Captopril

Pharmacologic Category

Angiotensin-Converting Enzyme (ACE) Inhibitor; Antihypertensive

Dosing: Adult

Acute coronary syndrome:

Myocardial infarction with left ventricular dysfunction:

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.

Non-ST elevation acute coronary syndrome (off-label use):

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 (AHA/ACC [Amsterdam 2014]). Dosing is based on expert opinion and general dosing range in manufacturer's labeling.

ST-elevation myocardial infarction (off-label use):

Acute hypertension (urgency/emergency) (off-label use): Oral, sublingual: 25 mg, may repeat as needed; consider alternative therapy if BP is nonresponsive within 20 to 30 minutes (Angeli 1991; Castro del Castillo 1988; Ceyhan 1990; Damasceno 1997; Tschollar 1985). Note: May be given sublingually, but therapeutic advantage has not been demonstrated over oral administration (Karakilic 2012).

Aldosteronism, primary (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 (Agharazii 2001; ES [Funder 2016]; Wu 2010).

Diabetic nephropathy: Oral: Initial: 25 mg 3 times daily. May be taken with other antihypertensive therapy if required to further lower BP.

Heart failure with reduced ejection fraction: Oral: Initial dose: 6.25 mg 3 times daily; as tolerated, may increase every 1 to 2 weeks to a target dose of 50 mg 3 times daily (ACCF/AHA [Yancy 2017]; Meyer 2020). In hospitalized patients, the dose may be titrated at 1- to 2-day intervals (Meyer 2020).

Hypertension:

Note: For initial treatment in patients with BP ≥20/10 mm Hg above goal, may be used in combination with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker, thiazide diuretic). For patients <20/10 mm Hg above goal, some experts recommend an initial trial of monotherapy; however, over time, many patients will require combination therapy (ACC/AHA [Whelton 2018]; Mann 2020).

Oral: Initial dose: 12.5 to 25 mg 2 to 3 times daily; may increase at 1- to 2-week intervals based on patient response up to 50 mg 3 times daily (ACC/AHA [Whelton 2018]).

Raynaud phenomenon (off-label use): Oral: 12.5 mg twice daily; may gradually increase to 25 mg 3 times daily (Tosi 1987). Clinical trial evaluated patients for up to 3 months. Additional data is necessary to further define the role of captopril in the treatment of this condition.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow 2011).

Dosing: Renal Impairment: Adult

Manufacturers' recommendations: Reduce initial daily dose and titrate slowly (1- to 2-week intervals) with smaller increments. Slowly back titrate to determine the minimum effective dose once the desired therapeutic effect has been reached.

Alternative recommendations (Aronoff 2007):

CrCl 10 to 50 mL/minute: Administer at 75% of normal dose every 12 to 18 hours.

CrCl <10 mL/minute: Administer at 50% of normal dose every 24 hours.

Intermittent hemodialysis (IHD): Administer after hemodialysis on dialysis days

Peritoneal dialysis: Dose for CrCl 10 to 50 mL/minute; supplemental dose is not necessary

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

Heart failure (afterload reduction): Limited data available: Note: Initiate therapy at lower end of range and titrate upward to prevent symptomatic hypotension (Momma 2006):

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 (Artman 1987; Park 2014; Scammell 1987; Shaw 1988).

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 (Artman 1987; Momma 2006; Park 2014); in adults, the target dose is 150 mg/day (ACCF/AHA [Yancy 2013]).

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 (AAP [Flynn 2017]); 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 (Mirkin 1985; Park 2014); titrate dose carefully upward as needed to maximum of 6 mg/kg/day; monitor for hypotension (AAP [Flynn 2017]; Park 2014).

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 (AAP [Flynn 2017]; NHLBI 2012); in adults, the dose is titrated as needed up to 150 mg/day (usual dose) (ACC/AHA [Whelton 2017]).

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) (ACC/AHA [Whelton 2017]; Park 2014).

Dosing: Renal Impairment: Pediatric

Infants, Children, and Adolescents: The following adjustments have been recommended (Aronoff 2007). 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).

Calculations

Use: Labeled Indications

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

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

Hypertension: Management of hypertension.

