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Ribociclib/simvastatin Rhabdomyolysis, drug toxicity and neutropenia: case report

A 68-year-old woman developed rhabdomyolysis secondary to simvastatin toxicity following concomitant administration of ribociclib and simvastatin. Additionally she developed neutropenia during treatment with ribociclib for metastatic breast cancer [routes not stated; not all durations of treatments to reaction onset and outcomes stated]. The woman was diagnosed with stage IV left breast cancer with bone metastasis. She started receiving first-line therapy with ribociclib and letrozole. Ribociclib was administered at 600 mg/day for 3 weeks followed by 7 days off. She also had hypercholesterolaemia and hypertension. She had been receiving simvastatin 40 mg/day for many years. Following 3 weeks of ribociclib treatment, she presented with general weakness and a progressive paraplegia. She was in a confused state and had pain in her limbs for 4 days. She had difficulty walking due to the pain. Blood test revealed elevated creatine kinase and serum creatinine levels. She had grade 3 neutropenia, but did not have any signs of infection. A diagnosis of ricociclib induced neutropenia was established. The woman was hospitalised, and simvastatin and ribociclib were stopped. The next day, pain in her limbs was more and she developed tetraplegia; she could not move her both limbs. Her serum creatinine and creatine kinase levels, liver transaminases, aspartate aminotransferase and alanine aminotransferase continued to increase. Due to the elevated creatine kinase together with tetraplegia and muscles pain, she was diagnosed with rhabdomyolysis. Rehydration was started with sodium chloride (NaCl 0.9%) and bicarbonate. Consequently, her renal function improved. But after 4 days (on day 6), creatine kinase continued to increase and she developed liver impairment. Therefore, she was transferred to the ICU. Liver echography showed no abnormality. She was negative for polymyositis antibodies. Thus, she was diagnosed with simvastatin induced rhabdomyolysis, occurred due to increase in simvastatin plasma concentrations to toxic levels (toxicity) following interaction of simvastatin with ribociclib. The hydration was intensified. Nicardipine was also initiated due to increased blood pressure. Approximately one week later, her clinical status improved and she was able to walk alone. Subsequently, her blood values normalised and she was discharged with recovery. Nicardipine was discontinued. One month following the discharge, ribociclib was re-initiated at 200 mg/day and the dose was increased gradually (400mg the second week and 600mg the third week). She tolerated the treatment well. Ribociclib was continued at 600 mg/day for 3 weeks followed by seven days off. Six months following the re-start of ribociclib, she tolerated the treatment well. Simvastatin was stopped and no other lipid-modifying drugs were prescribed. The interaction was considered to be ’probable’ based on the score of 7 on Drug Interaction Scale. Streicher C, et al. Severe rhabdomyo