Dosing but not coating affected gastrointestinal side effects of oral erythromycin
ACP J Club. 1991 Jan-Feb;114:15. doi:10.7326/ACPJC-1991-114-1-015
Ellsworth AJ, Christensen DB, Volpone-McMahon MT. Prospective comparison of patient tolerance to enteric-coated vs nonenteric-coated erythromycin. J Fam Pract. 1990;31:265-70. [PubMed ID: 2202773]
To compare the gastrointestinal side effects of 2 oral erythromycin preparations in outpatients.
Randomized, unblinded, controlled trial with follow-up of 7 to 14 days.
University-based family medicine clinic.
368 patients (mean age 35 y) were enrolled, of whom 357 (97%) were analyzed. [No information was reported about how many patients declined participation.]
Patients prescribed erythromycin in doses of 250 mg or 500 mg by their physicians were randomized to receive nonenteric-coated tablets (Erythromycin Base Film-tabs, Abbott) (n = 179) or enteric-coated erythromycin capsules (Eryc, Parke-Davis) (n = 178). Each dose was to be taken 4 times daily on an empty stomach for 7 to 14 days.
Main outcome measures
Gastrointestinal side effects and compliance were assessed by patient diary and by telephone interviews at days 3 and 7 of therapy.
Minimal differences were found in the incidence of side effects (nausea, vomiting, diarrhea, gas, abdominal cramps, and abdominal pain) when the 2 product formulations were compared at equal doses. However, patients taking 2 g/day reported most side effects more frequently than those taking 1 g/day at both day 3 and day 7 (P < 0.01) regardless of the product they took. The dropout rate was also greater in the 2 g/day group (6% vs 0%, P < 0.01). Compliance, measured by telephone interview, log, and pill count, did not differ between products but was less in the 2 g/day group (82% to 83%) than the 1 g/day (> 90%) group (P < 0.05). 30% to 40% of patients in the various groups did not follow instructions to take medication on an empty stomach.
Gastrointestinal side effects were similar for an enteric-coated and noncoated erythromycin preparation for equal dose sizes but were more frequent for 2 g/day than 1 g/day. Compliance for pill taking was high, but many patients failed to take pills on an empty stomach.
Source of funding: Parke-Davis.
Address for article reprint: Dr. A. Ellsworth, Family Medical Centre, UWMC-Roosevelt, Pharmacy and Family Medicine, Seattle, WA 98195, USA. FAX 206-598-5769.
Erythromycin is an extremely useful antibiotic in primary care and referral internal medicine. Given the acceptable absorption of the oral form and the expense and more serious side effects of the parenteral form (gastrointestinal plus phlebitis and, rarely, deafness  ), the oral form is preferred when possible.
The proliferation of oral erythromycin products (presently 17 on the Canadian market ) has been related primarily to claims of superior gastrointestinal tolerability. This study supports what many have suspected all along. The incidence of side effects is dose-related, and it is unlikely that the more expensive, "exotic" formulations, such as Eryc, have any clinically important advantage in terms of their predisposition to cause gastrointestinal distress.
The high pill compliance rates in the study may be inflated by the self-report methods of measuring them (3) or by the telephone monitoring of side effects and compliance. Of potential concern is the lower rates of compliance with instructions to take the medication on an empty stomach. This would presumably affect the absorption of the nonenteric-coated form more than that of the enteric-coated one. However, previous work (4) suggests that bioavailability differences have not been shown to affect therapeutic outcomes.
Anne Holbrook, PharmD, MD
McMaster UniversityHamilton, Ontario, Canada