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Captopril: Drug information

Captopril: Drug information
(For additional information see "Captopril: Patient drug information" and see "Captopril: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Fetal toxicity:

When pregnancy is detected, discontinue captopril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus.

Brand Names: Canada
  • APO-Capto;
  • CO Captopril;
  • TEVA-Captopril
Pharmacologic Category
  • Angiotensin-Converting Enzyme (ACE) Inhibitor;
  • Antihypertensive
Dosing: Adult
Acute coronary syndrome

Acute coronary syndrome:

Non-ST elevation acute coronary syndrome:

Note: Patients should be hemodynamically stable before initiation. Use as a component of an appropriate medical regimen, which may also include antiplatelet agent(s), a beta-blocker, and a statin. Continue angiotensin-converting enzyme inhibitor therapy indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40%, hypertension, or stable chronic kidney disease (Ref). Dosing is based on general dosing range in manufacturer's labeling.

Oral: Initial: 6.25 mg; if tolerated, increase to 12.5 mg 3 times daily; then increase to 25 mg 3 times daily during next several days and then gradually increase over next several weeks to target dose of 50 mg 3 times daily as tolerated.

ST-elevation myocardial infarction:

Note: Patients should be hemodynamically stable before initiation. Use as a component of an appropriate medical regimen, which may also include antiplatelet agent(s), a beta-blocker, and a statin (Ref). Dosing is based on general dosing range in manufacturer's labeling.

Oral: Initial: 6.25 mg; if tolerated, increase to 12.5 mg 3 times daily; then increase to 25 mg 3 times daily during next several days and then gradually increase over next several weeks to target dose of 50 mg 3 times daily as tolerated.

Heart failure with reduced ejection fraction

Heart failure with reduced ejection fraction:

Note: If tolerated, an angiotensin II receptor-neprilysin inhibitor is generally preferred over an angiotensin-converting enzyme inhibitor (Ref).

Oral: Initial: 6.25 mg 3 times daily; increase dose (eg, double) as tolerated every ≥1 to 2 weeks to a target dose of 50 mg 3 times daily (Ref). In hospitalized patients, may titrate more rapidly as tolerated (Ref).

Hypertension, chronic

Hypertension, chronic:

Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (Ref). For severe asymptomatic hypertension, may consider short-term use for BP lowering (eg, over hours) if there is concern that severe BP elevation will precipitate an acute cardiovascular event, such as in patients with known aortic or intracranial aneurysms (Ref).

Oral: Initial: 6.25 to 25 mg 2 to 3 times daily; for patients in an acute care setting, may titrate as frequently as every 8 hours (based on pharmacokinetic properties), as needed, up to 50 mg 3 times daily; if additional BP control is needed, consider combination therapy (Ref). In an ambulatory setting, patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication adjustment within 1 week. Consider transitioning to an appropriate longer-acting antihypertensive to improve adherence for chronic use (Ref).

Primary aldosteronism

Primary aldosteronism (diagnostic agent) (off-label use): Note: Administer after patient has been sitting or standing for at least 1 hour.

Oral: 25 to 50 mg as a single dose (Ref).

Proteinuric chronic kidney disease, diabetic or nondiabetic

Proteinuric chronic kidney disease, diabetic (labeled use) or nondiabetic (off-label use):

Oral: Initial: 12.5 to 25 mg two to three times daily depending on initial BP; titrate gradually (eg, by doubling the dose every 2 to 4 weeks) up to the maximally tolerated dose, not to exceed 50 mg three times daily. If proteinuria target is not met despite optimized dosage, consider additional therapies (eg, sodium-glucose cotransporter-2 inhibitor) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Kidney impairment prior to treatment initiation:

Altered kidney function (Ref): Oral:

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl 10 to <50 mL/minute: Initial: Administer the usual indication-specific dose every 12 to 24 hours. Titrate slowly based on tolerability and response; consider a maximum dose of 50 mg every 12 hours.

CrCl <10 mL/minute: Initial: Administer the usual indication-specific dose every 24 hours. Titrate slowly based on tolerability and response; consider a maximum dose of 50 mg every 24 hours.

Hemodialysis, intermittent (thrice weekly): Dialyzable (~35%) (Ref):

Note: Avoid use if an AN69 hemofilter is used (associated with anaphylactoid reaction) (Ref).

Oral: Initial: Administer the usual indication-specific dose every 24 hours. When scheduled dose falls on a dialysis day, administer after dialysis. Titrate slowly based on tolerability and response; consider a maximum dose of 50 mg every 24 hours (Ref).

Peritoneal dialysis: Dialyzable: Oral: Initial: Administer the usual indication-specific dose every 24 hours. Titrate slowly based on tolerability and response; consider a maximum dose of 50 mg every 24 hours (Ref).

CRRT: Note: Avoid use if an AN69 hemofilter is used (associated with anaphylactoid reaction) (Ref).

Oral: Initial: Administer usual indication-specific dose every 12 to 24 hours (Ref). Titrate slowly based on tolerability and response; consider a maximum dose of 50 mg every 12 hours.

PIRRT (eg, sustained, low-efficiency diafiltration): Note: Avoid use if an AN69 hemofilter is used (associated with anaphylactoid reaction) (Ref).

Oral: Initial: Administer usual indication-specific dose every 12 to 24 hours (Ref). When scheduled dose falls on a PIRRT day, administer after PIRRT (Ref). Titrate slowly based on tolerability and response; consider a maximum dose of 50 mg every 12 hours.