Myocardial infarction with left ventricular dysfunction: To improve survival following myocardial infarction (MI) (eg, ST-elevation MI or non-ST-elevation MI) in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction of ≤40%, and to reduce the incidence of overt heart failure and subsequent hospitalizations for heart failure in these patients.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Acute hypertension (urgency/emergency)Level of Evidence [B]

Data from 1 nonrandomized clinical trial, 4 randomized, active-comparator trials, and case reports support the use of captopril (oral or sublingual) for treatment of hypertensive crisis ^Ref.

Aldosteronism, primary (diagnostic test)Level of Evidence [B, G]

Data from 2 prospective, head-to-head studies in patients with hypertension who were suspected to have aldosteronism support the use of captopril to confirm the diagnosis of primary aldosteronism ^Ref. A retrospective analysis also supports the use of captopril to confirm the diagnosis of primary aldosteronism ^Ref.

Based on the Endocrine Society guidelines for the management of primary aldosteronism, captopril may be used as a confirmatory diagnostic test to establish primary aldosteronism in patients with a positive aldosterone-to-renin ratio test.

Non-ST-elevation acute coronary syndromeLevel of Evidence [G]

Based on the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), an angiotensin-converting enzyme (ACE) inhibitor should be initiated and continued indefinitely after NSTE-ACS in patients with a left ventricular ejection fraction (LVEF) ≤40% and in those with hypertension, diabetes mellitus, or stable chronic kidney disease (CKD) unless contraindicated. Use of an ACE inhibitor may also be useful in all other patients with cardiac or other vascular disease.

Raynaud phenomenonLevel of Evidence [C]

Initial data from limited trials indicate that captopril may provide minor benefit in patients with Raynaud phenomenon, but results regarding the effect of captopril on the frequency, severity, or duration of vasospasm attacks are conflicting ^Ref.

Stable coronary artery diseaseLevel of Evidence [G]

Based on the ACC/AHA guideline for the diagnosis and management of patients with stable ischemic heart disease, an ACE inhibitor or angiotensin II receptor blocker should be prescribed in all patients with stable ischemic heart disease who also have hypertension, diabetes mellitus, LVEF <40%, or CKD unless contraindicated.

ST-elevation myocardial infarctionLevel of Evidence [G]

Based on the ACCF/AHA guidelines for the management of patients with ST-elevation acute coronary syndromes (STE-ACS), an ACE inhibitor should be initiated within the first 24 hours to all patients with STE-ACS with anterior location, heart failure, or LVEF ≤40%, unless contraindicated. It is also reasonable to initiate an ACE inhibitor in all patients with STE-ACS.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Angiotensin-Converting Enzyme Inhibitors

Clinical Practice Guidelines

Atrial Fibrillation:

AHA/ACC/HRS, "2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation," March 2014

Cardiovascular Health:

NHLBI, Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, October 2011

Chronic Kidney Disease:

KDIGO 2012 Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease, January 2013

Coronary Artery Bypass Graft Surgery:

“2011 ACC/AHA Guideline for Coronary Artery Bypass Graft Surgery,” November 2011

AHA Scientific Statement, "Secondary Prevention After Coronary Artery Bypass Graft Surgery,” February 2015

Diabetes Mellitus:

AACE/ACE, “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm - 2019 Executive Summary,” January 2019

ADA, “Standards of Medical Care in Diabetes - 2020,” January 2020

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Heart Failure:

ACC/AHA, “2013 ACC/AHA Guideline for the Management of Heart Failure,” June 2013

ACC/AHA/HFSA, “2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure,” May 2016

Canadian Cardiovascular Society, “2012 Heart Failure Management Guidelines Update: Focus on Acute and Chronic Heart Failure,” 2012

“HFSA 2010 Comprehensive Heart Failure Practice Guideline,” July 2010

Hypertension:

"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," November 2017.

AHA/ACC/ASH, “Treatment of Hypertension in Patients with Coronary Artery Disease: A Scientific Statement by the American Heart Association, American College of Cardiology and American Society of Hypertension,” May 2015

"ACC/AHA Expert Consensus Document on Hypertension in the Elderly," 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH “Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension,” January 2014

Eighth Joint National Committee (JNC 8), "2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults," December 2013.

