Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 26 January 2017

Indication(s)

INDICATIONS AND USAGE Captopril and Hydrochlorothiazide tablets are indicated for the treatment of hypertension.

The blood pressure lowering effects of captopril and thiazides are approximately additive.

This fixed combination drug may be used as initial therapy or substituted for previously titrated doses of the individual components.

When captopril and hydrochlorothiazide are given together it may not be necessary to administer captopril in divided doses to attain blood pressure control at trough (before the next dose).

Also, with such a combination, a daily dose of 15 mg of hydrochlorothiazide may be adequate.

Treatment may, therefore, be initiated with Captopril and Hydrochlorothiazide tablets 25 mg/15 mg once daily.

Subsequent titration should be with additional doses of the components (captopril, hydrochlorothiazide) as single agents or as Captopril and Hydrochlorothiazide tablets 50 mg/15 mg, 25 mg/25 mg, or 50 mg/25 mg (see DOSAGE AND ADMINISTRATION). In using Captopril and

Hydrochlorothiazide, consideration should be given to the risk of neutropenia/agranulocytosis (see WARNINGS).

Captopril and Hydrochlorothiazide may be used for patients with normal renal function, in whom the risk is relatively low.

In patients with impaired renal function, particularly those with collagen vascular disease, Captopril and Hydrochlorothiazide should be reserved for hypertensives who have either developed unacceptable side effects on other drugs, or have failed to respond satisfactorily to other drug combinations.

ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients (see WARNINGS: Captopril: Head and Neck Angioedema and Intestinal Angioedema).

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Advisory information

contraindications

CONTRAINDICATIONS CaptoprilThis product is contraindicated in patients who are hypersensitive to captopril or any other angiotensin-converting enzyme inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor).

HydrochlorothiazideHydrochlorothiazide is contraindicated in anuria.

It is also contraindicated in patients who have previously demonstrated hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs.

Special warnings and precautions

PRECAUTIONS General Captopril Impaired Renal FunctionSome patients with renal disease, particularly those with severe renal artery stenosis, have developed increases in BUN and serum creatinine after reduction of blood pressure with captopril.

Captopril dosage reduction and/or discontinuation of diuretic may be required.

For some of these patients, it may not be possible to normalize blood pressure and maintain adequate renal perfusion (see CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS: Altered Laboratory Findings).

HyperkalemiaElevations in serum potassium have been observed in some patients treated with ACE inhibitors, including captopril.

When treated with ACE inhibitors, patients at risk for the development of hyperkalemia include those with: renal insufficiency; diabetes mellitus; and those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes; or other drugs associated with increases in serum potassium.

(See PRECAUTIONS: Information for Patients and Drug Interactions: Captopril; ADVERSE REACTIONS: Altered Laboratory Findings.)

CoughPresumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy.

ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Surgery/AnesthesiaIn patients undergoing major surgery or during anesthesia with agents that produce hypotension, captopril will block angiotensin II formation secondary to compensatory renin release.

If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

HemodialysisRecent clinical observations have shown an association of hypersensitivity-like (anaphylactoid) reactions during hemodialysis with high-flux dialysis membranes (e.g., AN69) in patients receiving ACE inhibitors as medication.

In these patients, consideration should be given to using a different type of dialysis membrane or a different class of medication.

(See WARNINGS: Captopril: Anaphylactoid reactions during membrane exposure).

HydrochlorothiazidePeriodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

All patients receiving thiazide therapy should be observed for clinical signs 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 may include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

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

Interference with adequate oral electrolyte intake will also contribute to hypokalemia.

Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).

Because captopril reduces the production of aldosterone, concomitant therapy with captopril reduces the diuretic-induced hypokalemia.

Fewer patients may require potassium supplements and/or foods with a high potassium content (see Drug Interactions: Captopril: Agents Increasing Serum Potassium).

Any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease).

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 frank gout may be precipitated in certain patients receiving thiazide therapy.

Latent diabetes mellitus may become manifest during thiazide administration.