Alterations in kidney function during treatment:Small, transient increases in serum creatinine are likely to occur within 4 weeks following initiation of therapy or an increase in dose. If serum creatinine increases by >30%, review for possible etiologies (eg, acute kidney injury, volume depletion, concomitant medications, renal artery stenosis) before determining if dose reduction or discontinuation of captopril therapy should be considered (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution, particularly in patients with ascites due to cirrhosis (Ref).

Dosing: Adjustment for Toxicity: Adult

Hyperkalemia: Assess for alternative or contributing factors (eg, diet, concomitant medications) of increased potassium before determining if dose reduction or discontinuation of captopril therapy should be considered (Ref).

Dosing: Older Adult

Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Ref).

Dosing: Pediatric

(For additional information see "Captopril: Pediatric drug information")

Heart failure

Heart failure (afterload reduction): Limited data available: Note: Initiate therapy at lower end of range and titrate upward to prevent symptomatic hypotension (Ref):

Infants: Oral: Initial: 0.1 to 0.3 mg/kg/dose every 6 to 24 hours; titrate as needed; reported daily dose range: 0.3 to 3.5 mg/kg/day divided every 6 to 12 hours; maximum daily dose: 6 mg/kg/day (Ref).

Children and Adolescents: Oral: Initial: 0.3 to 0.5 mg/kg/dose every 8 to 12 hours; titrate as needed; in clinical trials, usual reported dosage range was 0.9 to 3.9 mg/kg/day in divided doses; maximum daily dose: 6 mg/kg/day (Ref); in adults, the target dose is 150 mg/day (Ref).

Hypertension

Hypertension: Limited data available: Note: Dosage must be titrated according to patient's response; use lowest effective dose; lower doses (~1/2 of those listed) should be used in patients who are sodium- and water-depleted due to diuretic therapy.

Weight-directed dosing:

Infants: Oral: Initial: 0.05 mg/kg/dose every 6 to 24 hours (Ref); higher initial doses of 0.15 to 0.3 mg/kg/dose every 6 to 24 hours have been recommended by some experts and may be needed in patients with severe hypertension (Ref); titrate dose carefully upward as needed to maximum of 6 mg/kg/day; monitor for hypotension (Ref).

Children and Adolescents: Oral: Initial: 0.3 to 0.5 mg/kg/dose every 8 hours; may titrate as needed up to maximum daily dose: 6 mg/kg/day in 3 divided doses (Ref); in adults, the dose is titrated as needed up to 150 mg/day (usual dose) (Ref).

Fixed dosing: Adolescents: Oral: Initial: 12.5 to 25 mg/dose every 8 to 12 hours; increase by 25 mg/dose at 1- to 2-week intervals based on patient response; in adults, the dose is increased as needed up to 150 mg/day (usual dose) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: The following adjustments have been recommended (Ref). Note: Renally adjusted dose recommendations are based on doses of 0.1 to 0.5 mg/kg/dose every 6 to 8 hours; maximum daily dose: 6 mg/kg/day.

GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose

GFR <10 mL/minute/1.73 m2: Administer 50% of dose

Intermittent hemodialysis: Administer 50% of dose

Peritoneal dialysis (PD): Administer 50% of dose

Continuous renal replacement therapy (CRRT): Administer 75% of dose

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Adverse Reactions (Significant): Considerations
Acute kidney injury

Use may be associated with increased blood urea nitrogen (azotemia) and increased serum creatinine, resulting in oliguria and acute kidney injury (AKI). Increases in serum creatinine are expected due to pharmacologic mechanism and generally stabilize within 20% to 30% of the baseline; higher increases may indicate high efferent tone (such as with hypovolemia, congestive heart failure, or renal artery stenosis) (Ref).

Mechanism: Related to pharmacologic action; inhibits efferent arteriolar vasoconstriction, which can lead to a reduction in the glomerular filtration rate (GFR). Kidney hypoperfusion from systemic hypotension may also occur (Ref).

Onset: Intermediate; increases in serum creatinine generally occur within 2 weeks of initiation and stabilize within 2 to 4 weeks (Ref). However, more immediate increases can occur in patients with other risk factors for AKI (Ref).

Risk factors:

• Patients with low renal blood flow whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II (Ref):

- Low effective circulating volume (sodium or volume depletion)

- Congestive heart failure

- Hypotension or shock

- Renal artery stenosis

• High dose at initiation (Ref)

• Older patients (Ref)

• Preexisting kidney impairment (Ref)

• Concurrent diuretic and/or nonsteroidal anti-inflammatory drug use (Ref)

Angioedema

Angioedema may occur rarely; edema may manifest in the head and neck (potentially compromising airway) or the intestine (presenting as abdominal pain). Use is contraindicated in patients with idiopathic or hereditary angioedema or previous angioedema associated with any angiotensin-converting enzyme inhibitors or neprilysin inhibitors (Ref).

Mechanism: Related to pharmacologic action (ie, increased bradykinin and substance P, vascular permeability, vasodilation) (Ref).

Onset: Varied; may occur at any time during treatment. Most cases occur within the first week of therapy but may also occur years after therapy (Ref).

Risk factors:

• Black patients (estimated 4- to 5-fold higher risk); the mechanism for this is not completely understood but may be related to genetic variants) (Ref)

• Females (Ref)

• Smoking history (Ref)

• Previous history of angioedema (Ref)

• Age >65 years (Ref)

• Seasonal allergies (Ref)

• Concurrent use of mechanistic target of rapamycin (mTOR) inhibitors (eg, everolimus) (Ref)

• Concurrent use of neprilysin inhibitor (contraindicated)

Cough

A dry, hacking, nonproductive cough that is typically associated with tickling or scratching in the throat may occur with angiotensin-converting enzyme inhibitors (ACEI) in adult and pediatric patients (Ref). Recurrence is likely with rechallenge (Ref). Resolution of cough typically occurs 1 to 4 weeks after ACEI discontinuation but may persist for up to 3 months (Ref).

