Interaction Potential between Clarithromycin and Individual Statins - a Systematic Review

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftBasic & Clinical Pharmacology & Toxicology Online
Antal sider11
ISSN1742-7843
DOI
StatusE-pub ahead of print - 11. okt. 2019

Fingeraftryk

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Clarithromycin
Pravastatin
Lovastatin
Area Under Curve
Simvastatin
Cytochrome P-450 CYP3A
Rhabdomyolysis
Azithromycin
Muscular Diseases
Drug Combinations
Drug-Related Side Effects and Adverse Reactions
Drug Interactions
PubMed
Cohort Studies
Language
Pharmacokinetics
Guidelines
Liver

Emneord

  • miniReview
  • case report
  • clarithromycin
  • drug-drug interaction
  • statins

Citer dette

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title = "Interaction Potential between Clarithromycin and Individual Statins - a Systematic Review",
abstract = "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.",
keywords = "miniReview, case report, clarithromycin, drug-drug interaction, statins",
author = "Christensen, {Mette Marie} and Haastrup, {Maija Bruun} and Thomas {\O}hlenschl{\ae}ger and Peter Esbech and Pedersen, {Sidsel Arnspang} and Ann-Cathrine Dunvald and Stage, {Tore Bjerregaard} and Henriksen, {Daniel Pilsgaard} and Pedersen, {Andreas James Thestrup}",
note = "{\circledC} 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).",
year = "2019",
month = "10",
day = "11",
doi = "10.1111/bcpt.13343",
language = "English",
journal = "Basic & Clinical Pharmacology & Toxicology",
issn = "1742-7835",
publisher = "Wiley-Blackwell",

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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 - 2019/10/11

Y1 - 2019/10/11

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

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DO - 10.1111/bcpt.13343

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JO - Basic & Clinical Pharmacology & Toxicology

JF - Basic & Clinical Pharmacology & Toxicology

SN - 1742-7835

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