Captopril (Monograph)

Drug class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA class: CV800
CAS number: 62571-86-2

Captopril is also contained as an ingredient in the following combinations:
Captopril and Hydrochlorothiazide

Medically reviewed by Drugs.com on Oct 26, 2023. Written by ASHP.

Warning

May cause fetal and neonatal morbidity and mortality if used during pregnancy.⁴⁰¹ ⁴⁰² (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
If pregnancy is detected, discontinue captopril as soon as possible.¹¹⁵ ⁴⁰²

Introduction

Sulfhydryl ACE inhibitor.¹ ³ ⁴ ⁵

Uses for Captopril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).¹¹⁵ ³¹⁷ ¹²⁰⁰

ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ¹²⁰⁰ While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.⁵⁰¹ ⁵⁰² ⁵⁰⁴ ¹²⁰⁰

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).⁵⁰¹ ⁵⁰² ⁵⁰³ ⁵⁰⁴ ⁵¹⁵ ¹²⁰⁰ ¹²⁰¹

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.¹²⁰⁰ (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200
Category	SBP (mm Hg)		DBP (mm Hg)
Normal	<120	and	<80
Elevated	120–129	and	<80
Hypertension, Stage 1	130–139	or	80–89
Hypertension, Stage 2	≥140	or	≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.¹²⁰⁰ However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.⁵⁰¹ ⁵⁰³ ⁵⁰⁴ ⁵⁰⁵ ⁵⁰⁶ ⁵⁰⁷ ⁵⁰⁸ ⁵¹⁵ ⁵²³ ⁵²⁶ ⁵³⁰ ¹²⁰⁰ ¹²⁰¹ ¹²⁰⁷ ¹²⁰⁹ ¹²²² ¹²²³ ¹²²⁹

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.¹²⁰⁰ In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.¹²⁰⁰ These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.¹²⁰⁰ ¹²⁰² ¹²¹⁰

Other hypertension guidelines generally have based target BP goals on age and comorbidities.⁵⁰¹ ⁵⁰⁴ ⁵³⁶ Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with⁵⁰¹ ⁵⁰⁴ ⁵³⁶ those recommended by the 2017 ACC/AHA hypertension guideline.¹²⁰⁰

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the current ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.¹²²² ¹²²³ ¹²²⁴ ¹²²⁹

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient’s BP treatment goal.¹²⁰⁰ ¹²²⁰

For decisions regarding when to initiate drug therapy (BP threshold), the current ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.¹²⁰⁰ ¹²⁰⁷ ASCVD risk assessment recommended by ACC/AHA for all adults with hypertension.¹²⁰⁰

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).¹²⁰⁰

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.¹²⁰⁰

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.¹²⁰⁰ Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.⁵⁰² ¹²⁰⁰

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.¹²⁰⁰ Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.¹²⁰⁰

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.³⁷⁹ ³⁸⁰ ³⁸⁶ ³⁹⁹ ⁴⁰⁰ ⁵⁰¹ ⁵⁰⁴ ¹²⁰⁰ However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.¹²⁰⁰

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.⁵⁰¹ ⁵⁰² ⁵⁰⁴ ⁵²³ ⁵²⁴ ⁵²⁵ ⁵²⁶ ⁵²⁷ ⁵³⁴ ⁵³⁵ ⁵³⁶ ⁵⁴³ ¹²⁰⁰ ¹²¹⁴ ¹²¹⁵

Has been used in the management of hypertensive urgencies^{† [off-label]}.²³¹ ²³² ²³³ ²³⁴ ²³⁵ ²³⁶ ²³⁷ ²³⁸ ³¹³ ³¹⁴

Diabetic Nephropathy

Management of diabetic nephropathy manifested by proteinuria (urinary protein excretion >500 mg/24 hours) in patients with type 1 diabetes mellitus and diabetic retinopathy.¹¹⁵ ²⁶² ²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁸ ²⁶⁹

