LOVASTATIN AND RELATED DRUGS
- USES: HMG-CoA reductase inhibitors are used in the treatment of hypercholesterolemia. The following agents are available in the United States: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. Atorvastatin, lovastatin, pravastatin, and simvastatin are also available in combination with other agents (atorvastatin/amlodipine; lovastatin/niacin; pravastatin/aspirin; simvastatin/ezetimibe; simvastatin/niacin; simvastatin/sitagliptin). PHARMACOLOGY: HMG-CoA reductase inhibitors competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, preventing conversion of HMG-CoA to mevalonate, the rate determining enzyme for cholesterol synthesis. EPIDEMIOLOGY: Exposure is common but overdose is rare. MILD TO MODERATE TOXICITY: Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses. Ingestion of up to 6 grams of lovastatin has been reported without specific effects or sequelae. SEVERE TOXICITY: Severe toxicity is not expected, unless a coingestant is present. ADVERSE EFFECTS: Nausea, flatulence, diarrhea, abdominal pain, myopathy, myalgias, rhabdomyolysis, elevated liver enzymes, hepatitis, dermatitis, diplopia, blepharoptosis (ptosis), ophthalmoplegia, tendinitis, and tendon rupture have been reported in patients receiving statins. Other reported adverse effects (rare) include hyperkalemia (lovastatin), photosensitivity (simvastatin), dermatomyositis (simvastatin and pravastatin), limb compartment syndrome (simvastatin and atorvastatin), acute renal failure (lovastatin), pancreatitis (pravastatin and lovastatin/gemfibrozil), chest pain (pravastatin), atrial fibrillation (simvastatin), vasculitis (atorvastatin), hemolytic anemia (lovastatin), thrombocytopenic purpura (atorvastatin), thrombotic thrombocytopenic purpura (simvastatin), akathisia (lovastatin), extrapyramidal effects (lovastatin), nasopharyngitis (atorvastatin), upper respiratory infection (pravastatin), cough (pravastatin), lung fibrosis (simvastatin), peripheral neuropathy (lovastatin and simvastatin).
Range of Toxicity:
LOVASTATIN AND RELATED DRUGS
- TOXICITY: ADULTS: LOVASTATIN: Single doses up to 200 mg of lovastatin have been well tolerated without significant adverse effects in adult human volunteers. Overdoses of up to 5 to 6 grams of lovastatin have been well tolerated; no specific symptoms occurred. SIMVASTATIN: The maximum reported dose of simvastatin ingestion is 3.6 g with no specific symptoms; recovery was complete without sequelae. CHILDREN: FLUVASTATIN: Two children (a 2-year-old and a 3-year-old) ingested up to 80 mg of fluvastatin. Vomiting was induced in the children, and no capsules were present in emesis; both children recovered without any adverse effects. THERAPEUTIC DOSE: ADULTS: ATORVASTATIN: Initial dose is 10 or 20 mg once daily, may be increased up to a maximum of 80 mg once daily. FLUVASTATIN: 20 to 80 mg daily. LOVASTATIN: extended-release lovastatin is 20 to 60 mg daily, in single doses; regular lovastatin is 10 to 80 mg daily, in single or divided doses. PITAVASTATIN: 1 to 4 mg once daily. PRAVASTATIN: 10 to 80 mg daily, in single doses. ROSUVASTATIN: 5 to 40 mg daily. SIMVASTATIN: 5 to 80 mg daily. CHILDREN: ATORVASTATIN: Initial dose is 10 mg once daily, may be increased up to a maximum of 20 mg once daily. FLUVASTATIN: 20 to 80 mg daily. LOVASTATIN OR PITAVASTATIN OR ROSUVASTATIN: Safety and efficacy have not been established in children. PRAVASTATIN: 20 to 40 mg daily, in single doses. SIMVASTATIN: 10 to 40 mg daily.
LOVASTATIN AND RELATED DRUGS
- Support: MANAGEMENT MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Severe toxicity is not expected after an overdose.
- Decontamination: PREHOSPITAL: Significant toxicity has not been reported after acute overdose of these agents. Prehospital gastrointestinal decontamination is generally not necessary unless coingestants are involved. HOSPITAL: Significant toxicity has not been reported after acute overdose of these agents. Gastrointestinal decontamination is generally not necessary. Consider activated charcoal only after very large ingestions or if coingestants with significant toxicity are involved.
- Airway management: Airway management is very unlikely to be necessary unless more toxic coingestants are involved.
- Antidote: None
- Rhabdomyolysis: Administer sufficient 0.9% saline to maintain urine output of 2 to 3 mL/kg/hr. Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output. Urinary alkalinization is NOT routinely recommended.
- Monitoring of patient: Monitor vital signs, serum electrolytes, CBC, and liver enzymes in symptomatic patients. Monitor serum creatinine, BUN, CK, and urine myoglobin for indications of renal impairment secondary to rhabdomyolysis in symptomatic patients.
- Enhanced elimination procedure: Hemodialysis is NOT expected to significantly enhance the clearance of these drugs due to extensive protein binding and large volumes of distribution.
- Patient disposition: HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess electrolyte and fluid balance and gastrointestinal function. Patients that remain asymptomatic can be discharged. ADMISSION CRITERIA: Patients should be admitted for severe vomiting, profuse diarrhea, severe abdominal pain, dehydration, and electrolyte abnormalities. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.