HEMICLOR

HEMICLOR (chlorthalidone) is an antihypertensive/diuretic supplied as 12.5 mg tablets for oral use. Chlorthalidone is a monosulfamyl diuretic that differs chemically from thiazide diuretics in that a double ring system is incorporated in its structure. It is a racemic mixture of 2-chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl) benzenesulfonamide, with the following structural formula: Molecular Formula: C 14 H 11 ClN 2 O 4 S Molecular Weight: 338.8 g/mol Chlorthalidone is practically insoluble in water, soluble in acetone and in methanol, slightly soluble in 96% ethanol, practically insoluble in dichloromethane. It dissolves in diluted solutions of alkali hydroxides. Each HEMICLOR tablet contains the following inactive ingredients: calcium stearate, colloidal silicon dioxide, microcrystalline cellulose, pregelatinized starch and sodium starch glycolate. structure

HEMICLOR is a thiazide-like diuretic indicated for the treatment of hypertension in adults, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions ( 1.1 ). 1.1 Hypertension HEMICLOR is indicated for the treatment of hypertension in adults, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal 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 the class to which this drug principally belongs. 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 one 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 blood 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. HEMICLOR may be used alone or in combination with other antihypertensives.

The recommended starting dose is 12.5 mg or 25 mg orally once daily ( 2.1 ). Dose may be doubled after 2 to 4 weeks as needed based on individual response, up to a maximal dose of 100 mg once daily ( 2.1 ) 2.1 Recommended Dosage Therapy should be initiated with the lowest possible dose. The recommended adult initial dose of HEMICLOR is 12.5 mg or 25 mg given orally with food once daily. Double the dosage every 2 to 4 weeks as needed based on individual patient response, up to a maximum of 100 mg once daily. Dosage above 100 mg daily usually does not increase effectiveness.

Chlorthalidone is contraindicated in patients with anuria, or hypersensitivity to chlorthalidone or other sulfonamide-derived drugs. Anuria ( 4 ). Hypersensitivity to chlorthalidone or other sulfonamide-derived drugs ( 4 ).

The following adverse reactions are described in more detail elsewhere in the label; Acute Kidney Injury [see Warnings and Precautions (5.1) ] Electrolyte Abnormalities [see Warnings and Precautions (5.2) ] Metabolic Disturbances [see Warnings and Precautions (5.3) ] The following adverse reactions have been observed with chlorthalidone, but there is not enough systematic collection of data to support an estimate of their frequency. Gastrointestinal System Reactions: anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis. Central Nervous System Reactions: dizziness, paresthesias, headache. Hematologic Reactions: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia. Dermatologic-Hypersensitivity Reactions: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis) (cutaneous vasculitis), Lyell’s syndrome (toxic epidermal necrolysis). Cardiovascular Reaction: Orthostatic hypotension. Other Adverse Reactions: muscle spasm, weakness, restlessness, impotence, xanthopsia. The most frequently expected adverse drug reactions among patients receiving thiazide-like diuretics are electrolyte abnormalities and metabolic disturbances ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Effect of chlorthalidone on other drugs Insulin requirements in diabetic patients may be increased, decreased or unchanged. Higher dosage of oral hypoglycemic agents may be required. Chlorthalidone may increase the responsiveness to tubocurarine. Chlorthalidone may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use. Lithium renal clearance is reduced by chlorthalidone, increasing the risk of lithium toxicity. Monitor serum lithium levels during concomitant use. Insulin requirements and oral hypoglycemic agent dosages may require adjustments ( 7 ). Possible increased responsiveness to tubocurarine ( 7 ). Possible decreased arterial responsiveness to norepinephrine ( 7 ). Lithium renal clearance is reduced by chlorthalidone, increasing the risk of lithium toxicity ( 7 ).