“National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents,” May 2005

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, "2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease," July 2014

ACC/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

ACC/AHA, "2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes,” September 2014

ACC/AHA, “2013 ACC/AHA Guideline for the Management of ST-Elevation Myocardial Infarction,” December 2012

Ischemic Stroke:

AHA/ASA, “2014 Guidelines for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack," May 2014

Prevention:

“ACC/AHA Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2011 Update,” November 2011

Surgery:

ACC/AHA, “2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery,” August 2014

Valvular Heart Disease:

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” March 2014

Administration: 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 (Allen 1996).

Administration: Pediatric

Oral: Administer on an empty stomach 1 hour before or 2 hours after meals/feeds; if crushing tablet and dissolving in water, allow adequate time for complete dissolution (>10 minutes) (Bhatt 2011)

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); protect from moisture.

Extemporaneously Prepared

1 mg/mL Oral Solution (ASHP Standard Concentration) (ASHP 2017)

A 1 mg/mL oral solution may be made by allowing two 50 mg tablets to dissolve in 50 mL of distilled water. Add the contents of one 500 mg sodium ascorbate injection ampul or one 500 mg ascorbic acid tablet and allow to dissolve. Add quantity of distilled water sufficient to make 100 mL. Label “shake well” and “refrigerate.” Stable for 56 days refrigerated or 28 days (ascorbic acid tablet) or 14 days (sodium ascorbate injection) at room temperature.

Nahata MC, Morosco RS, Hipple TF. Stability of captopril in liquid containing ascorbic acid or sodium ascorbate. Am J Hosp Pharm. 1994;51(13):1707-1708.[PubMed 7942898]

Nahata MC, Morosco RS, Hipple TF. Stability of captopril in three liquid dosage forms. Am J Hosp Pharm. 1994;51(1):95-96.[PubMed 8135269]

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat high blood pressure.

• It is used to treat heart failure (weak heart).

• It is used to help heart function after a heart attack.

• It is used to protect kidney function in diabetic patients who have protein loss.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Change in taste

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling.

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Severe dizziness

• Passing out

• Persistent cough

• Severe abdominal pain

• Severe nausea

• Vomiting

• Chest pain

• Fast heartbeat

• Bruising

• Bleeding

• Severe loss of strength and energy

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

International issues:

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).

Documentation of allergenic cross-reactivity for ACE inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

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

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: At any time during treatment (especially following first dose) angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). African-Americans and patients with idiopathic or hereditary angioedema may be at an increased risk. Risk may also be increased with concomitant use of mammalian target of rapamycin inhibitor (eg, everolimus) therapy or a neprilysin inhibitor (eg, sacubitril). Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Use in patients with previous angioedema associated with ACE inhibitor therapy is contraindicated.

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

• Cough: 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. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation.

• Hematologic effects: Captopril has been associated with neutropenia with myeloid hypoplasia and agranulocytosis; anemia and thrombocytopenia have also occurred. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Closely monitor CBC with differential for the first 3 months of therapy and periodically thereafter in these patients. Onset of neutropenia is usually within 3 months of captopril initiation. Neutrophil count generally returns to baseline within 2 weeks of discontinuation. If neutropenia develops (neutrophil count <1,000/mm³), discontinue therapy.

• Hyperkalemia: May occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.

• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions 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 anaphylactoid reactions 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 six months (whether or not captopril was continued).

• Renal function deterioration: May be associated with deterioration of renal function and/or increases in BUN and serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function (Bakris 2000).

Disease-related concerns:

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

• Ascites: 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 renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2012]).

• 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, MI, stroke). Fluid replacement, if needed, may restore BP; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.

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

• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (ACC/AHA [Gersh 2011]).

• Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.

• Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation, which may lead to further renal impairment. In a retrospective cohort study of elderly patients (≥65 years of age) with myocardial infarction 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).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Black patients: ACE inhibitors effectiveness is less in black patients than in non-blacks. In addition, ACE inhibitors cause a higher rate of angioedema in black than in nonblack patients.

• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

• 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).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Due to frequent decreases in glomerular filtration (also CrCl) with aging, elderly patients may have exaggerated responses to ACE inhibitors; differences in clinical response due to hepatic changes are not observed. ACE inhibitors may be preferred agents in elderly patients with congestive heart failure and diabetes mellitus. Diabetic proteinuria is reduced and insulin sensitivity is enhanced. In general, the side effect profile is favorable in the elderly and causes little or no CNS confusion; use lowest dose recommendations initially. Many elderly may be volume depleted due to diuretic use and/or blunted thirst reflex resulting in inadequate fluid intake.

The AHA/ACC/ASH 2015 scientific statement on the treatment of hypertension in patients with CAD warns to use caution to avoid decreases in DBP <60 mm Hg especially in patients >60 years of age since reduced coronary perfusion may occur. When lowering SBP in older hypertensive patients with wide pulse pressures, very low DBP values (<60 mm Hg) may result. In patients with obstructive CAD, clinicians should lower blood pressure slowly and carefully monitor for any untoward signs or symptoms, especially those resulting from myocardial ischemia and worsening heart failure (AHA/ACC/ASH [Rosendorff 2015]).

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.

Pregnancy Risk Factor

Pregnancy Considerations

Captopril crosses the placenta (Hurault de Ligny 1987).

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 203 2019; ESC [Regitz-Zagrosek 2018]); however, outcomes observed may also be influenced by maternal disease (ACC/AHA [Whelton 2018]).

[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. 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. Their use in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Infants exposed to an ACE inhibitor in utero should be monitored for hyperkalemia, hypotension, and oliguria. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function, although data related to the effectiveness in neonates is limited.

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 203 2019).

When treatment of hypertension in pregnancy is indicated, ACE inhibitors should generally be avoided due to their adverse fetal events; use in pregnant women should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019). ACE inhibitors are not recommended for the treatment of heart failure in pregnancy (Regitz-Zagrosek [ESC 2018]).

ACE inhibitors should be avoided in sexually active females of reproductive potential not using effective contraception (ADA 2020). ACE inhibitors should generally be avoided for the treatment of hypertension in women planning a pregnancy; use should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019). When treatment is needed in females of reproductive potential with diabetic nephropathy, the ACE inhibitor should be discontinued at the first positive pregnancy test (Cabiddu 2016; Spotti 2018).

Breast-Feeding Considerations

Captopril is present in breast milk.

The relative infant dose (RID) of captopril is 0.01% to 0.02% when calculated using the highest breast milk concentration located and 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).

The RID of captopril was calculated using an average peak milk concentration of 4.7 ng/mL, providing an estimated daily infant dose via breast milk of 705 ng/kg/day. This milk concentration was obtained following maternal administration captopril 100 mg three times a day for 7 doses to 12 normotensive lactating women. 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).

According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother. Available guidelines consider captopril to be acceptable for use in breastfeeding women (ESC [Bauersachs 2016]; ESC [Regitz-Zagrosek 2018]; WHO 2002) unless high doses are required (ACOG 203 2019).

Lexicomp Pregnancy & Lactation, In-Depth

Captopril

Briggs' Drugs in Pregnancy & Lactation

Captopril

Adverse Reactions

Frequency not defined:

Cardiovascular: Angina pectoris, cardiac arrest, cardiac arrhythmia, cardiac failure, flushing, myocardial infarction, orthostatic hypotension, Raynaud's phenomenon, syncope

Central nervous system: Ataxia, cerebrovascular insufficiency, confusion, depression, drowsiness, myasthenia, nervousness

Dermatologic: Bullous pemphigoid, erythema multiforme, exfoliative dermatitis, pallor, Stevens-Johnson syndrome

Endocrine & metabolic: Gynecomastia, hyponatremia (symptomatic)

Gastrointestinal: Cholestasis, dyspepsia, glossitis, pancreatitis

Genitourinary: Impotence, nephrotic syndrome, oliguria, urinary frequency

Hematologic & oncologic: Agranulocytosis, anemia, pancytopenia, thrombocytopenia

Hepatic: Hepatic necrosis (rare), hepatitis, increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases, jaundice

