Atorvastatin

Combination with ezetimibe

Ezetimibe plus atorvastatin was also well tolerated in 628 patients, with a safety profile similar to that of atorvastatin alone and to placebo. When co-administered with atorvastatin, ezetimibe provided significant incremental reductions in LDL cholesterol and triglycerides and increased HDL cholesterol [ ].

Ezetimibe given with simvastatin and atorvastatin is well tolerated, with a safety profile similar to the statin alone and to placebo [ ]. However, there are concerns about the use of ezetimibe in patients with impaired oxidation of fatty acids, as in familial combined hyperlipidemia. Of more than 300 patients with intolerance of lipid-lowering therapies a subgroup had common features, including raised fasting respiratory exchange ratios while not taking lipid-lowering drugs and hypertriglyceridemia [ ]. An interaction of ezetimibe with statins was suspected in two men aged 43 and 53 years, both of whom had raised creatine kinase activity and one of whom also had myalgia [ ]. However, co-administration of ezetimibe and lovastatin in 48 healthy men resulted in no significant changes in laboratory test results, including enzymes indicative of muscle or liver damage [ ].

Nervous system

A peripheral neuropathy has been reported with atorvastatin.

• A 60-year-old woman had painless horizontal diplopia, vertigo, blurry vision, and paresthesia in both arms after taking atorvastatin 10 mg/day [ ]. Neurological improvement began 2 days after drug withdrawal. Antiacetylcholine receptor antibodies were 10 times the upper limit of the reference range.

Although some features of this patient’s external ophthalmoplegia were similar to myasthenia and there was a reversible rise in antiacetylcholine receptor antibody titer, a negative edrophonium test and a negative repetitive stimulation test on electromyography argued against a myasthenia-like drug reaction.

• A 57-year-old man in good health took atorvastatin 5 mg and aspirin 75 mg/day and had progressive numbness and burning in both feet for 6 months [ ]. Muscle punch biopsies showed a neuropathic process affecting small-caliber sensory nerve fibers. The symptoms resolved 3 months after withdrawal of atorvastatin.

Peripheral neuropathy has also been reported in a case–control study [ ].

Sensory systems

In 696 patients taking atorvastatin and 235 taking lovastatin for 1 year there were no significant differences in the distribution of lenticular opacities or cortical opacities and spokes between the two drugs [ ].

Metabolism

Co-enzyme Q10 concentrations were measured in blood from hypercholesterolemic subjects before and after exposure to atorvastatin 80 mg/day for 14 and 30 days in 34 subjects eligible for statin treatment [ ]. The mean blood concentration of co-enzyme Q10 was 1.26 μg/ml at baseline, and fell to 0.62 after 30 days of atorvastatin therapy. There was a statistically significant fall detectable after 14 days of treatment. The authors concluded that widespread inhibition of co-enzyme Q10 synthesis could explain the exercise intolerance, myalgia, and myoglobinuria that are observed with statin treatment.

Hematologic

Thrombocytopenia occurred in a 46-year-old man coinciding with atorvastatin treatment; he had already tolerated simvastatin [ ].

Leukopenia with oral ulceration has been attributed to atorvastatin in a patient with insulin allergy who had received a pancreatic transplant; the symptoms resolved on withdrawal [ ].