Medical Case Studies

  • Abbreviation: Med. Case Stud.
  • Language: English
  • ISSN: 2141-6532
  • DOI: 10.5897/MCS
  • Start Year: 2010
  • Published Articles: 40

Full Length Research Paper

Tacrolimus adverse events in transplant recipients with diarrhoea or calcium channel blockers: Systematic review

Sandrine Leroy
  • Sandrine Leroy
  • Centre for Statistics in Medicine, University of Oxford, Oxford, United-Kingdom.Department of Pediatric Nephrology, Armand-Trousseau Hospital, AP-HP and University Paris VI, Paris, France.
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Sonia Fargue
  • Sonia Fargue
  • Department of Biology, University College London, London, United-Kingdom.Department of Pediatric Nephrology - Reference Centre for Rare Renal Diseases, Femme Mère Enfant Hospital, University of Lyon, Lyon, France.
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Albert Bensman
  • Albert Bensman
  • Department of Pediatric Nephrology, Armand-Trousseau Hospital, AP-HP and University Paris VI, Paris, France.
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Georges Deschênes
  • Georges Deschênes
  • Department of Pediatric Nephrology, Robert-Debré Hospital, AP-HP, Paris, France.
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Evelyne Jacqz-Aigrain
  • Evelyne Jacqz-Aigrain
  • Department of Pediatric Pharmacology - Pharmacogenetics and Clinical Investigation Center - CIC9202, Robert-Debré Hospital, AP-HP, Paris, France
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Tim Ulinski
  • Tim Ulinski
  • Department of Pediatric Nephrology, Armand-Trousseau Hospital, AP-HP and University Paris VI, Paris, France
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  •  Accepted: 24 November 2011
  •  Published: 31 December 2011

Abstract

Tacrolimus is widely used for solid-organ transplant immunosuppression. Adverse events can happen in recipients with diarrhoea or calcium channel blockers (CCBs) co-administration. We undertook a systematic review on adverse events in recipients treated with Tacrolimus for whom a raised tacrolimus trough level (≥10 ng/ml) was reported, in a situation of diarrhoea or CCB co-administration. From 312 identified studies, 16 were included, representing 65 patients. Sixty-one (94%) patients were suffering from diarrhoea, 3 (5%) received concomitant CCBs, and one (2%) presented with both; 46 (71%) were adults, 45 (69%) were kidney transplant recipients. Only 9 (14%) suffered from clinical symptoms: nephrotoxicity was reported in 9%, and required dialysis in 2%, neurotoxicity in 7%, multi-organ failure in 4%, and transient liver dysfunction in 2%. One patient was found to carry polymorphisms on CYP450 and P-glycoprotein, both involved in the tacrolimus metabolism and influenced by diarrhoea and CCB administration. Although, the risk of adverse events related to raised tacrolimus through blood level in situations of diarrhea or CCB administration is well-known and can be severe, published data is still scarce. The determination of the exact frequency of such events and the risk factors involved, such as pharmacogenetic background, would require observational cohort studies.

 

Key words: Calcium channel blocker, cytochrome P450, diarrhoea, P-glycoprotein, transplantation, systematic review, tacrolimus.

Abbreviation

 

Abbreviations: CCB, Calcium channel blocker; CYP, Cytochrome P450; MDR1,Multi-drug resistant 1; P-gp, P-glycoprotein; SNP, Single protein nucleotide.