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Metoprolol Tartrate And Hydrochlorothiazide

FDA Drug Information • Also known as: Metoprolol Tartrate And Hydrochlorothiazide

Brand Names
Metoprolol Tartrate And Hydrochlorothiazide
Drug Class
Thiazide Diuretic [EPC]
Route
ORAL
Dosage Form
TABLET
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Metoprolol tartrate and hydrochlorothiazide tablets, USP have the antihypertensive effect of metoprolol tartrate, a beta adrenoreceptor blocker, and hydrochlorothiazide, a thiazide diruetic. It is available as tablets for oral administration. The 50/25 tablets contain 50 mg of metoprolol tartrate and 25 mg of hydrochlorothiazide; the 100/25 tablets contain 100 mg of metoprolol tartrate and 25 mg of hydrochlorothiazide; and the 100/50 tablets contain 100 mg of metoprolol tartrate and 50 mg of hydrochlorothiazide. Metoprolol tartrate is (±)-1-(Isopropylamino)-3-[ p -(2-methoxyethyl)phenoxy]-2-propanol L-(+)-tartrate (2:1) salt, and its structural formula is: Metoprolol tartrate, USP is a white, crystalline powder. It is very soluble in water; freely soluble in methylene chloride, in chloroform, and in alcohol; slightly soluble in acetone; and insoluble in ether. Its molecular weight is 684.81. Hydrochlorothiazide is 6-Chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, and its structural formula is: Hydrochlorothiazide, USP is a white, or practically white, practically odorless, crystalline powder. It is freely soluble in sodium hydroxide solution, in n- butylamine, and in dimethylformamide; sparingly soluble in methanol; slightly soluble in water; and insoluble in ether, in chloroform, and in dilute mineral acids. Its molecular weight is 297.74. Inactive Ingredients: Anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, FD&C Yellow No. 6 Aluminum Lake, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch (corn) and sodium lauryl sulfate. Metoprolol Tartrate Structural Formula Hydrochlorothiazide Structural Formula

What Is Metoprolol Tartrate And Hydrochlorothiazide Used For?

1 INDICATIONS AND USAGE 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. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Metoprolol tartrate and hydrochlorothiazide tablets may be administered with other antihypertensive agents. Limitation of Use Metoprolol tartrate and hydrochlorothiazide tablets are not indicated for initial therapy of hypertension. If the fixed combination represents the dose titrated to the individual patient’s needs, therapy with the fixed combination may be more convenient than with the separate components. Metoprolol tartrate and hydrochlorothiazide is the combination tablet of metoprolol...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

  • Usual dose range: Hydrochlorothiazide 12.5 to 25 mg and metoprolol tartrate 100 mg dosed once daily. ( 2.1 ) 2.1 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.

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS The following adverse reactions are described in more detail elsewhere in the label;

  • Worsening angina or myocardial infarction [see Warnings and Precautions (5) ]
  • Worsening heart failure [see Warnings and Precautions (5) ]
  • Worsening AV block [see Contraindications (4) ] To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.2 Post-Marketing Experience The following adverse reactions have been reported in postmarketing experience: adverse reactions have been identified during post approval use of metoprolol tartrate and hydrochlorothiazide tablets. 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 metoprolol tartrate. 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.

    • Drug Interactions

    7 DRUG INTERACTIONS

  • Catecholamine-depleting drugs (e.g., MAO inhibitors): Hypotension, bradycardia. ( 7.1 )
  • CYP2D6 inhibitors: Increased metoprolol concentration. ( 12.3 )
  • Digitalis glycosides, clonidine, diltiazem and verapamil: Bradycardia. ( 5.4 , 7.1 )
  • Clonidine: Rebound hypertension following clonidine withdrawal. ( 7.1 )
  • Antidiabetic drugs: Dosage adjustment may be required. ( 7.2 )
  • Cholestyramine and colestipol: Reduced absorption of thiazides. ( 7.2 )
  • Lithium: Risk of lithium toxicity. ( 7.2 )
  • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic, and antihypertensive effects of diuretics. ( 7.2 ) 7.1 Drug Interactions with Metoprolol 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. 7.2 Drug Interactions with Hydrochlorothiazide 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,...

