Get your patient on Lopressor Hct - Metoprolol Tartrate And Hydrochlorothiazide tablet (Metoprolol Tartrate And Hydrochlorothiazide)

Titrate doses of individual components before switching to LOPRESSOR HCT.

Administer LOPRESSOR HCT 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.

Following abrupt cessation of therapy with beta adrenergic blockers, exacerbations of angina pectoris and myocardial infarction may occur. When discontinuing chronically administered LOPRESSOR HCT, 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.

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.

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 .

Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of LOPRESSOR HCT. 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 LOPRESSOR HCT. If severe bradycardia develops, reduce or stop LOPRESSOR HCT.

Avoid initiation of high-dose regimen of LOPRESSOR HCT 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 )].

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.

LOPRESSOR HCT 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.

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 LOPRESSOR HCT.

Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.

If LOPRESSOR HCT 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.

Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may precipitate a thyroid storm.

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.

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 LOPRESSOR HCT contains hydrochlorothiazide, if these symptoms occur, discontinue LOPRESSOR HCT. Consider prompt medical or surgical treatment if the intraocular pressure remains uncontrolled.

Hydrochlorothiazide can exacerbate or activate systemic lupus erythematosus.

The following adverse reactions have been reported in postmarketing experience: adverse reactions have been identified during post approval use of LOPRESSOR HCT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Metoprolol

Confusional state, an increase in blood triglycerides and a decrease in High Density Lipoprotein (HDL). Very rare reports of hepatitis, jaundice and non-specific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic dehydrogenase elevations have also been reported.

Hydrochlorothiazide

Digestive: Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, anorexia.

Cardiovascular: Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics).

Neurologic: Vertigo, dizziness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, restlessness.

Musculoskeletal: Muscle spasm.

Hematologic: Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Metabolic: Hyperglycemia, glycosuria, hyperuricemia.

Hypersensitive Reactions: Necrotizing angiitis, Stevens-Johnson syndrome, respiratory distress including pneumonitis and pulmonary edema, purpura, urticaria, rash, photosensitivity.

Other beta-adrenergic agent reactions

A variety of adverse reactions have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to Lopressor.

Central Nervous System: Reversible mental depression progressing to catatonia; visual disturbances; hallucinations; an acute reversible syndrome characterized by disorientation for time and place, emotional lability, clouded sensorium, and decreased performance on neuropsychometrics.

Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Hypersensitive Reactions: Laryngospasm and respiratory distress.

Catecholamine Depleting Drugs:

The concomitant use of catecholamine-depleting drugs (e.g., reserpine, monoamine oxidase (MAO) inhibitors) with beta adrenergic blockers may have an additive affect and increase the risk of hypotension or bradycardia.

CYP2D6 Inhibitors:

Drugs that are strong inhibitors of CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone were shown to double metoprolol concentrations. While there is no information about moderate or weak inhibitors, these too are likely to increase metoprolol concentration. Increases in plasma concentration decrease the cardioselectivity of metoprolol [see Clinical Pharmacology (12.3)] . Monitor patients closely when the combination cannot be avoided.

Digitalis, Clonidine, and Calcium Channel Blockers:

Digitalis glycosides, clonidine, diltiazem and verapamil slow atrioventricular conduction and decrease heart rate. Concomitant use with beta blockers can increase the risk of bradycardia.

If clonidine and a beta blocker, such as metoprolol are coadministered, withdraw the beta-blocker several days before the gradual withdrawal of clonidine because beta-blockers may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, delay the introduction of beta-blockers for several days after clonidine administration has stopped.

Antidiabetic drugs (oral agents and insulin) : Dosage adjustment of the antidiabetic drug may be required.

Ion exchange resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively. Stagger the dosage of hydrochlorothiazide and ion exchange resins (e.g., cholestyramine and colestipol resins) such that hydrochlorothiazide is administered at least 4 hours before or 4-6 hours after the administration of resins to minimize the interaction.