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.⁵³⁵ ⁵³⁶ ¹²³²

Heart Failure

Management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).¹¹⁵ ²¹⁰ ²⁴⁶ ²⁴⁷ ²⁴⁸ ²⁴⁹ ²⁵⁰ ²⁵² ²⁵³ ²⁵⁴ ²⁵⁶ ²⁵⁷ ²⁹² ³⁰⁴ ³²⁰ ⁵²⁴ ⁷⁰⁰

Some evidence indicates that therapy with an ACE inhibitor may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.⁷⁰⁰ ⁷⁰²

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.⁷⁰⁰ ⁷⁰¹ ⁷⁰³

Left Ventricular Dysfunction After Acute MI

Treatment of clinically stable patients with left ventricular dysfunction (ejection fraction ≤40%) to improve survival following MI and to reduce the incidence of overt heart failure and subsequent hospitalizations for heart failure.¹¹⁵ ⁵²⁴

Expert guidelines recommend initiation of an oral ACE inhibitor within the first 24 hours of acute MI in patients with an anterior infarct, heart failure, or ejection fraction ≤40% who do not have any contraindications (e.g., hypotension, shock, renal dysfunction).⁵²⁷ Use with caution (and with gradual upward titration) during initial postinfarction period because of the possibility of hypotension or renal dysfunction.⁵²⁷ ¹¹⁰⁰

Continue therapy indefinitely in patients with left ventricular dysfunction or other compelling indications (e.g., hypertension, diabetes mellitus, CKD).⁵²⁵ ¹¹⁰⁰

Captopril Dosage and Administration

General

BP Monitoring and Treatment Goals

Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.¹²⁰⁰
If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.¹²¹⁶
If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic).¹²⁰⁰ ¹²¹⁶ Many patients will require at least 2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.¹²⁰⁰ ¹²¹⁶ ¹²²⁰

Administration

Oral Administration

Administer orally 1 hour before meals to maximize absorption.¹¹⁵

Dosage

Pediatric Patients

Hypertension

Oral

Dosage has been reduced in proportion to body weight; titrate carefully.¹¹⁵ Initiate drug at the low end of the dosage range per some experts; may increase dosage every 2–4 weeks until BP controlled, maximum dosage (6 mg/kg per day) reached, or adverse effects occur.¹¹⁵⁰

Infants: Some experts recommend initial dosage of 0.05 mg/kg 1–4 times daily.¹¹⁵⁰

Children: Some experts recommend initial dosage of 0.5 mg/kg 3 times daily.¹¹⁵⁰

Adults

Hypertension

Captopril Therapy

Oral

Manufacturer recommends initial dosage of 25 mg 2 or 3 times daily; if response is inadequate after 1–2 weeks, dosage may be increased to 50 mg 2 or 3 times daily.¹¹⁵

Lower initial dosages (e.g., 6.25 mg twice daily to 12.5 mg 3 times daily) may be effective in some patients, particularly those already receiving a diuretic.^a (See Hypotension under Cautions.)

Usual maintenance dosage: Manufacturers recommend 25–150 mg 2 or 3 times daily (usually not necessary to exceed 150 mg daily).¹¹⁵

Captopril/Hydrochlorothiazide Fixed-combination Therapy

Oral

If combination therapy is initiated with captopril/hydrochlorothiazide fixed-combination preparation, initial dosage of captopril 25 mg and hydrochlorothiazide 15 mg once daily; adjust dosage (generally at 6-week intervals) by administering each drug separately or by advancing the fixed-combination preparation.¹⁰² ²⁵⁹

Hypertensive Crises

Oral

Severe (e.g., accelerated, malignant) hypertension: 25 mg 2 or 3 times daily, initiated promptly under close supervision with frequent monitoring of BP.¹¹⁵ May continue previous diuretic therapy, but discontinue other hypotensive agents.¹¹⁵ May increase dosage at intervals of ≤24 hours under continuous supervision until optimum BP response is attained or 450 mg daily is given.¹¹⁵ Adjunctive therapy with other hypotensive agents may be necessary.^a

