PMID- 19376416
OWN - NLM
STAT- MEDLINE
DCOM- 20090729
LR  - 20161125
IS  - 0041-1345 (Print)
IS  - 0041-1345 (Linking)
VI  - 41
IP  - 3
DP  - 2009 Apr
TI  - Severe rhabdomyolysis and acute renal failure secondary to concomitant use of 
      simvastatin with rapamycin plus tacrolimus in liver transplant patient.
PG  - 1021-4
LID - 10.1016/j.transproceed.2009.02.019 [doi]
AB  - OBJECTIVE: To report a severe interaction between simvastatin and rapamycin 
      resulting in rhabdomyolysis and acute renal failure in a liver transplant 
      patient. BACKGROUND: A 56-year-old man with hepatitis C virus cirrhosis (Child B) 
      was diagnosed with hepatocellular carcinoma and underwent liver transplantation 
      in April 2007. He was immunosuppressed with tacrolimus (FK) and mycophenolate 
      mofetil (MMF). Postoperative complications were arterial hypertension and renal 
      insufficiency. In June 2007, liver dysfunction was detected and acute rejection 
      was diagnosed by biopsy. He received three 500-mg boluses of methylprednisolone 
      and FK levels were maintained between 10 and 12 ng/mL. Laboratory values revealed 
      persistent rejection and MMF was stopped with initiation of rapamicin. One month 
      later, hyperlipidemia appeared as a consequence of rapamicin therapy; simvastatin 
      was administered. In August 2007, the patient was readmitted due to severe 
      muscule pain and the inability to ambulate. Laboratory values were: total 
      bilirubin 16 mg/dL, serum creatinine 4.3 mg/dL, and total creatine kinase (CK) 
      42,124 U/L. With the suspicion of rhabdomyolysis, leading to worsening of his 
      basal renal insufficiency, rapamycin and tacrolimus were stopped. Hemodialysis 
      was initiated owing to renal failure and hyperkalemia. Some hours later, the 
      patient developed ventricular fibrillation and respiratory failure and succumbed. 
      DISCUSSION: Calcineurin inhibitors (CNI), corticosteroids, and mammalian target 
      of rapamycin (m-TOR) inhibitors are associated with adverse dyslipidemic effects. 
      To reduce the overall cardiovascular risk in these patients, lipid-lowering 
      drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, 
      have been widely used. CNI and m-TOR inhibitors, as well as most statins, are 
      metabolized by cytochrome P450 (CYP)3A4; thus, pharmacokinetic interactions 
      between these drugs are possible. Previous reports have indicated an increased 
      risk of rhabdomyolysis in the presence of concomitant drugs that inhibit 
      simvastatin metabolism. CONCLUSIONS: Concomitant administration of statin therapy 
      and drugs that inhibit cytochrome P450 (CYP)3A4 increased the risk of 
      rhabdomyolysis in a patient suffering liver and renal dysfunction.
FAU - Dopazo, C
AU  - Dopazo C
AD  - Department of Hepatobiliopancreatic Surgery and Transplants, Hospital Vall 
      Hebron, Universidad Autonoma Barcelona, Barcelona, Spain. cdopazo@vhebron.net
FAU - Bilbao, I
AU  - Bilbao I
FAU - Lazaro, J L
AU  - Lazaro JL
FAU - Sapisochin, G
AU  - Sapisochin G
FAU - Caralt, M
AU  - Caralt M
FAU - Blanco, L
AU  - Blanco L
FAU - Castells, L
AU  - Castells L
FAU - Charco, R
AU  - Charco R
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Immunosuppressive Agents)
RN  - AGG2FN16EV (Simvastatin)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Acute Kidney Injury/*chemically induced
MH  - Anticholesteremic Agents/adverse effects
MH  - Drug Therapy, Combination
MH  - Fatal Outcome
MH  - Hepatitis C/surgery
MH  - Humans
MH  - Hypertension
MH  - Immunosuppressive Agents/*adverse effects
MH  - Liver Cirrhosis/surgery
MH  - Liver Transplantation/*adverse effects/immunology
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/adverse effects/analogs & derivatives
MH  - Postoperative Complications
MH  - Rhabdomyolysis/*chemically induced
MH  - Simvastatin/*adverse effects
MH  - Tacrolimus/*adverse effects
EDAT- 2009/04/21 09:00
MHDA- 2009/07/30 09:00
CRDT- 2009/04/21 09:00
PHST- 2009/04/21 09:00 [entrez]
PHST- 2009/04/21 09:00 [pubmed]
PHST- 2009/07/30 09:00 [medline]
AID - S0041-1345(09)00156-0 [pii]
AID - 10.1016/j.transproceed.2009.02.019 [doi]
PST - ppublish
SO  - Transplant Proc. 2009 Apr;41(3):1021-4. doi: 10.1016/j.transproceed.2009.02.019.