New series #clarithromycin. Day 1. 1st macrolide antibiotic erythromycin was isolated from streptomyces erythraeus
in 1952. #clarithromycin is a semi-synthetic derivative, marketed in the 90s, with ↑ bioavailability, longer t½ & a superior ADR profile, especially re GI issues.
in 1952. #clarithromycin is a semi-synthetic derivative, marketed in the 90s, with ↑ bioavailability, longer t½ & a superior ADR profile, especially re GI issues.
(cont) #clarithromycin has greater lipophilicity allowing ↑ penetration into lung tissue & enhanced treatment of intracellular pathogens i.e. H. influenzae
Day 2: Indications #clarithromycin include upper & lower RTIs, H.pylori, penicillin alternative e.g otitis media, strep throat, skin & soft tissue infections & Lyme disease.Adult dose range oral 250-500mg x2 daily. Children > 1 month weight-dependent dose #prescribing
(cont). Bacterial resistance to 2nd generation macrolides such as clarithromycin is increasing; common mechanisms are upregulation of bacterial efflux pumps & reduced drug binding affinity e.g because of bacterial modification of the target ribosome unit.
Day 3:#clarithromycin kinetics; stable orally, good absorption, hepatic metabolism, renal excretion, t½ 3-7hrs depending on dose. More lipophilic compared to erythromycin/ ↑ volume of distribution. Inhibition CYP3A4 & p-glycoprotein, leading to multiple drug-drug interactions.
Day 4: #clarithromycin & active metabolite 14-OH clarithromycin interfere with bacterial protein synthesis. They bind to a part of the ribosome which inhibits peptide translation. Classed as bacteriostatic, can be ‘cidal’ depending on bacteria e.g S.pyogenes & drug concentration
Day 5: Common ADRs #clarithromycin; insomnia, headache, GI disturbance, rash. Serious; hepatitis, Stevens-Johnson syndrome, DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Contraindications: hypokalaemia, history cholestatic jaundice, QT prolongation (not exhaustive)
Day 6: #clarithromycin drug-drug interactions; CYP3A4 inducers e.g rifampicin can cause sub-therapeutic levels. ↑ effects of midazolam & warfarin. Inhibits statin b/down increasing risk of serious ADRs e.g myopathy.Digoxin more exposure (inhib PgP) + several other serious DDIs!
