For Control of Hypertension: The adult initial dose of hydrochlorothiazide capsules is one capsule given once daily whether given alone or in combination with other antihypertensives. Total daily doses greater than 50 mg are not recommended.
Hydrochlorothiazide is the 3,4-dihydro derivative of chlorothiazide. Its chemical name is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its molecular formula is CHClNOS; its molecular weight is 297.75; and its structural formula is: It is a white, or practically white, crystalline powder, which is slightly soluble in water, but freely soluble in sodium hydroxide solution. Hydrochlorothiazide capsules, for oral administration, are available containing 12.5 mg of hydrochlorothiazide, USP. In addition, each capsule also contains the following inactive ingredients: colloidal silicon dioxide, D&C yellow No. 10 aluminum lake, FD&C blue No. 1 aluminum lake, FD&C blue No. 2 aluminum lake, FD&C red No. 40 aluminum lake, gelatin, magnesium stearate, microcrystalline cellulose, pharmaceutical glaze, pregelatinized starch, propylene glycol, silicon dioxide, sodium lauryl sulfate, synthetic black iron oxide and titanium dioxide.
Hydrochlorothiazide blocks the reabsorption of sodium and chloride ions, and it thereby increases the quantity of sodium traversing the distal tubule and the volume of water excreted. A portion of the additional sodium presented to the distal tubule is exchanged there for potassium and hydrogen ions. With continued use of hydrochlorothiazide and depletion of sodium, compensatory mechanisms tend to increase this exchange and may produce excessive loss of potassium, hydrogen and chloride ions. Hydrochlorothiazide also decreases the excretion of calcium and uric acid, may increase the excretion of iodide and may reduce glomerular filtration rate. Metabolic toxicities associated with excessive electrolyte changes caused by hydrochlorothiazide have been shown to be dose-related.<br/>Pharmacokinetics and Metabolism: Hydrochlorothiazide is well absorbed (65% to 75%) following oral administration. Absorption of hydrochlorothiazide is reduced in patients with congestive heart failure. Peak plasma concentrations are observed within 1 to 5 hours of dosing, and range from 70 to 490 ng/mL following oral doses of 12.5 to 100 mg. Plasma concentrations are linearly related to the administered dose. Concentrations of hydrochlorothiazide are 1.6 to 1.8 times higher in whole blood than in plasma. Binding to serum proteins has been reported to be approximately 40% to 68%. The plasma elimination half-life has been reported to be 6 to 15 hours. Hydrochlorothiazide is eliminated primarily by renal pathways. Following oral doses of 12.5 to 100 mg, 55% to 77% of the administered dose appears in urine and greater than 95% of the absorbed dose is excreted in urine as unchanged drug. In patients with renal disease,plasma concentrations of hydrochlorothiazide are increased and the elimination half-life is prolonged. When hydrochlorothiazide capsules are administered with food, its bioavailability is reduced by 10%, the maximum plasma concentration is reduced by 20%, and the time to maximum concentration increases from 1.6 to 2.9 hours.<br/>Pharmacodynamics: Acute antihypertensive effects of thiazides are thought to result from a reduction in blood volume and cardiac output, secondary to a natriuretic effect, although a direct vasodilatory mechanism has also been proposed. With chronic administration, plasma volume returns toward normal, but peripheral vascular resistanceis decreased. The exact mechanism of the antihypertensive effect of hydrochlorothiazide is not known. Thiazides do not affect normal blood pressure. Onset of action occurs within 2 hours of dosing, peak effect is observed at about 4 hours, and activity persists for up to 24 hours.<br/>Clinical Studies: In an 87 patient 4-week double-blind, placebo controlled, parallel group trial, patients who received hydrochlorothiazide capsules had reductions in seated systolic and diastolic blood pressure that were significantly greater than those seen in patients who received placebo. In published placebo-controlled trials comparing 12.5 mg of hydrochlorothiazide to 25 mg,the 12.5 mg dose preserved most of the placebo-corrected blood pressure reduction seen with 25 mg.
Hydrochlorothiazide is contraindicated in patients with anuria. Hypersensitivity to this product or other sulfonamide derived drugs is also contraindicated.
The 12.5 mg hydrochlorothiazide capsule is a hard-shell gelatin capsule with a white opaque cap and a white opaque body axially printed with MYLAN over 810 in black ink on both the cap and body. The capsule is filled with white to off-white powder. They are available as follows: NDC 0378-0810-01bottles of 100 capsules NDC 0378-0810-05bottles of 500 capsules Store at 20��to 25��C (68��to 77��F). [See USP for Controlled Room Temperature.] Protect from light, moisture and freezing. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
dailymed-ingredient:D&C_yellow_No._10_aluminum_lake, dailymed-ingredient:FD&C_blue_No._1_aluminum_lake, dailymed-ingredient:FD&C_blue_No._2_aluminum_lake, dailymed-ingredient:FD&C_red_No._40_aluminum_lake, dailymed-ingredient:colloidal_silicon_dioxide, dailymed-ingredient:gelatin, dailymed-ingredient:magnesium_stearate, dailymed-ingredient:microcrystalline_cellulose, dailymed-ingredient:pharmaceutical_glaze, dailymed-ingredient:pregelatinized_starch, dailymed-ingredient:propylene_glycol, dailymed-ingredient:silicon_dioxide, dailymed-ingredient:sodium_lauryl_sulfate, dailymed-ingredient:synthetic_black_iron_oxide, dailymed-ingredient:titanium_dioxide
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. In the event of overdosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The oral LDof hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
The adverse reactions associated with hydrochlorothiazide have been shown to be dose related. In controlled clinical trials, the adverse events reported with doses of 12.5 mg hydrochlorothiazide once daily were comparable to placebo. The following adverse reactions have been reported for doses of hydrochlorothiazide 25 mg and greater and, within each category, are listed in the order of decreasing severity. Body as a Whole: Weakness. Cardiovascular: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs). Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia. Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia. Hypersensitivity: Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura. Metabolic: Electrolyte imbalance , hyperglycemia, glycosuria, hyperuricemia. Musculoskeletal: Muscle spasm. Nervous System/Psychiatric: Vertigo, paresthesia, dizziness, headache, restlessness. Renal: Renal failure, renal dysfunction, interstitial nephritis. Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia. Special Senses: Transient blurred vision, xanthopsia. Urogenital: Impotence. Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.
Hydrochlorothiazide capsules are indicated in the management of hypertension either as the sole therapeutic agent, or in combination with other antihypertensives. Unlike potassium sparing combination diuretic products, hydrochlorothiazide may be used in those patients in whom the development of hyperkalemia cannot be risked, including patients taking ACE inhibitors.<br/>Usage in Pregnancy: The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia. Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Diuretics are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances this edema may cause extreme discomfort which is not relieved by rest. In these cases a short course of diuretics may provide relief and may be appropriate.