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

If progressive renal impairment becomes evident, as indicated by a rising nonprotein nitrogen or blood urea nitrogen (BUN), a careful reappraisal of therapy is necessary with consideration given to withholding or discontinuing diuretic therapy.

Thiazides may decrease serum PBI levels without signs of thyroid disturbance.

Calcium excretion is decreased by thiazides.

Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy.

The common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been seen. Thiazides should be discontinued before carrying out tests for parathyroid function.

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

Information for PatientsPatients should be advised to immediately report to their physician any signs or symptoms suggesting angioedema (e.g., swelling of face, eyes, lips, tongue, larynx and extremities; difficulty in swallowing or breathing; hoarseness) and to discontinue therapy.

(See WARNINGS: Captopril: Head and Neck Angioedema and Intestinal Angioedema.)

Patients should be told to report promptly any indication of infection (e.g., sore throat, fever), which may be a sign of neutropenia, or of progressive edema which might be related to proteinuria and nephrotic syndrome.

All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume.

Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with the physician.

Patients should be advised not to use potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes without consulting their physician.

(See PRECAUTIONS: General and Drug Interactions: Captopril; ADVERSE REACTIONS: Captopril.)

Patients should be warned against interruption or discontinuation of medication unless instructed by the physician.

Heart failure patients on captopril therapy should be cautioned against rapid increases in physical activity.

Patients should be informed that Captopril and Hydrochlorothiazide tablets should be taken one hour before meals (see DOSAGE AND ADMINISTRATION).

PregnancyFemale patients of childbearing age should be told about the consequences of second - and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester.

These patients should be asked to report pregnancies to their physicians as soon as possible.

Laboratory TestsSerum electrolyte levels should be regularly monitored (see WARNINGS: Captopril and Hydrochlorothiazide; PRECAUTIONS: General: Hydrochlorothiazide).

Drug Interactions Captopril Hypotension-Patients On Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, as well as those on severe dietary salt restrictions or dialysis, may occasionally experience a precipitous reduction of blood pressure usually within the first hour after receiving the initial dose of captopril.

The possibility of hypotensive effects with captopril can be minimized by either discontinuing the diuretic or increasing the salt intake approximately one week prior to initiation of treatment with captopril or initiating therapy with small doses (6.25 or 12.5 mg).

Alternatively, provide medical supervision for at least one hour after the initial dose.

If hypotension occurs, the patient should be placed in a supine position and, if necessary, receive an intravenous infusion of normal saline.

This transient hypotensive response is not a contraindication to further doses which can be given without difficulty once the blood pressure has increased after volume expansion.

Agents Having Vasodilator Activity: Data on the effect of concomitant use of other vasodilators in patients receiving captopril for heart failure are not available; therefore, nitroglycerin or other nitrates (as used for management of angina) or other drugs having vasodilator activity should, if possible, be discontinued before starting captopril.

If resumed during captopril therapy, such agents should be administered cautiously, and perhaps at lower dosage.

Agents Causing Renin Release: Captopril 's effect will be augmented by antihypertensive agents that cause renin release.

For example, diuretics (e.g., thiazides) may activate the renin-angiotensin-aldosterone system.

Agents Affecting Sympathetic Activity: The sympathetic nervous system may be especially important in supporting blood pressure in patients receiving captopril alone or with diuretics.

Therefore, agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) should be used with caution.

Beta-adrenergic blocking drugs add some further antihypertensive effect to captopril, but the overall response is less than additive.

Agents Increasing Serum Potassium: Since captopril decreases aldosterone production, elevation of serum potassium may occur.

Potassium-sparing diuretics such as spironolactone, triamterene, or amiloride, or potassium supplements, should be given only for documented hypokalemia, and then with caution, since they may lead to a significant increase of serum potassium.

Salt substitutes containing potassium should also be used with caution.

Inhibitors Of Endogenous

Prostaglandin Synthesis: It has been reported that indomethacin may reduce the antihypertensive effect of captopril, especially in cases of low renin hypertension.

