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Rhabdomyolysis after concomitant use of cyclosporine and simvastatin in a patient transplanted for multiple myeloma

Bone Marrow Transplantation volume 36, pages 739–740 (2005)Cite this article

Since nonmyeloablative host conditioning regimens are associated with reduced regimen-related toxicities, advanced age and most comorbid medical conditions are no longer absolute contraindications for allogeneic hematopoietic cell transplantation (HCT).1 Consequently, patients receiving nonmyeloablative transplants are often taking several nontransplant-related prescription medications and therefore are at a higher risk for drug–drug interactions. We describe a case of an elderly patient who presented with an adverse drug reaction due to an interaction between the immunosuppressive regimen and simvastatin following a nonmyeloablative HCT for advanced stage multiple myeloma.

A 66-year-old male taking simvastatin for a dyslipidemia was diagnosed with stage IIIA IgG kappa multiple myeloma and received 5 months of therapy with thalidomide, dexamethasone, and pamidronate, and had an excellent clinical response with complete resolution of bone pain and a >75% reduction in his M-protein. He received cyclophosphamide (4 gm/m2) and granulocyte-colony stimulating factor (G-CSF) followed by apheresis of blood mononuclear cells with cryopreservation of the unmanipulated product. He was infused with his autologous product (CD34+ cell dose=4.9 × 106/kg) after conditioning with melphalan (200 mg/m2), and had an unremarkable medical course with an absolute neutrophil count recovery (>1500/μl) by day 12 after transplantation. At 75 days after his autologous transplant, he received nonmyeloablative low-dose total body irradiation (TBI), 200 cGy in a single fraction, followed by infusion of G-CSF-mobilized blood mononuclear cells from his HLA-compatible 64-year-old healthy brother. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine dose adjusted for trough levels of 400–600 ng/ml for the first 56 days followed by gradual tapering until discontinuation by 6 months after transplantation, and mycophenalate mofetil (MMF) 15 mg/kg orally twice daily for 28 days after transplantation. At 22 days after transplantation, the patient developed bilateral lower extremity weakness that progressed over 3 days to the extent that he was no longer able to bear weight and ambulate. The only other noteworthy complaint was constant aching in his thighs. He denied any fever, back pain, weakness of his upper extremities, loss of sensation in his lower extremities or perineum, bowel incontinence, or urinary retention. His medications included simvastatin 80 mg daily, cyclosporine and MMF as above, nifedipine for hypertension, levothyroxine for hypothyroidism, and glyburide for non-insulin-dependent diabetes mellitus. On examination, the patient appeared well with normal vital signs. The relevant findings were no neurologic deficits in the upper extremities but muscle strength was 1/5 in the hip flexors bilaterally, 2/5 for bilateral knee flexion and extension, with intact strength throughout the remainder of the distal lower extremities. Sensation in the lower extremities and perineum were intact. Rectal tone was normal. Palpation of the spine revealed no tenderness, but palpation of bilateral quadriceps muscles elicited pain. The remainder of the examination was unremarkable. Laboratory evaluation revealed a urine dipstick with 3+ blood, but no red cells on microscopy, an elevated serum creatinine of 2.0 mg/dl, AST 555 U/l, ALT 274 U/l, and a total creatinine kinase of 29 253 U/l. The remainder of the laboratory test results was unremarkable. Magnetic resonance imaging showed no evidence of spinal cord compression. Electromyography studies showed profuse spontaneous activity with myopathic abnormalities of motor unit action potential in multiple lower extremity muscle groups. Following a presumed diagnosis of statin–cyclosporine-induced rhabdomyolysis, the patient was hydrated, and simvastatin and cyclosporine were discontinued. The serum creatinine returned to baseline within 7 days and the creatinine kinase normalized within 14 days. The patient was discharged to home after 14 days in the hospital as he had recovered the ability to ambulate. Medications at discharge included tacrolimus for GVHD prophylaxis and gemfibrozil for treatment of hyperlipidemia. By 2 months after discharge, he had recovered to his baseline functional status.

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  1. Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, S101, Stanford, 94305, CA, USA

    J Tong, G Laport & R Lowsky

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Tong, J., Laport, G. & Lowsky, R. Rhabdomyolysis after concomitant use of cyclosporine and simvastatin in a patient transplanted for multiple myeloma. Bone Marrow Transplant 36, 739–740 (2005). https://doi.org/10.1038/sj.bmt.1705128

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