HYDROCHLOROTHIAZIDE

Hydrochloro‑thiazide 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 C 7 H 8 ClN 3 O 4 S 2 ; its molecular weight is 297.74; 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. Hydrochloro‑thiazide is supplied as 12.5 mg capsules for oral use. Each capsule contains the following inactive ingredients: colloidal silicon dioxide, corn starch, lactose monohydrate, and magnesium stearate. The hard gelatin shell consists of gelatin, titanium dioxide, sodium lauryl sulphate, FD&C Blue #1, D&C Red #28, D&C Yellow #10, black iron oxide and shellac. Chemical Structure

Hydrochloro‑thiazide capsules are indicated in the management of hypertension either as the sole therapeutic agent, or in combination with other antihypertensives. Unlike potassium sparing combina‑tion diuretic products, hydrochloro‑thiazide capsules may be used in those patients in whom the development of hyperkalemia cannot be risked, including patients taking ACE inhibitors. Usage in Pregnancy: The rou‑tine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unneces‑sary hazard. Diuretics do not prevent development of tox‑emia 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 indi‑cated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy. Dependent edema in pregnan‑cy 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 unneces‑sary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular dis‑ease), but which is associated with edema, including general‑ized edema in the majority of pregnant women. If this edema produces discomfort, in‑creased 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.

For Control of Hypertension: The adult initial dose of hydrochloro‑thiazide 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 capsules are con‑traindicated in patients with anuria. Hypersensitivity to this product or other sulfonamide derived drugs is also con‑traindicated.

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 (see PRECAUTIONS ), hyperglycemia, glycosuria, hyperuricemia. Musculoskeletal: Muscle spasm. Nervous System/Psychiatric: Vertigo, paresthesia, dizziness, headache, restlessness. Renal: Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS ). 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. Postmarketing Experience: The following adverse reaction has been identified during post-approval use of hydrochlorothiazide. Because the reaction is reported voluntarily from a population of uncertain size, it is not possible to reliably estimate the frequency or establish a causal relationship to drug exposure. Non-melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

When given concurrently the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics: potentiation of ortho‑static hypotension may occur. Antidiabetic drugs: (oral agents and insulin) dosage adjustment of the antidiabetic drug may be required. Other antihypertensive drugs: ‑additive effect or potentiation. Cholestyramine and colestipol resins: Cholestyramine and colestipol resins bind the hydrochlorothiazide and re‑duce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively. Corticosteroid, ACTH: intensi‑fied electrolyte depletion, particularly hypokalemia. Pressor amines (e.g., norepinephrine): possible decreased response to pressor amines but not sufficient to preclude their use. Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): possible increased responsiveness to the muscle relaxant. Lithium: generally should not be given with diuretics. Diuretic agents reduce the renal clear‑ance of lithium and greatly increase the risk of lithium tox‑icity. Refer to the package insert for lithium preparations before use of such preparations with hydrochloro‑thiazide. Non-steroidal anti-inflammatory drugs: In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. When hydrochloro‑thiazide and non-steroidal anti-inflammatory agents are used concomitantly, the patients should be observed closely to determine if the desired effect of the diuretic is obtained.