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Article Author:
Francheska Marte
Article Author:
Parvathy Sankar
Article Editor:
Manouchkathe Cassagnol
5/3/2020 5:26:18 PM
For CME on this topic:
Captopril CME
PubMed Link:


FDA-Approved Indications


  • Initial therapy for patients with normal renal function
  • In patients with impaired renal function, captopril should be reserved for those patients that have developed unacceptable side effects or failed to respond to other drug therapy[1]
  • Effective alone and in combination with other antihypertensive agents

Left Ventricular Dysfunction after Myocardial Infarction

  • Improves survival following myocardial infarction in clinically stable patients with left ventricular ejection fraction less than 40% and reduces the incidence of hospitalization[1]

Diabetic Nephropathy

  • Treatment of diabetic nephropathy (proteinuria greater than 500 mg per day) in patients with type I insulin-dependent diabetes mellitus and retinopathy
  • Decreases the rate of progression of renal insufficiency[1]

Off-Label Indications

Acute Hypertensive Crisis

  • Maybe given sublingually but the therapeutic advantage has not been demonstrated over oral administration [2]
  • Consider alternative therapy if blood pressure is nonresponsive within 20 to 30 minutes[3]

Raynaud Phenomenon

  • A clinical trial evaluated patients up to 3 months, additional studies required to determine full effectiveness [4]

Mechanism of Action

The benefits of captopril in hypertension and heart failure result primarily from suppression of the renin-angiotensin-aldosterone system (RAAS).[5] As an angiotensin-converting enzyme (ACE) inhibitor, it inhibits ACE, which converts angiotensin I to angiotensin II. Angiotensin II binds to AT1 receptors on smooth muscles to produce vasoconstriction and an increase in blood pressure. Angiotensin II also stimulates the adrenal cortex to secrete aldosterone. Aldosterone causes the distal tubules and collecting ducts of the kidneys to reabsorb water and sodium in exchange for potassium, which results in an expansion in extracellular volume and an increase in blood pressure.[6] Inhibition of ACE leads to decreased plasma angiotensin II, leading to vasodilation and decreased aldosterone secretion. Small increases in serum potassium, as well as sodium and fluid loss, may occur due to a decrease in aldosterone secretion.[1] Administration of captopril results in a reduction of peripheral arterial resistance in hypertensive patients. ACE also metabolizes bradykinin, a peptide that causes vasodilation. ACE inhibitors impede the breakdown of bradykinin, resulting in vasodilation and a bradykinin-evoked cough.


Captopril should be taken 1 hour before meals. Therapy initiation requires analysis of recent antihypertensive drug treatment, the extent of blood pressure elevation, and salt restriction. If possible, the previous antihypertensive drug regimen should be stopped one week before starting captopril. The daily dose of captopril may be increased every 24 hours under continuous medical supervision. For patients with significant renal impairment, the initial daily dosage should be reduced and smaller increments utilized for titration.


  • Initial dose: 25 mg twice per day (BID) or three times per day (TID)
  • Unsatisfactory reduction of blood pressure after one to two weeks: increase dose to 50 mg BID or TID
  • The dose of captopril may increase to 100 mg BID or TID and if necessary to 150 mg BID or TID if further blood pressure reduction is required
  • The usual dose range is 25 to 150 mg BID or TID. The maximum daily dose of 450 mg should not be exceeded[7]

Heart Failure

  • Initial dose in patients vigorously treated with diuretics, hyponatremic and hypovolemic patients: 6.25 or 1.25 mg TID with titration to the usual daily dosage within several days[8]
  • The initial dose in most patients: 25 mg TID
    • After a dose of 50 mg TID, further increases in dosage should delay for at least two weeks[8]

Left Ventricular Dysfunction after Myocardial Infarction

  • After a single dose of 6.25 mg, captopril therapy should be initiated at 12.5 mg TID and then increased to 25 mg TID during several days
  • Long-term use: Target maintenance dose of 50 mg TID
  • Therapy can be initiated as early as three days following myocardial infarction[9]

Diabetic Nephropathy

  • Long-term use: 25 mg TID[10]

Acute Hypertensive Crisis

  • Dosed orally, sublingually 25 mg; consider alternative therapy if blood pressure is nonresponsive  within 20 to 30 minutes[3]

