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Generic name: reserpine and chlorothiazide
Dosage form: Tablets
Drug class: Antiadrenergic agents (peripheral) with thiazides

Medically reviewed by Last updated on Feb 19, 2021.


This fixed combination drug is not indicated for initial therapy of hypertension. Hypertension requires therapy titrated to the individual patient. If the fixed combination represents the dosage so determined, its use may be more convenient in patient management. The treatment of hypertension is not static, but must be re-evaluated as conditions in each patient warrant.

Diupres Description

Diupres1 combines two antihypertensives: DIURIL1 (Chlorothiazide) and reserpine.

Registered trademark of MERCK & CO., Inc., COPYRIGHT © MERCK & CO., Inc., 1986 All rights reserved


Chlorothiazide is a diuretic and antihypertensive. Its chemical name is 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H6ClN3O4S2 and its structural formula is:

Chlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 295.73, which is very slightly soluble in water, but readily soluble in dilute aqueous sodium hydroxide. It is soluble in urine to the extent of about 150 mg per 100 mL at pH 7.


The chemical name of reserpine is 11, 17α-dimethoxy-18β-[(3,4,5-trimethoxybenzoyl)oxy]-3β, 20α-yohimban-16β-carboxylic acid methyl ester. It is a crystalline alkaloid derived from Rauwolfia serpentina. Its empirical formula is C33H40N2O9 and its structural formula is:

Reserpine is a white or pale buff to slightly yellowish, odorless, crystalline powder with a molecular weight of 608.69, is insoluble in water and freely soluble in glacial acetic acid.

Diupres is supplied as tablets in two strengths for oral use:

Diupres-2501, contains 250 mg of chlorothiazide and 0.125 mg of reserpine.

Diupres-5001, contains 500 mg of chlorothiazide and 0.125 mg of reserpine,

Each tablet contains the following inactive ingredients: FD&C Red 3, gelatin, lactose, magnesium stearate, starch and talc.

Diupres - Clinical Pharmacology


The mechanism of the antihypertensive effect of thiazides is unknown. Chlorothiazide does not usually affect normal blood pressure.

Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy.

Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.

After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours.


Reserpine has antihypertensive, bradycardic, and tranquilizing properties. It lowers arterial blood pressure by depletion of catecholamines. Reserpine is beneficial in relieving anxiety, tension, and headache in the hypertensive patient. It acts at the hypothalamic level of the central nervous system to promote relaxation without hypnosis or analgesia. The sleep pattern shown by the electroencephalogram following barbiturates does not occur with this drug. In laboratory animals spontaneous activity and response to external stimuli are decreased, but confusion or difficulty of movement is not evident.

The bradycardic action of reserpine promotes relaxation and may eliminate sinus tachycardia. It is most pronounced in subjects with sinus tachycardia and usually is not prominent in persons with a normal pulse rate.

Miosis, relaxation of the nictitating membrane, ptosis, hypothermia, and increased gastrointestinal activity are noted in animals given reserpine, sometimes in subclinical doses. None of these effects, except increased gastrointestinal activity, has been found to be clinically significant in man with therapeutic doses.

Pharmacokinetics and Metabolism


Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life of chlorothiazide is 45-120 minutes. After oral doses, 10-15 percent is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.


Oral reserpine is rapidly absorbed from the gastrointestinal tract. Methylreserpate and trimethoxybenzoic acid are the primary metabolites which result from hydrolytic cleavage of reserpine. Maximal blood levels are achieved approximately 2 hours after the oral dosage of 3H-reserpine to six normal volunteers; within 96 hours approximately 8 percent was excreted in urine and 62 percent in feces. Reserpine appears in human breast milk. Reserpine crosses the placental barrier in guinea pigs.

Indications and Usage for Diupres

Hypertension (see box warning).


Chlorothiazide is contraindicated in anuria.

Diupres is contraindicated in hypersensitivity to chlorothiazide or other sulfonamide-derived drugs or to reserpine.

Electroshock therapy should not be given to patients while on reserpine, as severe and even fatal reactions have been reported with minimal convulsive electroshock dosage. After discontinuing reserpine, allow at least seven days before starting electroshock therapy.

Reserpine is contraindicated in patients:
–with active peptic ulcer
–with ulcerative colitis
–with a history of mental depression, especially suicidal tendencies
–on therapy with monoamine oxidase (MAO) inhibitors.



Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Thiazides may add to or potentiate the action of other antihypertensive drugs.

Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.

Lithium generally should not be given with diuretics (see PRECAUTIONS, Drug Interactions).


Reserpine may cause mental depression. Recognition of depression may be difficult because this condition may often be disguised by somatic complaints (masked depression). The drug should be discontinued at first signs of depression such as despondency, early morning insomnia, loss of appetite, impotence or self-deprecation. Drug-induced depression may persist for several months after drug withdrawal and may be severe enough to result in suicide.

The occurrence of mental depression due to reserpine in doses of 0.25 mg daily or less is unusual. In any event, Diupres should be discontinued at the first sign of depression.




All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting,

Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present or after prolonged therapy.

Interference with adequate oral electrolyte intake will contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Hypokalemia may be avoided or treated by use of potassium sparing diuretics or potassium supplements such as foods with a high potassium content.

Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.

Dilutional hyponatremia may occur in edematous patients in hot weather. Appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazides.

In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.

The antihypertensive effect of the drug may be enhanced in the postsympathectomy patient.

If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.

Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.


Since reserpine may increase gastric secretion and motility, it should be used cautiously in patients with a history of peptic ulcer, ulcerative colitis, or other gastrointestinal disorder. This compound may precipitate biliary colic in patients with gallstones, or bronchial asthma in susceptible persons.

Reserpine may cause hypotension including orthostatic hypotension.

Anxiety or depression, as well as psychosis, may develop during reserpine therapy. If depression is present when therapy is begun, it may be aggravated. Mental depression is unusual with reserpine doses of 0.25 mg daily or less. In any case, Diupres should be discontinued at the first sign of depression. Extreme caution should be used in treating patients with a history of mental depression, and the possibility of suicide should be kept in mind.

As with most antihypertensive therapy, caution should be exercised when treating hypertensive patients with renal insufficiency, since they adjust poorly to lowered blood pressure.

When two or more antihypertensives are given, the individual dosages may have to be reduced to prevent excessive drop in blood pressure. In hypertensive patients with coronary artery disease, it is important to avoid a precipitous drop in blood pressure.

Laboratory Tests

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals.

Drug Interactions


When given concurrently the following drugs may interact with thiazide diuretics.

Alcohol, barbiturates, or narcotics– potentiation of orthostatic 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– Both cholestyramine and colestipol resins have the potential of binding thiazide diuretics and reducing diuretic absorption from the gastrointestinal tract.

Corticosteroids, ACTH– intensified 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 clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with Diupres.

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. Therefore, when Diupres and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.


In hypertensive patients on reserpine therapy significant hypotension and bradycardia may develop during surgical anesthesia. The anesthesiologist should be aware that reserpine has been taken, since it may be necessary to give vagal blocking agents parenterally to prevent or reverse hypotension and/or bradycardia.

Use reserpine cautiously with digitalis and quinidine; cardiac arrhythmias have occurred with reserpine preparations.

Barbiturates enhance the central nervous system depressant effects of reserpine.

Monoamine oxidase (MAO) inhibitors: See CONTRAINDICATIONS.

Drug/Laboratory Test Interactions

Thiazides should be discontinued before carrying out tests for parathyroid function (see PRECAUTIONS, General).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity and mutagenicity studies have not been conducted with combinations of reserpine/chlorothiazide.

In a two-litter study in the rat at an oral dose of 50.0/0.25 mg/kg, the combination of chlorothiazide/reserpine did not impair fertility or produce abnormalities in the fetus.


Carcinogenicity studies have not been done with chlorothiazide.

Chlorothiazide was not mutagenic in vitro in the Ames microbial mutagen test (using a maximum concentration of 5 mg/plate and Salmonella typhimurium strains TA 98 and TA 100) and was not mutagenic and did not induce mitotic non-disjunction in diploid-strains of Aspergillus nidulans.

Chlorothiazide had no adverse effects on fertility in female rats at doses up to 60 mg/kg/day and no adverse effects on fertility in male rats at doses up to 40 mg/kg/day.


Reserpine at a concentration of 1 to 5000 mcg/plate had no mutagenic activity against four strains of S. typhimurium in vitro in the Ames microbial mutagen test with or without metabolic activation. Reserpine did not induce malignant transformation of mouse fibroblasts in vitro at concentrations of 0.3 to 10 mcg/mL.

