Spironolactone Interactions
Alpha-blockers
Angiotensin II receptor antagonists
Angiotensin-converting enzyme inhibitors (ACE inhibitors)
- Arsenic Trioxide
- Aspirin, ASA
Beta-blockers
Calcium-channel blockers
Central-acting adrenergic agents
Corticosteroids
- Corticotropin, ACTH
- Cyclosporine
- Digoxin
- Drospirenone; Ethinyl Estradiol
- Ephedra, Ma Huang
- Eplerenone
- Ethanol
- food
- Hawthorn, Crataegus laevigata
- Heparin
- Horse Chestnut, Aesculus hippocastanum
- Lithium
Loop diuretics
- Magnesium Citrate
- Mitotane
Nonsteroidal antiinflammatory drugs (NSAIDs)
- Potassium Salts
Potassium-sparing diuretics
Salicylates
Thiazide diuretics
- Trimethoprim
Vasodilators
- Warfarin
Spironolactone Interactions
Spironolactone should not be used concomitantly with other potassium-sparing diuretics (amiloride or spironolactone) or with eplerenone because of the increased risk of developing hyperkalemia. Simultaneous use of cyclosporine or tacrolimus with spironolactone can also increase the risk of hyperkalemia, and is generally not recommended. In addition, ACE inhibitors, angiotensin II receptor antagonists, trimethoprim, heparin, potassium supplements, potassium-containing medications (e.g., penicillin G potassium), and any substance containing potassium salts (e.g., blood, salt substitutes, low-salt milk) can increase the risk of hyperkalemia developing in patients receiving spironolactone, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are concurrently administered with spironolactone.
Spironolactone can have additive effects when administered with other antihypertensive agents, including alpha-blockers, beta-blockers, calcium-channel blockers, central-acting adrenergic agents, loop diuretics, thiazide diuretics, or vasodilators. These effects can be used to therapeutic advantage but occasionally can cause orthostatic hypotension. Dosages must be adjusted accordingly.
Spironolactone can produce false increases in serum digoxin assays. There also can be a reduction in renal clearance and attenuation of the positive inotropic effects of digoxin. Patients receiving digoxin and spironolactone concurrently should be monitored carefully for altered responses to digoxin therapy.
Lithium clearance can be decreased in patients receiving diuretics due changes in sodium excretion; concomitant administration could result in lithium toxicity.
NSAIDs can cause sodium and fluid retention as well as increase peripheral vascular resistance. NSAIDs can decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Concomitant administration of NSAIDs with diuretics can also increase the risk for renal insufficiency secondary to decreased renal blood flow. Patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment. Among NSAIDs, indomethacin, naproxen, and piroxicam may have the greatest pressor effect, while the effects of sulindac and nabumetone may be significantly less. Concomitant use of NSAIDs and potassium-sparing drugs, such as spironolactone, can cause hyperkalemia.
Licorice extract, which contains glycyrrhizic acid, possesses aldosterone-like properties. Thus, licorice candy and food products containing licorice extract should be avoided by patients taking spironolactone in order to not antagonize the drug’s therapeutic actions.
Hawthorn, Crataegus laevigata may lower peripheral vascular resistance. Hawthorn use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients receiving hawthorn concurrently with antihypertensive medications should receive periodic blood pressure monitoring.
Spironolactone has been associated with a decreased anticoagulation response to warfarin. Monitor coagulation parameters and adjust warfarin dosage as needed.
Drug interactions with Horse chestnut, Aesculus hippocastanum are not well documented. Escin, an active saponin in the horse chestnut seed, appears to have weak diuretic activity, but the exact mechanism is not clear. The effect appears to be dose-dependent and may be additive with traditional diuretics.
Diuretic-induced electrolyte abnormalities can potentiate the cardiac toxicity of arsenic trioxide.
Aspirin, ASA has been shown to inhibit the active tubular secretion of canrenone, the active metabolite of spironolactone, however, this effect on canrenone pharmacokinetics did not compromise the clinical action of spironolactone significantly. In addition, aspirin or other salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Thus, the effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of salicylates including aspirin. Concomitant use of aspirin or other salicylates with potassium-sparing diuretics, such as triamterene or spironolactone, may cause hyperkalemia.
The manufacturer of spironolactone lists corticosteroids and corticotropin, ACTH as potential drugs that interact with spironolactone. The information states that intensified electrolyte depletion, particularly hypokalemia, may occur. However, spironolactone itself does not induce hypokalemia. Hypokalemia is one of the indications for spironolactone therapy. Therefore, drugs which induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of spironolactone therapy when used to treat hypokalemia.
Drospirenone has antimineralocorticoid effects and may increase serum potassium. The concurrent use of potassium-sparing diuretics may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium if spironolactone is used concurrently with drospirenone; ethinyl estradiol (Yasmin®), particularly during the 1st month of treatment.
Ephedra, Ma huang can antagonize all types of antihypertensive agents. Blood pressure should be monitored closely in patients using antihypertensive agents with ephedra.
The use of saline laxatives (e.g., magnesium citrate) with potassium-sparing diuretics may interfere with the potassium-sparing effect of such diuretics due to excess fluid and electrolyte loss. In addition, potassium-sparing diuretics may interfere with the kidneys ability to regulate magnesium concentrations; long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia, especially in patients with renal insufficiency.
Ethanol interacts with antihypertensive agents by potentiating their hypotensive effect.
An isolated case report indicated that mitotane activity might be antagonized by the concurrent administration of spironolactone. Until more data are available to confirm an interaction, the use of spironolactone with mitotane should be approached with caution.
[ Last revised: 1/11/2006 10:17:00 AM ]
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