Hydrochlorothiazide and Metoprolol

Metoprolol tartrate and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including metoprolol. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals.

Metoprolol is a beta1-selective (cardioselective) adrenergic receptor blocker. This preferential effect is not absolute however, and at higher plasma concentrations, metoprolol also inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature. Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at plasma concentrations much greater than required for beta-blockade. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction. The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated.

• Usual dose range: Hydrochlorothiazide 12.5 to 25 mg and metoprolol tartrate 100 mg dosed once daily. Recommended Dosage Titrate doses of individual components before switching to metoprolol tartrate and hydrochlorothiazide tablets. Administer metoprolol tartrate and hydrochlorothiazide tablets with or immediately following meals. Hydrochlorothiazide is usually given at a dosage of 12.5 mg to 50 mg per day. The usual initial dosage of metoprolol is 100 mg daily in single or divided doses. Dosage may be increased gradually until optimum blood pressure control is achieved. Once daily dosing may not maintain the full effect for the entire dosing period, particularly at lower doses. In such patients, consider administration in divided doses. Dosing regimens that exceed 50 mg of hydrochlorothiazide per day are not recommended.

Metoprolol tartrate and hydrochlorothiazide tablets are contraindicated in patients with: • Cardiogenic shock or decompensated heart failure. • Sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place. • Anuria • Hypersensitivity to metoprolol tartrate or hydrochlorothiazide or to other sulfonamide-derived drugs. • Hypersensitivity to metoprolol tartrate or hydrochlorothiazide or other sulfonamide-derived drugs. • Cardiogenic shock or decompensated heart failure. • Sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place. • Anuria.

• Abrupt cessation may exacerbate myocardial ischemia. • May worsen congestive heart failure. • Bronchospasm: Avoid beta-blockers. • Bradycardia. • Avoid discontinuing therapy prior to major surgery. • Diabetes: May mask symptoms of hypoglycemia and alter glucose levels, monitor. • Monitor serum electrolytes and creatinine periodically. • Peripheral vascular disease: Can aggravate symptoms of arterial insufficiency. • Pheochromocytoma: First initiate therapy with an alpha blocker. • Abrupt withdrawal in thyrotoxicosis might precipitate a thyroid storm. • Patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

The following adverse reactions are described in more detail elsewhere in the label, • Worsening angina or myocardial infarction • Worsening heart failure • Worsening AV block

• Catecholamine-depleting drugs (e.g., MAO inhibitors): Hypotension, bradycardia. • CYP2D6 inhibitors: Increased metoprolol concentration. • Digitalis glycosides, clonidine, diltiazem and verapamil: Bradycardia. • Clonidine: Rebound hypertension following clonidine withdrawal. • Antidiabetic drugs: Dosage adjustment may be required. • Cholestyramine and colestipol: Reduced absorption of thiazides. • Lithium: Risk of lithium toxicity. • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic, and antihypertensive effects of diuretics.

Store at 20° to 25°C (68° to 77°F). Protect from moisture.