Raynaud phenomenon

  • Initial dose 12.5 mg twice daily; may be gradually increased to 25 mg TID[4]

Adverse Effects

Adverse Effects

  • Proteinuria (1 of 100 patients) which subsides or clears within six months even when captopril therapy is continued[11]
  • Renal insufficiency, renal failure, nephrotic syndrome, polyuria, oliguria and urinary frequency (1 to 2 of 1000 patients)[12]
  • Neutropenia (less than 1000/mm3)/agranulocytosis with myeloid hypoplasia
  • Rash with pruritus and occasionally with fever, arthralgia, and eosinophilia (4 to 7 of 100 patients)[11]
  • Angina pectoris, myocardial infarction, Raynaud syndrome and congestive heart failure (2 to 3 of 1000 patients)[13]
  • Dysgeusia (diminution or loss of taste perception) which is reversible and usually self-limited (2 to 4 of 100 patients)[13]
  • Anaphylactoid and other related reactions due to the inhibition of the metabolism of eicosanoids and polypeptides, including bradykinin
  • Head and neck angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx[11]
  • Intestinal angioedema- abdominal pain with or without nausea vomiting[11]
  • Flushing or pallor 
  • Tachycardia, chest pain, and palpitations


  • Hypertension: Increases in BUN and serum creatinine have been observed in some patients with renal disease[12]
  • Heart Failure: Elevations of BUN and serum creatinine greater than 20% above normal or baseline with long-term treatment[8]
  • Hyperkalemia: Elevations in serum potassium
  • Surgery/Anesthesia: In patients undergoing major surgery with anesthesia with agents that produce hypotension, captopril will block angiotensin II formation, and hypotension may result
  • Nursing: Concentrations of captopril in human milk are approximately one percent of those in maternal blood
  • Pregnancy: Category D
    • Drug use that acts on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death[12]
    • Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death[12]
    • Captopril must be discontinued as soon as possible when pregnancy is confirmed
  • Breastfeeding considerations
    • Present in breast milk at an approximate concentration of 1% of those in maternal blood 
    • May considered acceptable for use in breastfeeding
    • Monitor the weight of breastfeeding child for the first four weeks[14]


  • Hypersensitivity to captopril, any component of the formulation or any other ACEI
  • Angioedema related to previous treatment with ACEI
  • Concomitant aliskiren use in patients with diabetes mellitus
  • Coadministration with or within 36 hours of switching to or from a neprilysin inhibitor (sacubitril)


In general, the patient's BUN, electrolytes, serum creatinine, and blood pressure requires routine monitoring. If captopril is initiated in patients with impaired renal function and/or collagen vascular disease, the complete blood count with differential should be evaluated before starting treatment and at two-week intervals for about three months, then periodically after that.[12] All patients treated with captopril receive counsel to report any signs of infection, including sore throat or fever. Patients with heart failure should be followed closely for the first two weeks of treatment and whenever the dose of captopril is titrated, especially in patients with preexisting hypotension, hyponatremia, diabetes, azotemia, or those taking potassium supplements due to the potential for excessive hypotension, arrhythmia and conduction defects.[15] According to the latest hypertension guidelines, patients with or without CVD or increased ASVD risk should maintain a blood pressure of less than 130/80 mm Hg while on therapy. On the other hand, according to the diabetes guidelines, adult patients (18 to 65 years) with both diabetes and hypertension have a goal blood pressure of less than 140/90 mm Hg.[16]


Correction of hypotension is the primary concern through volume expansion with an intravenous infusion of normal saline. Excessive hypotension has been rarely seen in hypertensive patients but is a possible consequence of captopril use in salt/volume depleted persons. ACE inhibitors have rarely shown an association with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.[1] If a marked elevation of hepatic transaminases or jaundice occurs, captopril should be discontinued. A persistent, dry, hacking, nonproductive cough that occurs within the first few months of treatment can also occur with captopril therapy. ACE inhibitor-induced cough results from the inhibition of the degradation of bradykinin and generally resolves within 1 to 4 weeks after discontinuation.

Enhancing Healthcare Team Outcomes

Captopril is a widely prescribed drug in clinical medicine. Healthcare workers (physicians and nurse practitioners) who prescribe this medication for hypertension should be aware of its side effects and the need to monitor electrolytes and renal function. In some patients, captopril may produce a chronic cough, and in such scenarios, the drug should be discontinued, and another class of antihypertensive used. The pharmacist should keep track of the patient's medications to avoid polypharmacy and drug interactions.