Other nonsteroidal anti-inflammatory agents (e.g., aspirin) may also have this effect.

Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy.

These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended.

If a diuretic is also used, it may increase the risk of lithium toxicity (see PRECAUTIONS: Drug Interactions: Hydrochlorothiazide: Lithium).

HydrochlorothiazideWhen administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, Barbiturates, or Narcotics: potentiation of orthostatic hypotension may occur.

Amphotericin B, Corticosteroids, or Corticotropin (ACTH): may intensify electrolyte imbalance, particularly hypokalemia.

Monitor potassium levels; use potassium replacements if necessary.

Anticoagulants (Oral): dosage adjustments of anticoagulant medication may be necessary since hydrochlorothiazide may decrease their effects.

Antigout Medications: dosage adjustments of antigout medication may be necessary since hydrochlorothiazide may raise the level of blood uric acid.

Other Antihypertensive Medications (e.g., Ganglionic or Peripheral Adrenergic Blocking Agents): dosage adjustments may be necessary since hydrochlorothiazide may potentiate their effects.

Antidiabetic Drugs (Oral Agents and Insulin): since thiazides may elevate blood glucose levels, dosage adjustments of antidiabetic agents may be necessary.

Calcium Salts: Increased serum calcium levels due to decreased excretion may occur.

If calcium must be prescribed, monitor serum calcium levels and adjust calcium dosage accordingly.

Cardiac Glycosides: enhanced possibility of digitalis toxicity associated with hypokalemia.

Monitor potassium levels (see PRECAUTIONS: Drug Interactions:

Captopril).

Cholestyramine and Colestipol Resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.

Diazoxide: enhanced hyperglycemic, hyperuricemic, and antihypertensive effects.

Be cognizant of possible interaction; monitor blood glucose and serum uric acid levels.

Lithium: diuretic agents reduce the renal clearance of lithium and increase the risk of lithium toxicity.

These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended (see PRECAUTIONS: Drug Interactions: Captopril: Lithium).

MAO Inhibitors: dosage adjustments of one or both agents may be necessary since hypotensive effects are enhanced.

Nondepolarizing Muscle Relaxants, Preanesthetics and Anesthetics Used in Surgery (e.g., Tubocurarine Chloride and Gallamine Triethiodide): effects of these agents may be potentiated; dosage adjustments may be required.

Monitor and correct any fluid and electrolyte imbalances prior to surgery if feasible.

Nonsteroidal Anti-inflammatory Agents: in some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing or thiazide diuretics.

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

Methenamine: possible decreased effectiveness due to alkalinization of the urine.

Pressor Amines (e.g., Norepinephrine): decreased arterial responsiveness, but not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

Use caution in patients taking both medications who undergo surgery.

Administer preanesthetic and anesthetic agents in reduced dosage, and if possible, discontinue hydrochlorothiazide therapy one week prior to surgery.

Probenecid or Sulfinpyrazone: increased dosage of these agents may be necessary since hydrochlorothiazide may have hyperuricemic effects.

Drug/Laboratory Test Interactions CaptoprilCaptopril may cause a false-positive urine test for acetone.

HydrochlorothiazideHydrochlorothiazide may cause diagnostic interference of the bentiromide test.

Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenicity and fertility studies have not been conducted with captopril and hydrochlorothiazide tablets, however, in animals they have been conducted with the individual components as noted below.

Mutagenecity studies indicate that captopril in a 2:1 combination with hydrochlorothiazide was not mutagenic or clastogenic, with or without metabolic activation, in the following in_vitro assays: 1) Ames reverse-mutation in Salmonella; 2) forward mutation study in Saccharomyces pombe; 3) mitotic gene conversion test in Saccharomyces cerevisiae; and 4) sister-chromatid-exchange study in human lymphocytes.

In a cytogenetics study using human lymphocytes, there were no increases in chromosomal abnormalities without metabolic activation, nor with metabolic activation at 28 hours post-treatment.

