It's not just the donepezil - kidney toxicity is a risk factor with quite a few medicines, so old folks getting lots of meds are really at risk. Note that the articles below are dated 2006 and 2012. This is a known issue.
Many Potential Sources for Drug-induced Rhabdomyolysis OCTOBER 01, 2006 Cheryl A. Grandinetti, PharmD The first known description of rhabdomyolysis can be found in the Bible (Numbers 11:31-33). It tells of a plague inflicted on the Israelites who ate quail that had fed on hemlock.1 Rhabdomyolysis is a potentially life-threatening condition resulting from skeletal muscle injury and a rapidly rising intracytoplasmic calcium concentration. Excess intracytoplasmic calcium causes muscle destruction and fiber necrosis, leading to excessive potassium, phosphate, myoglobin, creatine kinase, and urate release into the systemic circulation.2
Early complications of rhabdomyolysis include hypokalemia (causing cardiac arrhythmia and possibly cardiac arrest), hypocalcemia, and hepatic dysfunction. Late complications, occurring after 12 to 24 hours, include acute renal failure and disseminated intravascular coagulation (DIC).2-4
Direct muscle injury, excessive physical exertion, muscle ischemia, hypothermia, hyperthermia, infection, toxins, recreational drugs, and pharmaceuticals can cause rhabdomyolysis. Drug-induced rhabdomyolysis is one of the most common forms, ranging from an asymptomatic to a life-threatening illness. The underlying cause will determine the clinical course. Myoglobin destruction causes the cardinal sign of rhabdomyolysis: teacolored urine. Muscle weakness, myalgias, swelling, stiffness, and cramps also may occur.2-4
The most sensitive biochemical indicator, a creatine kinase reading at least 5 times higher than normal, is the accepted diagnostic standard. A ratio of blood urea nitrogen to serum creatinine of 6:1 or less indicates increased creatinine release from skeletal muscle and renal dysfunction.2,5 An increase or decrease in potassium, phosphate, or calcium may occur, depending on the severity, duration, and management of the patient's rhabdomyolysis. Arterial blood gas analysis can detect hypoxia and acidosis; urinalysis can reveal protein, brown casts, and uric acid crystals; an electrocardiogram may show abnormalities; and clotting studies diagnose DIC.2,4
More than 150 recreational drugs, pharmaceuticals, and toxins (Table5-10) may alter myocyte function, resulting in rhabdomyolysis. Calcium metabolism inhibition by the sarcoplasmic reticulum, impaired adenosine triphosphate production causing cell membrane disruption, and carbohydrate metabolism alterations are proposed direct mechanisms. Indirect mechanisms include prolonged immobilization and muscle compression from drug-induced coma, seizures, myoclonus, and trauma (ie, tissue ischemia and crush injury), resulting from drug-induced altered mental status, agitation, and delirium.4
Ciprofloxacin and Rhabdomyolysis: A New Connection Posted on February 21, 2012 by AJKDblog in Interview // 1 Comment
Myoglobin-associated kidney injury is seen in severe rhabdomyolysis. Although certain drugs have been associated with this injury, ciprofloxacin is not a common agent. A recent teaching case was published in the American Journal of Kidney Diseases describing this association, and the corresponding author Dr. Qi Qian (QQ) from Mayo Clinic spoke about these findings with Dr. Kellie Calderon (eAJKD), eAJKD advisory board member.
eAJKD: You present a case of acute kidney injury in a patient with recurrent pulmonary infections following solid-organ transplantation. While on multiple medications, he developed rhabdomyolysis after ciprofloxacin administration. With so many potential offenders, please describe your differential diagnosis going into the kidney biopsy?
QQ: The patient had a history of a1-antitrypsin deficiency, which was the reason for double lung transplant. Immunosuppression included tacrolimus, so calcineurin inhibitor toxicity was a consideration even trough levels had not been elevated. He had chronic bronchiectasis and recurrent pulmonary infections, so we considered infection-related decreased kidney function but repeated evaluation of urinary sediment was bland. On further questioning, the patient described previous reactions to ciprofloxacin which lead us to consider this as a possible cause. Acute allergic interstitial nephritis was in the differential despite the patient being on chronic steroids.
eAJKD: How essential was biopsy in determining the cause of acute kidney injury?
QQ: On light microscopy, crystals were noted. Stains were strongly positive for myoglobin. We were surprised. Without the biopsy, it would have been difficult to make a firm diagnosis in this case.
eAJKD: In your review of the literature, you have identified at least forty cases of rhabdomyolysis induced by a fluoroquinolone. Is this the first case of biopsy-proven kidney injury as a result?
QQ: Yes, this is the first biopsy-proven case report of myoglobin-induced kidney injury. Most reports are associations, reported only with elevated serum creatinine kinase levels in the setting of fluoroquinolone use.
eAJKD: Interestingly, the patient your describe had previously reported ankle pain as an adverse reaction to ciprofloxacin. We are now aware of the risk of tendon rupture as a complication of fluoroquinolone use, particularly in older patients receiving long-term steroid therapy and recipients of organ transplants. Do you believe there is a common link between the risk of fluoroquinolone-induced musculoskeletal complications and rhabdomyolysis?
QQ: I believe that rhabdomyolysis in our patients was a multifactorial event. He was certainly on a few medications that have been described to cause myotoxicity. His advanced age and chronic
