TY - JOUR
T1 - Interaction Potential between Clarithromycin and Individual Statins - a Systematic Review
AU - Christensen, Mette Marie
AU - Haastrup, Maija Bruun
AU - Øhlenschlæger, Thomas
AU - Esbech, Peter
AU - Pedersen, Sidsel Arnspang
AU - Dunvald, Ann-Cathrine
AU - Stage, Tore Bjerregaard
AU - Henriksen, Daniel Pilsgaard
AU - Pedersen, Andreas James Thestrup
N1 - © 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
PY - 2020/4
Y1 - 2020/4
N2 - The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence base for drug-drug interactions between clarithromycin and currently marketed statins and to present management strategies for these drug combinations. We conducted a systematic literature review following PRISMA guidelines with English language studies retrieved from PubMed and EMBASE (from inception through March 2019). We included 29 articles (16 case reports, 5 observational, 5 clinical pharmacokinetic and 3 in vitro studies). Based on mechanistic/clinical studies involving clarithromycin or the related macrolide erythromycin (both strong inhibitors of CYP3A4 and of hepatic statin uptake transporters OATP1B1 and OATP1B3), clarithromycin is expected to substantially increase systemic exposure to simvastatin and lovastatin (>5-fold increase in area under the plasma concentration time curve (AUC)), moderately increase AUCs of atorvastatin and pitavastatin (2-4-fold AUC increase) and slightly increase pravastatin exposure (≈ 2-fold AUC increase) while having little effect on fluvastatin or rosuvastatin. The 16 cases of statin-clarithromycin adverse drug reactions (rhabdomyolysis (n = 14) or less severe clinical myopathy) involved a CYP3A4-metabolized statin (simvastatin, lovastatin or atorvastatin). In line, a cohort study found concurrent use of clarithromycin and CYP3A4-metabolized statins to be associated with a doubled risk of hospitalisation with rhabdomyolysis or other statin-related adverse events as compared with azithromycin-statin co-administration. If clarithromycin is necessary, we recommend 1) avoiding co-administration with simvastatin, lovastatin or atorvastatin; 2) withholding or dose-reducing pitavastatin; 3) continuing pravastatin therapy with caution, limiting pravastatin dose to 40 mg daily and 4) continuing fluvastatin or rosuvastatin with caution.
AB - The high prevalence of statin and clarithromycin utilization creates potential for overlapping use. The objectives of this MiniReview were to investigate the evidence base for drug-drug interactions between clarithromycin and currently marketed statins and to present management strategies for these drug combinations. We conducted a systematic literature review following PRISMA guidelines with English language studies retrieved from PubMed and EMBASE (from inception through March 2019). We included 29 articles (16 case reports, 5 observational, 5 clinical pharmacokinetic and 3 in vitro studies). Based on mechanistic/clinical studies involving clarithromycin or the related macrolide erythromycin (both strong inhibitors of CYP3A4 and of hepatic statin uptake transporters OATP1B1 and OATP1B3), clarithromycin is expected to substantially increase systemic exposure to simvastatin and lovastatin (>5-fold increase in area under the plasma concentration time curve (AUC)), moderately increase AUCs of atorvastatin and pitavastatin (2-4-fold AUC increase) and slightly increase pravastatin exposure (≈ 2-fold AUC increase) while having little effect on fluvastatin or rosuvastatin. The 16 cases of statin-clarithromycin adverse drug reactions (rhabdomyolysis (n = 14) or less severe clinical myopathy) involved a CYP3A4-metabolized statin (simvastatin, lovastatin or atorvastatin). In line, a cohort study found concurrent use of clarithromycin and CYP3A4-metabolized statins to be associated with a doubled risk of hospitalisation with rhabdomyolysis or other statin-related adverse events as compared with azithromycin-statin co-administration. If clarithromycin is necessary, we recommend 1) avoiding co-administration with simvastatin, lovastatin or atorvastatin; 2) withholding or dose-reducing pitavastatin; 3) continuing pravastatin therapy with caution, limiting pravastatin dose to 40 mg daily and 4) continuing fluvastatin or rosuvastatin with caution.
KW - miniReview
KW - case report
KW - clarithromycin
KW - drug-drug interaction
KW - statins
U2 - 10.1111/bcpt.13343
DO - 10.1111/bcpt.13343
M3 - Journal article
C2 - 31628882
SN - 1742-7835
VL - 126
SP - 307
EP - 317
JO - Basic & Clinical Pharmacology & Toxicology
JF - Basic & Clinical Pharmacology & Toxicology
IS - 4
ER -