Mechanism: Various proposed mechanisms. May be related to pharmacologic action (increase in bradykinin and substance P, resulting in accumulation in the lungs and bronchoconstriction) (Ref).

Onset: Varied; within hours to 4 weeks after initiation but can be delayed for up to 6 months (Ref).

Risk factors:

• Females (Ref)

• Possibly certain genetic variants (some of which may be independent of the bradykinin pathway) (Ref)

Dermatologic reactions

Various cutaneous reactions have been reported, including skin rash (Ref) and rarer events, such as toxic epidermal necrolysis (Ref), lichenoid eruption (Ref), drug rash with eosinophilia and systemic symptoms (DRESS) (Ref), linear IgA bullous dermatosis (LABD) (Ref), and pemphigus (Ref). Skin rash is often transitory, lasting for hours or days and may resolve upon continued therapy with captopril (Ref). Skin photosensitivity has also been described (Ref).

Mechanism:

Skin rash: Not well described; may be dose-related (ie, enhances cutaneous histamine reaction) (Ref) or non–dose-related.

Pemphigus: Unknown, but the sulfhydryl group found in captopril may cause biochemical modifications of antigens or bind to desmosomal proteins, resulting in autoantibody formation (Ref).

Delayed hypersensitivity reactions including TEN and DRESS: Non–dose-related; immunologic (ie, involving a T-cell mediated drug-specific immune response) (Ref).

Onset:

Skin rash: Can occur in the first few weeks of treatment, although most cases occur within the first few days (Ref).

Lichenoid eruptions: May occur up to 2 years after captopril initiation (Ref). The mean time interval between initiation of captopril and pemphigus onset was ~6 months (Ref).

Delayed hypersensitivity reactions including DRESS and TEN: Varied; typically 1 to 8 weeks after drug exposure (Ref), although may occur within days (Ref).

Risk factors:

• Skin rash:

- High doses (Ref)

- Kidney impairment (Ref)

• Cross-reactions with other angiotensin-converting enzyme inhibitors not consistent (Ref)

Hematologic effects

Rare but serious bone marrow suppression with decreases in hematological cell lines have occurred in patients taking captopril, which can manifest as neutropenia (Ref), agranulocytosis (Ref), thrombocytopenia (Ref), hemolytic anemia (Ref), or pancytopenia (Ref). Most cases have been reported in adults; a few pediatric cases have been reported (Ref). Some reported cases have been fatal (Ref), whereas in other cases, bone marrow recovery occurred after captopril reintroduction without incident (Ref). Reports of bone marrow suppression appear to be more common in patients taking captopril than in patients taking other angiotensin-converting enzyme inhibitors (Ref). Due to the infrequency of reports on bone marrow suppression and the low-quality of the available evidence, a causal relationship between captopril and hematologic effects has not been demonstrated. Neutrophil count generally returns to baseline within 2 weeks of discontinuation.

Mechanism: Unknown, likely idiosyncratic. Postulated mechanisms for bone marrow suppression include an immune-mediated reaction against bone marrow precursor cells or a direct toxic effect of reactive metabolites on blood cells and precursors (Ref).

Onset: Neutropenia: Varied; usually within 3 months of initiation.

Risk factors:

• High captopril doses ≥150 mg/day (Ref)

• Baseline kidney dysfunction, including renal transplantation (Ref)

• Concurrent immunosuppressive drugs (Ref)

• Connective tissue disorders such as systemic lupus erythematosus and scleroderma (Ref)

• Patients with Trisomy 21 may be at increased risk (Ref)

Hyperkalemia

Hyperkalemia (elevated serum potassium) may occur on therapy with angiotensin-converting enzyme inhibitors (ACEI), including captopril (Ref).

Mechanism: Related to pharmacologic action; inhibits formation of circulating angiotensin II, which leads to efferent arteriole vasodilation and subsequent lowering of glomerular filtration rate, which lowers potassium elimination. Additionally, interferes with the generation and release of aldosterone from the adrenal cortex, leading to an impairment of potassium excretion from the kidney (Ref).

Risk factors:

• Disease states associated with hyperkalemia (congestive heart failure, diabetes mellitus, chronic kidney disease) (Ref)

• Concurrent use of medications which cause hyperkalemia (ACEI, angiotensin II receptor antagonists, spironolactone, nonsteroidal anti-inflammatory drugs, beta blockers, heparin, tacrolimus, cyclosporine) (Ref)

• Acute kidney injury (elevated BUN and/or serum creatinine) (Ref)

• High dietary intake of potassium or concomitant use of potassium supplements (including potassium-containing salt substitutes) (Ref)

• Baseline elevated potassium level (≥5 mmol/L) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Chest pain (1%), palpitations (1%), tachycardia (1%)

Dermatologic: Alopecia (≤2%), pruritus (2%), skin rash (4% to 7%; including maculopapular rash, urticaria; in patients with rash, a positive ANA and/or eosinophilia has been noted in 7% to 10%)

Gastrointestinal: Abdominal pain (≤2%), ageusia (≤4%), anorexia (≤2%), aphthous stomatitis (≤2%), constipation (≤2%), diarrhea (≤2%), dysgeusia (≤4%; diminished taste perception), gastric irritation (≤2%), nausea (≤2%), peptic ulcer (≤2%), vomiting (≤2%), xerostomia (≤2%)

