Side Effects of Capoten (captopril)

Capoten (captopril) is an angiotensin converting enzyme (ACE) inhibitor used to treat high blood pressure (hypertension), heart failure, and to prevent kidney failure due to high blood pressure and diabetes. 

Angiotensin II is a very potent chemical that causes the muscles surrounding blood vessels to contract, thereby narrowing the vessels. The narrowing of the vessels increases the pressure within the vessels causing high blood pressure (hypertension). 

Angiotensin II is formed from angiotensin I in the blood by the enzyme angiotensin converting enzyme or ACE. ACE inhibitors are medications that slow (inhibit) the activity of the enzyme ACE and decrease the production of angiotensin II. As a result, blood vessels enlarge or dilate, and blood pressure is reduced. 

The lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, progression of the disease in the blood vessels within the kidney caused by high blood pressure or diabetes is slowed. 

Common side effects of Capoten include

• dry and persistent cough,
• abdominal pain,
• constipation,
• diarrhea,
• rash,
• dizziness,
• fatigue,
• headache,
• loss of taste,
• loss of appetite,
• nausea,
• vomiting,
• fainting, and
• numbness or tingling in the hands or feet.

Serious side effects of Capoten include

• kidney failure,
• increased levels of potassium in the blood, and rarely,
• liver failure and angioedema (swelling of lips and throat that can obstruct breathing).

Drug interactions of Capoten include potassium supplements, salt substitutes or diuretics, for example, spironolactone, that increase potassium in the blood, because it may lead to excessive potassium levels (hyperkalemia).

• Potassium levels should be monitored whenever ACE inhibitors are used in combination with these drugs.
• There have been reports of increased lithium levels when lithium is used in combination with ACE inhibitors. The reason for this interaction is not known, but the increased levels may lead to toxicity from lithium.
• There have been reports that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin, and naproxen may reduce the effects of ACE inhibitors.
• Combining Capoten or other ACE inhibitors with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients who are elderly, volume-depleted (including those on diuretic therapy), or with poor kidney function may result in reduced kidney function, including kidney failure.
• These effects are usually reversible. Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and low blood pressure) may occur when injectable gold (sodium aurothiomalate), used in the treatment of rheumatoid arthritis, is combined with ACE inhibitors, including Capoten. 

When pregnancy is detected, discontinue Capoten as soon as possible. Adverse outcomes are usually associated with use of ACE inhibitors in the second and third trimester of pregnancy. 

Capoten is secreted in breast milk and should be avoided by breastfeeding mothers.

• Captopril generally is well tolerated, and side effects are usually mild and transient.
• A dry, persistent cough has been reported commonly with the use of captopril and other ACE inhibitors. Coughing resolves after discontinuing the drug.
• Other side effects include
  • abdominal pain,
  • constipation,
  • diarrhea,
  • rash,
  • dizziness,
  • fatigue,
  •  headache,
  • loss of taste,
  •  loss of appetite,
  •  nausea,
  • vomiting,
  • fainting and numbness or
  •  tingling in the hands or feet.

Captopril and other ACE inhibitors also may cause kidney failure and increased levels of potassium in the blood. Serious but, fortunately, very rare side effects are liver failure and angioedema (swelling of lips and throat that can obstruct breathing).

Reported incidences are based on clinical trials involving approximately 7000 patients.

• Renal: About one of 100 patients developed proteinuria.
• Each of the following has been reported in approximately 1 to 2 of 1000 patients and are of uncertain relationship to drug use:
  • renal insufficiency,
  • renal failure,
  • nephrotic syndrome,
  • polyuria,
  • oliguria, and
  • urinary frequency.
• Hematologic: Neutropenia/agranulocytosis has occurred. Cases of anemia, thrombocytopenia, and pancytopenia have been reported.
• Dermatologic: Rash, often with pruritus, and sometimes with fever, arthralgia, and eosinophilia, occurred in about 4 to 7 (depending on renal status and dose) of 100 patients, usually during the first four weeks of therapy. It is usually maculopapular, and rarely urticarial. The rash is usually mild and disappears within a few days of dosage reduction, short-term treatment with an antihistaminic agent, and/or discontinuing therapy; remission may occur even if captopril is continued. Pruritus, without rash, occurs in about 2 of 100 patients. Between 7 and 10 percent of patients with skin rash have shown an eosinophilia and/or positive ANA titers. A reversible associated pemphigoid-like lesion, and photosensitivity, have also been reported.
• Flushing or pallor has been reported in 2 to 5 of 1000 patients.
• Cardiovascular: Hypotension may occur.
• Tachycardia, chest pain, and palpitations have each been observed in approximately 1 of 100 patients.
• Angina pectoris, myocardial infarction, Raynaud's syndrome, and congestive heart failure have each occurred in 2 to 3 of 1000 patients.
• Dysgeusia: Approximately 2 to 4 (depending on renal status and dose) of 100 patients developed a diminution or loss of taste perception. Taste impairment is reversible and usually self-limited (2 to 3 months) even with continued drug administration. Weight loss may be associated with the loss of taste.
• Angioedema: Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis or larynx has been reported in approximately one in 1000 patients. Angioedema involving the upper airways has caused fatal airway obstruction.
• Cough: Cough has been reported in 0.5 to 2% of patients treated with captopril in clinical trials.
• The following have been reported in about 0.5 to 2 percent of patients but did not appear at increased frequency compared to placebo or other treatments used in controlled trials:
  • gastric irritation,
  • abdominal pain,
  • nausea,
  • vomiting,
  • diarrhea,
  • anorexia,
  • constipation,
  • aphthous ulcers,
  • peptic ulcer,
  • dizziness,
  • headache,
  • malaise,
  • fatigue,
  • insomnia,
  • dry mouth,
  • dyspnea,
  • alopecia,
  • paresthesias.
• Other clinical adverse effects reported since the drug was marketed are listed below by body system. In this setting, an incidence or causal relationship cannot be accurately determined.
• Body as a whole: Anaphylactoid reactions.
• General: Asthenia, gynecomastia.
• Cardiovascular: Cardiac arrest, cerebrovascular accident/insufficiency, rhythm disturbances, orthostatic hypotension, syncope.
• Dermatologic: Bullous pemphigus, erythema multiforme (including Stevens-Johnson syndrome), exfoliative dermatitis.
• Gastrointestinal: Pancreatitis, glossitis, dyspepsia.
• Hematologic: Anemia, including aplastic and hemolytic.
• Hepatobiliary: Jaundice, hepatitis, including rare cases of necrosis, cholestasis.
• Metabolic: Symptomatic hyponatremia.
• Musculoskeletal: Myalgia, myasthenia.
• Nervous/Psychiatric: Ataxia, confusion, depression, nervousness, somnolence.
• Respiratory: Bronchospasm, eosinophilic pneumonitis, rhinitis.
• Special Senses: Blurred vision.
• Urogenital: Impotence.
• As with other ACE inhibitors, a syndrome has been reported which may include:
  • fever,
  • myalgia,
  • arthralgia,
  • interstitial nephritis,
  • vasculitis,
  • rash or other dermatologic manifestations,
  • eosinophilia and
  • an elevated ESR.

