Enalapril-HydrochlorothiazideSkip to the navigation
Common brand names:Vaseretic
Summary of Interactions with Vitamins, Herbs, & Foods
Replenish Depleted Nutrients
Magnesium and Potassium
Potassium-depleting diuretics, including thiazide diuretics, cause the body to lose potassium; they may also cause cellular magnesium depletion,1 although this deficiency may not be reflected by a low blood level of magnesium.2 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.3
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.4 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.5 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.6 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.7
Thiazide diuretics can increase urinary zinc loss.8
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.9 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.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Reduce Side Effects
In a double-blind study of patients who had developed a cough attributed to an ACE inhibitor, supplementation with iron (in the form of 256 mg of ferrous sulfate per day) for four weeks reduced the severity of the cough by a statistically significant 45%, compared with a nonsignificant 8% improvement in the placebo group.11
In a short-term study of nine overweight men, enalapril plus a low-salt diet reduced blood pressure more than a low-salt diet alone.12 Additionally, enalapril plus a low-salt diet resulted in better insulin response than the low-salt diet alone. The importance of this preliminary information for overweight people with high blood pressure is unclear.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
Potential Negative Interaction
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.13 Thiazide diuretics and digitalis-containing products should be used only under the direct supervision of a doctor trained in their use.
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.14
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.15
Licorice (Glycyrrhiza glabra) may increase the side effects of potassium-depleting diuretics, including thiazide diuretics.16 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.
One case was reported in which ginkgo use was associated with high blood pressure in a person treated with a thiazide diuretic.17 Ginkgo was not proven to be the cause of this reaction.The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
An uncommon yet potentially serious side effect of taking ACE inhibitors is increased blood potassium levels.18 , 19 , 20 This problem is more likely to occur in people with advanced kidney disease. Taking potassium supplements,21 potassium-containing salt substitutes (No Salt, Morton Salt Substitute, and others),22 , 23 , 24 or large amounts of high-potassium foods at the same time as ACE inhibitors could cause life-threatening problems.25 Therefore, people should consult their healthcare practitioner before supplementing additional potassium and should have their blood levels of potassium checked periodically while taking ACE inhibitors.
An uncommon yet potentially serious side effect of taking ACE inhibitors is increased blood potassium levels.26 , 27 , 28 This problem is more likely to occur in people with advanced kidney disease. Taking potassium supplements,29 potassium-containing salt substitutes (No Salt, Morton Salt Substitute, and others),30 , 31 , 32 or large amounts of high-potassium foods (such as bananas and other fruit) at the same time as taking ACE inhibitors could cause life-threatening problems.33 Therefore, people should consult their healthcare practitioner before supplementing additional potassium and should have their blood levels of potassium checked periodically while taking ACE inhibitors.
Thiazide diuretics decrease calcium loss in the urine due to actions on the kidneys.34 As a result, it may be less important for some people taking thiazide diuretics to supplement calcium than it is for other people.
Diuretics, including thiazide diuretics, cause increased loss of sodium in the urine. By removing sodium from the body, diuretics also cause water to leave the body. This reduction of body water is the purpose of taking diuretics. Therefore, there is usually no reason to replace lost sodium, although strict limitation of salt intake in combination with the actions 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 their dose of diuretics lowered.
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.35 However, there is no evidence to suggest that people taking diuretics have different requirements for vitamin D.
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.36 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.
1. Martin B, Milligan K. Diuretic-associated hypomagnesiumia in the elderly. Arch Intern Med 1987;147:1768-71.
2. Kroenke K, Wood DR, Hanley JF. The value of serum magnesium determination in hypertensive patients receiving diuretics. Arch Intern Med 1987;147:1553-6.
3. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A consequence of magnesium deficiency. Arch Intern Med 1992;152:40-5.
4. Wahr JA, Parks R, Boisvert D, et al. Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. JAMA 1999;281:2203-10.
5. 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.
6. 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.
7. Ruml LA, Pak CYO. Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Kidney Dis 1999;34:107-13.
8. Reyes AJ, Leary WP, Lockett CJ, et al. Diuretics and zinc. S Afr Med J 1982;62:373-5.
9. 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.
10. Golik A, Zaidenstein R, Dishi V, et al. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr 1998;17:75-8.
11. Lee SC, Park SW, Kim DK, et al. Iron supplementation inhibits cough associated with ACE inhibitors. Hypertension 2001;38:166-70.
12. Egan BM, Stepniakowski K. Effects of enalapril on the hyperinsulinemic response to severe salt restriction in obese young men with mild systemic hypertension. Am J Cardiol 1993;72:53-7.
13. 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.
14. Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic Institute, 1997, 102-3.
15. 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.
16. 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.
17. Shaw D et al. Traditional remedies and food supplements: a 5-year toxicological study (1991-1995). Drug Safety 1997;17:342-56.
18. Good CB, McDermott L, McCloskey B. Diet and serum potassium in patients on ACE inhibitors. JAMA 1995;274:538.
19. Rush JE, Merrill DD. The Safety and tolerability of lisinopril in clinical trials. J Cardiovasc Pharmacol 1987;9(Suppl 3):S99-107.
20. Sifton DW, ed. Physicians' Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2000, 1965-8.
21. Burnakis TG, Mioduch HJ. Combined therapy with captopril and potassium supplementation. A potential for hyperkalemia. Arch Intern Med 1984;144:2371-2.
22. Burnakis TG. Captopril and increased serum potassium levels. JAMA 1984;252:1682-3 [letter].
23. Ray K, Dorman S, Watson R. Severe hyperkalemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction. J Hum Hypertens 1999;13:717-20.
24. Sifton DW, ed. Physicians' Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2000, 1965-8.
25. Stoltz ML. Severe hyperkalemia during very-low-calorie diets and angiotensin converting enzyme use. JAMA 1990;264:2737-8 [letter].
26. Good CB, McDermott L, McCloskey B. Diet and serum potassium in patients on ACE inhibitors. JAMA 1995;274:538.
27. Rush JE, Merrill DD. The Safety and tolerability of lisinopril in clinical trials. J Cardiovasc Pharmacol 1987;9(Suppl 3):S99-107.
28. Sifton DW, ed. Physicians' Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2000, 1965-8.
29. Burnakis TG, Mioduch HJ. Combined therapy with captopril and potassium supplementation. A potential for hyperkalemia. Arch Intern Med 1984;144:2371-2.
30. Burnakis TG. Captopril and increased serum potassium levels. JAMA 1984;252:1682-3 [letter].
31. Ray K, Dorman S, Watson R. Severe hyperkalemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction. J Hum Hypertens 1999;13:717-20.
32. Sifton DW, ed. Physicians' Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2000, 1965-8.
33. Stoltz ML. Severe hyperkalemia during very-low-calorie diets and angiotensin converting enzyme use. JAMA 1990;264:2737-8 [letter].
34. 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.
35. 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.
36. 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.
Last Review: 04-29-2014
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