[1] Chen YJ,Li LJ,Tang WL,Song JY,Qiu R,Li Q,Xue H,Wright JM, First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. The Cochrane database of systematic reviews. 2018 Nov 14     [PubMed PMID: 30480768]
[2] Karakiliç E,Büyükcam F,Kocalar G,Gedik S,Atalar E, Same effect of sublingual and oral captopril in hypertensive crisis. European review for medical and pharmacological sciences. 2012 Nov     [PubMed PMID: 23161035]
[3] Damasceno A,Ferreira B,Patel S,Sevene E,Polónia J, Efficacy of captopril and nifedipine in black and white patients with hypertensive crisis. Journal of human hypertension. 1997 Aug     [PubMed PMID: 9322826]
[4] Tosi S,Marchesoni A,Messina K,Bellintani C,Sironi G,Faravelli C, Treatment of Raynaud's phenomenon with captopril. Drugs under experimental and clinical research. 1987     [PubMed PMID: 3297593]
[5] Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation., Gan Z,Huang D,Jiang J,Li Y,Li H,Ke Y,, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 2018 Sep 3     [PubMed PMID: 30183974]
[6] Lezama-Martinez D,Flores-Monroy J,Fonseca-Coronado S,Hernandez-Campos M,Valencia-Hernandez I,Martinez-Aguilar L, Combined Antihypertensive Therapies that Increase Expression of Cardioprotective Biomarkers Associated with the Renin-Angiotensin and Kallikrein-Kinin Systems. Journal of cardiovascular pharmacology. 2018 Oct 29     [PubMed PMID: 30422889]
[7] Treating essential hypertension. The first choice is usually a thiazide diuretic.,, Prescrire international, 2014 Sep     [PubMed PMID: 25325125]
[8] Clinical pharmacokinetics of drugs in patients with heart failure: an update (part 2, drugs administered orally)., Ogawa R,Stachnik JM,Echizen H,, Clinical pharmacokinetics, 2014 Dec     [PubMed PMID: 25248847]
[9] Angiotensin converting enzyme (ACE) inhibitory peptides: production and implementation of functional food., De Leo F,Panarese S,Gallerani R,Ceci LR,, Current pharmaceutical design, 2009     [PubMed PMID: 19925416]
[10] Medicinal chemistry of drugs used in diabetic cardiomyopathy., Adeghate E,Kalasz H,Veress G,Teke K,, Current medicinal chemistry, 2010     [PubMed PMID: 20015035]
[11] Angiotensin-converting enzyme inhibitors and angioedema., Sánchez-Borges M,González-Aveledo LA,, Allergy, asthma & immunology research, 2010 Jul     [PubMed PMID: 20592919]
[12] Angiotensin-converting enzyme inhibitor nephrotoxicity in neonates with cardiac disease., Lindle KA,Dinh K,Moffett BS,Kyle WB,Montgomery NM,Denfield SD,Knudson JD,, Pediatric cardiology, 2014 Mar     [PubMed PMID: 24233240]
[13] Case study of patents related to captopril, Squibb's first blockbuster., Antunes AM,Guerrante RD,Ávila JP,Lins Mendes FM,Fierro IM,, Expert opinion on therapeutic patents, 2016 Dec     [PubMed PMID: 27573807]
[14] Regitz-Zagrosek V,Roos-Hesselink JW,Bauersachs J,Blomström-Lundqvist C,Cífková R,De Bonis M,Iung B,Johnson MR,Kintscher U,Kranke P,Lang IM,Morais J,Pieper PG,Presbitero P,Price S,Rosano GMC,Seeland U,Simoncini T,Swan L,Warnes CA, 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. European heart journal. 2018 Sep 7     [PubMed PMID: 30165544]
[15] Are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers especially useful for cardiovascular protection?, Ong HT,, Journal of the American Board of Family Medicine : JABFM, 2009 Nov-Dec     [PubMed PMID: 19897698]
[16] Muntner P,Whelton PK,Woodward M,Carey RM, A Comparison of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline and the 2017 American Diabetes Association Diabetes and Hypertension Position Statement for U.S. Adults With Diabetes. Diabetes care. 2018 Nov     [PubMed PMID: 30150235]