Palbociclib in combination with simvastatin induce severe rhabdomyolysis: a case report

Abstract

BackgroundPalbociclib is a selective well-tolerated antineoplastic drug used in the treatment of advanced HER2-negative, estrogen-receptor positive breast cancer that has shown significant improvement in progression-free survival. We present a patient that developed severe rhabdomyolysis with tetra-affection and loss of gait after initiating the first cycle of Palbociclib concomitantly with Simvastatin 40 mg treatment.Case presentationA 71-year-old woman with metastatic breast cancer developed tetraparesis and near fatal rhabdomyolysis after initiation of first cycle Palbociclib. For 10 years prior to this treatment, the patient had been treated with Simvastatin without myalgia or other neuromuscular complaints prior to the first cycle of Palbociclib. The patient was admitted at the neurology department, where Palbociclib and Simvastatin were discontinued. The patient was aggressively hydrated and treated with intravenous immunoglobulin therapy with slowly remission and finally regaining independent gait function. Evaluation showed a negative myositis antibody work-up. Muscle magnetic resonance imaging showed edema in multiple foci, but skeletal muscle biopsy did not show necrosis. Post discharge genetic analysis showed single heterozygosity for nucleotide polymorphism rs4149056.ConclusionWe present a patient who developed severe rhabdomyolysis induced by a combination of Palbociclib and Simvastatin treatment. Rhabdomyolysis was most likely induced by toxic plasma concentrations of Simvastatin due to Palbociclibs inhibition of the CYP3A4 enzyme in combination with a decreased hepatic uptake of Simvastatin due to single nucleotide polymorphism rs4149056. The study underscores that combining Simvastatin and Palbociclib should be done cautiously and genetic testing of the rs4149056 SNP is warranted. If present, Simvastatin should be discontinued or replaced with a lesser myopathic statin in regard to patients risk of cardiovascular events.

Lactic acidosis, a potential toxicity from drug–drug interaction related to concomitant ribociclib and metformin in preexisting renal insufficiency: A case report

“…Previously, concomitant simvastatin with palbociclib showed statin‐induced rhabdomyolysis in a case study. 11 Changing ribociclib to palbociclib may report similar adverse reactions. According to effect in membrane transporters, both palbociclib and ribociclib can potentially inhibit different membrane transporters and different locations.…”

Severe rhabdomyolysis induced by possible drug–drug interaction between Ribociclib and Simvastatin

“…The second case describes a severe rhabdomyolysis after only one cycle of Palbociclib on a woman treated with Simvastatin. 13 Palbociclib is a weak inhibitor of CYP 3A4 enzyme whereas Ribociclib is a strong inhibitor. Potential risk of drug–drug interaction should be higher with Ribociclib.…”

Simvastatin in vitiligo: an update with recent review of the literature

“…Statins may lead to certain adverse effects like headache, flushing, myalgia, dizziness, nausea, and abdominal cramps. Rare but serious adverse effects with long‐term use include rhabdomyolysis 41 and acute hemolysis; 42 thus, careful monitoring is mandatory especially in cases of long‐term usage. The risk of side effects is more in patients above 80 years of age, women, individuals with pre‐existing liver or kidney disease, alcoholics, and patients with hypothyroid.…”

“…The effective dose of simvastatin for repigmentation of vitiligo is 80 mg/day in humans 2 . Experimental animal models have shown, as a result of the lipophilic property of simvastatin, topical formulation may be used at a concentration of 1.0 mmol/l for vitiligo lesions, which is more effective with minimal risk of adverse effects than systemic statins 41 …”