Hypertensive urgency^{† [off-label]}: Acute therapy (e.g., 12.5–25 mg, repeated once or twice if necessary at intervals of 30–60 minutes or longer) has been used. ²³¹ ²³² ²⁵⁹

Diabetic Nephropathy

Oral

25 mg 3 times daily.¹¹⁵ ²⁶²

Heart Failure

Oral

Manufacturers recommend initial dosage of 25 mg 3 times daily;¹¹⁵ in patients with normal or low BP who may be volume- and/or salt-depleted, initial dosage of 6.25 or 12.5 mg 3 times daily.¹¹⁵ Increase dosage gradually to 50 mg 3 times daily; delay further dosage increases for ≥2 weeks to assess response.¹¹⁵

ACCF and AHA recommend initial dosage of 6.25 mg 3 times daily, with gradual titration to 50 mg 3 times daily.⁵²⁴ Generally titrate dosage to prespecified target (i.e., ≥150 mg daily) or highest tolerated dosage rather than according to response.⁵²⁴

Left Ventricular Dysfunction After Acute MI

Oral

Manufacturers recommend initiation of therapy ≥3 days post-MI with single dose of 6.25 mg, followed by 12.5 mg 3 times daily.¹¹⁵ Increase dosage over next several days to 25 mg 3 times daily and then over next several weeks (as tolerated) to 50 mg 3 times daily.¹¹⁵

Some clinicians recommend initiation of therapy within the first 24 hours following MI.⁵²⁷

Recommended maintenance dosage: 50 mg 3 times daily.¹¹⁵

Prescribing Limits

Pediatric Patients

Hypertension

Oral

Maximum 6 mg/kg daily.¹¹⁵⁰

Adults

Hypertension

Oral

Maximum 450 mg daily.¹¹⁵

Dosage of captopril/hydrochlorothiazide fixed-combination generally should not exceed captopril 150 mg and hydrochlorothiazide 50 mg daily.¹⁰²

Heart Failure

Oral

Maximum dosage recommended by manufacturer is 450 mg daily.¹¹⁵ Experts suggest maximum dosage of 50 mg 3 times daily.⁵²⁴

Special Populations

Renal Impairment

Manufacturers recommend initial dosage of <75 mg daily; increase dosage in small increments at 1- to 2-week intervals.¹¹⁵ After desired therapeutic effect has been attained, slowly reduce dosage to minimum effective level.¹¹⁵

Patients with Cl_cr 10–50 mL/minute: 75% of usual captopril dosage or administration of usual dose every 12–18 hours suggested by some clinicians.²¹¹

Cl_cr <10 mL/minute: 50% of usual dosage or administration of usual dose every 24 hours suggested by some clinicians.²¹¹

Patients undergoing hemodialysis may require supplemental dose after dialysis.²¹¹

Fixed-combination captopril/hydrochlorothiazide tablets usually are not recommended for patients with severe renal impairment.¹⁰²

Geriatric Patients

Hypertension

Usual adult dosages generally have been used; dosages of 6.25–12.5 mg 1–4 times daily used occasionally.¹⁷⁵

Volume-and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.¹¹⁵ ¹¹⁶ ¹⁴⁸ ¹⁵³ (See Dosage: Heart Failure, under Dosage and Administration.)

