Labetalol

Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were treated with alpha1-blockers. There appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery.

Severe hepatocellular injury has been reported (rare). The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology. Periodically monitor LFTs. If liver injury or jaundice occurs, discontinue labetalol and do not restart.

Symptomatic hypotension with or without syncope may occur with labetalol; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Initiation with a low dose and gradual up-titration may help to decrease the occurrence of hypotension or syncope. Advise patients to avoid driving or other hazardous tasks during initiation of therapy due to the risk of syncope. Orthostatic hypotension may occur with IV administration; patient should remain supine during and for up to 3 hours after IV administration Disease-related concerns:

In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.

Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms. May also reduce release of insulin in response to hyperglycemia; dosage of antidiabetic agents may need to be adjusted.

Use with extreme caution in patients with compensated heart failure and monitor for a worsening of the condition.

Use with caution in patients with hepatic impairment; bioavailability is increased due to decreased first-pass metabolism.

Use beta blockers with caution in patients with myasthenia gravis.

Beta blockers may precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud disease; use with caution and monitor for progression of arterial obstruction.

Labetalol may be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma; however, patients may experience paradoxical hypertensive responses due to inadequate alpha-1 blockade (Manger 2002; Mazza 2014). Adequate alpha-1 blockade should be initiated prior to use of any beta-blocker in this setting; use with caution in patients with pheochromocytoma or consider alternative therapy. If possible, obtain diagnostic tests for pheochromocytoma prior to use since labetalol may spuriously cause falsely elevated levels of plasma catecholamine and urinary metanephrine (Bravo 2002; MacCarthy 1983).

Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.

Use with caution in patients with a history of psychiatric illness. Although the risk is small, labetalol may cause or exacerbate CNS depression; however, the use of beta-blockers should not be withheld if benefit exceeds this risk (Verbeek 2011).

Beta blockers may mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary. Dosage form specific issues:

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling. Other warnings/precautions:

Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.

Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.