Troleandomycin and Atorvastatin: Interaction Details

a) The coadministration of clarithromycin (a macrolide antimicrobial related to troleandomycin) with atorvastatin significantly increased atorvastatin exposure. In a randomized, open-label, placebo-controlled study, healthy subjects (n=36) received atorvastatin 10 milligrams (mg) daily for 8 days. On study days 6 through 8, subjects received one of 3 concomitant treatments: clarithromycin 500 mg twice daily, azithromycin 500 mg once daily, or placebo. Atorvastatin plasma concentrations were analyzed over 24 hours on study days 5 and 8. Whereas the time to maximum atorvastatin concentration was not significantly affected, the coadministration of clarithromycin with atorvastatin significantly increased atorvastatin geometric mean maximum serum concentration and area under the concentration-time curve (by 56% and 82%, respectively; p less than 0.01, both measures). No significant changes from baseline were observed during placebo or azithromycin co-treatment ³.

b) Severe rhabdomyolysis associated with 3rd degree heart block developed in a 51-year-old woman receiving a multidrug regimen comprising atorvastatin, esomeprazole, and clarithromycin. The patient had previously taken atorvastatin 10 milligrams (mg) daily without incident for over a year, prior to presenting with symptoms of severe weakness, dyspnea, chest pain, and bradycardia. Electrocardiographic exam revealed a 3rd degree heart block pattern and serum creatine kinase (CK) was 7348 Units/Liter (U/L), with a CK-MB (muscle-brain) concentration of 186 U/L. Urinalysis confirmed the presence of myoglobinuria. The patient reported having symptoms of increasing fatigue, mild chest pain and dyspnea that began with the coadministration of esomeprazole, approximately 6 weeks prior to admission. Clarithromycin 500 mg twice daily was added to her therapy regimen 2 days before admission (3 dose total) for treatment of respiratory symptoms. Despite the withdrawal of all medications, CK and CK-MB continued to rise, peaking above 40,000 U/L and 396 U/L, respectively. Electrolyte hydration and forced diuresis was initiated and a permanent cardiac pacemaker was eventually required. Although the authors determined esomeprazole had the highest probability of causing increased atorvastatin exposure, they also suggested clarithromycin contributed to the event ¹.

c) Rhabdomyolysis developed in a 35-year-old man with human immunodeficiency virus infection (HIV) after clarithromycin was added to a long-standing regimen of atorvastatin and HIV protease inhibitors. The patient had previously tolerated chronic use of the combination of atorvastatin 40 milligrams (mg) with lopinavir/ritonavir (dose unspecified). Approximately 8 days after starting clarithromycin 500 mg twice daily for treatment of pneumonia (at which time his liver enzymes were within normal range), the patient developed continuous sharp muscle pain in both lower limbs. Physical examination revealed bilateral hip flexor/extensor weakness, and laboratory analysis revealed a serum creatine kinase (CK) concentration of 10,298 Units/Liter (U/L) accompanied by elevations in serum alanine aminotransferase (281 U/L) and alkaline phosphatase (850 U/L). Urinalysis confirmed the presence of myoglobin. Atorvastatin and clarithromycin were discontinued, an alkaline diuresis was initiated, and the CK concentration declined to within normal limits by day 7 of treatment ².