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CLARITHROMYCIN
DIR Classification
Classification:Moderate-DIR concern
Severity Score:3
Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF
- WARNINGS AND PRECAUTIONS
- QT Prolongation
- Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin. Fatalities have been reported.
- Avoid clarithromycin in the following patients:
- patients with known prolongation of the QT interval, ventricular cardiac arrhythmia, including torsades de pointes
- patients receiving drugs known to prolong the QT interval [see also Contraindications (4.2)]
- patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.
- Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Use in Specific Populations (8.5)] .
- [Serious Adverse Reactions Due to Concomitant Use with Other Drugs]
- Quetiapine: Use quetiapine and clarithromycin concomitantly with caution. Co-administration could result in increased quetiapine exposure and quetiapine related toxicities such as somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation. Refer to quetiapine prescribing information for recommendations on dose reduction if co-administered with CYP3A4 inhibitors such as clarithromycin [see Drug Interactions (7)] .
- DRUG INTERACTIONS
- Procainamide Not Recommended Disopyramide, Quinidine: There have been postmarketing reports of torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QTc prolongation during coadministration of clarithromycin with these drugs [see Warnings and Precautions (5.3)] .
- Serum concentrations of these medications should also be monitored. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with disopyramide and quinidine.
- Quetiapine Quetiapine: Quetiapine is a substrate for CYP3A4, which is inhibited by clarithromycin. Co-administration with clarithromycin could result in increased quetiapine exposure and possible quetiapine related toxicities. There have been postmarketing reports of somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation during concomitant administration. Refer to quetiapine prescribing information for recommendations on dose reduction if co-administered with CYP3A4 inhibitors such as clarithromycin.
- CONTRAINDICATIONS
- Cardiac Arrhythmias
- Concomitant administration of clarithromycin with cisapride and pimozide is contraindicated [see Drug Interactions (7)] .
- There have been postmarketing reports of drug interactions when clarithromycin is co-administered with cisapride or pimozide, resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) most likely due to inhibition of metabolism of these drugs by clarithromycin. Fatalities have been reported.
- ADVERSE REACTIONS
- QT Prolongation [see Warnings and Precautions (5.2)]
- Cardiac Disorders: Electrocardiogram QT prolonged, cardiac arrest, atrial fibrillation, extrasystoles, palpitations
Postmarketing Surveillance
Contingency Table:
Current Drug
Other Drugs
Rhabdomyolysis
326
42586
Other ADRs
15471
14101808
Odds Ratio = 6.978
Drug Property Information
ATC Code(s):
- A02BD05 - clarithromycin
- A02BD - Combinations for eradication of Helicobacter pylori
- A02B - DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 - DRUGS FOR ACID RELATED DISORDERS
- A - ALIMENTARY TRACT AND METABOLISM
- A02BD06 - clarithromycin
- A02BD - Combinations for eradication of Helicobacter pylori
- A02B - DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 - DRUGS FOR ACID RELATED DISORDERS
- A - ALIMENTARY TRACT AND METABOLISM
- A02BD07 - clarithromycin
- A02BD - Combinations for eradication of Helicobacter pylori
- A02B - DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 - DRUGS FOR ACID RELATED DISORDERS
- A - ALIMENTARY TRACT AND METABOLISM
- A02BD04 - clarithromycin
- A02BD - Combinations for eradication of Helicobacter pylori
- A02B - DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 - DRUGS FOR ACID RELATED DISORDERS
- A - ALIMENTARY TRACT AND METABOLISM
- A02BD11 - clarithromycin
- A02BD - Combinations for eradication of Helicobacter pylori
- A02B - DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 - DRUGS FOR ACID RELATED DISORDERS
- A - ALIMENTARY TRACT AND METABOLISM
- A02BD09 - clarithromycin
- A02BD - Combinations for eradication of Helicobacter pylori
- A02B - DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REFLUX DISEASE (GORD)
- A02 - DRUGS FOR ACID RELATED DISORDERS
- A - ALIMENTARY TRACT AND METABOLISM
- J01FA09 - clarithromycin
- J01FA - Macrolides
- J01F - "MACROLIDES, LINCOSAMIDES AND STREPTOGRAMINS"
- J01 - ANTIBACTERIALS FOR SYSTEMIC USE
- J - ANTIINFECTIVES FOR SYSTEMIC USE
Active Ingredient:clarithromycin
Active Ingredient UNII:H1250JIK0A
Drugbank ID:DB01211
PubChem Compound:84029
CAS Number:81103-11-9
Dosage Form(s):tablet, film coated, extended release
Route(s) Of Administrator:oral
Daily Dose:
- 500.0 mg/day J01FA09
Chemical Structure: 
SMILE Code:
CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)O)(C)O
CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)O)(C)O
Reference
COHORT STUDY:
1: Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study.
