LJM 1993-2820 1819-6357 Libyan Journal of Medicine, Vol. 5, No. 0, July 2010, pp. 1–2 sici xxx PUBMED Abbreviation Libyan Journal of Medicine LETTER TO THE EDITOR Letter to the Editor Ticlopidine is an effective anti-platelet agent used for prevention of thrombosis 123. It was reported that treatment with ticlopidine at the dose of 250 mg daily in kidney transplant patients caused significant reduction of cyclosporin A (CsA) blood levels 45. In heart transplant patients treated with higher doses of ticlopidine 500 mg daily, it was found to cause significant decrease of cyclosporin concentration but not in those treated with only 250 mg daily 12. It was thought that ticlopidine interacts with cyclosporin metabolism at cytochrome P450 123.We report three living kidney donor recipients whose blood level of cyclosporin decreased significantly under treatment with a very low dose of ticlopidine of 100 mg daily.The patients were on immunosuppressive treatment with steroids, CsA, and mycophenolate mofetil (MMF) or azathioprin. The total daily CsA dose was 125–150 mg. The patients developed severe hypertension 15 days to 4 months after kidney transplantation. Serum creatinine was normal except in patient number 2 (Table 1). Doppler ultrasonography confirmed significant stenosis of at least 70% degree in the artery of the transplanted kidney. Percutanuous transluminal angioplasty (PTA) with stent placement was performed. Anti-platelet treatment with aspirin (160 mg/day) and ticlopidine (100 mg/day) were given to prevent thrombosis. CsA blood levels were monitored by C₀ (before morning dose) (Fig. 1). Under ticlopidine treatment, CsA blood levels decreased in patient 1 from 137 to 112 ng/ml, in patient 2 it decreased from 120 to 100 ng/ml, and in patient 3 it decreased from 131 to 106 ng/ml. Consequently CsA dose had been increased by 50–75 mg/day. No signs of acute kidney transplant rejection were observed.

Cyclosporin A blood levels (C₀) and doses during 60 days of ticlopidine therapy: follow of blood CsA levels and doses in the three patients.

Characteristics Patient 1 Patient 2 Patient 3 Note: PTA, percutanuous transluminal angioplasty. Age (years) 18 26 20 Gender F M F HLA mismatch 3 3 3 Serum creatinine (mg/l) 8.5 15.4 7.1 Number of anti-hypertensive drugs 3 4 3 Diagnosis of stenosis after transplantation 2 months 15 days 4 months Date of PTA 2 months after the diagnosis 14 months after diagnosis 2 months after the diagnosis In summary: In kidney transplant patients, ticlopidine can cause a significant decrease in CsA blood level even at a low dose of ticlopidine. The interaction of ticlopidine with CsA seems to be not related to the doses. We recommend careful monitoring of CsA blood level in patients treated with ticlopidine.

Tarik Sqalli Houssaïni
Nephrology department
Ibn Sina University Hospital
Rabat, Morocco
Email: tariksqalli@hotmail.com

Asmaâ Laboudi, Hakima Rhou, Fatima Ezzaïtouni
Loubna Benamar, Naïma Ouzeddoun, Rabea Bayahia
Nephrology department
Ibn Sina University Hospital
Rabat, Morocco BoissonnatPDe LorgerilMPerrouxVSalenPBattAMBarthelemyJC A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients Eur J Clin Pharmacol. 199753 3945 De LorgerilMBoissonnatPDureauGGuidolletJRenaudS. Evaluation of ticlopidine, a novel inhibitor of platelet aggregation in heart transplant recipients Transplantation 199355 11956 CampanaCRegazziMBBuggiaIMolinaroM. Clinically significant drug interactions with cyclosporin. An update Clin Pharmacokinet. 199630 14179 FeriozziSMassimettiCAncaraniE. Treatment with ticlopidine is associated with reduction of cyclosporin A blood levels Nephron 200292 24950 VerdejoADe CosMAZubimendiJA. Probable interaction between cyclosporin A and low dose ticlopidine BMJ 2000320 1037