Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 26 January 2017
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
HydrochlorothiazideHydrochlorothiazide is contraindicated in anuria.
It is also contraindicated in patients who have previously demonstrated hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs.
PRECAUTIONS General Captopril
Captopril dosage reduction and/or
For some of these patients, it may not be possible to normalize
HyperkalemiaElevations in serum potassium have been observed in some patients treated with
When treated with
(See PRECAUTIONS: Information for Patients and Drug Interactions: Captopril;
CoughPresumably due to the
Surgery/AnesthesiaIn patients undergoing major surgery or during anesthesia with agents that produce hypotension,
If hypotension occurs and is considered to be due to this mechanism,
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
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
All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte
Warning signs or symptoms of fluid and electrolyte
Hypokalemia can sensitize or
Because captopril reduces the production of aldosterone, concomitant therapy with captopril reduces the diuretic-induced hypokalemia.
Dilutional hyponatremia may occur in edematous patients in hot weather;
Hyperuricemia may occur or
Latent diabetes mellitus may become manifest during thiazide administration.
Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on
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;
(See WARNINGS: Captopril: Head and Neck Angioedema and Intestinal Angioedema.)
Patients should be told to report
Other causes of volume
Patients should be advised not to use potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes
(See PRECAUTIONS: General and Drug Interactions: Captopril;
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
These patients should be asked to report pregnancies to their physicians as soon as
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
The possibility of hypotensive effects with captopril can be minimized by either
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
Agents Having Vasodilator Activity: Data on the effect of concomitant use of other vasodilators in patients receiving captopril for
If resumed during captopril therapy, such agents should be administered cautiously, and perhaps at lower dosage.
Agents Causing Renin Release:
For example, diuretics (e.g., thiazides) may activate the renin-angiotensin-aldosterone system.
Therefore, agents affecting
Potassium-sparing diuretics such as spironolactone, triamterene, or amiloride, or potassium supplements, should be given only for documented hypokalemia, and then with
Salt substitutes containing potassium should also be used with
Inhibitors Of Endogenous
Prostaglandin Synthesis: It has been reported that indomethacin may reduce the antihypertensive effect of captopril, especially in cases of
Other nonsteroidal anti-inflammatory agents (e.g., aspirin) may also have this effect.
These drugs should be coadministered with
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
Monitor potassium levels; use potassium replacements if necessary.
Anticoagulants (Oral): dosage
Antigout Medications: dosage
Other Antihypertensive Medications (e.g., Ganglionic or Peripheral Adrenergic Blocking Agents): dosage
Antidiabetic Drugs (Oral Agents and Insulin): since thiazides may elevate
If calcium must be prescribed, monitor serum calcium levels and
Monitor potassium levels (see PRECAUTIONS: Drug Interactions:
Cholestyramine and Colestipol Resins:
Lithium: diuretic agents reduce the renal clearance of lithium and increase the risk of lithium toxicity.
These drugs should be coadministered with
MAO Inhibitors: dosage
Nondepolarizing Muscle Relaxants, Preanesthetics and Anesthetics Used in Surgery (e.g., Tubocurarine Chloride and Gallamine Triethiodide): effects of these agents may be potentiated;
Monitor and correct any fluid and electrolyte
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,
Methenamine: possible decreased
Pressor Amines (e.g., Norepinephrine): decreased arterial responsiveness, but not
Administer preanesthetic and anesthetic agents in
Probenecid or Sulfinpyrazone:
Drug/Laboratory Test Interactions CaptoprilCaptopril may cause a false-positive
HydrochlorothiazideHydrochlorothiazide may cause diagnostic
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
A statistically significant
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/
HydrochlorothiazideTwo-year feeding studies in mice and
The NTP, however, found
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
Animal Toxicology CaptoprilChronic oral toxicity studies were conducted in
Significant drug-related toxicity included effects on hematopoiesis, renal toxicity, erosion/ulceration of the stomach, and variation of retinal
Reductions in hemoglobin and/or hematocrit values were seen in mice,
Anemia, leukopenia, thrombocytopenia, and bone marrow
The reductions in hemoglobin and hematocrit values in
Marked anemia was seen at all dose levels (8 to 30 times MRHD) in dogs, whereas
The anemia could be reversed upon discontinuation of dosing.
However, in the 47-week study at a dose 30 times MRHD, bone marrow
Captopril caused hyperplasia of the juxtaglomerular apparatus of the kidneys at doses 7 to 200 times the MRHD in
In the two-year rat study,
The effect was first observed in the 88th week of dosing, with a progressively
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
Nursing MothersBoth captopril and hydrochlorothiazide are excreted in human milk.
Because of the
(See PRECAUTIONS: Pediatric Use.)
Pediatric UseSafety and
Infants, especially newborns, may be more
Captopril and Hydrochlorothiazide should be used in pediatric patients only if other measures for controlling
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
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
It is usually maculopapular, and rarely urticarial.
Between 7 and 10 percent of patients with skin rash have shown eosinophilia and/or
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.
Angina pectoris, myocardial infarction, Raynaud 's syndrome, and
Dysgeusia: Approximately 2 to 4 (depending on renal status and dose) of 100 patients developed a
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
(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
In this setting,
Body as a Whole: Anaphylactoid reactions (see WARNINGS: Captopril: Anaphylactoid and Possibly Related Reactions and PRECAUTIONS: Hemodialysis).
General: asthenia, gynecomastia.
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
Metabolic: symptomatic hyponatremia.
Musculoskeletal: myalgia, myasthenia.
Respiratory: bronchospasm, eosinophilic pneumonitis, rhinitis.
As with other
Hydrochlorothiazide Gastrointestinal System: anorexia, gastric
Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, and hemolytic anemia.
Cardiovascular: orthostatic hypotension.
Hypersensitivity: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis; cutaneous vasculitis), fever, respiratory
Other: hyperglycemia, glycosuria, hyperuricemia, muscle spasm,
Altered Laboratory Findings Serum Electrolytes: Hyperkalemia: small
Hyponatremia: particularly in patients receiving a
BUN/Serum Creatinine: Transient elevations of BUN or serum creatinine especially in volume or salt
Liver Function Tests: Elevations of liver transaminases, alkaline phosphatase, and serum bilirubin have occurred.
DOSAGE AND ADMINISTRATION DOSAGE MUST BE INDIVIDUALIZED
Alternatively, therapy may be instituted with a single tablet of Captopril and Hydrochlorothiazide 25 mg/15 mg taken once daily.
Because the full effect of a
Captopril and Hydrochlorothiazide tablets should be taken one hour before meals.
These patients will take longer to reach steady-state captopril levels and will reach higher steady-state levels for a
Therefore, these patients may respond to smaller or less frequent doses of Captopril and Hydrochlorothiazide.
After the desired therapeutic effect has been achieved,
Captopril: Anaphylactoid Reactions During Membrane Exposure and PRECAUTIONS: Hemodialysis).
|Agency product number||9G64RSX1XD|
|Date Last Revised||02-12-2010|
|Type||HUMAN PRESCRIPTION DRUG|
|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|