Hypersensitivity: Anaphylactoid reaction, angioedema

Neuromuscular & skeletal: Myalgia, weakness

Ophthalmic: Blurred vision

Renal: Polyuria, renal failure, renal insufficiency

Respiratory: Bronchospasm, eosinophilic pneumonitis, rhinitis

1% to 10%:

Cardiovascular: Hypotension (1% to 3%), chest pain (1%), palpitations (1%), tachycardia (1%)

Dermatologic: Skin rash (maculopapular or urticarial [4% to 7%]; in patients with rash, a positive ANA and/or eosinophilia has been noted in 7% to 10%), pruritus (2%)

Endocrine & metabolic: Hyperkalemia (1% to 11%)

Gastrointestinal: Dysgeusia (2% to 4%; loss of taste or diminished perception)

Genitourinary: Proteinuria (1%)

Hematologic & oncologic: Neutropenia (≤4%; in patients with renal insufficiency or collagen-vascular disease)

Hypersensitivity: Hypersensitivity reaction (rash, pruritus, fever, arthralgia, and eosinophilia: 4% to 7%; depending on dose and renal function)

Renal: Increased serum creatinine, renal insufficiency (worsening; may occur in patients with bilateral renal artery stenosis or hypovolemia)

Respiratory: Cough (<1% to 2%)

Miscellaneous: Hypersensitivity reactions (rash, pruritus, fever, arthralgia, and eosinophilia) have occurred in 4% to 7% of patients (depending on dose and renal function); dysgeusia - loss of taste or diminished perception (2% to 4%)

<1%, postmarketing, and/or case reports: Abdominal pain, alopecia, angina pectoris, anorexia, aphthous stomatitis, aplastic anemia, arthralgia, cholestatic jaundice, constipation, diarrhea, dizziness, dyspnea, eosinophilia, fatigue, fever, gastric irritation, glomerulonephritis, Guillain-Barre syndrome, headache, hemolytic anemia, Huntington's chorea (exacerbation), hyperthermia, increased erythrocyte sedimentation rate, insomnia, interstitial nephritis, Kaposi's sarcoma, malaise, myalgia, nausea, paresthesia, peptic ulcer, pericarditis, psoriasis, seizure (in premature infants), systemic lupus erythematosus, vasculitis, visual hallucination (Doane, 2013), vomiting, xerostomia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

ACE Inhibitor Allergy/Hypersensitivity

Toxicology

Angiotensin-Converting Enzyme (ACE) Inhibitors

Metabolism/Transport Effects

Substrate of CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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 D: Consider therapy modification

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 amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. 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: In US labeling, 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 to the combination when possible. 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

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

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

CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

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

Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with 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: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Drospirenone. 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

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

Gold Sodium Thiomalate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. 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 D: Consider therapy modification

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

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): 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

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. Risk D: Consider therapy modification

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

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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 patient response to lithium closely following addition or discontinuation of concurrent ACE inhibitor treatment. 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

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

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

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

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

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

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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

Sirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. 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. Management: Consider avoiding this combination by temporarily suspending treatment with ACEIs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification

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. 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

TiZANidine: May enhance the hypotensive 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

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. 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.

Test Interactions

May lead to false-negative aldosterone/renin ratio (Funder 2016).

Genes of Interest

Monitoring Parameters

BUN, electrolytes, serum creatinine; BP. In patients with renal impairment and/or collagen vascular disease, closely monitor CBC with differential for the first 3 months of therapy and periodically thereafter.

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]).

Heart failure: Within 1 to 2 weeks after initiation and periodically thereafter, reassess renal function and serum potassium, especially in patients with preexisting hypotension, hyponatremia, diabetes mellitus, azotemia, or those taking potassium supplements (ACC/AHA [Yancy 2013]).

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2018]):

Confirmed hypertension and known CVD or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%: Target BP <130/80 mm Hg is recommended.

Confirmed hypertension without markers of increased ASCVD risk: Target BP <130/80 mm Hg may be reasonable.

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines (ADA 2020):

Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%: Target BP <140/90 mm Hg is recommended.

Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk ≥15%: Target BP <130/80 mm Hg may be appropriate if it can be safely attained.

Patients >65 years of age (healthy or complex/intermediate health): Target BP <140/90 mm Hg is recommended.

Patients >65 years of age (very complex/poor health): Target BP <150/90 mm Hg is recommended.