Genitourinary: Proteinuria (≤1%)

Hematologic & oncologic: Neutropenia (in patients with or without renal impairment with no collagen vascular disease: <1%; in patients with impaired renal function and collagen vascular disease [eg, systemic lupus erythematous, scleroderma]: 4%)

Nervous system: Dizziness (≤2%), fatigue (≤2%), headache (≤2%), insomnia (≤2%), malaise (≤2%), paresthesia (≤2%)

Respiratory: Cough (≤2%), dyspnea (≤2%)

<1%:

Cardiovascular: Acute myocardial infarction, angina pectoris, cardiac failure, flushing, Raynaud's disease

Dermatologic: Pallor

Genitourinary: Nephrotic syndrome, oliguria, urinary frequency

Hypersensitivity: Angioedema

Renal: Acute kidney injury, polyuria, renal insufficiency

Frequency not defined:

Cardiovascular: Hypotension

Hematologic & oncologic: Anemia, aplastic anemia,

Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases

Renal: Increased blood urea nitrogen, increased serum creatinine

Postmarketing:

Cardiovascular: Cardiac arrhythmia, cerebrovascular accident, cerebrovascular insufficiency, orthostatic hypotension, syncope

Dermatologic: Bullous pemphigoid, bullous skin disease (Friedman 1998), dermatitis (Martinez 2011), dermatologic disorder (linear IgA bullous dermatosis) (Friedman 1998), erythema multiforme, exfoliative dermatitis (Solinger 1982), lichenoid eruption (Ben Salem 2008), pemphigus (Ghaedi 2021), skin photosensitivity (Hofmann 2021), Stevens-Johnson syndrome, toxic epidermal necrolysis (Alkurtass 2003)

Endocrine & metabolic: Gynecomastia (Markusse 1988), hyperkalemia (Weir 2010), hyponatremia (symptomatic)

Gastrointestinal: Cholestasis (Kocab 2000), dyspepsia, glossitis, pancreatitis (Gorsane 2019)

Genitourinary: Impotence, membranous glomerulonephritis (Bailey 1992)

Hematologic & oncologic: Agranulocytosis (Suarez 1986), eosinophilia, hemolytic anemia (Trimble 2007), pancytopenia (Chisi 1999), positive ANA titer, thrombocytopenia (Kramer 1983)

Hepatic: Hepatic necrosis (rare), hepatitis (Vandenburg 1981), jaundice (Crantock 1991)

Hypersensitivity: Nonimmune anaphylaxis (Peces 2002)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Ammar 2019)

Nervous system: Ataxia, confusion, depression, drowsiness, myasthenia, nervousness, seizure (in infants) (Perlman 1989), visual hallucination (Doane 2013)

Neuromuscular & skeletal: Asthenia, myalgia

Ophthalmic: Blurred vision

Respiratory: Bronchospasm, eosinophilic pneumonitis, rhinitis

Contraindications

Hypersensitivity to captopril, any other angiotensin-converting enzyme (ACE) inhibitor, or any component of the formulation; angioedema related to previous treatment with an ACE inhibitor; concomitant use with aliskiren in patients with diabetes mellitus; coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate to severe kidney impairment (GFR <60 mL/minute/1.73 m2).

Warnings/Precautions

Concerns related to adverse effects:

• Cholestatic jaundice: A rare toxicity includes cholestatic jaundice, which may progress to fulminant hepatic necrosis (some fatal); discontinue if marked elevation of hepatic transaminases or jaundice occurs.

• Hypersensitivity reactions: Anaphylactic reaction/nonimmune anaphylaxis can occur with angiotensin-converting enzyme (ACE) inhibitors. Severe nonimmune anaphylaxis may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low-density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of nonimmune anaphylaxis have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses). Effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation. Close monitoring of patient is required especially with initial dosing and dosing increases; BP must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use, especially in patients with heart failure where a reduction in systolic BP is a desirable observation.

• Proteinuria: Total urinary proteins >1 g per day have been reported (<1%); nephrotic syndrome occurred in about one-fifth of proteinuric patients. In most cases, proteinuria subsided or cleared within 6 months (whether or not captopril was continued).

Disease-related concerns:

• Aortic stenosis: Use with caution in patients with aortic stenosis; may reduce coronary perfusion resulting in ischemia.

• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and kidney function carefully to avoid rapid development of kidney failure (AASLD [Runyon 2013]).

• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling BP (eg, myocardial infarction [MI], stroke). Fluid replacement, if needed, may restore BP; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs. In a retrospective cohort study of elderly patients (≥65 years of age) with MI and impaired left ventricular function, administration of an ACE inhibitor was associated with a survival benefit, including patients with serum creatinine concentrations >3 mg/dL (265 micromol/L) (Frances 2000).

• Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant kidney impairment; may be at increased risk for hematologic toxicity.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2020]).

• Kidney impairment: Use with caution in preexisting kidney insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation, which may lead to further kidney impairment.

Special populations:

• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2018).

• Surgery: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing noncardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).

Other warnings/precautions:

• Extemporaneous oral solutions: Extemporaneous preparations of liquid formulations may vary; this may affect the rate and extent of absorption causing intrapatient variability regarding dosing and safety profile for the patient; use with caution and monitor closely if dosage formulations are changed (Bhatt 2011; Mulla 2007).

