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Amiloride-Hydrochlorothiazide

Topic Contents

Amiloride-Hydrochlorothiazide

Drug Information

Common brand names:

Moduretic

Summary of Interactions with Vitamins, Herbs, & Foods

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • Folic Acid

    One study showed that people taking diuretics for more than six months had dramatically lower blood levels of folic acid and higher levels of homocysteine compared with individuals not taking diuretics.1 Homocysteine, a toxic amino acid byproduct, has been associated with atherosclerosis . Until further information is available, people taking diuretics for longer than six months should probably supplement with folic acid.

  • Magnesium and Potassium

    Potassium-depleting diuretics, including thiazide diuretics, cause the body to lose potassium; they may also cause cellular magnesium depletion,3 although this deficiency may not be reflected by a low blood level of magnesium.4 Magnesium loss induced by potassium-depleting diuretics can cause additional potassium loss. Until more is known, it has been suggested that people taking potassium-depleting diuretics, including thiazide diuretics, should supplement both potassium and magnesium.5

    People taking thiazide diuretics should be monitored by their prescribing doctor, who will prescribe potassium supplements if needed. Such supplementation is particularly critical before surgery in patients with a history of heart disease. In a preliminary study, people with low blood levels of potassium (in part related to diuretic use) had a higher incidence of serious problems resulting from surgery (including death) compared with those having normal potassium levels.6 A double-blind trial showed that thiazide diuretic use led to a reduction in blood levels of potassium in some participants. Those experiencing decreased potassium levels were also more likely to experience cardiovascular events, such as heart attacks, stroke, heart failure, aneurysm, and sudden cardiac death.7 Fruit is high in potassium, and increasing fruit intake (especially bananas) is another way of supplementing potassium.

    Magnesium supplementation for people taking thiazide diuretics is typically 300–600 mg per day, though higher amounts (over 800 mg per day) have been reported in a controlled study to reduce side effects of thiazides.8 Combining supplementation of both potassium and magnesium has been reported to correct abnormally low blood levels of potassium and also to protect against excessive loss of magnesium.9

  • Zinc

    Thiazide diuretics can increase urinary zinc loss.10

Reduce Side Effects

  • none

Support Medicine

  • none

Reduces Effectiveness

  • none

Potential Negative Interaction

  • Digitalis

    Digitalis (Digitalis purpurea) refers to a family of plants commonly called foxglove, which contains digitalis glycosides, chemicals with actions and toxicities similar to the prescription drug digoxin. Thiazide diuretics can increase the risk of digitalis-induced heart disturbances.12 Thiazide diuretics and digitalis-containing products should be used only under the direct supervision of a doctor trained in their use.

  • Diuretic Herbs

    Herbs that have a diuretic effect should be avoided when taking diuretic medications, as they may enhance the effect of these drugs and lead to possible cardiovascular side effects. These herbs include dandelion , uva ursi , juniper , buchu , cleavers , horsetail , and gravel root.13

    Use buckthorn (Rhamnus catartica, Rhamnus frangula, Frangula alnus) or alder buckthorn for more than ten days consecutively may cause a loss of electrolytes (especially the mineral potassium). Medications that also cause potassium loss, such as some diuretics, should be used with caution when taking buckthorn or alder buckthorn.14

  • Licorice

    Licorice (Glycyrrhiza glabra) may increase the side effects of potassium-depleting diuretics, including thiazide diuretics.15 Thiazide diuretics and licorice should be used together only under careful medical supervision. At the time of this writing, no evidence was found of interactions between deglycyrrhizinated licorice (DGL) and any diuretic was found in the medical literature.

  • Ginkgo

    One case was reported in which ginkgo use was associated with high blood pressure in a person treated with a thiazide diuretic.16 Ginkgo was not proven to be the cause of this reaction.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Magnesium

    Preliminary research in animals suggests that amiloride may reduce the urinary excretion of magnesium.17 It is unknown if this same effect would occur in humans. Nevertheless, persons taking more than 300 mg of magnesium per day and amiloride should consult with a doctor, as this combination may lead to potentially dangerous elevations in levels of magnesium in the body. The combination of amiloride and hydrochlorothiazide would likely eliminate this problem, as hydrochlorothiazide may deplete magnesium.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Explanation Required 

  • Calcium

    Thiazide diuretics decrease calcium loss in the urine due to actions on the kidneys.18 As a result, it may be less important for some people taking thiazide diuretics to supplement calcium than it is for other people.

  • Potassium

    As a potassium-sparing drug, amiloride reduces urinary loss of potassium.19 This can cause potassium levels to build up in the body. People taking this drug should avoid use of potassium chloride–containing products, such as Morton Salt Substitute, No Salt, Lite Salt, and others. Even eating several pieces of fruit per day can sometimes cause problems for people taking potassium-sparing diuretics, due to the high potassium content of fruit.

    However, one medication (Moduretic) contains the combination of the potassium-sparing drug amiloride and the potassium-depleting drug hydrochlorothiazide. With the use of Moduretic, potassium excess and potassium depletion are both possible. People taking this combination drug should have their potassium levels monitored by a doctor to determine whether their potassium intake should be increased, reduced, or kept the same.

