Dirithromycin

(BAN, USAN, rINN)
Dirithromycin Chemical formula
Synonyms: ASE-136BS; Dirithromycine; Dirithromycinum; Diritromicin; Diritromicina; Diritromicinas; Diritromisin; Diritromycin; Diritromysiini; LY-237216. (1R,2R,3R,6R,7S,8S,9R,10R,12R,13S,15R,17S)7-(2,6-Dideoxy-3C,3O-dimethyl3-ethyl-2,10-dihydroxy-15(2-methoxyethoxymethyl)2,6,8,10,12,17-hexamethyl-9-(3,4,6-trideoxy-3-dimethylaminolo[11.3.1]heptadecan-5-one; (9S)-9-Deoxo-11-deoxy-9,11-{imino[(1R)-2-(2-methoxyethoxy)-ethylidene]oxy}erythromycin.
Cyrillic synonym: Диритромицин.

💊 Chemical information

Chemical formula: C42H78N2O14 = 835.1.
CAS — 62013-04-1.
ATC — J01FA13.
ATC Vet — QJ01FA13.

Pharmacopoeias.

In Eur. and US.

Ph. Eur. 6.2

(Dirithromycin). A white or almost white powder. It exhibits polymorphism. Very slightly soluble in water; very soluble in dichloromethane and in methyl alcohol.

USP 31

(Dirithromycin). A white or practically white powder. Very slightly soluble in water; very soluble in dichloromethane and in methyl alcohol.

💊 Adverse Effects and Precautions

As for Erythromycin. The most frequent adverse effects of dirithromycin are gastrointestinal disturbances; headache has also occurred. Dirithromycin should be used with caution in patients with moderate to severe hepatic impairment since its active metabolite erythromycylamine is primarily eliminated in the bile. It should also be used with caution in those with severe renal impairment.

💊 Interactions

For a discussion of drug interactions of macrolide antibacterials, see Erythromycin.

Cytochrome P450 isoenzymes.

Dirithromycin is reported to have little or no effect on hepatic cytochrome P450 isoenzymes and may therefore produce fewer interactions than erythromycin with other drugs metabolised by this enzyme system. The lack of interactions between dirithromycin and theophylline, terfenadine, or warfarin would appear to support this.

💊 Antimicrobial Action

As for Erythromycin. Dirithromycin is reported to be generally less active than erythromycin in vitro, but may show greater activity in vivo than is indicated by in-vitro studies and may exert a postantibiotic effect.

💊 Pharmacokinetics

Dirithromycin is readily absorbed after oral doses and undergoes rapid non-enzymatic hydrolysis to its active metabolite erythromycylamine. Absorption is enhanced by food. Bioavailability is about 10%. Daily doses of dirithromycin 500 mg produce peak plasma concentrations of erythromycylamine of about 400 nanograms/mL. Erythromycylamine is widely distributed and tissue concentrations exceed those in plasma. Protein binding is 15 to 30%. Erythromycylamine is mainly excreted unchanged in the bile with only about 2% in the urine. The mean plasma half-life is about 8 hours and the mean urinary terminal elimination half-life is about 44 hours. Distribution into milk has been found in studies in rodents.
1. Sides GD, et al. Pharmacokinetics of dirithromycin. J Antimicrob Chemother 1993; 31 (suppl C): 65–75
2. LaBreque D, et al. Pharmacokinetics of dirithromycin in patients with impaired hepatic function. J Antimicrob Chemother 1993; 32: 741–50
3. Mazzei T, et al. Pharmacokinetics of dirithromycin in patients with mild or moderate cirrhosis. Antimicrob Agents Chemother 1999; 43: 1556–9.

💊 Uses and Administration

Dirithromycin is a prodrug of the macrolide antibacterial erythromycylamine, which has similar properties to those of erythromycin and is used in respiratory-tract, skin, and soft-tissue infections caused by susceptible organisms. Dirithromycin is given orally as enteric-coated tablets in a usual dose of 500 mg once daily.
1. Various. Dirithromycin: a new once-daily macrolide. J Antimicrob Chemother 1993; 31 (suppl C): 1–185
2. Brogden RN, Peters DH. Dirithromycin: a review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 48: 599–616
3. Wintermeyer SM, et al. Dirithromycin: a new macrolide. Ann Pharmacother 1996; 30: 1141–9
4. McConnell SA, Amsden GW. Review and comparison of advanced-generation macrolides clarithromycin and dirithromycin. Pharmacotherapy 1999; 19: 404–15.

💊 Preparations

USP 31: Dirithromycin Delayed-Release Tablets.

Proprietary Preparations

Belg.: Unibac†; Chile: Dynabac†; Fr.: Dynabac; Gr.: Dynabac†; Malaysia: Dynabac†; Turk.: Dynabac; USA: Dynabac†.
Published February 03, 2019.