Rhabdomyolysis precipitated by multitherapy is most frequently described during
statin treatment, due to impairment of
statin clearance by drugs sharing
cytochrome P450 biotransformation pathway. Modulation of
membrane transporters for
drug efflux, operated by substrates, can also affect drugs' tissue levels. We report
rhabdomyolysis in an elderly patient, in multitreatment with different potentially myotoxic medications, taking place seven months after
atorvastatin discontinuation. Affected by ischaemic
heart disease, arterial
hypertension and
dementia-related behaviour disturbances, the patient was receiving
angiotensin 2-receptor inhibitors, beta-blockers,
vasodilators,
diuretics, salycilates,
allopurinol,
proton pump inhibitors,
antipsychotics and
antidepressants. He had taken
atorvastatin for 14 years, with constantly normal
creatine-kinase plasma levels. Two months after addition of the antianginal
drug ranolazine,
creatine-kinase mildly increased and
atorvastatin was withdrawn. Nonetheless,
creatine-kinase progressively rose, with severe weakness and
rhabdomyolysis developing seven months later. Muscle biopsy showed a necrotizing
myopathy with no
inflammation or autoimmune changes. After
ranolazine withdrawal,
creatine-kinase and
myoglobin returned to normal levels and strength was restored. Several psychotropic and cardiovascular medications prescribed to the patient share either
cytochrome P450 biotransformation and permeability-
glycoprotein efflux transport. In the event of cardiovascular/neuropsychiatric
polypharmacy in geriatric patients, the risk of muscle severe adverse effects from pharmacokinetic
drug-drug interaction should be considered beyond the direct
myotoxicity of
statins.