A statistically significant increase was found at 22 hours with metabolic activation at the three concentrations tested (captopril/hydrochlorothiazide in a 2:1 combination at 5, 25, 50 mcg/mL total weight); however, there was no dose response, and the difference is probably attributable to the unusual absence of any abnormalities in the negative-control cultures in this test.

In an oral micronucleus study in mice, the captopril/hydrochlorothiazide combination (2:1 mixture at 2500 mg/kg total weight) was not genotoxic.

CaptoprilTwo-year studies with doses of 50 to 1350 mg/kg/day in mice and rats failed to show any evidence of carcinogenic potential.

Studies in rats have revealed no impairment of fertility.

HydrochlorothiazideTwo-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day).

The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in in_vitro assays using strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 of Salmonella typhimurium (Ames assay) and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in_vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophilia sex linked recessive lethal trait gene.

Positive test results were obtained only in the in_vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 mcg/mL, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation.

Animal Toxicology CaptoprilChronic oral toxicity studies were conducted in rats (2 years), dogs (47 weeks; 1 year), mice (2 years), and monkeys (1 year).

Significant drug-related toxicity included effects on hematopoiesis, renal toxicity, erosion/ulceration of the stomach, and variation of retinal blood vessels.

Reductions in hemoglobin and/or hematocrit values were seen in mice, rats, and monkeys at doses 50 to 150 times the maximum recommended human dose (MRHD).

Anemia, leukopenia, thrombocytopenia, and bone marrow suppression occurred in dogs at doses 8 to 30 times MRHD.

The reductions in hemoglobin and hematocrit values in rats and mice were only significant at 1 year and returned to normal with continued dosing by the end of the study.

Marked anemia was seen at all dose levels (8 to 30 times MRHD) in dogs, whereas moderate to marked leukopenia was noted only at 15 and 30 times MRHD and thrombocytopenia at 30 times MRHD.

The anemia could be reversed upon discontinuation of dosing.

Bone marrow suppression occurred to a varying degree, being associated only with dogs that died or were sacrificed in a moribund condition in the 1 year study.

However, in the 47-week study at a dose 30 times MRHD, bone marrow suppression was found to be reversible upon continued drug administration.

Captopril caused hyperplasia of the juxtaglomerular apparatus of the kidneys at doses 7 to 200 times the MRHD in rats and mice, at 20 to 60 times MRHD in monkeys, and at 30 times the MRHD in dogs.

Gastric erosions/ulcerations were increased in incidence at 20 and 200 times MRHD in male rats and at 30 and 65 times MRHD in dogs and monkeys, respectively.

Rabbits developed gastric and intestinal ulcers when given oral doses approximately 30 times MRHD for only five to seven days.

In the two-year rat study, irreversible and progressive variations in the caliber of retinal vessels (focal sacculations and constrictions) occurred at all dose levels (7 to 200 times MRHD) in a dose-related fashion.

The effect was first observed in the 88th week of dosing, with a progressively increased incidence thereafter, even after cessation of dosing.

Pregnancy Categories C (first trimester) and D (second and third trimesters) See WARNINGS: Captopril: Fetal/Neonatal Morbidity and Mortality.

Pregnancy-Nonteratogenic Effects HydrochlorothiazideThiazides cross the placental barrier and appear in cord blood.

The use of thiazides in pregnant women requires that the anticipated benefit be weighed against possible hazards to the fetus.

These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.

Nursing MothersBoth captopril and hydrochlorothiazide are excreted in human milk.

Because of the potential for serious adverse reactions in nursing infants from both drugs, a decision should be made whether to discontinue nursing or to discontinue therapy taking into account the importance of Captopril and Hydrochlorothiazide to the mother.

(See PRECAUTIONS: Pediatric Use.)

Pediatric UseSafety and effectiveness in pediatric patients have not been established.

There is limited experience reported in the literature with the use of captopril in the pediatric population; dosage, on a weight basis, was generally reported to be comparable to or less than that used in adults.

Infants, especially newborns, may be more susceptible to the adverse hemodynamic effects of captopril.