    • Contraindications

    4 CONTRAINDICATIONS 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. ( 4 )
  • Cardiogenic shock or decompensated heart failure. ( 4 )
  • Sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place. ( 4 )
  • Anuria. ( 4 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Untreated hypertension during pregnancy can lead to adverse outcomes for the mother and the fetus (see Clinical Considerations ) . Available data from published observational studies have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with metoprolol use during pregnancy. However, there are inconsistent reports of intrauterine growth restriction, preterm birth, and perinatal mortality with maternal use of beta blockers, including metoprolol, during pregnancy (see Data ) . There have been rare reports of jaundice, thrombocytopenia, and electrolyte imbalances in infants exposed to thiazide medications during pregnancy. In animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages up to 24 times, on a mg/m 2 basis, the daily dose of 200 mg in a 60-kg patient. The combination of metoprolol tartrate/hydrochlorothiazide administered to rats from mid-late gestation through lactation also produced increased post-implantation loss and decreased neonatal survival (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Consideration Disease-Associated Maternal and/or Embryo/Fetal Risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed...

    Overdosage

    10 OVERDOSAGE 10.1 Signs and Symptoms The most frequently observed signs expected with overdosage of a beta-adrenergic blocker are bradycardia and bradyarrhythmia, hypotension, heart failure, cardiac conduction disturbances and bronchospasm, atrioventricular block, hypoxia, impairment of consciousness/coma, cardiogenic shock, nausea and vomiting. With thiazide diuretics, acute intoxication is rare. The most prominent feature of overdose is acute loss of fluid, electrolytes and magnesium. Signs and symptoms of overdose may include hypotension, dizziness, muscle cramps, renal impairment or failure, and sedation/ impairment of consciousness. Altered laboratory findings can also occur (e.g., hypokalemia, hypomagnesemia, hyponatremia, hypochloremia, alkalosis, increased BUN). 10.2 Management Care should be provided at a facility that can provide appropriate supporting measures, monitoring and supervision as treatment is symptomatic and supportive and there is no specific antidote. Limited data suggest that neither metoprolol nor hydrochlorothiazide is dialyzable. If justified, gastric lavage and/or activated charcoal can be administered. Based on the expected pharmacologic actions and recommendations for other beta-adrenergic blockers and hydrochlorothiazide, the following measures should be considered when clinically warranted. Hemodialysis is unlikely to make a useful contribution to metoprolol elimination [see Clinical Pharmacology (12.3) ] . Bradycardia and Conduction Disturbances Use atropine, adrenergic-stimulating drugs or pacemaker. Hypotension or Shock Treat underlying bradycardia. Consider intravenous expansion, vasopressors, injection of glucagon (if necessary, followed by an intravenous infusion of glucagon), or intravenous administration of adrenergic drugs such as dobutamine. Heart Failure Treat bradycardia if present and support hemodynamics with inotropes if necessary. Bronchospasm Can usually be reversed by bronchodilators.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Metoprolol Tartrate and Hydrochlorothiazide Tablets, USP are available containing 50 mg or 100 mg of metoprolol tartrate, USP and 25 mg or 50 mg of hydrochlorothiazide, USP providing for the following available combinations: 50 mg/25 mg, 100 mg/25 mg or 100 mg/50 mg. The 50 mg/25 mg tablets are peach, round, scored tablets debossed with M above the score and 424 below the score on one side of the tablet and blank on the other side. They are available as follows: NDC 0378-0424-01 bottles of 100 tablets The 100 mg/25 mg tablets are peach, oval, scored tablets debossed with M to the left of the score and 434 to the right of the score on one side of the tablet and blank on the other side. They are available as follows: NDC 0378-0434-01 bottles of 100 tablets The 100 mg/50 mg tablets are peach, capsule-shaped, scored tablets debossed with M to the left of the score and 445 to the right of the score on one side of the tablet and blank on the other side. They are available as follows: NDC 0378-0445-01 bottles of 100 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.