A few chromosomal aberrations were induced by reserpine in vitro in cultured mouse mammary carcinoma cells but were considered negative in this study. The drug did not produce chromosomal aberrations in human peripheral leucocyte cultures although an increase in mitotic figures occurred. One study reported chromosomal aberrations and dominant lethal mutations in mice at doses up to 10 mg/kg of reserpine in the form of a pharmaceutical preparation. Another study did not show dominant lethal mutations in mice at IP doses of 0.92 and 4.6 mg/kg of reserpine.

Reserpine did not impair fertility in a two-litter study in the rat at an oral dose of 0.025 mg/kg.

Rodent studies have shown that reserpine is an animal tumorigen, causing an increased incidence of mammary fibroadenomas in female mice, malignant tumors of the seminal vesicle in male mice, and malignant adrenal medullary tumors in male rats. These findings arose in two year studies in which the drug was administered in the feed at concentrations of 5 and 10 ppm – about 100 to 300 times the usual human dose. The breast neoplasms are thought to be related to reserpine's prolactin-elevating effect. Several other prolactin-elevating drugs have also been associated with an increased incidence of mammary neoplasia in rodents.

The extent to which these findings indicate a risk to humans is uncertain. Tissue culture experiments show that about one-third of human breast tumors are prolactin-dependent in vitro, a factor of considerable importance if the use of the drug is contemplated in a patient with previously detected breast cancer. The possibility of an increased risk of breast cancer in reserpine users has been studied extensively; however, no firm conclusion has emerged. Although a few epidemiologic studies have suggested a slightly increased risk (less than twofold in all studies except one) in women who have used reserpine, other studies of generally similar design have not confirmed this. Epidemiologic studies conducted using other drugs (neuroleptic agents) that, like reserpine, increase prolactin levels and therefore would be considered rodent mammary carcinogens, have not shown an association between chronic administration of the drug and human mammary tumorigenesis. While long-term clinical observation has not suggested such an association, the available evidence is considered too limited to be conclusive at this time. An association of reserpine intake with pheochromocytoma or tumors of the seminal vesicles has not been explored.


Use of diuretics during normal pregnancy 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 toxemia.

Teratogenic Effects - Pregnancy Category C

There are no adequate and well-controlled studies with Diupres or other combinations of reserpine/chlorothiazide in animals or pregnant women. Diupres may cause fetal harm when given to a pregnant woman. Diupres should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Reserpine: Reproduction studies in rats have shown that reserpine is teratogenic at doses of 1-2 mg/kg (125-250 times the maximum recommended human dose) IM or IP given early in pregnancy. A variety of abnormalities was produced including anophthalmia, absence of axial skeleton, hydronephrosis, etc. Pregnancy in rabbits was interrupted when doses as low as 0.04 mg/kg (10 times the maximum recommended human dose) were given early or late in pregnancy.

Chlorothiazide: Thiazides cross the placental barrier and appear in cord blood.

Although reproduction studies performed with chlorothiazide doses of 50 mg/kg/day in rabbits, 60 mg/kg/day in rats and 500 mg/kg/day in mice revealed no external abnormalities of the fetus or impairment of growth and survival of the fetus due to chlorothiazide, such studies did not include complete examinations for visceral and skeletal abnormalities.

Nonteratogenic Effects

Reserpine: Reserpine has been demonstrated to cross the placental barrier in guinea pigs with depression of adrenal catecholamine stores in the newborn. There is some evidence that side effects such as nasal congestion, lethargy, depressed Moro reflex, and bradycardia may appear in infants born of reserpine-treated mothers.

Chlorothiazide: Chlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.

Nursing Mothers

Thiazides and reserpine appear in breast milk. Because of the potential for serious adverse reactions in nursing infants from Diupres, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of Diupres in pediatric patients have not been established.

Adverse Reactions

The following adverse reactions have been reported and, within each category, are listed in 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, paresthesias, 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.


Cardiovascular: Angina pectoris, arrhythmia, premature ventricular contractions, other direct cardiac effects (e.g., fluid retention, congestive heart failure), bradycardia.

Digestive: Vomiting, diarrhea, nausea, hypersecretion and increased motility, anorexia, dryness of mouth, increased salivation.

Hematologic: Thrombocytopenia purpura, excessive bleeding following prostatic surgery.

Hypersensitivity: Pruritis, rash, flushing of skin.

Metabolic: Weight gain.

Musculoskeletal: Muscular aches.

