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 tartrate, a beta adrenoceptor blocker and hydrochlorothiazide (HCTZ), a thiazide diuretic, indicated for the treatment of hypertension, to lower blood pressure.

Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

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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.