Advanced Practitioners Physical Assessment/Monitoring

Obtain BUN, serum creatinine, electrolytes, and CBC with differential (patients with renal impairment or collagen vascular disease). Monitor blood pressure. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Assess for signs of angioedema.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor blood pressure. Monitor for signs of angioedema. Instruct women of child-bearing age to notify provider immediately for pregnancy.

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

Dosage Forms: Canada

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

Tablet, Oral:

Generic: 6.25 mg, 12.5 mg, 25 mg, 50 mg, 100 mg

Anatomic Therapeutic Chemical (ATC) Classification

C09AA01

Generic Available (US)

Yes

Pricing: US

Tablets (Captopril Oral)

12.5 mg (per each): $1.20 - $1.72

25 mg (per each): $1.27 - $1.86

50 mg (per each): $2.03 - $2.90

100 mg (per each): $2.94 - $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.

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.

Pharmacodynamics/Kinetics

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: V_dss: 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 renal 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 renal 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)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Loss or diminished perception of taste; Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment.

An angiotensin-converting enzyme (ACE) Inhibitor cough is a dry, hacking, nonproductive cough that can potentially interfere with longer dental procedures if patient has this side effect.

Effects on Bleeding

No information available to require special precautions

Related Information

Index Terms

Capoten

FDA Approval Date

April 06, 1981

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Brand Names: International

Ace-Bloc (TW); Aceomel (IE); Acepress (ID, IT); Acepril (EG, GB, LK); Aceril (IL); Acetab (AE, BH, ET, QA); Aceten (IN); Adocor (DE); Amipril (BD); Angiopril (IN); Angiopril-25 (ZW); Antasten (AR); Apuzin (LK, MY); Asisten (UY); Atrisol (CR, DO, GT, HN, NI, PA, SV); Bloc-Med (PH); Brucap (CR, DO, GT, HN, NI, PA, SV); Caipolex (ZW); Capace (ZA); Capocard (JO, KW, QA, SA); Capomed (PH); Caporex (ZW); Capotec (PH); Capoten (AE, AU, BB, BE, BM, BR, BS, BZ, CL, CN, CO, CY, CZ, DK, EC, EG, ES, ET, FI, GB, GR, GY, HK, IE, IT, JM, JO, KE, KW, LB, LK, LU, NG, NL, NZ, PH, PK, PL, PT, QA, SA, SE, SR, TR, TT, TZ, UG, VE, ZA, ZM); Capotena (MX); Capotril (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Capril (BD, KR, SA, TH); Captace (AE, LB, PH); Captarsan (VN); Captensin (ID); Captodoc (DE); Captoflux (DE); Captohexal (EE, LU, NZ); Captolane (FR); Captolar (LK); Captopren (AE, CY, IL, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Captopril Pharmavit (HU); Captor (AT, IE); Captotec (BR); Captral (CR, DO, GT, HN, MX, NI, PA, SV); Cardiagen (DE); Catopil (BD); Catoplin (SG); Debax (AT); Dexacap (ID, SG, VN); Ecaten (MX); Epsitron (ET); Farcopril (AE, CY, EG, IQ, IR, JO, KW, LY, OM, QA, SA, SY, YE); Farmoten (ID); Gemzil (TH); Hiperil (PT); Huma-Captopril (HU); Hypopress (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Hypotensor (GR); Kapril (TR); Kaptopril (LV); Ketanine (SG); Kimapan (MY); Lopirin (AT, CH, DE); Lopril (FI, FR); Metopril (ID); Midopril (KW); Midrat (MX); Minitent (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE); Nolectin (PE); Normolose (MT); Noyada (GB, MT); Orbace (LB); Pertacilon (SG); Prelat (PH); Prilocapt (EG); Primace (PH); Properil (CL); Retensin (PH); Rilcapton (SG); Ropril (AE, CY, IQ, IR, JO, KW, LY, MT, OM, SA, SY, TR, YE); Smarten (TW); Tensicap (ID); Tensiomen (BG, SK); Tensiomin (HU); Tensobon (DE); Topril (BD); Vasosta (PH); Zapto (ZA); Zedace (AU)

Last Updated 3/10/20

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