Cautions for Captopril

Contraindications

Known hypersensitivity (e.g. history of angioedema) to captopril or another ACE inhibitor.¹¹⁵ ¹⁴⁷ ³²⁵ ³²⁶

Warnings/Precautions

Warnings

Hematologic Effects

Possible neutropenia or agranulocytosis; risk of neutropenia appears to depend principally on degree of renal impairment and presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma).¹¹⁵

Use with caution and only after careful risk/benefit assessment in patients with collagen vascular disease or those taking drugs known to affect leukocytes or immune response.¹¹⁵

If used in patients with renal impairment, determine complete and differential leukocyte counts prior to initiation of therapy, at about 2-week intervals for the first 3 months of therapy, and periodically thereafter.¹¹⁵ Discontinue therapy if confirmed neutrophil count is <1000/mm³.¹¹⁵

Proteinuria

Proteinuria possible, particularly in patients with prior renal disease and/or those receiving relatively high dosages (>150 mg daily).¹¹⁵ Usually occurs by the 8th month of treatment¹ ³ ⁴⁶ and subsides or clears within 6 months whether or not therapy is continued;¹¹⁵ however, may persist in some patients.^a

Hypotension

Possible excessive hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis, patients with severe heart failure).¹ ⁵ ¹⁷ ²³ ²⁵ ³¹ ⁶⁶ ⁸⁵ ¹¹⁵ ¹¹⁶ ¹⁴⁸ ¹⁵⁴ ¹⁵⁶

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.¹¹⁵

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).¹¹⁵

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.^a (See Special Populations under Dosage and Administration.) Discontinue other antihypertensive therapy, if possible, 1 week before initiating captopril, except in patients with severe hypertension.¹¹⁵ ^a Withholding diuretic therapy and/or increasing sodium intake approximately 3–7 days prior to initiation of captopril may minimize potential for severe hypotension.¹¹⁵ ¹¹⁶ ¹⁴⁸ ¹⁵³

Initiate therapy in patients with heart failure under close medical supervision; monitor closely for first 2 weeks following initiation of captopril or any increase in captopril or diuretic dosage.¹¹⁵

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.¹⁰² ¹¹⁵ ²³⁹ ²⁴⁰ ²⁴¹ ⁴⁰² (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁴⁰²

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.⁴⁰¹ ⁴⁰²

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.⁴⁰² Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.²³⁹

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.¹⁰² ¹¹⁵ ³⁷⁰

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.¹¹⁵

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible; if associated with laryngeal edema, may be fatal.¹¹⁵ Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.¹¹⁵ Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.¹¹⁵

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption¹¹⁵ ²⁷⁵ ²⁷⁶ ²⁷⁷ or following initiation of hemodialysis that utilized high-flux membrane.¹⁰² ¹¹⁵ ²⁴² ²⁴³ ²⁴⁴

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.¹⁰² ¹⁵⁵ ²⁷⁸

Not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitors.^a

General Precautions

Renal Effects

Transient increases in BUN and S_cr possible, especially in patients with preexisting renal impairment, sodium depletion, or hypovolemia; patients with renovascular hypertension, particularly those with bilateral renal-artery stenosis or those with renal-artery stenosis in a solitary kidney;⁵ ⁸⁶ ¹¹⁵ ¹¹⁷ ¹²² ¹²³ ¹²⁴ ²⁰⁷ ²⁰⁸ ²⁰⁹ ³⁷² or patients with chronic or severe hypertension in whom the glomerular filtration rate may decrease transiently.¹ ¹¹⁵

Possible increases in BUN and S_cr in patients with heart failure;¹¹⁵ ²⁰⁶ rapidity of onset and magnitude may depend in part on degree of sodium depletion.¹⁴⁸ ¹⁵⁶ ²⁰⁶ ³⁷²

Closely monitor renal function following initiation of therapy in such patients.⁸⁶ ⁸⁷ ¹¹⁵ ¹¹⁷ ¹²² ¹²³ ¹²⁴ ³³³ ³⁷² Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic and/or adequate sodium repletion.¹¹⁵ ¹⁵⁶ ²⁰⁶ ²⁰⁷ ²⁰⁹

Hyperkalemia

Possible hyperkalemia,⁵ ⁷ ³⁸ ⁶⁹ ⁷⁰ ⁸⁵ ¹¹⁵ ¹²² ¹²⁵ ¹²⁶ ¹⁶² ¹⁶³ ¹⁶⁴ ¹⁷⁷ especially in patients with impaired renal function, heart failure, or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).³⁸ ⁸⁵ ¹¹⁵ ¹²⁵ ¹²⁶ ¹⁴⁸ ¹⁶² ¹⁶³ ¹⁶⁴ ³⁷² (See Interactions.)

