Met XL

Dosage Form & Strength

Heart Failure: Recommended starting dose is 12.5 mg or 25 mg doubled every two weeks to the highest dose tolerated or up to 200 mg. Hypertension: Usual initial dosage is 25 to 100 mg once daily. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. Dosages above 400 mg per day have not been studied. Angina Pectoris: Usual initial dosage is 100 mg once daily. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is an unacceptable bradycardia. Dosages above 400 mg per day have not been studied.

Dosage in Special Population

Hepatic Impairment Consider initiating therapy at doses lower than those recommended for a given indication; gradually increase dosage to optimize therapy, while monitoring closely for adverse events. Renal Impairment No reduction in dosage is needed in patients with chronic renal failure Pregnancy Category C Nursing Mothers Metoprolol is excreted in breast milk in very small quantities. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug. Consider possible infant exposure when Metoprolol is administered to a nursing woman.

Adverse Effects

Most common adverse reactions: tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension, diarrhea, pruritus, rash.

Drug Interactions

Metoprolol: Catecholamine-depleting drugs may have an additive effect when given with beta-blocking agents. CYP2D6 Inhibitors are likely to increase metoprolol concentration Concomitant use of glycosides, clonidine, and diltiazem and verapamil with beta-blockers can increase the risk of bradycardia. Beta-blockers including metoprolol, may exacerbate the rebound hypertension that can follow the withdrawal of clonidine

Mechanism of Action

Hypertension: The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output (2) a central effect leading to reduced sympathetic outflow to the periphery (3) suppression of renin activity Heart Failure: The precise mechanism for the beneficial effects of beta-blockers in heart failure has not been elucidated

Pharmacokinetics

The half life of Metoprolol in Met XL is 3-7 hours

Drug Use in Pregnancy

Metoprolol: Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, use this drug during pregnancy only if clearly needed Nursing Mothers: Metoprolol is excreted in breast milk in very small quantities. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug. Consider possible infant exposure when Metoprolol-XL is administered to a nursing woman

Drug Use in Renal Impairment

Metoprolol: Renal Impairement:Renal Impairment: The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. No reduction in dosage is needed in patients with chronic renal failure

Drug Use in Hepatic Impairment

Metoprolol: Hepatic Impairment: Consider initiating Metoprolol therapy at low doses and gradually increase dosage to optimize therapy, while monitoring closely for adverse events

Drug Use in Pediatric Population

Metoprolol: Pediatric Use: Safety and effectiveness have not been established in patients < 6 years of age.

Drug Use in Geriatric Population

Metoprolol: Geriatrics: No notable difference in efficacy or safety vs. younger patients. Clinical studies of Metoprolol-XL in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. Of the 1,990 patients with heart failure randomized to Metoprolol-XL in the MERIT-HF trial, 50% (990) were 65 years of age and older and 12% (238) were 75 years of age and older. There were no notable differences in efficacy or the rate of adverse reactions between older and younger patients. In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.