Cyclosporine

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Also indexed as:

Neoral, Sandimmune, SangCya

Cyclosporine is a drug that suppresses the immune system. It is used in combination with other immune suppressive drugs to prevent rejection of transplanted organs by the immune system. There are two different forms of cyclosporine, Sandimmune and Neoral. These products differ in important ways and each is used in combination with different additional immunosupressant drugs. Inadequate immune suppression may result in organ rejection and serious complications. People taking cyclosporine should follow their prescribing doctor's directions exactly and discuss with their doctor any changes in drug therapy, vitamins, supplements, herbal products, or any other substances before making the changes.

Herbs

Summary of Interactions for Cyclosporine

Depletion or interference	Magnesium Red wine
Adverse interaction	None known
Side effect reduction/prevention	Ginkgo* Omega-3 fatty acids*
Supportive interaction	Vitamin E*
Reduced drug absorption/bioavailability	Chinese scullcap St. John's wort*
Other (see text)	Apple juice Grapefruit juice Milk Orange juice Pomegranate juice* Quercetin

An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.

Interactions with Supplements

Magnesium

Cyclosporine has been associated with low blood magnesium levels and undesirable side effects.^{1, 2, 3} Some doctors suggest monitoring the level of magnesium in red blood cells, rather than in serum, as the red blood cell test may be more sensitive for evaluating magnesium status.

Potassium

Cyclosporine can cause excess retention of potassium, potentially leading to dangerous levels of the mineral in the blood (hyperkalemia).⁴ Potassium supplements, potassium-containing salt substitutes (No Salt, Morton Salt Substitute, and others), and even high-potassium foods (primarily fruit) should be avoided by people taking cyclosporine, unless directed otherwise by their doctor.

Omega-3 fatty acids

Several studies have shown that in organ transplant patients treated with cyclosporine, addition of 4-6 grams per day of omega-3 fatty acids from fish oil helped reduce high blood pressure,^{5, 6, 7} though not every study has found fish oil helpful.⁸ It remains unclear to what extent fish oil supplementation will help people with high blood pressure taking cyclosporine following organ transplant.

Vitamin E

Twenty-six liver transplant patients (both adults and children) unable to achieve or maintain therapeutic cyclosporine blood levels during the early post-transplant period were given water-soluble vitamin E in the amount of 6.25 IU/2.2 pounds of body weight two times per day.⁹ Addition of vitamin E in the early post-transplant period reduced the required amount of cyclosporine and the cost of cyclosporine therapy by 26%. These results imply that the addition of vitamin E to established cyclosporine therapy allows for a decrease in the amount of cyclosporine. Combining vitamin E and cyclosporine requires medical supervision to avoid cyclosporine toxicity.

Quercetin

In an animal study, oral administration of quercetin (50 mg per 2.2 pounds of body weight) at the same time as cyclosporine decreased the absorption of cyclosporine by 43%.¹⁰ However, in a study of healthy human volunteers, supplementing with quercetin along with cyclosporine significantly increased blood levels of cyclosporine, when compared with administering cyclosporine alone.¹¹ Because the effect of quercetin supplementation on cyclosporine absorption or utilization appears to be unpredictable, individuals taking cyclosporine should not take quercetin without the supervision of a doctor.

Interactions with Herbs

Chinese scullcap

In a study in rats, oral administration of Chinese scullcap at the same time as cyclosporine significantly reduced the absorption of cyclosporine.¹² Chinese scullcap did not interfere with the availability of cyclosporine when cyclosporine was given intravenously. Because of the potential adverse interaction, people taking cyclosporine should not take Chinese scullcap.

Ginkgo

Ginkgo was reported to protect liver cells from damage caused by cyclosporine in a test tube experiment.¹³ A Ginkgo biloba extract partially reversed cyclosporine-induced reduced kidney function in a study of isolated rat kidneys.¹⁴ Human trials have not studied the actions of ginkgo to prevent or reduce the side effects of cyclosporine.

St. John's wort

Pharmacological research from Europe suggests that St. John's wort (Hypericum perforatum) may reduce plasma levels of cyclosporine.¹⁵ Two case reports also describe heart transplant patients taking cyclosporine who showed signs of acute transplant rejection after taking St. John's wort extract.¹⁶ In both cases, reduced plasma concentrations of cyclosporine were found. One report cites similar findings in three patients taking cyclosporine and St. John's wort together.¹⁷ Finally, similar drops in cyclosporine blood levels were reported in 45 kidney or liver transplant patients who began taking St. John's wort.¹⁸ Until more is known, people taking cyclosporine should avoid the use of St. John's wort.

Other Interactions

Food

Food increases the absorption of cyclosporine.¹⁹ A change in the timing of food and cyclosporine dosing may alter cyclosporine blood levels, requiring dose adjustment.

Grapefruit juice

In a randomized study of nine adults with cyclosporine-treated autoimmune diseases, grapefruit juice (5 ounces two times per day with cyclosporine, for ten days) caused a significant increase in cyclosporine blood levels compared with cyclosporine with water.²⁰ The rise in cyclosporine blood levels was associated with abdominal pain, lightheadedness, nausea, and tremor in one patient. A similar interaction between grapefruit juice and cyclosporine has been observed in healthy volunteers.²¹ Using grapefruit juice to reduce the amount of cyclosporine needed has not been sufficiently studied and cannot therefore be counted on to produce a predictable change in cyclosporine requirements. The same effects might be seen from eating grapefruit as from drinking its juice.