Monitor serum potassium concentration carefully in these patients.¹²⁶ ¹⁶² ¹⁶³

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.¹⁰² ¹¹⁵

Valvular Stenosis

Possible risk of decreased coronary perfusion in patients with aortic stenosis when treated with captopril.^a ¹¹⁵

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.¹⁰²

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).¹¹⁵ (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Distributed into milk.¹¹⁵ Discontinue nursing or the drug.¹¹⁵

Pediatric Use

Safety and efficacy not established; however, captopril has been used in children.¹¹⁵ Manufacturer states that captopril should be used only when other measures for controlling BP have not been effective.¹¹⁵

Possible excessive, prolonged, and unpredictable decreases in BP and associated complications (e.g., oliguria, seizures) in infants.¹¹⁵

Renal Impairment

Systemic exposure to captopril may be increased.¹¹⁵ (See Special Populations under Pharmacokinetics.) Initial dosage adjustment recommended in patients with severe renal impairment.¹¹⁵ (See Renal Impairment under Dosage and Administration.)

Deterioration of renal function may occur.¹¹⁵ ²¹¹ Possible increased risk of neutropenia/agranulocytosis,¹¹⁵ proteinuria,¹¹⁵ and hyperkalemia.¹¹⁵ (See Warnings and General Precautions under Cautions.)

Use of captopril/hydrochlorothiazide fixed combination usually is not recommended in patients with severe renal impairment.¹⁰²

Black Patients

BP reduction may be smaller in black patients compared with nonblack patients.¹¹⁵ ¹³⁹ ¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ³⁵¹ ¹²⁰⁰ (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.¹⁰² ¹¹⁵ ³²⁵ ³²⁶ ³²⁷ ³⁵¹ ³⁷⁹ ³⁸⁰ ¹²⁰⁰

Common Adverse Effects

Rash, pruritus, cough, dysgeusia, proteinuria, tachycardia, chest pain, palpitations.¹¹⁵

