blocking agents, should not be used in patients with pheochromocytoma unless they have received pretreatment with an α-adrenergic blocking agent (e.g., IV phentolamine). If labetalol is used in patients with known or suspected pheochromocytoma, appropriate methods for determining urinary catecholamines should be employed.
(See Laboratory Test Interferences: Urinary Catecholamines.)
Severe Hypertension and Hypertensive Crises
IV labetalol hydrochloride is used to control blood pressure in patients with severe hypertension or in hypertensive crises for the immediate reduction in blood pressure in patients in whom such reduction is considered an emergency (hypertensive emergencies). Hypertensive emergencies are those rare situations requiring immediate blood pressure reduction (not necessarily to normal ranges) to prevent or limit target organ damage. Such emergency situations include hypertensive encephalopathy, intracerebral hemorrhage, unstable angina pectoris, acute myocardial infarction, pulmonary edema, dissecting aortic aneurysm, and eclampsia, and labetalol generally is suitable for most hypertensive emergencies except when acute cardiac failure is present. Patients with hypertensive emergencies require hospitalization and are treated with an appropriate parenteral agent. Elevated blood pressure alone, in the absence of manifestations or other evidence of target organ damage, rarely requires emergency therapy. The risks of overly aggressive therapy in any hypertensive crisis must always be considered. Excessive falls in blood pressure should be avoided in any hypertensive crisis since they may precipitate renal, cerebral, or coronary ischemia.
Labetalol usually produces a prompt, but gradual reduction of blood pressure without substantial changes in heart rate or cardiac output. IV labetalol appears to adequately reduce blood pressure in about 80-90% of patients with severe hypertension or hypertensive emergencies, irrespective of etiology, and may be useful even when other drugs have failed. The exact effects of previous antihypertensive therapy on the efficacy of IV labetalol have not been fully determined. IV labetalol generally appears to be effective regardless of whether patients have received other hypotensive drugs, including β-blockers; however, in some studies, the drug was reported to be ineffective, usually in patients who received a single IV injection and who were receiving other hypotensive drugs, including β-blockers. The possibility of a diminished response to IV labetalol should be considered in patients receiving α- or β-blockers.
The comparative efficacy and safety of IV labetalol and other currently available parenteral hypotensive agents in the management of severe hypertension and hypertensive emergencies have not been fully evaluated, but IV labetalol is considered one of several parenteral drugs of choice for the management of these forms of hypertension. IV labetalol appears to be as effective as IV diazoxide (parenteral formulation no longer commercially available in the US), but may be less likely to induce excessive hypotension and adverse neurologic or cardiovascular sequelae. Because of its usual lack of substantial changes in heart rate or cardiac output, IV labetalol may be particularly useful in severely hypertensive patients with ischemic heart disease. In addition, IV labetalol has an advantage over most other parenteral hypotensive agents in that oral therapy with the drug may be continued after parenteral therapy when long-term control of blood pressure is necessary. IV labetalol also has been used effectively to control blood pressure and the rate of left ventricular pressure rise (dp/dt) in a few patients with acute dissection of the aorta; the drug produced a gradual reduction in blood pressure without a concomitant increase in heart rate.
Hypertensive urgencies are those situations in which there is a severe elevation in blood pressure without progressive target organ damage. Such urgencies include the upper levels of stage 2 hypertension associated with severe headache, shortness of breath, epistaxis, or severe anxiety. Hypertensive urgencies generally can be managed by intensification or reinstitution (e.g., following noncompliance) of the current antihypertensive regimen or with oral doses of short-acting antihypertensive agents such as labetalol followed by several hours of observation. However, there is no evidence suggesting that failure to aggressively reduce blood pressure in these patients is associated with any short-term risk. In fact, overly aggressive management of severe elevations in blood pressure not associated with impending or progressing organ damage can sometimes lead to cumulative hypotensive effects.
IV labetalol has been used effectively in a small number of patients for the management of hypertensive crises following discontinuance of clonidine, and oral labetalol has been used effectively in a small number of patients to prevent such crises during withdrawal from clonidine therapy. However, since severe rebound hypertension reportedly has occurred in at least one patient during gradual withdrawal of clonidine and concurrent oral administration of labetalol, some clinicians caution that labetalol not be used in such patients unless they have received pretreatment with an α-blocker (e.g., IV phentolamine).
Controlled Hypotension during Anesthesia
IV labetalol hydrochloride has been used effectively to produce controlled hypotension during anesthesia in order to reduce bleeding resulting from surgical procedures. When labetalol and halothane are used concomitantly, a synergistic hypotensive effect results, which may be used to therapeutic advantage.
(See Drug Interactions: Halothane.)Labetalol has also been effective in the management of uncontrolled hypertension before anesthesia and during surgery, and for the management and/or prevention of acute hypertensive responses during laryngoscopy.
Labetalol has been used in a limited number of patients for the management of chronic stable angina pectoris. Use of the drug has been associated with a reduction in the frequency and severity of anginal attacks, a decrease in nitrate dosage, and an increase in exercise tolerance. Further studies are needed to determine the safety and efficacy of labetalol in the management of chronic stable angina pectoris.
Labetalol has been used with good results for the management of the sympathetic overactivity syndrome associated with severe tetanus. The drug generally has been effective in stabilizing the cardiovascular disturbances, including hypertension, tachycardia, and increased systemic arteriolar resistance, that occur in patients with severe tetanus.