  • Sodium

    Diuretics, including amiloride, cause increased loss of sodium in urine. By removing sodium from the body, diuretics cause water to leave the body as well. This reduction of water in the body is the purpose of taking amiloride. Therefore, there is usually no reason to replace lost sodium, although strict limitation of salt intake in combination with the action of diuretics can sometimes cause excessive sodium depletion. On the other hand, people who restrict sodium intake and in the process reduce blood pressure may need to have the dose of their diuretics lowered.

  • Vitamin D

    The reduction in urinary calcium loss resulting from treatment with thiazide diuretics is due primarily to changes in kidney function and may also be due, in part, to changes in vitamin D metabolism.20 However, there is no evidence to suggest that people taking diuretics have different requirements for vitamin D.

  • Alder Buckthorn

    Use buckthorn (Rhamnus catartica, Rhamnus frangula, Frangula alnus) or alder buckthorn for more than ten days consecutively may cause a loss of electrolytes (especially the mineral potassium). Medications that also cause potassium loss, such as some diuretics, should be used with caution when taking buckthorn or alder buckthorn.21

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Buckthorn

    Use buckthorn (Rhamnus catartica, Rhamnus frangula, Frangula alnus) or alder buckthorn for more than ten days consecutively may cause a loss of electrolytes (especially the mineral potassium). Medications that also cause potassium loss, such as some diuretics, should be used with caution when taking buckthorn or alder buckthorn.22

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Hibiscus
    In experimental animals, co-administration of hibiscus (Hibiscus sabdariffa L.) extract and hydrochlorothiazide increased blood levels of hydrochlorothiazide and decreased the rate at which the body cleared the drug.23 Therefore, treatment with hibiscus could increase both the efficacy and the adverse effects of hydrochlorothiazide. People taking hydrochlorothiazide should not take hibiscus without medical supervision.
    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

References

1. Morrow LE, Grimsley EW. Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations. South Med J 1999;92:866–70.

2. Morrow LE, Grimsley EW. Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations. South Med J 1999;92:866–70.

3. Martin B, Milligan K. Diuretic-associated hypomagnesiumia in the elderly. Arch Intern Med 1987;147:1768–71.

4. Kroenke K, Wood DR, Hanley JF. The value of serum magnesium determination in hypertensive patients receiving diuretics. Arch Intern Med 1987;147:1553–6.

5. Whang R, Whang DD, Ryan MP. Refractory potassium repletion—a consequence of magnesium deficiency. Arch Intern Med 1992;152:40–5.

6. Wahr JA, Parks R, Boisvert D, et al. Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. JAMA 1999;281:2203–10.

7. Franse LV, Pahor M, Di Bari M, et al. Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program. Hypertension 2000;35:1025–30.

8. Ruml LA, Gonzalez G, Taylor R, et al. Effect of varying doses of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Ther 1999;6:45–50.

9. Ruml LA, Pak CYO. Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Kidney Dis 1999;34:107–13.

10. Reyes AJ, Leary WP, Lockett CJ, et al. Diuretics and zinc. S Afr Med J 1982;62:373–5.

11. Morrow LE, Grimsley EW. Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations. South Med J 1999;92:866–70.

12. Threlkeld DS, ed. Diuretics and Cardiovasculars, Thiazides and Related Diuretics. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1993, 135a–7c.

13. Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic Institute, 1997, 102–3.

14. European Scientific Cooperative on Phytotherapy (ESCOP). Frangulae cortex, frangula bark. Monographs on the Medicinal Uses of Plant Drugs. Exeter, UK: University of Exeter, Centre for Complementary Health Studies, 1997.

15. Shintani S, Murase H, Tsukagoshi H, Shiigai T. Glycyrrhizin (licorice)-induced hypokalemic myopathy. Report of two cases and review of the literature. Eur Neurol 1992;32:44–51.

16. Shaw D et al. Traditional remedies and food supplements: a 5-year toxicological study (1991–1995). Drug Safety 1997;17:342–56.

17. Devane J, Ryan MP. The effects of amiloride and triamterene on urinary magnesium excretion in conscious saline-loaded rats. Br J Pharmacol 1981;72:285–9.

18. Threlkeld DS, ed. Diuretics and Cardiovasculars, Thiazides and Related Diuretics. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Jul 1993, 135a–7c.

19. Ramsay LE, Hettiarachchi J, Fraser R, Morton JJ. Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. Clin Pharmacol Ther 1980;27:533–43.

20. Riis B, Christiansen C. Actions of thiazide on vitamin D metabolism: A controlled therapeutic trial in normal women early in the postmenopause. Metabolism 1985;34:421–4.

21. European Scientific Cooperative on Phytotherapy (ESCOP). Frangulae cortex, frangula bark. Monographs on the Medicinal Uses of Plant Drugs. Exeter, UK: University of Exeter, Centre for Complementary Health Studies, 1997.

22. European Scientific Cooperative on Phytotherapy (ESCOP). Frangulae cortex, frangula bark. Monographs on the Medicinal Uses of Plant Drugs. Exeter, UK: University of Exeter, Centre for Complementary Health Studies, 1997.

23. Ndu OO, Nworu CS, Ehiemere CO, et al. Herb-drug interaction between the extract of Hibiscus sabdariffa L. and hydrochlorothiazide in experimental animals. J Med Food 2011;14:640–4.

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