Warnings: Additional Pediatric Considerations

Neonates and young infants appear to be more sensitive to adverse effects (Gantenbein 2008). ACE inhibitors have been associated with nephrotoxicity in neonates; risk may be higher in preterm neonates; a retrospective study evaluated ACE inhibitor (captopril or enalapril) nephrotoxicity in 206 neonates (term [n=168] and preterm [n=38]) with cardiovascular disease; nearly 42% of neonates were in the pRIFLE (pediatric risk, injury, failure, loss, and end-stage renal disease) category of risk or higher; 30% of all patients were in the renal failure category; when separated out into term and preterm, >50% of preterm neonates were in the renal failure category while receiving an ACE inhibitor and were significantly more likely to be in the renal failure category compared to term neonates (Lindle 2014). Initiate dosing at lower end of the range in preterm neonates.

An observational study of 66 pediatric patients with heart failure reported hypotension in 15% of patients during therapy initiation at typical starting doses; close monitoring in an inpatient setting and low starting doses has been suggested in these patients (Momma 2006; Orchard 2010).

An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1 to 4 weeks after discontinuation of the ACE inhibitor; in pediatric patients, an isolated dry hacking cough lasting >3 weeks was reported in seven of 42 pediatric patients (17%) receiving ACE inhibitors (von Vigier 2000); a review of pediatric randomized-controlled ACE inhibitor trials reported a lower incidence of 3.2% (Baker-Smith 2010). Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 12.5 mg, 25 mg, 50 mg, 100 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Captopril Oral)

12.5 mg (per each): $1.27 - $1.70

25 mg (per each): $1.27 - $1.80

50 mg (per each): $2.36 - $2.90

100 mg (per each): $3.09 - $3.81

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Generic: 6.25 mg [DSC], 12.5 mg, 25 mg, 50 mg, 100 mg

Administration: Adult

Oral: Administer at least 1 hour before meals. Unstable in aqueous solutions; to prepare solution for oral administration, mix prior to administration and use within 10 minutes (Ref).

Administration: Pediatric

Oral: Administer on an empty stomach 1 hour before or 2 hours after meals/feeds; administration with food will decrease absorption; consistent administration times are recommended (Ref). If crushing tablet and dissolving in water, allow adequate time for complete dissolution (>10 minutes) (Ref); may also prepare and administer as an extemporaneous oral liquid.

Use: Labeled Indications

Acute coronary syndrome: To improve survival following myocardial infarction (MI) (eg, ST-elevation MI or non-ST-elevation MI) in clinically stable patients, including those with left ventricular dysfunction manifested as an ejection fraction of ≤40%.

Heart failure with reduced ejection fraction: Treatment of heart failure.

Hypertension, chronic: Management of hypertension.

Proteinuric chronic kidney disease, diabetic: Treatment of diabetic nephropathy (proteinuria >500 mg/day) in patients with type 1 insulin-dependent diabetes mellitus and retinopathy.

Use: Off-Label: Adult

Aldosteronism, primary (diagnostic test); Proteinuric chronic kidney disease, nondiabetic

Medication Safety Issues
Sound-alike/look-alike issues:

Captopril may be confused with calcitriol, Capitrol, carvedilol.

International issues:

Acepril [Great Britain] may be confused with Accupril which is a brand name for quinapril in the US.

Acepril: Brand name for captopril [Great Britain], but also the brand name for enalapril [Hungary, Switzerland]; lisinopril [Malaysia].

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification

Allopurinol: Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

Alteplase: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider therapy modification

Antacids: May decrease the serum concentration of Captopril. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Everolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy

Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor therapy

Finerenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy

Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor therapy

Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid combination

Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Risk C: Monitor therapy

Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme (ACE) inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider therapy modification

Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Racecadotril: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor therapy

Ranolazine: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid combination

Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Sirolimus Products: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy

Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

Sparsentan: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid combination

Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification

Urokinase: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Food Interactions

Captopril serum concentrations may be decreased if taken with food. Long-term use of captopril may lead to a zinc deficiency, which can result in altered taste perception. Management: Take on an empty stomach 1 hour before or 2 hours after meals.

Reproductive Considerations

Avoid use of angiotensin-converting enzyme (ACE) inhibitor therapy in patients who may become pregnant and who are not using effective contraception (ADA 2021).

Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. ACE inhibitors are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy unless treatment with an ACE inhibitor is absolutely necessary (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).

When ACE inhibitors are used for the treatment of proteinuric chronic kidney disease in patients who could become pregnant, discontinue use at the first positive pregnancy test (ADA 2021; Fakhouri 2022).

ACE inhibitors are not recommended for the treatment of heart failure in patients planning to become pregnant (AHA/ACC/HFSA [Heidenreich 2022]).

Pregnancy Considerations

Captopril crosses the placenta (Hurault de Ligny 1987).

Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 2019; ESC [Regitz-Zagrosek 2018]). Following exposure during the second or third trimesters, drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ACE inhibitor use during pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ACE inhibitor in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function

Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).

ACE inhibitors should be discontinued as soon as possible once pregnancy is detected. When treatment of chronic hypertension in pregnancy is indicated, agents other than ACE inhibitors are recommended (ACOG 2019; ESC [Cífková 2020]; SOGC [Magee 2022]). Use during pregnancy should only be considered for cases of hypertension refractory to other medications (ACOG 2019). Closely monitor pregnant patients on ACE inhibitors with serial ultrasounds.

ACE inhibitors are not recommended for the treatment of heart failure or proteinuric chronic kidney disease during pregnancy (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Regitz-Zagrosek 2018]; Fakhouri 2022).

Breastfeeding Considerations

Captopril is present in breast milk.

