Palonosetron
Phenothiazines
Photosensitizing Agents
Potassium-sparing diuretics
Retinoids
Salicylates
Sulfonamides
Tetracyclines
Hydrochlorothiazide, HCTZ (Microzide) Interactions
Hydrochlorothiazide can have additive effects when administered with other antihypertensive agents or diuretics. In some patients, these effects may be desirable, but orthostatic hypotension is possible. Dosages must be adjusted accordingly. In addition, potassium-sparing diuretics (amiloride hydrochloride, spironolactone, and triamterene) can reduce the risk of developing hypokalemia because of their potassium-sparing effects; these agents have been used as therapeutic alternatives to potassium supplements.
Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, increasing the potential for proarrhythmic effects (e.g., torsade de pointes) of arsenic trioxide, cardiac glycosides, dofetilide, or levomethadyl. Potassium levels should be within the normal range prior and during administration of these agents. In the absence of electrolyte imbalances, these agents can be used together safely. In a population pharmacokinetic analysis of plasma dofetilide concentrations, the mean dofetilide clearance of dofetilide was 16% lower in patients on thiazide diuretics.
The risk of developing severe hypokalemia can be increased when other hypokalemia-causing agents (e.g., cisplatin, corticosteroids, corticotropin, ACTH, amphotericin B) are coadministered with hydrochlorothiazide. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
Hypokalemia and/or ECG changes associated with loop diuretics or thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with non-potassium sparing diuretics.
Concomitant administration of hydrochlorothiazide to patients receiving nondepolarizing neuromuscular blockers (e.g., tubocurarine) can cause prolonged neuromuscular blockade due to hydrochlorothiazide-induced hypokalemia. Serum potassium concentrations should be determined and corrected (if necessary) prior to initiation of neuromuscular blockade therapy.
Thiazide diuretics reduce lithium renal clearance and can increase lithium serum concentrations. In some cases, thiazide diuretics can be used to counteract lithium-induced polyuria. Lithium dosage should be reevaluated and serum lithium concentrations monitored when a thiazide is added.
Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Enhanced hyperglycemia is possible during concurrent use of diazoxide and thiazide diuretics.
Hydrochlorothiazide can reduce the renal clearance of amantadine, with subsequent increased serum concentrations and possible toxicity. This interaction has been reported with a combination product of hydrochlorothiazide and triamterene. Since it is unclear which component was responsible for the interaction, caution should be exercised when administering either drug concurrently with amantadine.
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.
Cholestyramine (Questran® ), an ion exchange resin, binds hydrochlorothiazide and reduces its absorption from the gastrointestinal tract by up to 85% when co-administered as single doses. Although the manufacturer for Questran® recommends that other medicines be taken at least 1 hour before or 4 - 6 hours after cholestyramine, it has been recommended that thiazides be administered at least 4 hours before or after cholestyramine to minimize the reduction in absorption. By administering hydrochlorothiazide at least 4 hours before cholestyramine, the decrease in absorption of hydrochlorothiazide is approximately 30 - 35%. Although to a lesser extent than cholestyramine, colestipol also has been shown to inhibit the GI absorption and therapeutic response of thiazide diuretics. Single doses of colestipol resins reduce the absorption of HCTZ by up to 43%. Administering thiazide diuretics at least 2 hours before colestipol has been suggested to minimize the interaction.
Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of drugs like phenothiazines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin. Electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypercalcemia) may occur with administration of thiazide diuretics, electrolyte disturbances may increase the potential for proarrhythmic effects (e.g., QT prolongation, torsade de pointes) of selected phenothiazines (e.g., mesoridazine, thioridazine). In the absence of electrolyte imbalances, these agents can be used together safely with appropriate monitoring; clinicians should monitor for evidence of electrolyte disturbances or cardiac-related patient complaints. Thiazide diuretics may potentiate the orthostatic hypotension that can be seen with the use of the phenothiazine antipsychotics.
Thiazide diuretics may cause photosensitivity and may increase the photosensitization effects of drugs like griseofulvin, phenothiazines, retinoids, sulfonamides, sulfonylureas, tetracyclines, or photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
The occurrence of hypersensitivity reactions may be increased in patients with renal impairment who receive allopurinol and thiazide diuretics in combination.
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.
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.
Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide.
Ethanol, barbiturates, or opiate agonists may potentiate orthostatic hypotension when used concurrently with hydrochlorothiazide.
Thiazide diuretics can cause decreased arterial responsiveness to vasopressor amines (e.g., norepinephrine), but the effect is not sufficient to preclude their coadministration.
Thiazide diuretics may increase the risk of hypokalemia when used concurrently with methazolamide which may also cause hypokalemia. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. There may also be an additive diuretic or hyperuricemic effect.
Ephedra, Ma huang can antagonize all types of antihypertensive agents. Blood pressure should be monitored closely in patients using antihypertensive agents with ephedra.
Memantine reduced the bioavailability of hydrochlorothiazide by roughly 20% in a drug interaction study. The clinical significance of this pharmacokinetic interaction, if any, is unknown.
Palonosetron may rarely cause prolongation of the QT interval. A potassium- and/or magnesium-depleted state may increase the risk of cardiac arrhythmias; use thiazide diuretics cautiously with palonosetron and monitor serum electrolyte levels frequently, if indicated.
The simultaneous administration of thiazide diuretics and calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
[ Last revised: 9/27/2005 12:04:00 PM ]
References
. Rothkopf M, Vogel G, Lang W et al. Animal experiments on the question of the renal toleration of the horse chestnut saponin aescin. Arneimittelforschung 1977;27:598 - 605.
. Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429 - 36.
. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833 - 8.
. Blesken R. Crataegus in cardiology. Fortschr Med 1992;110:290 - 2.
. Zyloprim® (allopurinol) package insert. San Diego, CA: Prometheus Laboratories Inc.; 2001 July.
. Wilson TW, Rajput AH. Amantadine-dyazide interaction. Can Med Assoc J 1983;129:974 - 5.
. Questran® and Questran® Light (cholestyramine) package insert. Spring Valley, NY: Par Pharmaceutical Inc; 2002 July.
. Tikosyn™ (dofetilide) package insert. New York, NY: Pfizer Labs; 1999 Dec.
. The University of Arizona Center for Education and Research on Therapeutics (ArizonaCERT). QT drug lists. Retrieved April 15, 2004. Available on the World Wide Web at http://www.qtdrugs.org.
. Lanoxin® (digoxin) package insert. Research Triangle Park, NC: Glaxo Smith Kline; 2001 Aug.
. Neptazane® (methazolamide) package insert. Pearle River, NY: Lederle Pharmaceutical Division: 1998 Nov.
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