Captopril

Do not coadminister with captopril in patients with diabetes. Avoid use in patients with renal impairment (GFR < 60 ml/min) due to increased risk of hypotension, hyperkalemia, and acute renal failure.

Dual blockade of RAS associated with increased risks of hypotension, hyperkalemia, and changes in renal function including acute renal failure compared to monotherapy.

Coadministration in elderly, volume-depleted, or renal-compromised patients may result in deterioration of renal function including acute renal failure. NSAIDs may attenuate antihypertensive effect.

Drug Interactions: Captopril : 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 restrictions 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 captopril or initiating therapy with small doses (6.25 or 12.5 mg). Agents Having Vasodilator Activity : Data on the effect of concomitant use of other vasodilators in patients receiving captopril 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 captopril.

Increases digoxin serum concentration by 58% and AUC by 39%. Requires monitoring and dose adjustment.

Patients on diuretics may experience precipitous reduction of blood pressure within first hour after initial captopril dose, especially if recently started on diuretic therapy or on severe dietary salt restriction.

May substantially increase steady-state plasma lithium levels, sometimes resulting in lithium toxicity.

Dual blockade of RAS associated with increased risks of hypotension, hyperkalemia, and changes in renal function including acute renal failure compared to monotherapy.

Indomethacin can reduce the antihypertensive effects of captopril. May result in further deterioration of renal function in patients with compromised renal function.

P-glycoprotein (P-gp) Inhibitors (e.g., amiodarone, captopril, cyclosporine, quercetin, quinidine, verapamil) Clinical Impact Increase in plasma naldemedine concentrations [see Clinical Pharmacology (12.3) ] Intervention Monitor for potential naldemedine-related adverse reactions [see Adverse Reactions (6.1) ] .

Data on concomitant use with captopril for heart failure are not available. Should be discontinued before starting captopril if possible; if resumed, administer cautiously at lower dosage.

Data on concomitant use with captopril for heart failure are not available. Should be discontinued before starting captopril if possible; if resumed, administer cautiously at lower dosage.

Small decreases in blood pressure observed in some patients. Periodic systemic blood pressure monitoring recommended.

Concomitant administration of captopril does not influence captopril plasma disposition; terazosin maximum plasma concentrations increase linearly with dose at steady-state.

For example, diuretics (e.g., thiazides) may activate the renin-angiotensin-aldosterone system. Agents Increasing Serum Potassium Since captopril decreases aldosterone production, elevation of serum potassium may occur.

Examples: Ramipril, captopril Beta Blockers Clinical Impact: The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow, and salt and fluid retention.

Loop Diuretics Furosemide administered concurrently with captopril does not alter the pharmacokinetics of captopril in renally impaired hypertensive patients.

Drug Interactions No untoward clinical manifestations have been observed in limited experience with patients in whom milrinone was used concurrently with the following drugs: digitalis glycosides; lidocaine, quinidine; hydralazine, prazosin; isosorbide dinitrate, nitroglycerin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin; and potassium supplements.

Table 3: No observed clinically important drug interactions of Veltassa Angiotensin-converting enzyme (ACE) inhibitors Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril Angiotensin II receptor blockers (ARB) Azilsartan, candesartan, irbesartan, losartan, olmesartan, valsartan β-adrenoceptor blockers (β-blocker) Metoprolol Loop diuretics Furosemide, bumetanide, torasemide Mineralocorticoid receptor antagonists (MRA) Eplerenone, finerenone, spironolactone Neprilysin inhibitors Sacubitril Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Canagliflozin, dapagliflozin, empagliflozin Antibiotics Trimethoprim, amoxicillin, cephalexin Anticoagulants Warfarin, apixaban, rivaroxaban Anti-parathyroid agents and Thyroid preparations Cinacalcet Antithrombotic agents Clopidogrel, acetylsalicylic acid Blood glucose lowering drugs Glipizide Calcium channel blockers Amlodipine, verapamil Immunosuppressants Tacrolimus Others Lithium, allopurinol, atorvastatin, digoxin, phenytoin, riboflavin, sevelamer

Sixteen (16) drugs tested did not show an in vitro interaction with LOKELMA (allopurinol, apixaban, aspirin, captopril, cyclosporine, digoxin, ethinyl estradiol, lisinopril, magnesium, metformin, phenytoin, prednisone, propranolol, quinapril, spironolactone and ticagrelor).

In post-myocardial infarction patients, doubling of serum creatinine was observed in 4.2% of valsartan-treated patients and 3.4% of captopril-treated patients.