Data related to the presence of captopril in breast milk are available following maternal administration captopril 100 mg 3 times a day for 7 doses to 11 normotensive lactating patients. The mean peak milk concentration of captopril was 4.7 ng/mL. The maximum milk concentrations occurred 3.8 hours after the maternal dose. Captopril was not detected in all milk samples. Concentrations of captopril in breast milk were ~1% of those in maternal blood (Devlin 1981).

• Using a milk concentration of 4.7 ng/mL, the estimated daily infant dose via breast milk is 705 ng/kg/day providing a relative infant dose (RID) of 0.01% to 0.02% compared to an infant therapeutic dose of 3 to 6 mg/kg/day.

• In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of exposure to the infant and the benefits of treatment to the mother. When postpartum treatment with an angiotensin-converting enzyme (ACE) inhibitor is needed, available guidelines consider captopril to be acceptable for use in lactating patients (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Cífková 2020]; WHO 2002). Avoid breastfeeding if high maternal doses of an ACE inhibitor are needed (ACOG 2019).

Monitoring Parameters

Blood pressure; BUN, serum creatinine; electrolytes (eg, potassium [especially in patients on concomitant potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts]). In patients with kidney impairment and/or collagen vascular disease, closely monitor CBC with differential for the first 3 months of therapy and periodically thereafter. If angioedema is suspected, assess risk of airway obstruction (eg, involvement of tongue, glottis, larynx, and/or history of airway surgery).

Aldosteronism, primary (diagnostic test): Plasma renin activity, plasma aldosterone, and serum cortisol levels at baseline and 1 or 2 hours after challenge; patient should remain seated during this time (ES [Funder 2016]).

Mechanism of Action

Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Within 15 minutes; Peak effect: Blood pressure reduction: 1 to 1.5 hours after dose

Maximum effect: Antihypertensive: 60 to 90 minutes; may require several weeks of therapy before full hypotensive effect is seen

Duration: Dose related, may require several weeks of therapy before full hypotensive effect

Absorption: 60% to 75%; rapid

Distribution: Vdss: 0.7 L/kg (Duchin 1982)

Bioavailability: ~60% to 75% (Kubo 1985); reduced 30% to 40% by food

Protein binding: 25% to 30%

Metabolism: 50% metabolized

Half-life elimination:

Infants with CHF: 3.3 hours; range: 1.2 to 12.4 hours (Pereira 1991)

Children: 1.5 hours; range: 0.98 to 2.3 hours (Levy 1991)

Adults, healthy volunteers: ~1.7 hours (Duchin 1982). In 2 studies, patients with chronic kidney failure demonstrated ~2-fold longer half-lives as compared to normal subjects (Giudicelli 1984; Onoyama 1981). Half-life was up to 21 hours in patients with severe kidney impairment and up to 32 hours in patients on chronic hemodialysis in another study (Duchin 1984)

