In a study of 34 people with hypertension, six months of captopril or enalapril (ACE inhibitors related to trandolapril) treatment led to decreased zinc levels in certain white blood cells,1 raising concerns about possible ACE inhibitor–induced zinc depletion.
While zinc depletion has not been reported with ramipril, until more is known, it makes sense for people taking trandolapril long term to consider, as a precaution, taking a zinc supplement or a multimineral tablet containing zinc. (Such multiminerals usually contain no more than 99 mg of potassium, probably not enough to trigger the above-mentioned interaction.) Supplements containing zinc should also contain copper, to protect against a zinc-induced copper deficiency.
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.3
An uncommon yet potentially serious side effect of taking ACE inhibitors is increased blood potassium levels.4 , 5 , 6 This problem is more likely to occur in people with advanced kidney disease. Taking potassium supplements,7 potassium-containing salt substitutes (No Salt, Morton Salt Substitute, and others),8 , 9 , 10 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.11 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.
Vitamin D may interfere with the effectiveness of verapamil.12 People taking verapamil should ask their doctor before using vitamin D-containing supplements.
Grapefruit juice may increase verapamil blood levels.13 The importance of this interaction regarding verapamil effectiveness and side effects is unknown. Until more is known, it makes sense for people taking this drug to either avoid drinking grapefruit juice entirely or drink grapefruit juice only under the careful monitoring and supervision of the prescribing doctor. In theory, this last possibility might allow for a decrease in drug dose, but it could be dangerous in the absence of diligent monitoring. The same effects might be seen from eating grapefruit as from drinking its juice.
As pleurisy root and other plants in the Aesclepius genus contain cardiac glycosides, it is best to avoid use of pleurisy root with heart medications such as calcium channel blockers.14
Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice.15 , 16 The degree of inhibition is about the same for each of these juices. Therefore, it would be reasonable to expect that pomegranate juice might interact with verapamil in the same way that grapefruit juice does.
1. 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.
2. Threlkeld DS, ed. Diuretics and Cardiovasculars, Calcium Channel Blocking Agents. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Nov 1992, 150–b.
3. Lee SC, Park SW, Kim DK, et al. Iron supplementation inhibits cough associated with ACE inhibitors. Hypertension 2001;38:166–70.
4. Good CB, McDermott L, McCloskey B. Diet and serum potassium in patients on ACE inhibitors. JAMA 1995;274:538.
5. Rush JE, Merrill DD. The Safety and tolerability of lisinopril in clinical trials. J Cardiovasc Pharmacol 1987;9(Suppl 3):S99–107.
6. Sifton DW, ed. Physicians’ Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2000, 1965–8.
7. Burnakis TG, Mioduch HJ. Combined therapy with captopril and potassium supplementation. A potential for hyperkalemia. Arch Intern Med 1984;144:2371–2.
8. Burnakis TG. Captopril and increased serum potassium levels. JAMA 1984;252:1682–3 [letter].
9. 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.
10. Sifton DW, ed. Physicians’ Desk Reference. Montvale, NJ: Medical Economics Company, Inc., 2000, 1965–8.
11. Stoltz ML. Severe hyperkalemia during very-low-calorie diets and angiotensin converting enzyme use. JAMA 1990;264:2737–8 [letter].
12. Threlkeld DS, ed. Diuretics and Cardiovasculars, Calcium Channel Blocking Agents. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Nov 1992, 150–b.
13. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 274–5.
14. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press, 1996, 213–4.
15. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705–6.
16. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother 2006;40:1472–3.
Last Review: 05-01-2013
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