EU Conference: Workshop #6 Macrolide Indications: •Ocular Infections •Stomatologic Infections •Digestive tract Infections •Skin & Soft Tissue Infections(SSTI) Dr. S. Simonian (NL) © CBG-MEB 1 Introduction • Problem statement: – What is the (un-)labelled use of individual macrolides in ocular, stomatologic, GI and SSTI infections? – What is the ultimate list of practical indications in these areas? • Approach: – Review information documented in data sheets & clinical literature. – From current global situation to agreed ----> by reconciliation of clinical experience with regulatory process----> state of the art indications. Focus will be primarily on systemic macrolides. © CBG-MEB 2 General Indications Ocular infections 1 ? Conjunctivitis (neonatal) C. trachomatis 2 ? Blepharitis Staphylococcal Stomatologic infections Eikenella corrodens? ? Periodontal disease3 Streptococci spp. Digestive tract infections HP peptic ulcer H. pylori* CJ Acute enteritis4 C. jejuni Cholecystitis5 SSTI Acne P. acnes Impetigo, erysipelas Streptococci spp. Furuncles, abcesses S. aureus Lyme disease?? B. burgdorferi Bartonella infections in HIV-patients ? Unlabelled use Questionable * In combination with PPI and other ?? antibiotics (eg. amoxicillin) As unlabelled alternative to beta-lactams and tetracyclines in early Lyme disease. As second-line in case tetracyline is inappropriate. © CBG-MEB 3 Indication status: Labelled(!), unlabelled & in research Ery Rox Clar Azit Telit Jos Spir Ocular infections Conjunctivitis(of the newborn) ! Blepharitis ! Trachoma RD Stomatologic infections ! !* !* !* !! Periodontal disease ! RD Digestive tract infections HP peptic ulcer RD ! RD CJ Acute enteritis ! RD ! ….Cholecystitis SSTI Acne ! !* ! !* Impetigo, erysipelas ! ! ! ! ! ! Furuncles, abcesses ! ! ! ! ! ! Lyme disease RD RD RD ! Bartonella infections in HIV-patients RD Ery: erythromycin; Rox: roxithromycin; Clar: clarithromycin; Azit: azithromycin; Telit: telithromycin; Jos : josamycin; Spir : spiramycin. Dirithromycin & Miocamycin are not shown in the table, they are registered only in a few MSs (with limited indications). Questionable. Underlined in Red indicates: drug not registered in all EU MSs. As second-line in case tetracyline is inappropriate. RD: investigational. * in a few MSs. © CBG-MEB 4 Criteria for Deriving Practical Indications • Availability according to registration status: – Drugs registered throughout the entire EU ie. Erythromycin, clarithromycin & azithromycin. – Drugs registered in some EU countries ie. Roxithromycin, josamycin, spiramycin, dirithromycin*, miocamycin* • Evidence based up-to-date indications, taking into account resistance issues. • Efficacy/safety ratio of dosage regimen. • Justified changes in labelling with due respect to regulatory criteria, patent and liability issues. (* in a few MSs) © CBG-MEB 5 Practical Indications Ery Clar Azit Rox Jos Spir Ocular infections Conjunctivitis (of the newborn) ! (ophthalmic formulation) Stomatologic infections ??! Digestive tract infections HP peptic ulcer ! severe CJ Acute enteritis (eg. ! immunocompromised patients) SSTI (mild to moderately severe) ! Acne ! ? ? ? Impetigo, erysipelas ! ! ! ! ! ! Furuncles, abcesses ! ! ! ! ! ! Bartonella infections in HIV-patients ! Ery: erythromycin; Clar: clarithromycin; Azit: azithromycin; Rox: roxithromycin; Jos : josamycin; Spir : spiramycin. Telithromycin (Telit), Dirithromycin & Miocamycin are not shown in the table because they do not have the named indications (Telit) or .registered only in a few MSs (the latter two agents) Questionable. As second- line in case tetracyline is inappropriate. ?: The evidence is unclear. © CBG-MEB 6 Conclusions • The heterogeneity in registration status as to product and indications and available evidence of efficacy and safety (partly due to clinical trial programme) pose an important regulatory and liability barrier for harmonisation throughout the EU. • Harmonisation of selected practical (eg. SSTI) non-controversial indications is foreseeable for individual macrolides in the countries where they are marketed and for erythromycin in all EU countries. Appropriate posology needs to be agreed upon. • Due consideration should be given to regional resistance prevalence especially in infections caused by Staphylococci, Streptococci, C. jejuni, H. pylori in justified indications. © CBG-MEB 7.