Dutoprol (hydrochlorothiazide/metoprolol succinate)
Exacerbations of angina pectoris and myocardial infarction reported following abrupt discontinuation. When discontinuing chronically administered drug, particularly in patients with ischemic heart disease, gradually reduce dose over a period of 1-2 weeks and monitor patients. Promptly resume therapy, at least temporarily, and take other measures appropriate for the management of unstable angina if angina markedly worsens or acute coronary insufficiency develops. Caution against interruption or discontinuation of therapy without the physician's advice. Coronary artery disease may be unrecognized; avoid abrupt discontinuation of therapy even in patients treated only for HTN.
Selective beta1 blocker/thiazide diuretic
Management of HTN.
Initial: 25mg-12.5mg qd
Titrate: May titrate at intervals of 2 weeks
Max: 200mg-25mg qd
May be administered with other antihypertensive drugs
Take with or without food
Tab, Extended-Release: (Metoprolol-HCTZ) 25mg-12.5mg, 50mg-12.5mg, 100mg-12.5mg* *scored
Cardiogenic shock, decompensated heart failure (HF), sinus bradycardia, sick sinus syndrome, >1st-degree heart block (unless a permanent pacemaker is in place), anuria, hypersensitivity to sulfonamide-derived drugs.
Bradycardia, including sinus pause, heart block, and cardiac arrest reported; increased risk in patients with 1st-degree atrioventricular (AV) block, sinus node dysfunction, or conduction disorders (eg, Wolff-Parkinson-White). Reduce dose or d/c if severe bradycardia develops. Metoprolol: Worsening cardiac failure may occur during up-titration; if symptoms occur, increase diuretics and restore clinical stability (compensated HF) before advancing the dose of therapy; may need to reduce dose of therapy or temporarily d/c therapy. May cause bronchospasm; avoid with bronchospastic disease, but may use with caution if unresponsive/intolerant to other antihypertensives. Avoid initiation of high-dose regimen in patients with cardiovascular (CV) risk factors undergoing noncardiac surgery; associated with bradycardia, hypotension, stroke and death. Chronically administered therapy should not be routinely withdrawn prior to major surgery; however, may augment risks of general anesthesia and surgical procedures. May mask tachycardia occurring with hypoglycemia. May precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease (PVD). Associated with a paradoxical increase in BP in patients with pheochromocytoma; initiate an α-blocker first if used in patients with pheochromocytoma. May mask certain clinical signs of hyperthyroidism (eg, tachycardia); abrupt withdrawal may precipitate thyroid storm. HCTZ: May cause hypokalemia, hyponatremia, and hypomagnesemia. May alter glucose tolerance and increase serum cholesterol and TG levels. Reduces clearance of uric acid; may cause or exacerbate hyperuricemia and precipitate gout. Decreases urinary Ca2+ excretion; may cause elevations of serum Ca2+. Increased risk for developing acute renal failure in patients with chronic kidney disease, severe HF, or volume depletion. May cause acute transient myopia and acute angle-closure glaucoma (idiosyncratic reactions); d/c therapy if these symptoms occur and consider prompt medical or surgical treatment if the intraocular pressure remains uncontrolled. May exacerbate or activate systemic lupus erythematosus (SLE). Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.
Metoprolol: Additive effect and increased risk of hypotension or bradycardia with catecholamine-depleting drugs (eg, reserpine, MAOIs). CYP2D6 inhibitors (eg, quinidine, fluoxetine, paroxetine, propafenone) may increase levels. Increased risk of significant bradycardia with nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem), digoxin, or clonidine. If clonidine and Dutoprol are both to be discontinued, withdraw Dutoprol several days before the gradual withdrawal of clonidine to reduce risk of rebound HTN. Delay the introduction of Dutoprol for several days after discontinuation of clonidine if switching to therapy. May decrease responsiveness to epinephrine; consider other medications in patients treated for severe anaphylaxis. HCTZ: Dose adjustment of antidiabetic drugs (eg, oral agents, insulin) may be required. Impaired absorption with anionic exchange resins (eg, cholestyramine and colestipol resins); administer at least 4 hrs before or 4-6 hrs after resin administration. Reduces the renal clearance of lithium and increases the risk of lithium toxicity; monitor serum lithium levels. NSAIDs may reduce diuretic, natriuretic, and antihypertensive effects.
PREGNANCY AND LACTATION
Category C, safety not known in nursing.
MECHANISM OF ACTION
Metoprolol: β1-selective adrenergic receptor blocker; has not been established. Proposed to competitively antagonize catecholamines at peripheral adrenergic-neuron sites, have central effect leading to reduced sympathetic outflow to periphery, and suppress renin activity. HCTZ: Thiazide diuretic; has not been established. Affects renal tubular mechanism of electrolyte reabsorption and increases excretion of Na+ and Cl-.
Absorption: Metoprolol: Complete. Absolute bioavailability (50%) (immediate-release); Tmax=10-12 hrs. HCTZ: Absolute bioavailability (70%); Tmax=2-5 hrs. Distribution: Metoprolol: Plasma protein binding (12%, albumin); found in breast milk. HCTZ: Plasma protein binding (40-70%, albumin); crosses the placenta; found in breast milk. Metabolism: Metoprolol: Liver via CYP2D6. Elimination: Metoprolol: Urine (<5% unchanged); T1/2=3-7 hrs. HCTZ: Urine (70% unchanged); T1/2=10 hrs.
Assess for hypersensitivity to drug or to other sulfonamide-derived drugs, cardiogenic shock, decompensated HF, sinus bradycardia, sick sinus syndrome, AV heart block, presence of pacemaker, anuria, bronchospastic disease, CV risk factors, PVD, pheochromocytoma, history of penicillin allergy, SLE, renal/hepatic impairment, pregnancy/nursing status, any other conditions where treatment is contraindicated or cautioned, and possible drug interactions.
Monitor for signs/symptoms of withdrawal, HF, bronchospasm, bradycardia, hypoglycemia, precipitation/aggravation of symptoms of PVD, paradoxical increase in BP, hyperthyroidism, electrolyte and metabolic effects, idiosyncratic reactions, exacerbation/activation of SLE, and other adverse reactions. Monitor serum electrolytes periodically. Monitor HR and rhythm.
Advise to take regularly and continuously, ud. Instruct not to interrupt or d/c therapy without consulting the physician. Inform that therapy may cause bronchospasm; instruct to inform physician if patient starts to wheeze or have difficulty in breathing. Inform that patient may need blood tests to monitor serum electrolytes. Advise to report decreased visual acuity or ocular pain and d/c and to contact physician right away if these symptoms occur. Inform that hypersensitivity reactions may occur. Instruct to inform other physicians that they are taking diuretics.
25°C (77°F); excursions permitted to 15-30°C (59-86°F).
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