[Patel AM, Shariff S, Bailey DG, Juurlink DN, Gandhi S, Mamdani M, Gomes T, Fleet J, Hwang YJ, Garg AX, Ann Intern Med. 2013 Jun 18;158(12):869-76.]ABSTRACT
BACKGROUND: Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations of statins that are metabolized by CYP3A4.
OBJECTIVE: To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin.
DESIGN: Population-based cohort study.
SETTING: Ontario, Canada, from 2003 to 2010.
PATIENTS: Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72,591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68,478).
MEASUREMENTS: The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription.
RESULTS: Atorvastatin was the most commonly prescribed statin (73%) followed by simvastatin and lovastatin. Compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis (absolute risk increase, 0.02% [95% CI, 0.01% to 0.03%]; relative risk [RR], 2.17 [CI, 1.04 to 4.53]) or with acute kidney injury (absolute risk increase, 1.26% [CI, 0.58% to 1.95%]; RR, 1.78 [CI, 1.49 to 2.14]) and for all-cause mortality (absolute risk increase, 0.25% [CI, 0.17% to 0.33%]; RR, 1.56 [CI, 1.36 to 1.80]).
LIMITATIONS: Only older adults were included in the study. The absolute risk increase for rhabdomyolysis may be underestimated because the codes used to identify it were insensitive.
CONCLUSION: In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity.
PMID: 23778904
OBJECTIVE: To measure the frequency of statin toxicity after coprescription of a statin with clarithromycin or erythromycin.
DESIGN: Population-based cohort study.
SETTING: Ontario, Canada, from 2003 to 2010.
PATIENTS: Continuous statin users older than 65 years who were prescribed clarithromycin (n = 72,591) or erythromycin (n = 3267) compared with those prescribed azithromycin (n = 68,478).
MEASUREMENTS: The primary outcome was hospitalization with rhabdomyolysis within 30 days of the antibiotic prescription.
RESULTS: Atorvastatin was the most commonly prescribed statin (73%) followed by simvastatin and lovastatin. Compared with azithromycin, coprescription of a statin with clarithromycin or erythromycin was associated with a higher risk for hospitalization with rhabdomyolysis (absolute risk increase, 0.02% [95% CI, 0.01% to 0.03%]; relative risk [RR], 2.17 [CI, 1.04 to 4.53]) or with acute kidney injury (absolute risk increase, 1.26% [CI, 0.58% to 1.95%]; RR, 1.78 [CI, 1.49 to 2.14]) and for all-cause mortality (absolute risk increase, 0.25% [CI, 0.17% to 0.33%]; RR, 1.56 [CI, 1.36 to 1.80]).
LIMITATIONS: Only older adults were included in the study. The absolute risk increase for rhabdomyolysis may be underestimated because the codes used to identify it were insensitive.
CONCLUSION: In older adults, coprescription of clarithromycin or erythromycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity.
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The content of this database of rhabdomyolysis is intended for educational and scientific research purposes only. It is not intended as a substitute for professional medical advice, diagnosis or treatment.
The views presented in this website do not necessarily reflect current or future opinion or policy of the US Food and Drug Administration. Any mention of commercial products is for clarification and not intended as endorsement.