a few articles have come out on statins recently. one in the annals of internal medicine assessed toxicity in patients on macrolide antibiotics. the issue here is that 3 statins (atorvastatin, simvastatin, lovastatin) are metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4), as are clarithromycin and erythromycin (but not azithromycin). studies in healthy volunteers show that taking clarithro or erythro lead to 10-fold serum increases in simvastatin and lovastatin levels and 4-fold increase in atorvastatin. in this setting, and since statin toxicity is greatest in older individuals, a large population-based cohort study was done in Ontario, looking at all people >65yo on statins and prescribed erythro (done minimally), clarithro and azithro (see doi:10.7326/0003-4819-158-12-201306180-00004). results:
–75K people on combo of statin and clarithro or erythro, 65K on azithro between 2003-2010
–clarithro/erythro assoc with
–2-fold increased risk of hospitalization with rhabdomyolysis (though only an absolute increased risk of 0.02%) — as a reference here, baseline risk of rhabdo for all ages is 0.5-1/10K person-yrs, though higher in older people
–78% increase in acute kidney injury (1.3% absolute increase risk)
–56% increased all-cause mortality (0.25% absolute increase)
so, this suggests a few things:
-either avoid clarithro/erythro in those on these statins, or hold the statin therapy during short course of these antibiotics. consider using azithro as alternative (my guess is that one of the more common usages of clarithro now is in treating h. pylori infections. clarithro has been tested in many studies on hpylori treatment. there are some intriguing but limited data on azithro, including the fact that azithro 500mg on an empty stomach maintains tissue levels of the antibiotic for many days, with one study finding a 3-day course of PPI plus tinidazole 1000-2000mg, and azithro 500 had a 85% cure rate (other data are less impressive, though may be related to azithro being taken with food, which decreases its blood levels). at this point, i would still stay with clarithro, given the abundance of studies.
-the CYP3A4 issue also applies to other drugs, including several of the HIV meds, which affects which statin to use (and given that HIV is now more of a chronic disease with long life-expectancy though a higher risk of heart disease, statins are frequently prescribed)
-one confusing issue is that non-CYP3A4 metabolized statins (eg rosuvastatin) still seems to have some drug-drug interactions with the HIV meds. i have a patient with diabetes and essentially every cardiac risk factor known plus HIV. the preferred statin is pravastatin (though not strong enough for this patient), so i started rosuvastatin after speaking with HIV pharmacologist, but was told to give only 1/2 the dose since ritonivir doubles the rosuvastatin serum level. i raise this just to show that the whole situation is more complex than just the P-450 metabolism.
geoff