Medications> Gastroparesis>

INDICATIONS

• Multiple anti-infective indications

• Diabetic gastroparesis (low dose erythromycin)

MECHANISM

• Enhances gastrointestinal motility especially during the between-meal period, probably due to agonism at the motilin receptors, which are found mainly in the gastric antrum and proximal duodenum.
• Increases gastric emptying.

USUAL ADULT DOSING

• Diabetic gastroparesis: 150 to 250 mg PO 3 to 4 times per day, 30 minutes before meals.

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

• Usual dose

• Category B

• Excreted in breast milk. American Academy of Pediatrics considers erythromycin to be compatible with breast feeding

ADVERSE DRUG REACTIONS

• GI side effects are dose related; therefore, erythromycin dose should be titrated based on clinical response and side effects.

• GI: abdominal pain, diarrhea, loss of appetite, nausea, vomiting

• GI: LFTs elevation, acquired hypertrophic pyloric stenosis, pseudomembranous enterocolitis secondary to Clostridium difficile.
• Rash (reversible)
• Cardiac: prolonged QTc (generally observed with high dose IV or co-administration of erythromycin with potent CYP3A4 inhibitor)
• Ototoxicity (generally observed with high dose IV)

• Pancreatitis
• Dermatologic: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
• Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome have been reported.
• Cholestatic hepatitis (1:1000 especially with estolate salt formulation, reversible)
• Torsades de pointes (especially in women)

DRUG INTERACTIONS

• Erythromycin is a substrate and known inhibitor of cytochrome P450-3A4and 1A2 ; there are multiple drug-drug interactions and ANY CYP3A4 substrate will be significantly increased with erythromycin co-administration. Potent inhibitors of CYP3A4 (e.g HIV protease inhibitors, azole antifungal) will significantly increase erythromycin concentrations and should be avoided.
• Cisapride, terfenadine, astemizole, pimozide, ergot alkaloids and ziprasidone co-administration with erythromycin is contraindicated.
• Some statins (simvastatin, lovastatin) should be avoided due to increased risk of myopathy and rhabdomyolysis; atorvastatin, pravastatin, and rosuvastatin can be considered with close monitoring.
• Colchicine, digoxin, diltiazem, verapamil, amiodarone, cyclosporine, tacrolimus, sirolimus, corticosteroid, buprenorphine, buspirone, and theophylline serum concentrations may be increased with erythromycin co-administration; use with close monitoring.
• Carbamazepine, clozapine, diazepam, sertraline, ranolazine, and tramadol serum concentrations may be increased.; avoid co-administration or use with caution.
• Midazolam and fentanyl: Avoid co-administration; severe sedation and respiratory depression have been reported with co-administration.
• Calcium channel blockers (e.g diltiazem, amlodipine, nifedipine): serum concentration may be increased.; lower calcium channel blocker dose may be needed.

PHARMACOKINETIC

COMMENTS

• Commonly used as a chronic treatment for gastroparesis, but should be used with caution in the elderly and those with comorbid conditions.
• Checking for drug-drug interaction is critical before using erythromycin.
• May reduce fasting glucose levels in patients with type 2 diabetes but the mechanism is unclear.

REFERENCES

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