Labetalol Hydrochloride (Trandate)

1. Health Canada Product Monograph — Labetalol Hydrochloride

• Used to treat high blood pressure (hypertension), typically in combination with other antihypertensive agents such as a thiazide diuretic.
• May be used alone as initial therapy in patients for whom a combined alpha-beta blocker is judged preferable to starting with a diuretic.
• May be combined with diuretics and other antihypertensive agents to manage more severe hypertension.

• No teratogenic effects were observed in animal reproduction studies, but the safety of labetalol in human pregnancy has not been formally established; the drug crosses the placenta and has been found to bind to the eyes of animal fetuses, so it should be used in pregnant women only if the expected benefit to the mother justifies the potential risk to the fetus.

• Labetalol passes into breast milk, and breastfeeding mothers should stop nursing if continued treatment with this medication is considered essential.

• Both the bioavailability and half-life of labetalol are increased in older adults, and the blood-pressure-lowering response is greater in this age group, so lower doses are typically required in elderly patients.

• No pediatric safety or efficacy data are available, so this medication is not authorized for use in patients under 18 years of age.

• The usual starting dose is 100 mg twice daily, whether used alone or with a diuretic, with the dose typically adjusted every few days to weekly based on response.
• The usual maintenance dose ranges from 200 mg to 400 mg twice daily, and some patients may require as much as 1200 mg per day divided into two doses.
• Lower doses are generally needed in patients with liver impairment or in the elderly, since drug clearance is reduced in these groups.
• The tablets should preferably be taken after food.
• When stopping treatment in a patient with angina, the dose should be reduced gradually over about two weeks under close observation rather than stopped abruptly, to avoid rebound worsening of chest pain or a cardiac event.

• Dizziness or a drop in blood pressure on standing (postural hypotension) may occur.
• Tiredness or a general feeling of being unwell may occur.
• Headache may occur.
• Nausea or vomiting may occur.
• Indigestion may occur.
• Constipation may occur.
• Dry mouth or sore throat may occur.
• Nasal congestion may occur.
• A tingling sensation, especially of the scalp, may occur.
• Aches, pains, or muscle cramps may occur.
• Blurred vision may occur.
• Nosebleeds may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Severe drops in blood pressure on standing, sometimes leading to fainting, can occur, especially if the dose is increased too quickly.
• Bronchospasm (airway tightening) can occur, even in patients without a prior history of lung disease.
• Severe slowing of the heart rate (bradycardia) can occur.
• New or worsening heart failure can develop during treatment.
• Liver injury, including jaundice and, rarely, hepatic necrosis and death, has occurred with both short-term and long-term treatment, sometimes progressing with only minimal early symptoms; liver function should be tested at the first sign of possible liver trouble, such as unusual tiredness, dark urine, persistent loss of appetite, yellowing of the skin or eyes, or pain in the upper right abdomen.
• Severe allergic reactions, including swelling of the face or throat (angioedema), can occur, and patients with a history of severe allergic reactions may be more difficult to treat while on this medication.
• Autoimmune-type reactions, including a lupus-like syndrome and positive antinuclear antibody tests, have rarely been reported, usually resolving after the drug is stopped.
• Erectile or ejaculatory difficulty can occur in men.

• Use with caution in patients with diabetes or a tendency toward low blood sugar, since beta-blockade can mask the warning signs of hypoglycemia such as a racing heart.
• Use with caution in patients with an overactive thyroid, since beta-blockade can mask the usual signs of worsening thyroid disease, and abrupt withdrawal may trigger a thyroid crisis.
• Use with caution in patients with a suspected or known adrenal gland tumour (pheochromocytoma), since unusual blood pressure responses have been reported.
• Use with caution in patients with severe circulation problems in the arms or legs, since beta-blockers can worsen these symptoms.
• Use with caution when combined with verapamil-type calcium channel blockers, since the combination can additively slow the heart rate and impair the heart's conduction system.
• Patients with angina should never stop this medication abruptly, since doing so has been linked to worsening chest pain or a heart attack.

• Contraindicated in patients who are hypersensitive to labetalol or to any ingredient in the tablet formulation.
• Contraindicated in patients with sinus bradycardia or sick sinus syndrome.
• Contraindicated in patients with uncontrolled congestive heart failure.
• Contraindicated in cardiogenic shock or other states of poor blood flow (hypoperfusion).
• Contraindicated in patients with asthma or a history of chronic obstructive lung disease.
• Contraindicated in patients with greater than first-degree atrioventricular (AV) heart block.
• Contraindicated in patients with severe peripheral arterial circulatory disorders.

• Combined use with halothane general anesthesia can cause additive drops in blood pressure, and high concentrations of halothane together with labetalol may excessively depress heart function, so the anesthesiologist should always be informed that a patient is taking this medication.
• Labetalol blunts the reflex increase in heart rate normally caused by nitroglycerin without blocking its blood-pressure-lowering effect, so combined use in angina patients may produce an additional antihypertensive effect.
• Cimetidine increases the amount of labetalol absorbed from the gut, which may require closer attention to blood pressure control.
• Combined use with tricyclic antidepressants has been associated with a higher rate of tremor.
• Combined use with fingolimod may add to labetalol's heart-rate-lowering effect and is not recommended; if unavoidable, closer monitoring, including overnight monitoring at the start of treatment, is advised.
• Combined use with Class I antiarrhythmic drugs or verapamil-type calcium channel blockers may add to labetalol's depressant effect on the heart.
• Combined use with other blood pressure medications or diuretics can add to the blood-pressure-lowering effect, so doses may need to be adjusted.
• Because labetalol can mask the warning signs of low blood sugar, patients on insulin or oral diabetes medications should be monitored more closely.
• Epinephrine given to treat a severe allergic reaction may produce an unpredictable or exaggerated blood pressure response in patients taking labetalol.

• Taking the tablets with food increases the amount of unchanged drug absorbed, although peak blood levels remain about the same, so it is recommended to take Trandate preferably after a meal.

• Taken twice daily, preferably after food, at consistent times each day.

• Store between 15 and 30 degrees C, and keep out of the reach and sight of children.

• Trandate is a combined alpha- and beta-blocker used to treat high blood pressure, either on its own or together with other blood pressure medications.
• The usual regimen starts at 100 mg twice daily and is adjusted by your healthcare professional, typically taken after food, up to a maintenance dose of 200 to 400 mg twice daily.
• Common effects include dizziness on standing, tiredness, headache, and nausea.
• Contact your doctor's office or prescriber immediately if you develop yellowing of the skin or eyes, dark urine, unusual fatigue, wheezing or difficulty breathing, a very slow heartbeat, or swelling of the face, lips, or throat.
• Do not stop taking this medication or change your dose without talking to your healthcare professional first, since stopping suddenly can trigger chest pain or a heart attack, especially if you have angina.
• Store the tablets at room temperature, and let your prescriber know about all other medications you take, including anesthetics if you are having surgery.