Pomegranate juice

Pomegranate juice has been shown to inhibit the same enzyme that is inhibited by grapefruit juice.^{22, 23} 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 cyclosporine in the same way that grapefruit juice does.

Red wine

Ingestion of red wine along with cyclosporine has been found to reduce blood levels of the drug.²⁴ Individuals taking cyclosporine should, therefore, not consume red wine at the same time as they take the drug. It is not known whether red wine consumed at a different time of the day would affect the availability of cyclosporine. Until more is known, it seems prudent for people taking cyclosporine to avoid red wine altogether.

Milk, apple juice, and orange juice

Mixing Sandimmune solution with room-temperature milk, chocolate milk, orange juice, or apple juice may improve its flavor.²⁵

Mixing Neoral solution with room temperature orange or apple juice may improve its flavor, but combining it with milk makes an unpalatable mix.²⁶

References

1. June CH, Thompson CB, Kennedy MS, et al. Profound hypomagnesemia and renal magnesium wasting associated with the use of cyclosporine for marrow transplantation. Transplantation 1985;39:620-4.
2. Thompson CB, June CH, Sullivan KM, Thomas ED. Association between cyclosporine neurotoxicity and hypomagnesemia. Lancet 1984;ii:1116-20.
3. June CH, Thompson CB, Kennedy MS, et al. Correlation of hypomagnesemia with the onset of cyclosporine-associated hypertension in marrow transplant patients. Transplantation 1986;41:47-51.
4. Perazella MA. Drug-induced hyperkalemia: Old culprits and new offenders. Am J Med 2000;109:307-14 [review].
5. Ventura HO, Milani RV, Lavie CJ, et al. Cyclosporine-induced hypertension. Efficacy of omega-3 fatty acids in patients after cardiac transplantation. Circulation 1993;88(5 Pt 2):II281-5.
6. Andreassen AK, Harmann A, Offstad J, et al. Hypertension prophylaxis with omega-3 fatty acids in heart transplant recipients. J Am Coll Cardiol 1997;29:1324-31.
7. Homan van der Heide JJ, Bilo HJ, Tegzess AM, Donker AJ. The effects of dietary supplementation with fish oil on renal function in cyclosporine-treated renal transplant recipients. Transplantation 1990;49:523-7.
8. Kooijmans-Coutinho MF, Rischen-Vos J, Hermans J, et al. Dietary fish oil in renal transplant recipients treated with cyclosporine-A: No beneficial effects shown. J Am Soc Nephrol 1996;7:513-8.
9. Pan SH, Lopez RR Jr, Sher LS, et al. Enhanced oral cyclosporine absorption with water-soluble vitamin E early after liver transplantation. Pharmacotherapy 1996;16:59-65.
10. Hsiu SL, Hou YC, Wang YH, et al. Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats. Life Sci 2002;72:227-35.
11. Choi JS, Choi BC, Choi KE. Effect of quercetin on the pharmacokinetics of oral cyclosporine. Am J Health Syst Pharm 2004;61:2406-9.
12. Lai MY, Hsiu SL, Hou YC, et al. Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis. Planta Med 2004;70:132-7.
13. Barth SA, Inselmann G, Engemann R, Heidemann HT. Influences of Ginkgo biloba on cyclosporine A included lipid peroxidation in human liver microsomes in comparison to vitamin E, glutathione and N-acetylcysteine. Biochem Pharmacol 1991;41:1521-6.
14. Bagnis C, Deray G, Dubois M, et al. Prevention of cyclosporine nephrotoxicity with a platelet-activating factor (PAF) antagonist. Nephrol Dial Transplant 1996;11:507-13.
15. Mai I, Schmider J, et al. Unpublished results, May, 1999. Reported in: Johne A, Brockmöller, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
16. Rauschitzka F, Meir P, Turina M, et al. Acute transplant rejection due to Saint John's wort. Lancet 2000;355:548-9 [letter].
17. Ernst E. Second thoughts about safety of St. John's wort. Lancet 1999;354:2014-6 [letter].
18. Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St. John's wort with ciclopsorin. Lancet 2000;355:1912 [letter].
19. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 87.
20. Ioannides-Demos LL, Christophidis N, Ryan P, et al. Dosing implication of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases. J Rheumatol 1997;24:49-54.
21. Paine MF, Widmer WW, Pusek SN, et al. Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine. J Clin Nutr 2008;87:863-71.
22. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705-6.
23. Summers KM. Potential drug-food interactions with pomegranate juice. Ann Pharmacother 2006;40:1472-3.
24. Tsunoda SM, Harris RZ, Christians U, et al. Red wine decreases cyclosporine bioavailability. Clin Pharmacol Ther 2001;70:462-7.
25. Threlkeld DS, ed. Miscellaneous Products, Immunosuppressive Drugs, Cyclosporine. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1998, 738a-8k.
26. Threlkeld DS, ed. Miscellaneous Products, Immunosuppressive Drugs, Cyclosporine. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1998, 738a-8k.

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Last Review: 01-21-2009

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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires February 2010.

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