Metoprolol Tartrate And Hydrochlorothiazide

5 WARNINGS AND PRECAUTIONS • Abrupt cessation may exacerbate myocardial ischemia. (5.1) • May worsen congestive heart failure. (5.2) • Bronchospasm: Avoid beta-blockers. (5.3) • Bradycardia. (5.4) • Avoid discontinuing therapy prior to major surgery. (5.5) • Diabetes: May mask symptoms of hypoglycemia and alter glucose levels; monitor. (5.6). • Monitor serum electrolytes and creatinine periodically. (5.7) • Peripheral vascular disease: Can aggravate symptoms of arterial insufficiency. (5.9) • Pheochromocytoma: First initiate therapy with an alpha blocker. (5.10) • Abrupt withdrawal in thyrotoxicosis might precipitate a thyroid storm. (5.11) • Patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. (5.12) 5.1 Abrupt Cessation of Therapy Following abrupt cessation of therapy with beta adrenergic blockers, exacerbations of angina pectoris and myocardial infarction may occur. When discontinuing chronically administered metoprolol tartrate and hydrochlorothiazide, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1 to 2 weeks and monitor the patient. If angina markedly worsens or acute coronary ischemia develops, promptly resume therapy and take measures appropriate for the management of unstable angina. Warn patients not to interrupt therapy without their physician’s advice. Because coronary artery disease is common and may be unrecognized, avoid abruptly discontinuing metoprolol tartrate in patients treated only for hypertension. 5.2 Heart Failure Worsening cardiac failure may occur during up-titration of beta-blockers. If such symptoms occur, increase diuretics and restore clinical stability before advancing the dose of metoprolol. It may be necessary to lower the dose of metoprolol tartrate or temporarily discontinue it. Such episodes do not preclude subsequent successful titration of metoprolol tartrate. 5.3 Bronchospastic Disease Beta adrenergic blockers can cause bronchospasm. Patients with bronchospastic diseases should, in general, not receive beta-blockers. Because of its relative beta 1 cardio-selectivity, however, metoprolol tartrate may be used in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Because beta 1 -selectivity is not absolute, use the lowest possible dose of metoprolol tartrate and have bronchodilators (e.g., beta 2 -agonists) readily available or administered concomitantly . 5.4 Bradycardia Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of metoprolol tartrate and hydrochlorothiazide. Patients with first-degree atrioventricular block, sinus node dysfunction, conduction disorders (including Wolff-Parkinson-White) or on concomitant drugs [see Drug Interactions (7)] that cause bradycardia may be at increased risk. Monitor heart rate in patients receiving metoprolol tartrate and hydrochlorothiazide. If severe bradycardia develops, reduce or stop metoprolol tartrate and hydrochlorothiazide. 5.5 Major Surgery Avoid initiation of high-dose regimen of metoprolol tartrate and hydrochlorothiazide in patients with cardiovascular risk factors undergoing non-cardiac surgery, since use in such patients has been associated with bradycardia, hypotension, stroke and death. Chronically administered beta-adrenergic blockers should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures [see Warnings and Precautions (5.1)]. 5.6 Masked Symptoms of Hypoglycemia Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at anytime during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to seek emergency treatment. 5.7 Electrolyte and Metabolic Effects Metoprolol tartrate and hydrochlorothiazide contains hydrochlorothiazide which can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which may be difficult to treat despite potassium repletion. Monitor serum electrolytes periodically. Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides. Hydrochlorothiazide reduces clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients. Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels. 5.8 Renal Impairment Patients with chronic kidney disease, severe heart failure, or volume depletion may be at increased risk for developing acute renal failure on drugs containing hydrochlorothiazide, including metoprolol tartrate and hydrochlorothiazide. 5.9 Peripheral Vascular Disease Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. 5.10 Pheochromocytoma If metoprolol tartrate and hydrochlorothiazide is used in the setting of pheochromocytoma, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta- mediated vasodilatation in skeletal muscle. 5.11 Thyrotoxicosis Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may precipitate a thyroid storm. 5.12 Anaphylactic Reaction While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine used to treat an allergic reaction. 5.13 Acute Myopia and Second Angle-Closure Glaucoma Hydrochlorothiazide, a sulfonamide, can cause acute transient myopia and acute angle-closure glaucoma (idiosyncratic reactions). Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of hydrochlorothiazide initiation. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy. Untreated acute angle-closure glaucoma can lead to permanent vision loss. Given that metoprolol tartrate and hydrochlorothiazide contains hydrochlorothiazide, if these symptoms occur, discontinue metoprolol tartrate and hydrochlorothiazide. Consider prompt medical or surgical treatment if the intraocular pressure remains uncontrolled. 5.14 Exacerbation of Systemic Lupus Erythematosus Hydrochlorothiazide can exacerbate or activate systemic lupus erythematosus.