Metxl AM

Indications

Metxl AM is indicated for the treatment of hypertension

Adverse Effects

Metoprolol Most common adverse reactions: tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension, diarrhea, pruritus, rash. Amlodipine Commonly reported side effects of amlodipine include: edema. Other side effects include: fatigue, palpitations, and flushing. See below for a comprehensive list of adverse effects.

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

Amlodipine: Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle The precise mechanism by which amlodipine relieves angina has not been fully determined but amlodipine reduces total ischaemic burden by the following two actions: 1. Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements 2. The mechanism of action of amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm Metoprolol: 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 AM is 3-7 hours; half life of Amlodipine in Met XL AM is 35-50 hours

Drug Use in Pregnancy

Amlodipine: Pregnancy: The safety of amlodipine in human pregnancy has not been established In animal studies, reproductive toxicity was observed at high doses Use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother and foetus Breast-feeding: It is not known whether amlodipine is excreted in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with amlodipine should be made taking into account the benefit of breast-feeding to the child and the benefit of amlodipine therapy to the mother Fertility: Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In one rat study, adverse effects were found on male fertility Metoprolol: Pregnancy Category C: Metoprolol tartrate has been shown to increase post-implantation loss and decrease neonatal survival in rats at doses up to 22 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. Distribution studies in mice confirm exposure of the fetus when metoprolol tartrate is administered to the pregnant animal. These studies have revealed no evidence of impaired fertility or teratogenicity. 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 failures

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.