s-1743 and Rhabdomyolysis

Polymyositis occurring in patients treated with omeprazole has been signalled as a possible adverse drug reaction (ADR) by the New Zealand Intensive Medicines Monitoring Programme (IMMP) and the WHO Collaborating Centre for International Drug Monitoring: the Uppsala Monitoring Centre (UMC). Polymyositis and other myopathies have also been reported in post-marketing data and in the medical literature in association with proton pump inhibitor (PPI) use. We wished to follow-up these signals and investigate the evidence of causality for the association of polymyositis and other myopathy with PPI use.. Spontaneously reported ADRs from national monitoring centres are sent to the WHO ADR database (VigiBase). VigiBase was searched for case reports of the PPIs, omeprazole, pantoprazole, lansoprazole, esomeprazole and rabeprazole, with terms indicative of myopathy, and further information was elicited from the national centres to help establish causality. Literature sources were reviewed for the occurrence of the above terms in combination with PPIs.. In total, there were 292 reports of various myopathies with PPIs, excluding 868 cases of 'myalgia'. In this analysis, 69 patients recovered when the drug was withdrawn and, in 15 patients, the reaction re-occurred when the drug was reinstated. In one-third of the 292 cases, the PPI was the single administered drug, and the PPI was the single suspected drug by the reporter in 57% of reports where concomitant medication was used. In this analysis, three index cases are documented. One involves the same patient taking three different PPIs (lansoprazole, esomeprazole and rabeprazole) at different time periods, with myalgia and muscle weakness occurring with all three drugs. In the two other index cases, myopathies with esomeprazole and omeprazole were reported with positive rechallenge, and causality was assessed as 'possible' and 'certain' by the reporting centres. In 27 cases myositis or polymyositis was reported. Other myopathies were reported, including 35 cases with rhabdomyolysis. In 9 of these cases, the PPI was withdrawn and the reaction abated. The PPI was reinstated in one patient, but the reaction did not re-occur. Time to onset was given in 17 of the rhabdomyolysis cases, rhabdomyolysis occurred with the first week in 9 cases, and in 3 cases the reaction occurred between 14 days to 3 months of treatment. In 12 of these patients, an HMG-CoA reductase inhibitor (statin) was taken concomitantly.. Case reports from the WHO ADR database, including index cases involving four out of five PPIs, along with evidence of a possible mechanism, provide compelling evidence that there is a causal association between members of the PPI drug class and myopathy including polymyositis. Evidence was also obtained to support the view that PPI use may be associated with occurrence of other myopathies, including the serious reaction rhabdomyolysis.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adverse Drug Reaction Reporting Systems; Enzyme Inhibitors; Esomeprazole; Humans; Lansoprazole; Muscular Diseases; Myositis; Omeprazole; Pantoprazole; Polymyositis; Proton Pump Inhibitors; Rabeprazole; Rhabdomyolysis

Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration.. A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of Tc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis.. His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence.. We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis.

Topics: Adult; Chest Pain; Conservative Treatment; Esomeprazole; Humans; Infusions, Intravenous; Male; Proton Pump Inhibitors; Rhabdomyolysis

Topics: Aged; Anti-Ulcer Agents; Comorbidity; Esomeprazole; Heart Failure; Humans; Male; Proton Pump Inhibitors; Rhabdomyolysis

To report rhabdomyolysis (RML) causing third-degree atrioventricular block secondary to a possible interaction between atorvastatin, esomeprazole, and clarithromycin.. A 51-year-old white woman presented to the emergency department with severe weakness, near syncope, shortness of breath, and chest pain. On admission, her electrocardiogram demonstrated bradycardia (40 beats/min) and third-degree heart block. A creatine kinase (CK) level was >7000 U/L. Her medication history was significant for long-term use of atorvastatin (>1 y), a 6-week history of esomeprazole use, and three 500-mg doses of clarithromycin just prior to admission. Her symptoms of weakness, shortness of breath, and chest pain coincided with starting the esomeprazole. During her hospitalization, the woman required pacemaker placement and her CK continued to rise to >40,000 U/L. Screening for other causes of RML, such as thyrotoxicosis, infection, and immune or hepatic diseases, was negative. She gradually improved over a 26-day hospitalization.. This is a case of RML resulting in third-degree atrioventricular blockade. An objective causality assessment of the adverse reaction via the Naranjo probability scale revealed a probable association with atorvastatin and a possible association with esomeprazole and clarithromycin. The pharmacokinetic profiles of these agents suggest that a possible contribution to this reaction was P-glycoprotein (PGP) inhibition by esomeprazole altering atorvastatin's normally significant first-pass clearance.. PGP drug interactions with atorvastatin and other hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may be associated with unreported risks for RML. Further investigation into PGP impact on HMG-CoA appears warranted.

Topics: Atorvastatin; Clarithromycin; Drug Interactions; Esomeprazole; Female; Heart Block; Heptanoic Acids; Humans; Middle Aged; Pyrroles; Rhabdomyolysis