Nervous System/Psychiatric: Mental depression, dull sensorium, syncope, paradoxical anxiety, excessive sedation, nightmares, headache, dizziness, nervousness, parkinsonism (usually reversible with decreased dosage or discontinuance of therapy).

Respiratory: Dyspnea, epistaxis, nasal congestion, enhanced susceptibility to colds.

Special Senses: Optic atrophy, uveitis, deafness, glaucoma, conjunctival injection, blurred vision.

Urogenital: Dysuria, impotence, decreased libido, nonpuerperal lactation.


Overdosage may lead to excessive sedation, mental depression, severe hypotension, extrapyramidal reactions.

There is no specific antidote. 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. In the event of severe hypotension from the reserpine component, intravenous use of a vasopressor is indicated [e.g., ARAMINE1 (Metaraminol Bitartrate), levarterenol, phenylephrine]. Anticholinergics may be needed to relieve gastrointestinal distress from reserpine. Because the effects of the rauwolfia alkaloids are prolonged, the patient should be closely observed for at least 72 hours.

Reserpine is not dialyzable. The degree to which chlorothiazide is removed by hemodialysis has not been established.

The oral LD50 of chlorothiazide is 8.5 g/kg, greater than 10 g/kg, and greater than 1 g/kg, in the mouse, rat and dog, respectively. The oral LD50 of reserpine in the mouse is 390 mg/kg.

Diupres Dosage and Administration

The initial dosage of Diupres should conform to the dosages of the individual components established during titration (see box warning).

The usual adult dosage of Diupres-2501 is 1 or 2 tablets once or twice a day; that of Diupres-5001 is 1 tablet once or twice a day.

Dosage may require adjustment according to the blood pressure response of the patient. For maintenance, dosage should be adjusted to the lowest requirement of the individual patient. Doses higher than 0.25 mg daily of reserpine should be used cautiously, because occurrence of serious mental depression and other side effects may increase considerably (see WARNINGS).

How is Diupres Supplied

No. 3261 — Tablets Diupres-250 are pink, round, scored, compressed tablets, coded MSD 230 on one side and Diupres on the other. Each tablet contains 250 mg of chlorothiazide and 0.125 mg of reserpine. They are supplied as follows:

NDC 0006-0230-68 in bottles of 100

NDC 0006-0230-82 in bottles of 1000.

No. 3262 — Tablets Diupres-500 are pink, round, scored, compressed tablets, coded MSD 405 on one side and Diupres on the other. Each tablet contains 500 mg of chlorothiazide and 0.125 mg of reserpine. They are supplied as follows:

NDC 0006-0405-68 in bottles of 100

NDC 0006-0405-82 in bottles of 1000.


Keep container tightly closed. Protect from light, moisture, freezing, -20°C (-4°F) and store at room temperature, 15-30°C (59-86°F).

Dist. by: MERCK & CO., Inc., West Point, PA 19486, USA

Issued March 1995

Printed in USA


reserpine and chlorothiazide tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0006-0230
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
reserpine (reserpine) reserpine 0.125 mg
chlorothiazide (chlorothiazide) chlorothiazide 250 mg
Inactive Ingredients
Ingredient Name Strength
FD&C Red 3
magnesium stearate
Product Characteristics
Color PINK (Pink) Score 2 pieces
Shape ROUND (Round) Size 9mm
Flavor Imprint Code MSD;230;Diupres
Coating false Symbol false
# Item Code Package Description
1 NDC:0006-0230-68 100 TABLET (100 TABLET) in 1 BOTTLE
2 NDC:0006-0230-82 1000 TABLET (1000 TABLET) in 1 BOTTLE
reserpine and chlorothiazide tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0006-0405
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
reserpine (reserpine) reserpine 0.125 mg
chlorothiazide (chlorothiazide) chlorothiazide 500 mg
Inactive Ingredients
Ingredient Name Strength
FD&C Red 3
magnesium stearate
Product Characteristics
Color PINK (Pink) Score 2 pieces
Shape ROUND (Round) Size 11mm
Flavor Imprint Code MSD;405;Diupres
Coating false Symbol false
# Item Code Package Description
1 NDC:0006-0405-68 100 TABLET (100 TABLET) in 1 BOTTLE
2 NDC:0006-0405-82 1000 TABLET (1000 TABLET) in 1 BOTTLE
Labeler - Merck & Co., Inc.
Merck & Co., Inc.