Class: Angiotensin-Converting Enzyme Inhibitors
VA Class: CV800
CAS Number: 62571-86-2
Uses for Captopril
ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.500 501 502 504 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).500 501 502 503 504 515
ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease, or cerebrovascular disease or post-MI.500 501 502 504 520 523 524 525 526 527 534 535 536 543
Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.379 380 386 399 400 500 501 504 However, diminished response to an ACE inhibitor is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504
The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530
JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515
In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;367 385 388 389 500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541
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.520 535 536
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.115 319 321 374
Captopril Dosage and Administration
BP Monitoring and Treatment Goals
When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501
If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501
Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)
Administer orally 1 hour before meals to maximize absorption.115
Dosage has been reduced in proportion to body weight; titrate carefully.115 Some experts recommend an initial dosage of 0.9–1.5 mg/kg daily (given as 0.3–0.5 mg/kg 3 times daily).398 Increase dosage as necessary to a maximum of 6 mg/kg daily.398
JNC 8 expert panel recommends initial dosage of 50 mg daily (given in 2 divided doses) and target dosage of 150–200 mg daily (given in 2 divided doses) based on dosages used in randomized controlled studies.501
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
Some experts have recommended usual dosage range of 25–100 mg daily given in 2 divided doses; rationale for this lower dosage range is that it may be preferable to add another antihypertensive drug rather than continue to increase dosage of captopril.397 500
If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501
Captopril/Hydrochlorothiazide Fixed-combination TherapyOral
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
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
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
Some clinicians recommend initial dosage of 6.25 or 12.5 mg 3 times daily, with gradual titration over several weeks to 50 mg 3 times daily, regardless of BP, salt/volume status, or concomitant diuretic therapy.321 333 377 Generally titrate dosage to prespecified target (i.e., ≥150 mg daily) or highest tolerated dosage rather than according to response.333 377
Left Ventricular Dysfunction after Acute MI
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 <24 hours post-MI with initial dose of 6.25 mg, followed by 12.5 mg 2 hours later, 25 mg 10–12 hours later, and then 50 mg twice daily as tolerated.319 Recommended maintenance dosage: 50 mg 3 times daily.115
Maximum 6 mg/kg daily.398
Maximum 450 mg daily.115
Dosage of captopril/hydrochlorothiazide fixed-combination generally should not exceed captopril 150 mg and hydrochlorothiazide 50 mg daily.102
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 Clcr 10–50 mL/minute: 75% of usual captopril dosage or administration of usual dose every 12–18 hours suggested by some clinicians.211
Clcr <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
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
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 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
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
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
If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.115
Anaphylactoid reactions and/or angioedema possible; if associated with laryngeal edema, may be fatal.115 333 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
Not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitors.a
Transient increases in BUN and Scr 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 86 115 117 122 123 124 207 208 209 333 372 or patients with chronic or severe hypertension in whom the glomerular filtration rate may decrease transiently.1 115
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
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 85 115 125 126 148 162 163 164 333 372 (See Interactions.)
Use of Fixed Combinations
When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.102
Category C (1st trimester); Category D (2nd and 3rd trimesters).115 (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)
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
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
Common Adverse Effects
Rash, pruritus, cough, dysgeusia, proteinuria, tachycardia, chest pain, palpitations.115
Interactions for Captopril
Specific Drugs and Laboratory Tests
Drug or Test
Adrenergic neuron blocking agents (guanethidine)
Possible increased hypotensive effect115
Use with caution115
Antidiabetic agents, oral
Possible hypoglycemia in diabetic patients101
Consider risk of hypoglycemia if used concomitantly101
Pharmacokinetic interaction unlikely115
β-Adrenergic blocking agents
Increased (but less than additive) hypotensive effect115
Further documentation of interaction necessarya
Possible additive hypotensive effectsa
Pharmacokinetic interaction with furosemide unlikely115
Adjust dosage carefullya (see Dosage under Dosage and Administration)
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)
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
Possible hypoglycemia in diabetic patients101
Consider risk of hypoglycemia101
Possible increased serum lithium concentrations, particularly in patients receiving concomitant diuretic therapy115
Use with caution; monitor serum lithium concentrations frequently115
Possible decreased antihypertensive response to captopril;283 284 285 286 287 288 289 290 333 364 potential for acute reduction of renal function;285 291 possible attenuation of hemodynamic actions of ACE inhibitors in patients with heart failure333 364
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
Test for urine acetone
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
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 of action generally is 2–6 hours but appears to increase with increasing doses.a
Crosses the placenta and is distributed into milk.115
Plasma Protein Binding
Tight containers at ≤30°C.115
Tablets (Captopril and Hydrochlorothiazide)
Tight containers at ≤30°C.102
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
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
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.)
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
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
25 mg Captopril and Hydrochlorothiazide 15 mg*
Captopril and Hydrochlorothiazide Tablets
25 mg Captopril and Hydrochlorothiazide 25 mg*
Captopril and Hydrochlorothiazide Tablets
50 mg Captopril and Hydrochlorothiazide 15 mg*
Captopril and Hydrochlorothiazide Tablets
50 mg Captopril and Hydrochlorothiazide 25 mg*
Captopril and Hydrochlorothiazide Tablets
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
Date published: May 01, 2004
Last reviewed: December 11, 2014
Date modified: February 08, 2016
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a. AHFS drug information 2015. McEvoy GK, ed. Captopril. Bethesda, MD: American Society of Hospital Pharmacists; 2015:.
b. Par. Capoten prescribing information. Spring Valley, NY; 2002 May.
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