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ERYTHROMYCIN
DIR Classification
Classification:Most-DIR concern
Severity Score:4
Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF
- WARNINGS
- QT Prolongation
- Erythromycin 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 erythromycin. Fatalities have been reported. Erythromycin should be avoided in patients with known prolongation of the QT interval, 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.
- PRECAUTIONS
- Drug Interactions
- In addition, there have been reports of interactions of erythromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate.
- Erythromycin has been reported to significantly alter the metabolism of the nonsedating antihistamines terfenadine and astemizole when taken concomitantly. Rare cases of serious cardiovascular adverse events, including electrocardiographic QT/QT c interval prolongation, cardiac arrest, torsades de pointes, and other ventricular arrhythmias have been observed. (See CONTRAINDICATIONS.) In addition, deaths have been reported rarely with concomitant administration of terfenadine and erythromycin.
- There have been post-marketing reports of drug interactions when erythromycin was co-administered with cisapride, resulting in QT prolongation, cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation, and torsades de pointes, most likely due to the inhibition of hepatic metabolism of cisapride by erythromycin. Fatalities have been reported. (See CONTRAINDICATIONS.)
- ADVERSE REACTIONS
- Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes. (See WARNINGS).
Postmarketing Surveillance
Contingency Table:
Current Drug
Other Drugs
Rhabdomyolysis
48
42864
Other ADRs
2964
14114315
Odds Ratio = 5.333
Drug Property Information
ATC Code(s):
- D10AF52 - erythromycin
- D10AF - Antiinfectives for treatment of acne
- D10A - ANTI-ACNE PREPARATIONS FOR TOPICAL USE
- D10 - ANTI-ACNE PREPARATIONS
- D - DERMATOLOGICALS
- D10AF02 - erythromycin
- D10AF - Antiinfectives for treatment of acne
- D10A - ANTI-ACNE PREPARATIONS FOR TOPICAL USE
- D10 - ANTI-ACNE PREPARATIONS
- D - DERMATOLOGICALS
- J01FA01 - erythromycin
- J01FA - Macrolides
- J01F - "MACROLIDES, LINCOSAMIDES AND STREPTOGRAMINS"
- J01 - ANTIBACTERIALS FOR SYSTEMIC USE
- J - ANTIINFECTIVES FOR SYSTEMIC USE
- S01AA17 - erythromycin
- S01AA - Antibiotics
- S01A - ANTIINFECTIVES
- S01 - OPHTHALMOLOGICALS
- S - SENSORY ORGANS
Active Ingredient:erythromycin
Active Ingredient UNII:63937KV33D
Drugbank ID:DB00199
PubChem Compound:12560
CAS Number:114-07-8
Dosage Form(s):capsule, coated pellets
Route(s) Of Administrator:oral
Daily Dose:
- 1000.0 mg/day J01FA01
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)O)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)O)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.
OTHER REFERENCE(S):
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[Patel Amit M,Shariff Salimah,Bailey David G,Juurlink David N,Gandhi Sonja,Mamdani Muhammad,Gomes Tara,Fleet Jamie,Hwang Y Joseph,Garg Amit X]Ann Intern Med.2013 Jun 18;158(12):869-76. doi: 10.7326/0003-4819-158-12-201306180-00004. PMID: 23778904
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