Excessive, prolonged and unpredictable decreases in blood pressure and associated complications, including oliguria and seizures, have been reported.

Captopril and Hydrochlorothiazide should be used in pediatric patients only if other measures for controlling blood pressure have not been effective.

Adverse reactions

ADVERSE REACTIONS CaptoprilReported incidences are based on clinical trials involving approximately 7000 patients.

Renal: About one of 100 patients developed proteinuria (see WARNINGS).

Each of the following has been reported in approximately 1 to 2 of 1000 patients and are of uncertain relationship to drug use: renal insufficiency, renal failure, nephrotic syndrome, polyuria, oliguria, and urinary frequency.

Hematologic: Neutropenia/agranulocytosis has occurred (see WARNINGS).

Cases of anemia, thrombocytopenia, and pancytopenia have been reported.

Dermatologic: Rash, often with pruritus, and sometimes with fever, arthralgia, and eosinophilia, occurred in about 4 to 7 (depending on renal status and dose) of 100 patients, usually during the first four weeks of therapy.

It is usually maculopapular, and rarely urticarial.

The rash is usually mild and disappears within a few days of dosage reduction, short-term treatment with an antihistaminic agent, and/or discontinuing therapy; remission may occur even if captopril is continued.

Pruritus, without rash, occurs in about 2 of 100 patients.

Between 7 and 10 percent of patients with skin rash have shown eosinophilia and/or positive ANA titers.

A reversible associated pemphigoid-like lesion, and photosensitivity, have also been reported.

Flushing or pallor has been reported in 2 to 5 of 1000 patients.

Cardiovascular: Hypotension may occur; see WARNINGS and PRECAUTIONS (Drug Interactions) for discussion of hypotension with captopril therapy.

Tachycardia, chest pain, and palpitations have each been observed in approximately 1 of 100 patients.

Angina pectoris, myocardial infarction, Raynaud 's syndrome, and congestive heart failure have each occurred in 2 to 3 of 1000 patients.

Dysgeusia: Approximately 2 to 4 (depending on renal status and dose) of 100 patients developed a diminution or loss of taste perception.

Taste impairment is reversible and usually self-limited (2 to 3 months) even with continued drug administration.

Weight loss may be associated with the loss of taste.

Angioedema: Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been reported in approximately one in 1000 patients.

Angioedema involving the upper airways has caused fatal airway obstruction.

(See WARNINGS: Captopril: Head and Neck Angioedema and Intestinal Angioedema and PRECAUTIONS: Information for Patients).

Cough: Cough has been reported in 0.5 to 2 % of patients treated with captopril in clinical trials (see PRECAUTIONS: General: Captopril: Cough).

The following have been reported in about 0.5 to 2 percent of patients but did not appear at increased frequency compared to placebo or other treatments used in controlled trials: gastric irritation, abdominal pain, nausea, vomiting, diarrhea, anorexia, constipation, aphthous ulcers, peptic ulcer, dizziness, headache, malaise, fatigue, insomnia, dry mouth, dyspnea, alopecia, paresthesias.

Other clinical adverse effects reported since the drug was marketed are listed below by body system.

In this setting, an incidence or causal relationship can not be accurately determined.

Body as a Whole: Anaphylactoid reactions (see WARNINGS: Captopril: Anaphylactoid and Possibly Related Reactions and PRECAUTIONS: Hemodialysis).

General: asthenia, gynecomastia.

Cardiovascular: cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.

Dermatologic: bullous pemphigus, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis.

Gastrointestinal: pancreatitis, glossitis, dyspepsia.

Hematologic: anemia, including aplastic and hemolytic.

Hepatobiliary: jaundice, hepatitis, including rare cases of necrosis, cholestasis.

Metabolic: symptomatic hyponatremia.

Musculoskeletal: myalgia, myasthenia.

Nervous/Psychiatric: ataxia, confusion, depression, nervousness, somnolence.

Respiratory: bronchospasm, eosinophilic pneumonitis, rhinitis.

