AfyaIndex — Drug Search

01 Risk first

Safety essentials

The information most likely to change a prescribing or dispensing decision.

Critical warning

BOXED WARNING 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 hydrochlorothiazide should be discontinued as soon as possible. See WARNINGS: Captopril: Fetal/Neonatal Morbidity and Mortality .

Contraindications

CONTRAINDICATIONS Captopril : This 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).
Hydrochlorothiazide : Hydrochlorothiazide is contraindicated in anuria.
It is also contraindicated in patients who have previously demonstrated hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs.

Precautions

WARNINGS Captopril : Anaphylactoid and Possible Related Reactions : Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including captopril) may be subject to a variety of adverse reactions, some of them serious.
Head and Neck Angioedema : Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been seen in patients treated with ACE inhibitors, including captopril.
If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal.
Emergency therapy, including but not necessarily limited to, subcutaneous administration of a 1:1000 solution of epinephrine should be promptly instituted.
Swelling confined to the face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuation of treatment
some cases required medical therapy.
(See PRECAUTIONS: Information for Patients and ADVERSE REACTIONS: Captopril .) Intestinal Angioedema : Intestinal angioedema has been reported in patients treated with ACE inhibitors.
These patients presented with abdominal pain (with or without nausea or vomiting)
in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal.
The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.
Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anaphylactoid Reactions During Desensitization : Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.

02 Point of care

Dosing matrix

Population and organ-function guidance, shown together for faster comparison.

Adult

DOSAGE & 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 Impairment: Because 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 ).

Paediatric

Pediatric Use Safety 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 un-predictable 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.

Renal

Essential monitoring; beneficial long-term in proteinuric CKD if stable creatinine/K.

CrCl 0–120: Confirm renal dosing in product SmPC / primary label.

Hepatic

Rare hepatic reactions; prodrug activation may be reduced in severe liver disease.

03 Clinical use

Use, effects & interactions

Indications

INDICATIONS & 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 ).

Adverse effects

ADVERSE REACTIONS Captopril : Reported 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

Drug interactions

Open multi-drug checker ↗

ACE inhibitor / thiazide diuretic to be used in-patients stabilized on the individual components in the same proportions.
Fixed-dose/multi-ingredient product.
Clinical details partially inherited from component monographs: Captopril.
Confirm combination SmPC for exact dosing.

04 Pharmacology

Mechanism & disposition

: The mechanism of action of captopril has not yet been fully elucidated.

Block RAS pathwayVasodilation↓ BP / proteinuria benefit

Read complete mechanism

: The mechanism of action of captopril has not yet been fully elucidated. Its beneficial effects in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. However, there is no consistent correlation between renin levels and response to the drug. Renin, an enzyme synthesized by the kidneys, is released into the circulation where it acts on a plasma globulin substrate to produce angiotensin I, a relatively inactive decapeptide. Angiotensin I is then converted by angiotensin converting enzyme (ACE) to angiotensin II, a potent endogenous vasoconstrictor substance. Angiotensin II also stimulates aldosterone secretion from the adrenal cortex, thereby contributing to sodium and fluid retention. Captopril prevents the conversion of angiotensin I to angiotensin II by inhibition of ACE, a peptidyldipeptide carboxy hydrolase. This inhibition has been demonstrated in both healthy human subjects and in animals by showing that the elevation of blood pressure caused by exogenously administered angiotensin I was attenuated or abolished by captopril. In animal studies, captopril did not alter the pressor responses to a number of other agents, including angiotensin II and norepinephrine, indicating specificity of action. ACE is identical to “bradykininase”, and captopril may also interfere with the degradation of the vasodepressor peptide, bradykinin. Increased concentrations of bradykinin or prostaglandin E 2 may also have a role in the therapeutic effect of captopril. Inhibition of ACE results in decreased plasma angiotensin II and increased plasma renin activity (PRA), the latter resulting from loss of negative feedback on renin release caused by reduction in angiotensin II. The reduction of angiotensin II leads to decreased aldosterone secretion, and, as a result, small increases in serum potassium may occur along with sodium and fluid loss. The antihypertensive effects persist for a longer period of time than does demonstrable inhibition of circulating ACE. It is not known whether the ACE present in vascular endothelium is inhibited longer than the ACE in circulating blood.

Onset

Hours; full effect weeks

Duration

12–24 hours

Route

ORAL

Absorption

occurs with peak blood levels at about one hour. The presence of food in the gastrointestinal tract reduces absorption by about 30 to 40 percent; captopril therefore should be given one hour before meals. Based on carbon-14 labeling, average minimal absorption is approximately 75...

Elimination

half-life for total radioactivity in blood is probably less than three hours. An accurate determination of

Half-life

for total radioactivity in blood is probably less than three hours. An accurate determination of half-life of unchanged captopril is not, at present, possible, but it is probably less than two hours. In patients with renal impairment, however, retention of captopril occurs (see D...

05 Special populations

Pregnancy, lactation & diet

Pregnancy

Pregnancy Female 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.

Lactation

Nursing Mothers Both 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. )

06 Kenya market

Brands & loaded prices

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Captopril+HCT