Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Diuretics: (thiazide or loop diuretics): Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with captopril (see section 4.4). The hypotensive effects can be reduced by discontinuation of the diuretic, by increasing volume or salt intake or by initiating therapy with a low dose of captopril. However, no clinically significant drug interactions have been found in specific studies with hydrochlorothiazide or furosemide.
Potassium sparing diuretics, potassium supplements or potassium-containing salt substitutes:
Although serum potassium usually remains within normal limits, hyperkalaemia may occur in some patients treated with captopril. Potassium sparing diuretics (e.g. spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Care should also be taken when cilazapril is co- administered with other agents that increase serum potassium, such as trimethoprim and cotrimoxazole (trimethoprim/sulfamethoxazole) as trimethoprim is known to act as a potassium- sparing diuretic like amiloride. Therefore, the combination of captopril with the above-mentioned drugs is not recommended. If concomitant use is indicated, they should be used with caution and with frequent monitoring of serum potassium.
Ciclosporin
Hyperkalaemia may occur during concomitant use of ACE inhibitors with ciclosporin. Monitoring of serum potassium is recommended.

Heparin
Hyperkalaemia may occur during concomitant use of ACE inhibitors with heparin.
Monitoring of serum potassium is recommended.
Other antihypertensive agents: Captopril has been safely co-administered with other commonly used anti-hypertensive agents (e.g. beta-blockers and long-acting calcium channel blockers).
Concomitant use of these agents may increase the hypotensive effects of captopril. Treatment with nitroglycerine and other nitrates, or other vasodilators (such as minoxidil), should be used with caution.
Alpha blocking agents: concomitant use of alpha blocking agents may increase the antihypertensive effects of captopril and increase the risk of orthostatic hypotension.

Treatments of acute myocardial infarction: Captopril may be used concomitantly with acetylsalicylic acid (at cardiologic doses), thrombolytics, beta-blockers and/or nitrates in patients with myocardial infarction.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors. Concomitant use of thiazide diuretics may increase the risk of lithium toxicity and enhance the already increased risk of lithium toxicity with ACE inhibitors. Use of captopril with lithium is not recommended, but if the combination proves necessary, careful monitoring of serum lithium levels should be performed (see section 4.4)
Non-steroidal anti-inflammatory medicinal products: It has been described that non-steroidal anti-inflammatory medicinal products (NSAIDs) (such as Indomethacin, Ibuprofen) and ACE inhibitors exert an additive effect on the increase in serum potassium whereas renal function may decrease. These effects are, in principle, reversible. Rarely, acute renal failure may occur, particularly in patients with compromised renal function such as the elderly or dehydrated.
Chronic administration of NSAIDs may reduce the antihypertensive effect of an ACE inhibitor.
Clonidine: It has been suggested that the anti-hypertensive effect of captopril can be delayed when patients treated with clonidine are changed to captopril.
Allopurinol, procainamide, cytostatic or immunosuppressive agents: concomitant administration with ACE inhibitors may lead to an increased risk for leucopenia especially when the latter are used at higher than currently recommended doses.
Probenecid: The renal clearance of captopril is reduced in the presence of probenecid.
Tricyclic antidepressants/Antipsychotics: ACE inhibitors may enhance the hypotensive effects of certain tricyclic antidepressants and antipsychotics (see section 4.4). Postural hypotension may occur.
Sympathomimetics: may reduce the antihypertensive effects of ACE inhibitors; patients should be carefully monitored.
Antidiabetics: pharmacological studies have shown that ACE inhibitors, including captopril, can potentiate the blood glucose-reducing effects of insulin and oral antidiabetics such as sulphonylurea in diabetics. Should this very rare interaction occur, it may be necessary to reduce the dose of the antidiabetic during simultaneous treatment with ACE inhibitors.
Clinical chemistry: Captopril may cause a false-positive urine test for acetone.
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS- acting agent (see sections 4.3, 4.4 and 5.1).
Medicines increasing the risk of angioedema
Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated as this increases the risk of angioedema (see section 4.3 and 4.4).
Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may lead to an increased risk for angioedema (see section 4.4).