DRUG INTERACTIONS
Theophylline
Erythromycin use in patients who are receiving high doses of
theophylline may be associated with an increase in serum theophylline levels
and potential theophylline toxicity. In case of theophylline toxicity and/or
elevated serum theophylline levels, the dose of theophylline should be reduced
while the patient is receiving concomitant erythromycin therapy.
There have been published reports suggesting that when oral
erythromycin is given concurrently with theophylline there is a significant
decrease in erythromycin serum concentrations of approximately 35 percent. The
mechanism by which this interaction occurs is unknown. The decrease in
erythromycin concentrations due to coadministration of theophylline could
result in subtherapeutic concentrations of erythromycin.
Hypotension, bradyarrhythmias, and lactic acidosis have been
observed in patients receiving concurrent verapamil, belonging to the calcium
channel blockers drug class.
Concomitant administration of erythromycin and digoxin has
been reported to result in elevated digoxin serum levels.
There have been reports of increased anticoagulant effects
when erythromycin and oral anticoagulants were used concomitantly. Increased
anticoagulation effects due to interactions of erythromycin with oral
anticoagulants may be more pronounced in the elderly.
Erythromycin is a substrate and inhibitor of the 3A isoform
subfamily of the cytochrome P450 enzyme system (CYP3A). Co-administration of
erythromycin and a drug primarily metabolized by CYP3A may be associated with
elevations in drug concentrations that could increase or prolong both the
therapeutic and adverse effects of the concomitant drug. Dosage adjustments may
be considered, and when possible, serum concentrations of drugs primarily
metabolized by CYP3A should be monitored closely in patients concurrently
receiving erythromycin.
The following are examples of some clinically significant
CYP3A based drug interactions. Interactions with other drugs metabolized by the
CYP3A isoform are also possible. The following CYP3A based drug interactions
have been observed with erythromycin products in post-marketing experience:
Ergotamine/dihydroergotamine
Post-marketing reports indicate
that co-administration of erythromycin with ergotamine or dihydroergotamine has
been associated with acute ergot toxicity characterized by vasospasm and
ischemia of the extremities and other tissues including central nervous system.
Concomitant administration of erythromycin with ergotamine or dihydroergotamine
is contraindicated (see CONTRAINDICATIONS).
Triazolobenzodiazepines (such as triazolam and alprazolam)
and related benzodiazepines Erythromycin has been reported to decrease the
clearance of triazolam and midazolam, and thus, may increase the pharmacologic
effect of these benzodiazepines.
HMG-CoA Reductase Inhibitors
Erythromycin has been reported to increase concentrations of
HMG-CoA reductase inhibitors (for example, lovastatin and simvastatin). Rare
reports of rhabdomyolysis have been reported in patients taking these drugs
concomitantly.
Sildenafil (Viagra)
Erythromycon has been reported to increase the systemic
exposure (AUC) of sildenafil. Reduction of sildenafil dosage should be
considered. (See Viagra package insert.)
There have been spontaneous or published reports of CYP3A
based interactions of erythromycin with carbamazepine, cyclosporine, tacrolimus, alfentanil, disopyramide, bromocriptine, rifabutin, quinidine
methylprednisolone, cilostazol, and vinblastine.
Concomitant administration of erythromycin with cisapride,
pimozide, astemizole, or terfenadine is contraindicated (see CONTRAINDICATIONS).
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/QTc 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 coadministered 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).
Colchicine
Colchicine is a substrate for both CYP3A4 and the efflux
transporter P-glycoprotein (Pgp). Erythromycin is considered a moderate
inhibitor of CYP3A4. A significant increase in colchicine plasma concentration
is anticipated when co-administered with moderate CYP3A4 inhibitors such as
erythromycin. If co-administration of colchicine and erythromycin is necessary,
the starting dose of colchicine may need to be reduced, and the maximum
colchicine dose should be lowered. Patients should be monitored for clinical symptoms
of colchicine toxicity (see WARNINGS).
Drug/Laboratory test interactions
Erythromycin interferes with the fluorometric determination
of urinary catecholamines.