Metoprolol Tartrate/HCTZ (hydrochlorothiazide/metoprolol tartrate)
Exacerbation of angina and, in some cases, myocardial infarction (MI) reported following abrupt discontinuation. When discontinuing therapy, avoid abrupt withdrawal even without overt angina pectoris. Caution patients against interruption of therapy without physician's advice.
OTHER BRAND NAMES
Selective beta1 blocker/thiazide diuretic
Management of HTN.
If fixed combination represents dose titrated to patient's needs; therapy with combination may be more convenient than with separate components
100-200mg of metoprolol and hydrochlorothiazide (HCTZ) 25-50mg per day given qd or in divided doses
Max HCTZ: 50mg/day
May gradually add another antihypertensive when necessary, beginning with 50% of the usual recommended starting dose
Start at lower end of dosing range
Tab: (Metoprolol/HCTZ) 50mg/25mg*, 100mg/25mg*, 100mg/50mg*; (Lopressor HCT) 50mg/25mg*, 100mg/25mg* *scored
Sinus bradycardia, >1st-degree heart block, cardiogenic shock, overt cardiac failure, sick sinus syndrome, severe peripheral arterial circulatory disorders, anuria, hypersensitivity to sulfonamide-derived drugs.
Not for initial therapy. Caution with hepatic dysfunction and in elderly. Metoprolol: May cause/precipitate heart failure; d/c if cardiac failure continues despite adequate treatment. Avoid with bronchospastic diseases, but may use with caution if unresponsive to/intolerant of other antihypertensives. Avoid withdrawal of chronically administered therapy prior to major surgery; however, may augment risks of general anesthesia and surgical procedures. Caution with diabetic patients; may mask tachycardia occurring with hypoglycemia. Paradoxical BP increase reported with pheochromocytoma; give in combination with and only after initiating α-blocker therapy. May mask hyperthyroidism. Avoid abrupt withdrawal in suspected thyrotoxicosis; may precipitate thyroid storm. HCTZ: Caution with severe renal disease; may precipitate azotemia. If progressive renal impairment becomes evident, d/c therapy. May precipitate hepatic coma in patients with liver dysfunction/disease. Sensitivity reactions are more likely to occur with history of allergy or bronchial asthma. May exacerbate/activate systemic lupus erythematosus (SLE). May cause idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma; d/c HCTZ as rapidly as possible. Fluid/electrolyte imbalance (eg, hyponatremia, hypochloremic alkalosis, hypokalemia) may develop. May cause hyperuricemia and precipitation of frank gout. Latent diabetes mellitus (DM) may manifest during therapy. Enhanced effects seen in postsympathectomy patients. D/C prior to parathyroid function test. Decreased Ca2+ excretion observed. Altered parathyroid gland, with hypercalcemia and hypophosphatemia observed with prolonged therapy. May increase urinary excretion of Mg2+, resulting in hypomagnesemia.
Fatigue, lethargy, dizziness, vertigo, flu syndrome, drowsiness, somnolence, hypokalemia, headache, bradycardia.
Metoprolol: May exhibit additive effect with catecholamine-depleting drugs (eg, reserpine). Digitalis glycosides may increase risk of bradycardia. Some inhalation anesthetics may enhance cardiodepressant effect. May be unresponsive to usual doses of epinephrine. Potent CYP2D6 inhibitors (eg, certain antidepressants, antipsychotics, antiarrhythmics, antiretrovirals, antihistamines, antimalarials, antifungals, stomach ulcer drugs) may increase levels. Increased risk for rebound HTN following clonidine withdrawal; d/c metoprolol several days before withdrawing clonidine. Effects can be reversed by β-agonists (eg, dobutamine, isoproterenol). HCTZ: Hypokalemia can sensitize/exaggerate cardiac response to toxic effects of digitalis. Risk of hypokalemia with steroids or adrenocorticotropic hormone. Insulin requirements may change in diabetic patients. May decrease arterial responsiveness to norepinephrine. May increase responsiveness to tubocurarine. May increase risk of lithium toxicity. Rare reports of hemolytic anemia with methyldopa. NSAIDs may reduce diuretic, natriuretic, and antihypertensive effects. Impaired absorption reported with cholestyramine and colestipol. Alcohol, barbiturates, and narcotics may potentiate orthostatic hypotension. May potentiate other antihypertensive drugs (eg, ganglionic or peripheral adrenergic-blocking drugs).
PREGNANCY AND LACTATION
Category C, not for use in nursing.
MECHANISM OF ACTION
Metoprolol: β1-adrenergic receptor blocker; not 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; not established. Affects renal tubular mechanism of electrolyte reabsorption and increases excretion of Na+ and Cl-.
Absorption: Metoprolol: Rapid and complete. HCTZ: Rapid; Tmax=1-2.5 hrs. Distribution: Found in breast milk. Metoprolol: Plasma protein binding (12%); found in CSF. HCTZ: Vd=3.6-7.8L/kg; plasma protein binding (67.9%); crosses the placenta. Metabolism: Metoprolol: Liver (extensive) via CYP2D6 (oxidation). Elimination: Metoprolol: Urine (<5%, unchanged); T1/2=2.8 hrs (extensive metabolizers), 7.5 hrs (poor metabolizers). HCTZ: Urine (72-97%); T1/2=10-17 hrs.
Assess for history of heart failure, sulfonamide hypersensitivity, SLE, hyperthyroidism, DM, pheochromocytoma, hepatic/renal impairment, any other conditions where treatment is contraindicated/cautioned, pregnancy/nursing status, and possible drug interactions. Obtain baseline serum electrolytes.
Monitor for signs/symptoms of cardiac failure, hypoglycemia, thyrotoxicosis, electrolyte imbalance, exacerbation/activation of SLE, hyperuricemia or precipitation of gout, hypersensitivity reactions, hepatic/renal dysfunction, myopia, angle-closure glaucoma, and other adverse reactions. Monitor serum electrolytes.
Instruct to take regularly and continuously, ud, with or immediately following meals. If dose is missed, instruct to take next dose at scheduled time (without doubling the dose) and not to d/c without consulting physician. Instruct to avoid driving, operating machinery, or engaging in tasks requiring alertness until response to therapy is determined. Advise to contact physician if difficulty in breathing or other adverse reactions occur, and to inform physician/dentist of drug therapy before undergoing any type of surgery.
(Lopressor HCT) 25°C (77°F); excursions permitted to 15-30°C (59-86°F). (Metoprolol/HCTZ) 20-25°C (68-77°F). Protect from moisture.
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