Time to peak: Within 1 to 2 hours

Excretion: Urine (>95%) within 24 hours (40% to 50% as unchanged drug)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Acetab | Apo capto | Capocard | Capoten | Captace | Captophar | Midopril;
  • (AT) Austria: Capace | Captopril genericon pharma | Debax;
  • (AU) Australia: Acenorm | Apo captopril | Capace | Capoten | Captohexal | Captopril bc | Cm captopril | Dbl captopril | Enzace | Sbpa captopril | Topace | Tw captopril | Zedace;
  • (BD) Bangladesh: Acetor | Angiten | Capotril | Capril | Cardopril | Topril;
  • (BE) Belgium: Capoten | Capriltop | Captopril bc | Captopril bexal | Captopril eurogenerics | Captopril merck-generics | Captopril ratiopharm | Captopril sandoz | Captopril teva generics belgium | Captoprimed | Doccaptopri;
  • (BF) Burkina Faso: Captopril denk | Captopril tm;
  • (BG) Bulgaria: Alkadil | Capoten | Tensiomin;
  • (BR) Brazil: Abepoten | Antipressin | Aorten | Aortt | Cabioten | Capobal | Capoten | Capotrat | Capotril | Capotrineo | Capox | Capril | Captil | Captobel | Captocord | Captolab | Captolin | Captomax | Captomed | Captomido | Capton | Captophex | Captopiril | Captopril brasterapica | Captopril laqfa | Captopron | Captosen | Captosif | Captotec | Captozen | Ductopril | Farmanguinhos captopril | Furp captopril | Genoptril | Hipocatril | Hipoten | Hipotensil | Iquego captopril | Labopril | Lafepe captopril | Normapril | Pressomax | Presstopril | Prilpressin | Ritpress | Teusil | Venopril;
  • (CH) Switzerland: Capto-basan | Captopril cophar | Captopril mepha | Captopril upsa | Captosol | Lopirin | Tensobon;
  • (CI) Côte d'Ivoire: Apo capto | Captopril generis | Lopril | Tensoprel;
  • (CL) Chile: Capoten | Properil;
  • (CN) China: Bo tong | Capoten | Pu li bo tong;
  • (CO) Colombia: Altran | Capoten | Captol | Captomed | Captopren | Captopril mk | Cardiopril | Cardopril | Drugsipres | Ecapress | Falaprex | Hipermed | Norpril | Presinorm | Redupres;
  • (CZ) Czech Republic: Alkadil | Apo capto | Capoten | Captopril al | Katopil | Tensiomin;
  • (DE) Germany: Ace hemmer | Ace-hemmer von R.A.N. | Ace-hemmer-ratiopharm | Acenorm | Adocor | Capto | Capto 1a pharma | Capto Corax | Capto dura m | Capto lich | Capto sanorania | Capto-isis | Capto-Puren | Captobeta | Captodoc | Captoflux | Captogamma | Captohexal | Captomerck | Captopress | Captopril 1a pharma | Captopril actavis | Captopril al | Captopril Aristo | Captopril atid | Captopril axsan | Captopril denk | Captopril freemed | Captopril gry | Captopril Pfleger | Captopril sandoz | Captopril Stada | Captopril Temmler | Captopril Verla | Captoreal | Captowieb | Cardiagen | Coronorm | Epicordin | Esparil | Jucapt | Lopirin | Mundil | Phamopril | Sansanal | Sigacap | Tensiomin | Tensobon | Tensostad;
  • (DK) Denmark: Captopril nm;
  • (DO) Dominican Republic: Capoten | Capril | Captoprilan | Captoril | Ecapres | Fratopril | Tensoprel;
  • (EC) Ecuador: Capoten | Captopril Genfar | Captostar | Librapril;
  • (EE) Estonia: Angiopress | Angiopril | Capoten | Captohexal | Captopril AbZ | Captopril cox | Kapteks | Katopil | Nycapril | Tensiomin;
  • (EG) Egypt: Acepril | Angiopress | Capoten | Capotil | Capotril | Farcoprel | Farcopril | Hypopress | Lontensin | Lotensine;
  • (ES) Spain: Alopresin | Capoten | Captopril alter | Captopril Apotex | Captopril apothecon | Captopril bayvit | Captopril bexal | Captopril cinfa | Captopril edigen | Captopril esteve | Captopril mabo | Captopril merck | Captopril mundogen | Captopril normon | Captopril pharmagenus | Captopril ratiopharm | Captopril rubio | Captopril tamarang | Captopril tarbis | Captopril ur | Captosina | Cesplon | Cesplon cor | Dardex | Dilabar | Garanil | Tensoprel;
  • (FI) Finland: Capoten | Captomin | Captopril actavis | Captopril alpharma | Captopril generics | Captopril Merck NM | Captopril pliva | Captopril sandoz | Captostad | Lopril;
  • (FR) France: Captirex | Captolane | Captopril arrow | Captopril Bayer | Captopril biogaran | Captopril g gam | Captopril gnr | Captopril irex | Captopril ivax | Captopril merck | Captopril Qualimed | Captopril ratiopharm | Captopril rpg | Captopril sandoz | Captopril Teva | Captopril Zydus | Lopril | Oltens;
  • (GB) United Kingdom: Acepril d.f | Captomex | Captopril cox | Captopril kent | Captopril sandoz | Ecopace | Hyteneze | Kaplon | Tensopril;
  • (GR) Greece: Capoten | Hypotensor | Neo ipertas | Normolose | Odupril | Pertacilon | Sancap;
  • (HK) Hong Kong: Apo capto | Capoten | Capril | Captopril Stada | Rilcapton | Tensiomin;
  • (HU) Hungary: Capin | Captogamma | Huma-captoril | Tensiomin;
  • (ID) Indonesia: Acendril | Acepress | Capoten | Captensin | Casipril | Dexacap | Farmoten | Forten | Inapril | Locap | Lotensin | Metopril | Otaryl | Otoryl | Praten | Scantensin | Tenofax | Tensicap | Tensobon | Vapril;
  • (IE) Ireland: Aceomel | Actopril | Capoten | Caprill | Captor | Geroten | Tensopril;
  • (IL) Israel: Aceril | Apocapen | Capti;
  • (IN) India: Aceten | Alcoryl | Capotril;
  • (IQ) Iraq: Caporil | Captoneer | Captopril 25 kindi | Captopril 50 kindi | Captopril awa | Captopril mdi | Captosaf;
  • (IT) Italy: Acepress | Aceprilex | Capoten | Captopril actavis | Captopril doc | Captopril drm | Captopril eg | Maxipril | Tenpril;
  • (JO) Jordan: Capocard | Capoten | Midopril | Miniten;
