Multi-drug intoxication fatality involving atorvastatin: A case report.

Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 µg/L) and creatine kinase (219 µkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 µg/L and 57.5 µg/L, resp. (serum) and 8.15 µg/L and 602.3 µg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.

Management of a mixed overdose of calcium channel blockers, ß-blockers and statins.

We describe a case of extreme mixed overdose of calcium channel blockers, ß-blockers and statins. The patient was successfully treated with aggressive resuscitation including cardiac pacing and multiorgan support, glucagon and high-dose insulin for toxicity related to calcium channel blockade and ß-blockade, and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and muscle weakness.

[Case of severe rhabdomyolosis after protracted overdose of simvastatin]. / Et tilfaelde af svaer rabdomyolyse efter laengerevarende overdosering med simvastatin.

The mechanisms of statin-induced muscle injury are not fully understood, and early recognition of statin myopathy is critical in order to prevent serious sequelae. The case of a 57-year-old woman who had accidentally taken a quadrupled dose of simvastatin over a period of 18 days is presented. The patient was admitted to hospital with severe rhabdomyolysis and treated with forced diuresis. Despite the rhabdomyolysis, the patient's kidney function was not affected, but reduced muscle function was observed which was still not fully regained 6 months later.

Pattern of statin exposures reported to Texas poison centers, 1998-2004.

Information on the management of potentially adverse exposures to statins is limited. This study examined the pattern of 2331 statin exposures reported to Texas poison control centers during 1998-2004. In particular comparisons were made between exposures among pediatric (age < or = 5 yr) and adult (age > or = 20 yr) patients. The number of exposures increased from 134 in 1998 to 516 in 2004. Of the total exposures, 55% were to statins alone. Of the exposures to statins alone, 57% of the patients were < or = 5 yr of age and 22% were > or = 60 yr of age. The majority of exposures to statins alone (a) involved female patients (53%), (b) were unintentional (94%), (c) occurred at home (91%), (d) were managed on-site/at home (89%), and (e) had a final medical outcome classified as no effect (94%). Pediatric and adult patients differed with respect to patient gender (45 versus 66% female), exposure reason (100 versus 88% unintentional, 1 versus 75% therapeutic error), exposure site (14 versus 2% at other residence), final medical outcome (4 versus 11% minor effect, none versus 4% moderate effects), report of specific adverse clinical exposures (0.2 versus 5% neurological effects, none versus 1% cardiovascular effects), and listed treatments (60 versus 24% decontamination by dilution, 13 versus 6% decontamination by food). In conclusion, reported statin exposures are increasing. The majority of potentially adverse statin exposures reported to poison control centers may be successfully managed at home with favorable outcomes. The pattern of exposures differs with age.

An assessment of statin safety.

Recently, statin safety and potential drug interactions have received close attention in the consumer and medical press. In particular, rosuvastatin, the most recent statin introduced into the US market, has been the object of much speculation. Many of these reports have lost sight of the proven efficacy of statins in coronary disease prevention at a time when coronary heart disease is the number one killer of adults, and have failed to frame the potential drug toxicity in the context of this benefit. Summarized here are the conclusions of the National Lipid Association's Statin Safety Assessment Task Force, which reviewed extensive new drug application (NDA) and postmarketing data for all the currently marketed statins regarding their effect on the liver, muscle, renal, and neurologic systems. The task force found that, overall, hepatic, renal, or neurologic function does not appear to be compromised by statin use. They do not recommend routine monitoring of these systems but do recommend ongoing surveillance of symptomatic patients. With respect to muscle toxicity, the task force's Muscle Expert Panel concluded that the incidence of myopathy and rhabdomyolysis is low and appears to be dose-related, rather than associated with the degree of low-density lipoprotein cholesterol lowering and also appears to be related to the individual statin used. For example, from the rosuvastatin NDA database and additional postmarketing data, the overall incidence of myopathy was found to be lower than that observed with other statins. Administrative claims data of hospitalization rates for adverse events in statin patients confirm the task force conclusion that, overall, statins are safe and well tolerated when used as monotherapy.

Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity.

BACKGROUND & AIMS: Studies that evaluate the risk of hepatotoxicity from statins in hyperlipidemic subjects with elevated baseline serum transaminases are lacking. We conducted a study to test the hypothesis that patients with elevated baseline liver enzymes have higher risk of statin hepatotoxicity. METHODS: Our study consisted of the following 3 cohorts of patients seen between January 1, 1998 and June 31, 2002: Cohort 1: 342 hyperlipidemic patients with elevated baseline enzymes (AST >40 IU/L or ALT >35 IU/L) who were prescribed a statin; cohort 2: 1437 hyperlipidemic patients with normal transaminases who were prescribed a statin; and cohort 3: 2245 patients with elevated liver enzymes but who were not prescribed a statin. The effect of statins on liver biochemistries was assessed over a 6-month period after statins were prescribed. Elevations in liver biochemistries during follow-up were categorized into mild-moderate or severe based on predefined criteria. RESULTS: The incidence of mild-moderate elevations and severe elevations in liver biochemistries in cohort 1 were 4.7% and 0.6%, respectively. Compared with cohort 1, individuals in cohort 2 had lower incidence of mild-moderate elevations (1.9%, P = 0.002) but not severe elevations (0.2%, P = 0.2). However, between cohorts 1 and 3, there were no differences in the incidence of mild-moderate elevations (4.7% vs. 6.4%, respectively, P = 0.2) or severe elevations (0.6% vs. 0.4%, respectively, P = 0.6). Statin discontinuation during the follow-up was similar between cohorts 1 and 2 (11.1% vs. 10.7%, respectively, P = 0.8). CONCLUSIONS: These data suggest that individuals with elevated baseline liver enzymes do not have higher risk for hepatotoxicity from statins.

Statin specific toxicity in organ transplant recipients: case report and review of the literature.

Statins are widely prescribed to organ transplant recipients with hyperlipidemia. We report the case of a cardiac transplant recipient who developed severe rhabdomyolysis and acute renal failure after being switched from pravastatin to simvastatin. The patient's other medications included cyclosporin A and diltiazem. Unlike pravastatin, the metabolism and tissue concentrations of simvastatin--and of other statins - can be greatly affected by these drugs. The propensity of the individual statins to interact with drugs commonly prescribed to transplant recipients is reviewed.