Toprol-XL (Metoprolol Succinate) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug Interactions

Catecholamine-depleting drugs (eg, reserpine, mono amine oxidase (MAO) inhibitors) may have an additive effect when given with beta-blocking agents. Patients treated with TOPROL-XL plus a catecholamine depletor should therefore be closely observed for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.

Drugs that inhibit CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone are likely to increase metoprolol concentration. In healthy subjects with CYP2D6 extensive metabolizer phenotype, coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. In four patients with cardiovascular disease, coadministration of propafenone 150 mg t.i.d. with immediate release metoprolol 50 mg t.i.d. resulted in two- to five-fold increases in the steady-state concentration of metoprolol. These increases in plasma concentration would decrease the cardioselectivity of metoprolol.

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the beta blocker should be withdrawn several days before the gradual withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped.

OVERDOSAGE

Acute Toxicity

There have been a few reports of overdosage with TOPROL-XL and no specific overdosage information was obtained with this drug, with the exception of animal toxicology data. However, since TOPROL-XL (metoprolol succinate salt) contains the same active moiety, metoprolol, as conventional metoprolol tablets (metoprolol tartrate salt), the recommendations on overdosage for metoprolol conventional tablets are applicable to TOPROL-XL.

Signs and Symptoms

Overdosage of TOPROL-XL may lead to severe hypotension, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impairment of consciousness/coma, nausea, vomiting, and cyanosis.

Treatment

In general, patients with acute or recent myocardial infarction or congestive heart failure may be more hemodynamically unstable than other patients and should be treated accordingly. When possible the patient should be treated under intensive care conditions. On the basis of the pharmacologic actions of metoprolol, the following general measures should be employed:

Elimination of the Drug: Gastric lavage should be performed.

Bradycardia: Atropine should be administered. If there is no response to vagal blockade, isoproterenol should be administered cautiously.

Hypotension: A vasopressor should be administered, eg, levarterenol or dopamine.

Bronchospasm: A beta₂-stimulating agent and/or a theophylline derivative should be administered.

Cardiac Failure: A digitalis glycoside and diuretics should be administered. In shock resulting from inadequate cardiac contractility, administration of dobutamine, isoproterenol, or glucagon may be considered.

CONTRAINDICATIONS

TOPROL-XL is contraindicated in severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place) (see WARNINGS) and in patients who are hypersensitive to any component of this product.