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Cyclosporine

Trade Names :

  • Neoral
  • Sandimmune
Cyclosporine helps prevent rejection of a transplanted organ by suppressing the immune system.
Grapefruit juice slows the body's normal breakdown of several drugs, including cyclosporine, allowing it to build up to potentially excessive levels in the blood. 1 A recent study indicates this effect can last for three days or more following the last glass of juice. 2
If you take cyclosporine, the safest approach is to avoid grapefruit juice altogether.
Like grapefruit juice, bitter orange ( citrus aurantium ) may raise levels of cyclosporine. 11-14
If you take cyclosporine, the safest approach is to avoid citrus aurantium altogether.
The substance berberine, found in goldenseal , oregon grape , and barberry , may increase levels of cyclosporine. 15
St. John's Wort
The herb St. John's wort (Hypericum perforatum) is primarily used to treat mild to moderate depression.
St. John's wort has the potential to accelerate the body's normal breakdown of certain drugs 3,4 including cyclosporine, resulting in lower blood levels of these drugs.
This interaction appears to have occurred in two heart transplant patients taking cyclosporine, leading to heart transplant rejection. 5 These individuals had been doing well after transplantation while taking standard immunosuppressive therapy that included cyclosporine. After starting St. John's wort for depression, however, they began experiencing problems and their blood levels of cyclosporine were found to have dipped below the therapeutic range. After St. John's wort was discontinued, cyclosporine levels returned to normal and no further episodes of rejection occurred.
Numerous cases of transplant rejection episodes involving the heart, kidney, and liver have also been reported in people using the herb. 6,7
Based on this evidence, if you are taking cyclosporine, you should not take St. John's wort.
Ipriflavone
The supplement ipriflavone is used to treat osteoporosis. A 3-year, double-blind trial of almost 500 women, as well as a small study, found worrisome evidence that ipriflavone can reduce white blood cell count in some people. 8,9 For this reason, anyone taking medications that suppress the immune system should avoid taking ipriflavone.
An animal study indicates that use of peppermint oil may increase cyclosporine levels in the body. 10 If you are taking cyclosporine and wish to use peppermint oil as well, notify your physician in advance, so that your blood levels of cyclosporine can be monitored and your dose adjusted if necessary. If you are already taking both peppermint oil and cyclosporine and stop taking the peppermint, your cyclosporine levels may fall. Again, consult your physician to make the necessary dosage adjustment.
The herb Scutellaria baicalensis (Chinese skullcap) may impair absorption of cyclosporine, according to a study in animals. 16

References

1 A to Z Drug Facts [book on CD-ROM]. 2nd ed. St. Louis, Mo: Facts and Comparisons; 2000.

2 Takanaga H, Ohnishi A, Murakami H, et al. Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin Pharmacol Ther . 2000;67:201–214.

3 Ernst E. Second thoughts about safety of St. John's wort. Lancet . 1999;354:2014–2016.

4 Guengerich FP. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol . 1999;39:1–17.

5 Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John's wort [letter]. Lancet . 2000;355:548–549.

6 Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St John's wort with cyclosporin. Lancet . 2000;355:1912.

7 Barone GW, Gurley BJ, Ketel BL, et al. Drug interaction between St. John's wort and cyclosporine. Ann Pharmacother . 2000;34:1013–1016.

8 Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int . 1997;61(suppl 1):S23–S27.

9 Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA . 2001;285:1482–1488.

10 Wacher VJ, Wong S, Wong HT. Peppermint oil enhances cyclosporine oral bioavailability in rats: comparison with D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS) and ketoconazole. J Pharm Sci . 2002;91:77-90.

11 Edwards DJ, Fitzsimmons ME, Schuetz EG et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther . 1999;65:237-44

12 Malhotra S, Bailey DG, Paine MF et al. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther . 2001;69:14-23.

13 Edwards DJ, Fitzsimmons ME, Schuetz EG et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther . 1999;65:237-44

14 Hou YC, Hsiu SL, Tsao CW et al. Acute intoxication of cyclosporin caused by coadministration of decoctions of the fruits of Citrus aurantium and the Pericarps of Citrus grandis. Planta Med . 2000;66:653-5.

15 Wu X, Li Q, Xin H et al. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol . 2005 Aug 26 [Epub ahead of print].

16 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

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