  • (JP) Japan: Apopril | Brealin | Capotec | Captopril hexal | Captoril bristol-myers | Captoril sankyo | Captoruna | Captowa | Corocalum | Dowpril | Kapuseal | Katonaplon | Kokapto | Ktplon | Mercapril | Onfrule;
  • (KE) Kenya: Acetan | Angiopril | Captocos | Captolab | Captopril denk | Cardopril | Ropril;
  • (KR) Korea, Republic of: Adolpan | Capoten | Capril | Captifen | Captil | Captogen | Captonal | Captopril ID | Cutoril | Ketanine | Ketonil | Mecaflil | Samjin captopril | Topril;
  • (KW) Kuwait: Acetab | Capocard | Capoten | Miniten;
  • (LB) Lebanon: Adocor | Apo capoten | Apo captopril | Capoten | Captace | Captopril Genericon | Orbace | Rivtopril | Tensiopril;
  • (LT) Lithuania: Alkadil | Angiopress | Angiopril | Apo capto | Capoten | Capril | Captohexal | Captopril AbZ | Captopril ac | Captopril arena | Captopril bp | Kaptex | Katopil | Novo captopril | Ropril | Tensiomin;
  • (LU) Luxembourg: Capoten | Captohexal | Captopril Mylan | Doccaptopri;
  • (LV) Latvia: Alkadil | Angiopress | Angiopril | Capoten | Capril | Captogamma | Captohexal | Captopril gry | Kaptex | Katopil | Novo captopril | Tensiomin;
  • (MA) Morocco: Capen | Convertal | Hipotensil | Lopril;
  • (MX) Mexico: Altiver | Atrisol | Biodezil | Bioxil | Brucap | Bucamex | Bugazon | Capotena | Capriwen | Captopril darier | Captopril GI | Captopril gi diba | Captopril gi kendr | Captopril gi pharm | Captopril gi serra | Captopril protein | Captopril raam | Captopril silanes | Captopril wandel | Captoser | Captral | Cardipril | Catona | Condabif | Ecapresan | Ecapril | Ecaten | Enlace | Genopril | Hipertex | Ipyrol | Katodem | Kenolan | Keyerpril | Lenpryl | Midrat | Miocap | Neulastrol | Novapres | Ormoten | Ospil | Proldin | Reductel | Reduprec | Rilten | Rodagen | Sabtres | Tenca i | Tensil | Toprilem | Tropisol | Varaxil | Viegnur;
  • (MY) Malaysia: Apo capto | Apuzin | Capoten | Capriten | Captohexal | Epsitron | Kimafan | Taguar;
  • (NG) Nigeria: C pril | Donypril | N & n captopril | Taguar;
  • (NL) Netherlands: Capoten | Captopril Accord | Captopril actavis | Captopril katwijk | Captopril ratiopharm | Captoril katwijk;
  • (NO) Norway: Capoten | Captopril Mylan;
  • (NZ) New Zealand: Apo captopril | Capoten | Captohexal | M captopril;
  • (PE) Peru: Caposan | Capoten | Capressior | Captomed | Melatil | Nolectin | Presicaptil;
  • (PH) Philippines: Ace-bloc | Biopril | Bloc Med | Capomed | Capotec | Capoten | Captace | Captobes | Captogen | Captor | Captril | Conamid | Hartylox | Hyperstop | Normil | Primace | Retensin | Ritemed Captopril | Spec Ace | Tensoril | Tgp capto | Typrilace | Unihype | Vasostad;
  • (PK) Pakistan: Acetopril | Aptil | Bentoril | Capace | Capoten | Capril | Captace | Captil | Capto | Catoper | G-cap | Garan | Katopil | Maripril | Nobeten | Plumax | Qutril | Ropril | Tensiomin | Vasokap | Vasotone | Vegaten;
  • (PL) Poland: Capoten | Captopril jelfa | Tensiomin | Tensobon;
  • (PR) Puerto Rico: Capoten;
  • (PT) Portugal: Calpix | Capoten | Capritin | Captopril merck-generics | Carencil | Convertal | Hipotensil | Pressil | Prilovase | Tensopril | Vidapril;
  • (QA) Qatar: Acetab | Apo-Capto | Capocard | Farcopril | Hypopress | Lotensine;
  • (RO) Romania: Alkadil | Capocard | Capoten | Captopril arena | Captopril eel | Captopril laropharm | Captopril lph | Farcopril | Hypotensor | Kapril;
  • (RU) Russian Federation: Aceten | Alkadil | Angiopril | Apo capto | Blocordil | Capocard | Capopharm | Capoten | Capto | Captopril akos | Captopril akri | Captopril biosynt | Captopril egis | Captopril fpo | Captopril n.s. | Captopril of | Captopril sandoz | Captopril sar | Captopril stad int | Captopril sti | Captopril Teva | Captopril ubf | Captopril velpharm | Gen captopril | Kapoten | Katopil | Kmp captopril | Novo captopril | Rilcapton | Tensiomin | Vero captopril;
  • (SA) Saudi Arabia: Acetab | Apo captopril | Capocard | Capoten | Captophar | Miniten | Novo captoril;
  • (SE) Sweden: Captopril actavis | Captopril Mylan | Captopril ratiopharm;
  • (SG) Singapore: Apo capto | Capoten | Catoplin | Dexacap | Ketanine | Pertacilon | Rilcapton;
  • (SI) Slovenia: Alkadil | Kaptopril;
  • (SK) Slovakia: Alkadil | Capoten | Katopil | Tensiomin;
  • (TH) Thailand: Capoten | Capril | Epsitron | Gemzil | Tensiomin;
  • (TN) Tunisia: Actopril | Capocard | Capril | Capto Pril Alliance | Captolane | Convertal | Lopril | Tensopril;
  • (TR) Turkey: Kapril | Kaptoril;
  • (TW) Taiwan: Aceloc | Acepril | Aceprotin | Apo capto | Apuzin | Asisten | C.p.t | Cabudan | Calatec | Capdon | Capomil | Caponal | Capoten | Capotil | Capril | Caproine | Captolin | Captolong | Captopin | Captopri | Captrol | Catopren | Ceporin | Hyperten | Kecap | Meriga | Rilcapton | Smarten | Suyea | Tecapril | Vasodil;
  • (UA) Ukraine: Aceten | Capoten | Capotril | Hypotensor | Katopil | Tensiomin;
  • (UG) Uganda: Angiopril | Captopril denk | Epsitron;
  • (UY) Uruguay: Asisten | Capoten | Captopril Pellier | Captopril teuto | Cercor | Isopril | Yaraten;
  • (VE) Venezuela, Bolivarian Republic of: Capoten | Captopril Penta | Captoril | Captoz | Ceplon | Lidinox | Presinorm | Prileno | Tabulan;
  • (VN) Viet Nam: Bidipril;
  • (ZA) South Africa: Aceten | Adco-captopril | Apo captopril | Bio Captopril | Capace | Capoten | Captohexal | Captomax | Cardiace | Merck-captopril | Rolab-captopril;
  • (ZM) Zambia: Capril | Kamtopril;
  • (ZW) Zimbabwe: Angiopril | Caipolex
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