Dosing algorithm for Tacrolimus in Tunisian Kidney transplant patients: Effect of CYP 3A4*1B and CYP3A4*22 polymorphisms.

Prescribing appropriate Tacrolimus (Tac) dosing is still a challenge for clinicians due to the interindividual variability in dose requirement and the narrow therapeutic index. Our objective is to identify potential factors that affects Tac exposure in Tunisian Kidney patients and to develop and validate a Tac dose requirement algorithm including genetic and nongenetic variables. A cross-sectional study was performed. To assess the implication of each covariate on Tac exposure, we classified the patients according to quartiles of exposure index (trough Tac concentration/Dose: C0/D). The total population was divided into the building (75%) and validation (25%) groups. Multiple linear regression was applied to determine the algorithm of Tac dose including the patient's genetic and nongenetic variables. A total of 685 samples issued from 102 kidney transplant patients were included in the study. The post-transplant time (PT), ATG therapy, CYP3A4, and CYP3A5 polymorphisms were significantly associated with trough Tac C0/D. However, the age, sex, body weight, and induction by basiliximab did not show any effect on C0/D. Predicted Tac dose was calculated as follows: Tac Dose = - 2,725 - (10-3 * PT day) + (0,09*weight) + (1,40*ATG) + (2,09* CYP3A4*1B allele) + (0,88*gender) + (0,05*Age) + (1,10*CYP3A4*22 allele) + (2,30* target ranges). Our study designed the first algorithm that predicts the Tac dose requirement in Tunisian Kidney transplant patients including genetic and non-genetic factors. The application of such an algorithm should reduce the number of patients with Tac trough concentration outside the target range and could minimize the time to reach a therapeutic C0.

[H1N1 influenza vaccines in Tunisia: efficiency and safety]. / Les vaccins anti A(H1N1) en Tunisie : efficacité et tolérance.

OBJECTIVE: We carried out this study in order to evaluate the effectiveness and the safety of the two H1N1 vaccines available in Tunisia: Focetria(®) and Panenza(®). METHODS: It's a prospective epidemiological study including 601 vaccinated subjects. The vaccine effectiveness was based on the occurrence of flu clinical symptoms after vaccination. The safety was based on the occurrence of unexpected events after vaccines administration. The vaccines imputability was established according to Begaud et al. method. RESULTS: The number of subjects vaccinated by Focetria(®) is more important than Panenza(®). The efficiency of vaccines would be 93.6%. Neither the medical statue nor the type of the vaccine used influence the occurrence of a flu episode after vaccination. We recorded 406 adverse effects (32.4%) with a high score of imputability (I3). Focetria(®) adverse effects were more frequent than Panenza(®) ones (p = 0.009). Almost all adverse events disappeared within few days. CONCLUSION: The two vaccines used in Tunisia remain enough efficient to face the influenza (H1N1) pandemia and are well tolerated independently of the demographic and pathological statue of the vaccinated person as well as nature of the vaccine used.

[DRESS syndrome: 11 case reports and a literature review]. / DRESS syndrome : étude de 11 cas et revue de la littérature.

AIM: Study the epidemiological, clinical, biological and chronological drug rash with eosinophilia and systemic symptoms (DRESS) characteristic and indicate the implicated drugs. METHODS: We carried a retrospective study including all DRESS cases notified to the Pharmacovigilance Unit of Monastir. RESULTS: Our cohort of eleven patients had a median age of 40 years. Clinical examination revealed skin eruption and fever among all patients. Laboratory findings showed marked eosinophilia among all patients, hepatic cytolysis among eight patients and creatinin serum level increase among four patients. An interstitial pulmonary syndrome was noted among two patients. After culprit-drug withdrawal, outcomes were favorable for all patients. Skin tests were positive with carbamazepin and cefotaxim and negative with sulfasalazine, allopurinol and terbinafine. CONCLUSION: Throughout this paper, we point out the contribution of skin tests to identify implicated drug in inducing DRESS and to testify cross reactivity and we point out the possibility of neosensitisation to a non related chemical drug after DRESS syndrome.