Special Senses: blurred vision.

Urogenital: impotence.

As with other ACE inhibitors, a syndrome has been reported which may include: fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash or other dermatologic manifestations, eosinophilia and an elevated ESR. Fetal/Neonatal Morbidity and Mortality See WARNINGS: Captopril: Fetal/Neonatal Morbidity and Mortality.

Hydrochlorothiazide Gastrointestinal System: anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, and sialadenitis.

Central Nervous System: dizziness, vertigo, paresthesias, headache, and xanthopsia.

Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, and hemolytic anemia.

Cardiovascular: orthostatic hypotension.

Hypersensitivity: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis; cutaneous vasculitis), fever, respiratory distress including pneumonitis, and anaphylactic reactions.

Other: hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, and transient blurred vision.

Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.

Altered Laboratory Findings Serum Electrolytes: Hyperkalemia: small increases in serum potassium, especially in patients with renal impairment (see PRECAUTIONS: Captopril).

Hyponatremia: particularly in patients receiving a low sodium diet or concomitant diuretics.

BUN/Serum Creatinine: Transient elevations of BUN or serum creatinine especially in volume or salt depleted patients or those with renovascular hypertension may occur.

Rapid reduction of longstanding or markedly elevated blood pressure can result in decreases in the glomerular filtration rate and, in turn, lead to increases in BUN or serum creatinine.

Hematologic: A positive ANA has been reported.

Liver Function Tests: Elevations of liver transaminases, alkaline phosphatase, and serum bilirubin have occurred.

Usage information

Dosing and administration

DOSAGE AND ADMINISTRATION DOSAGE MUST BE INDIVIDUALIZED ACCORDING TO PATIENT 'S RESPONSE. Captopril and Hydrochlorothiazide tablets may be substituted for the previously titrated individual components.

Alternatively, therapy may be instituted with a single tablet of Captopril and Hydrochlorothiazide 25 mg/15 mg taken once daily.

For patients insufficiently responsive to the initial dose, additional captopril or hydrochlorothiazide may be added as individual components or by using Captopril and Hydrochlorothiazide tablets 50 mg/15 mg, 25 mg/25 mg or 50 mg/25 mg, or divided doses may be used.

Because the full effect of a given dose may not be attained for 6 to 8 weeks, dosage adjustments should generally be made at 6 week intervals, unless the clinical situation demands more rapid adjustment.

In general, daily doses of captopril should not exceed 150 mg and of hydrochlorothiazide should not exceed 50 mg.

Captopril and Hydrochlorothiazide tablets should be taken one hour before meals.

Dosage Adjustment in Renal ImpairmentBecause captopril and hydrochlorothiazide are excreted primarily by the kidneys, excretion rates are reduced in patients with impaired renal function.

These patients will take longer to reach steady-state captopril levels and will reach higher steady-state levels for a given daily dose than patients with normal renal function.

Therefore, these patients may respond to smaller or less frequent doses of Captopril and Hydrochlorothiazide.

After the desired therapeutic effect has been achieved, the dose intervals should be increased or the total daily dose reduced until the minimal effective dose is achieved.

When concomitant diuretic therapy is required in patients with severe renal impairment, a loop diuretic (e.g., furosemide), rather than a thiazide diuretic is preferred for use with captopril; therefore, for patients with severe renal dysfunction the captopril-hydrochlorothiazide combination tablet is not usually recommended.

(See WARNINGS:

Captopril: Anaphylactoid Reactions During Membrane Exposure and PRECAUTIONS: Hemodialysis).

More information

Category Value
Authorisation number ANDA074896
Agency product number 9G64RSX1XD
Orphan designation No
Product NDC 54868-5787,54868-4062
Date Last Revised 02-12-2010
Type HUMAN PRESCRIPTION DRUG
RXCUI 197437
Marketing authorisation holder Physicians Total Care, Inc.
Warnings USE IN PREGNANCY When used in pregnancy during the second and third trimesters, ACE Inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, Captopril and Hydroc