Lithium : Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity. Monitor serum lithium concentrations during concurrent use.

Non-Steroidal Anti-Inflammatory Drugs : NSAIDs can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.

Metoprolol is a beta ₁ -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.  However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity.

The mechanism of antihypertensive effect of thiazide diuretics is unknown.

Metoprolol

Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia.

Significant beta-blocking effect (as measured by reduction of exercise heart rate) occurs within 1 hour after oral administration, and its duration is dose-related. For example, a 50% reduction of the maximum registered effect after single oral doses of 20, 50, and 100 mg occurred at 3.3, 5.0, and 6.4 hours, respectively, in normal subjects. After repeated oral dosages of 100 mg twice daily, a significant reduction in exercise systolic blood pressure was evident at 12 hours.

There is a linear relationship between the log of plasma levels and reduction of exercise heart rate.  However, antihypertensive activity does not appear to be related to plasma levels. Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihypertensive activity to dose, selection of proper dosage requires individual titration.

The onset of action of thiazides occurs in 2 hours and the peak effect at about 4 hours.  The action persists for approximately 6 to 12 hours.

Absorption

In man, absorption of metoprolol HCT is rapid and complete. Plasma levels following oral administration, however, approximate 50% of levels following intravenous administration, indicating about 50% first-pass metabolism.

Hydrochlorothiazide is rapidly absorbed, as indicated by peak plasma concentrations 1 to 2.5 hours after oral administration.  Plasma levels of the drug are proportional to dose; the concentration in whole blood is 1.6 to 1.8 times higher than in plasma.

Thiazides affect the renal tubular mechanism of electrolyte reabsorption.  At maximal therapeutic dosage, all thiazides are approximately equal in their diuretic potency. Thiazides increase excretion of sodium and chloride in approximately equivalent amounts. Natriuresis causes a secondary loss of potassium.

The mechanism of the antihypertensive effect of thiazides is unknown.  Thiazides do not affect normal blood pressure.

Effect of Food

Gastrointestinal absorption of hydrochlorothiazide is enhanced when administered with food.  Absorption is decreased in patients with congestive heart failure, and the pharmacokinetics are considerably different in these patients.

Distribution

Plasma levels achieved are highly variable after oral administration. Only a small fraction of the drug (about 12%) is bound to human serum albumin. Metoprolol is a racemic mixture of R- and S-enantiomers. Less than 5% of an oral dose of metoprolol is recovered unchanged in the urine; the rest is excreted by the kidneys as metabolites that appear to have no clinical significance.  The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. Consequently, no reduction in dosage is usually needed in patients with chronic renal failure.

Elimination

Thiazides are eliminated rapidly by the kidney. After oral administration of 25 mg to 100 mg doses, 72% to 97% of the dose is excreted in the urine, indicating dose-independent absorption. Hydrochlorothiazide is eliminated from plasma in a biphasic fashion with a terminal half-life of 10 to 17 hours. Plasma protein binding is 67.9%.  Plasma clearance is 15.9 to 30.0 L/hr; volume of distribution is 3.6 to 7.8 L/kg.

Specific Populations:

Geriatric Patients

In elderly subjects with clinically normal renal function, there are no significant differences in metoprolol pharmacokinetics compared to young subjects.

Racial or Ethnic Groups

Metoprolol is extensively metabolized by the cytochrome P450 enzyme system in the liver. The oxidative metabolism of metoprolol is under genetic control with a major contribution of the polymorphic cytochrome P450 isoform 2D6 (CYP2D6). There are marked ethnic differences in the prevalence of the poor metabolizers (PM) phenotype. Approximately 7% of Caucasians and less than 1% Asian are poor metabolizers.

CYP2D6 is absent in about 8% of Caucasians (poor metabolizers) and about 2% of most other populations. CYP2D6 can be inhibited by several drugs. Poor metabolizers of CYP2D6 will have increased (several-fold) metoprolol blood levels, decreasing metoprolol's cardioselectivity.