Drug Interactions

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Adrenergic neuron blocking agents (guanethidine)	Possible increased hypotensive effect¹¹⁵	Use with caution¹¹⁵
Antacids	Decreased rate and extent of captopril absorption¹⁹⁷ ²⁰¹	Clinical importance is uncertain¹⁹⁷ ²⁰¹
Antidiabetic agents, oral	Possible hypoglycemia in diabetic patients¹⁰¹	Consider risk of hypoglycemia if used concomitantly¹⁰¹
Allopurinol	Pharmacokinetic interaction unlikely¹¹⁵
β-Adrenergic blocking agents	Increased (but less than additive) hypotensive effect¹¹⁵
Cimetidine	Neuropathy reported^a	Further documentation of interaction necessary^a
Digoxin	Possible increased serum digoxin concentrations in patients with heart failure¹⁹⁸ ¹⁹⁹ ²⁰⁰	Monitor serum digoxin concentration;¹⁹⁸ ²⁰⁰ reduction of digoxin dosage not required upon initiation of captopril¹⁹⁸
Diuretics	Possible additive hypotensive effects^a Pharmacokinetic interaction with furosemide unlikely¹¹⁵	Adjust dosage carefully^a (see Dosage under Dosage and Administration)
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)	Possible hyperkalemia, especially in patients with renal impairment¹⁶² ³²⁹ ³³¹ ³³⁵	Use cautiously and only if hypokalemia is documented; monitor serum potassium carefully;⁸⁵ ¹¹⁵ ¹²⁵ ¹²⁶ ¹⁴⁸ ¹⁶² ¹⁶³ ¹⁶⁴ discontinue or reduce dosage of potassium-sparing diuretic as necessary⁸⁵ ¹²⁶ ¹⁴⁸ ¹⁶² ¹⁶³
Insulin	Possible hypoglycemia in diabetic patients¹⁰¹	Consider risk of hypoglycemia¹⁰¹
Lithium	Possible increased serum lithium concentrations, particularly in patients receiving concomitant diuretic therapy¹¹⁵	Use with caution; monitor serum lithium concentrations frequently¹¹⁵
NSAIAs	Possible decreased antihypertensive response to captopril;²⁸³ ²⁸⁴ ²⁸⁵ ²⁸⁶ ²⁸⁷ ²⁸⁸ ²⁸⁹ ²⁹⁰ ³⁶⁴ ⁷⁰⁶ potential for acute reduction of renal function;²⁸⁵ ²⁹¹ possible attenuation of hemodynamic actions of ACE inhibitors in patients with heart failure³³³ ³⁶⁴	Monitor BP carefully and be alert for evidence of impaired renal function;²⁸⁵ if interaction is suspected, discontinue NSAIA or modify captopril dosage or use another hypotensive agent²⁸⁵ ²⁸⁶
Potassium supplements or potassium-containing salt substitutes	Possible hyperkalemia, especially in patients with renal impairment¹⁶²	Use cautiously and only if hypokalemia is documented; monitor serum potassium carefully;⁸⁵ ¹¹⁵ ¹²⁵ ¹²⁶ ¹⁴⁸ ¹⁶² ¹⁶³ ¹⁶⁴ discontinue or reduce dosage of potassium supplement as necessary⁸⁵ ¹²⁶ ¹⁴⁸ ¹⁶² ¹⁶³
Probenecid	Possible increased blood concentrations of captopril and its metabolites²⁰³ ²⁰⁴ ²⁰⁵ ²¹³
Test for urine acetone	Possible false-positive results with sodium nitroprusside reagent⁵⁴ ¹¹⁵
Vasodilating agents (e.g., hydralazine, nitrates, prazosin)	Possible increased hypotensive effect¹¹⁵	If possible, discontinue vasodilating agent before starting captopril; if vasodilating agent is resumed during captopril therapy, administer with caution and possibly at a lower dosage¹¹⁵

Captopril Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration in fasting individuals,¹⁹ ²⁰ ⁸⁴ ¹¹⁵ with peak blood concentration attained in 1 hour.¹⁹ Approximately 60–75% of an oral dose is absorbed.¹⁹ ²⁰ ⁸⁴ ¹¹⁵

Onset

Hypotensive effect may be apparent within 15 minutes⁵ ⁶ ¹⁶ ²³ and usually is maximal in 1–2 hours after a single oral dose.¹ ³ ¹⁰ ¹⁵ ¹⁶ ¹⁷ ²¹ ²⁴ ²⁹ Several weeks of therapy may be required before full effect on BP is achieved.¹ ³ ⁵ ¹⁶ ²¹ ²⁸

Duration

Duration of action generally is 2–6 hours but appears to increase with increasing doses.^a

Food

Food may decrease absorption of captopril by up to 25–40%;¹ ³ ¹¹⁵ ¹⁹¹ ¹⁹⁵ ¹⁹⁶ ¹⁹⁷ ²⁰² effect may not be clinically important.¹⁹¹ ¹⁹² ¹⁹⁵

Distribution

Extent

Appears to be rapidly distributed into most body tissues, except CNS.¹ ⁵

Crosses the placenta and is distributed into milk.¹¹⁵

Plasma Protein Binding

25–30%¹ ³ ²² (mainly albumin).³

Elimination

Metabolism

About half the absorbed dose is rapidly metabolized.³ ⁵ ¹⁹ Captopril and its metabolites may undergo reversible interconversions.³

