Tenofovir induced Fanconi syndrome: A possible pharmacokinetic interaction
A 43-year old, HIV positive man was treated with stavudine, lamivudine and nevirapine as per National AIDS Control Organization (NACO) guidelines for 30 months. However, his CD4 count (56 cells/μL) and plasma viral load (1,27,734/mm of blood) failed to improve. Hence the patient was advised the second line antiretroviral therapy consisting of tenofovir 150 mg plus lamivudine 150 mg twice a day along with boosted lopinavir (LPV) 200 mg + 50 mg twice a day. He was also prescribed co-trimoxazole 960 mg once a day, along with multivitamins and folic acid. After a year on this therapy, patient complained of increased frequency of urination, ankle edema and knee pain. On investigations, serum creatinine and random blood sugar (RBS) were within the normal range. Urine examination showed albuminuria (1 g/L) and glycosuria (30 mmol/L) on two subsequent investigations on dates 28/09/2010, 27/10/2010. Serum phosphate was low (1.74, N: 2.7-4.5 mg/dL on 20/12/2010). His blood pressure was 118/78 mm of Hg, RBS was 132 mg/dL and radiological appearance of kidneys and urinary bladder was also normal. Considering the clinical presentation and time course of events the patient was diagnosed as a case of Fanconi syndrome.\nTenofovir was suspected to be the causal drug (Stopped on 5th January 2011) and patient was switched on alternative regimen consisting of abacavir 300 mg and lamivudine 150 mg, five tablets orally, twice a day, along with didanosine 400 mg at bed time on 5th January 2011. The boosted LPV was continued. After 5 months, increased urinary frequency, ankle edema and pain in knees were resolved and serum phosphate returned to normal level (2.8 mg/dL on 30/5/2011). Glycosuria become absent 1-month after the drug stopped, as investigations were done one dates 3/2/2011, 28/2/2011 and 27/6/2011. Albuminuria was absent when the patient was last followed up (27/6/2011). Causality assessment of the adverse drug event was carried out using WHO- Uppsala monitoring centre (UMC) criteria[] and Naranjo's Scale.[] Both the algorithms labeled tenofovir as “probable.” ADR was severe in nature as analysed on the Hartwig scale.[] Further, the preventability assessment carried out using Modified Schumock and Thornton criteria[] showed that the ADR was probably preventable.