Altered Laboratory Findings

• Serum Electrolytes: Hyperkalemia: small increases in serum potassium, especially in patients with renal impairment.
• Hyponatremia: particularly in patients receiving a low sodium diet or concomitant diuretics.
• BUN/Serum Creatinine: Transient elevations of BUN or serum creatinine especially in volume or salt depleted patients or those with renovascular hypertension may occur. Rapid reduction of longstanding or markedly elevated blood pressure can result in decreases in the glomerular filtration rate and, in turn, lead to increases in BUN or serum creatinine.
• Hematologic: A positive ANA has been reported.
• Liver Function Tests: Elevations of liver transaminases, alkaline phosphatase, and serum bilirubin have occurred.

Dual Blockade Of The Renin-Angiotensin System (RAS)

• Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
• Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy.
• In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Capoten and other agents that block the RAS.
• Do not coadminister aliskiren with Capoten in patients with diabetes. Avoid use of aliskiren with Capoten in patients with renal impairment (GFR < 60 ml/min).

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase – 2 Inhibitors (COX-2 Inhibitors)

• In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including captopril, may result in deterioration of renal function, including possible acute renal failure.
• These effects are usually reversible. Monitor renal function periodically in patients receiving captopril and NSAID therapy.
• The antihypertensive effect of ACE inhibitors, including captopril, may be attenuated by NSAIDs.
• Hypotension - Patients on Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, as well as those on severe dietary salt restriction or dialysis, may occasionally experience a precipitous reduction of blood pressure usually within the first hour after receiving the initial dose of captopril.

The possibility of hypotensive effects with captopril can be minimized by either discontinuing the diuretic or increasing the salt intake approximately one week prior to initiation of treatment with Capoten (captopril tablets, USP) or initiating therapy with small doses (6.25 or 12.5 mg). Alternatively, provide medical supervision for at least one hour after the initial dose.

If hypotension occurs, the patient should be placed in a supine position and, if necessary, receive an intravenous infusion of normal saline. This transient hypotensive response is not a contraindication to further doses which can be given without difficulty once the blood pressure has increased after volume expansion.

• Agents Having Vasodilator Activity: Data on the effect of concomitant use of other vasodilators in patients receiving Capoten for heart failure are not available; therefore, nitroglycerin or other nitrates (as used for management of angina) or other drugs having vasodilator activity should, if possible, be discontinued before starting Capoten. If resumed during Capoten therapy, such agents should be administered cautiously, and perhaps at lower dosage.
• Agents Causing Renin Release: Captopril's effect will be augmented by antihypertensive agents that cause renin release. For example, diuretics (e.g., thiazides) may activate the renin-angiotensinaldosterone system.
• Agents Affecting Sympathetic Activity: The sympathetic nervous system may be especially important in supporting blood pressure in patients receiving captopril alone or with diuretics. Therefore, agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) should be used with caution. Beta-adrenergic blocking drugs add some further antihypertensive effect to captopril, but the overall response is less than additive.
• Agents Increasing Serum Potassium: Since captopril decreases aldosterone production, elevation of serum potassium may occur. Potassium-sparing diuretics such as spironolactone, triamterene, or amiloride, or potassium supplements should be given only for documented hypokalemia, and then with caution, since they may lead to a significant increase of serum potassium. Salt substitutes containing potassium should also be used with caution.
• Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, it may increase the risk of lithium toxicity.
• Cardiac Glycosides: In a study of young healthy male subjects no evidence of a direct pharmacokinetic captopril-digoxin interaction could be found.
• Loop Diuretics: Furosemide administered concurrently with captopril does not alter the pharmacokinetics of captopril in renally impaired hypertensive patients.
• Allopurinol: In a study of healthy male volunteers no significant pharmacokinetic interaction occurred when captopril and allopurinol were administered concomitantly for 6 days.

Gold

• Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including Capoten.

Drug/Laboratory Test Interaction

• Captopril may cause a false-positive urine test for acetone.