Elimination Route

Excreted in urine (95%) as unchanged drug (40–50%) and metabolites.³ ¹⁹ ²⁰ ²² ¹¹⁵

Half-life

<2 hours.¹¹⁵

Special Populations

Elimination half-life is about 20–40 hours in patients with Cl_cr <20 mL/minute ³ and up to 6.5 days in anuric patients.⁵ ²²

Stability

Storage

Oral

Tablets

Tight containers at ≤30°C.¹¹⁵

Tablets (Captopril and Hydrochlorothiazide)

Tight containers at ≤30°C.¹⁰²

Actions

Suppresses the renin-angiotensin-aldosterone system.¹

Advice to Patients

Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.¹¹⁵ Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.¹¹⁵
Importance of reporting signs of infection (e.g., sore throat, fever).¹¹⁵
Risk of hypotension.¹¹⁵ Importance of informing clinicians promptly if lightheadedness or fainting occurs.¹¹⁵
Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.¹¹⁵
Importance of not discontinuing or interrupting therapy unless instructed by a clinician.¹¹⁵
Risks of use during pregnancy.¹¹⁵ ⁴⁰¹ ⁴⁰² (See Boxed Warning.)
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium) as well as any concomitant illnesses.¹¹⁵
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹¹⁵
Importance of taking 1 hour before meals.¹¹⁵
Importance of advising patients of other important precautionary information.¹¹⁵ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Captopril
Routes	Dosage Forms	Strengths	Brand Names
Oral	Tablets	12.5 mg*	Captopril Tablets
		25 mg*	Captopril Tablets
		50 mg*	Captopril Tablets
		100 mg*	Captopril Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Captopril and Hydrochlorothiazide
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	25 mg Captopril and Hydrochlorothiazide 15 mg*	Captopril and Hydrochlorothiazide Tablets
		25 mg Captopril and Hydrochlorothiazide 25 mg*	Captopril and Hydrochlorothiazide Tablets	Sandoz
		50 mg Captopril and Hydrochlorothiazide 15 mg*	Captopril and Hydrochlorothiazide Tablets
		50 mg Captopril and Hydrochlorothiazide 25 mg*	Captopril and Hydrochlorothiazide Tablets

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471.

524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327.

525. Smith SC, Benjamin EJ, Bonow RO et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation. 2011; 124:2458-73. http://www.ncbi.nlm.nih.gov/pubmed/22052934?dopt=AbstractPlus

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527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3695607&blobtype=pdf

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534. Qaseem A, Hopkins RH, Sweet DE et al. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013; 159:835-47. http://www.ncbi.nlm.nih.gov/pubmed/24145991?dopt=AbstractPlus

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706. Massie BM. Aspirin use in chronic heart failure: what should we recommend to the practitioner?. J Am Coll Cardiol. 2005; 46:963-6. http://www.ncbi.nlm.nih.gov/pubmed/16168276?dopt=AbstractPlus

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1205. Aronow WS, Frishman WH. Implications of the New National Guidelines for Hypertension. Cardiol Rev. 2018 Mar/Apr; 26:55-61. http://www.ncbi.nlm.nih.gov/pubmed/29419560?dopt=AbstractPlus

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1207. Burnier M, Oparil S, Narkiewicz K et al. New 2017 American Heart Association and American College of Cardiology guideline for hypertension in the adults: major paradigm shifts, but will they help to fight against the hypertension disease burden?. Blood Press. 2018; 27:62-65. http://www.ncbi.nlm.nih.gov/pubmed/29447001?dopt=AbstractPlus

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1210. SPRINT Research Group, Wright JT, Williamson JD et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015; 373:2103-16. http://www.ncbi.nlm.nih.gov/pubmed/26551272?dopt=AbstractPlus

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a. AHFS drug information 2018. McEvoy GK, ed. Captopril. Bethesda, MD: American Society of Hospital Pharmacists; 2018:.

b. Par. Capoten prescribing information. Spring Valley, NY; 2002 May.

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