Volume 184 - Issue 6
Pharmaceutical Benefits Scheme limitations on macrolides: implications for pertussis management
Authors: Kari A J Jarvinen, Bradley J McCall, Clare B Nourse, Joe G McCormack and Martyn H Tilse
Med J Aust 2006; 184 (6): 309. || doi: 10.5694/j.1326-5377.2006.tb00251.x
Published online: 20 March 2006
Published online: 20 March 2006
Kari A J Jarvinen,* Bradley J McCall,† Clare B Nourse,‡ Joe G McCormack,§ Martyn H Tilse¶
* Senior Public Health Registrar, † Public Health Medical Officer, Communicable Disease Control, Brisbane Southside Public Health Unit, 39 Kessels Road, Coopers Plains, QLD 4108; ‡ Paediatric Infectious Diseases Physician, § Director of Infectious Diseases, ¶ Director of Microbiology, Mater Health Services, South Brisbane, QLD. kari_jarvinenAThealth.qld.gov.au
To the Editor: Pertussis continues to be a significant public health problem in Australia. Children aged under 1 year are most at risk from severe, life-threatening complications from the disease.1 Traditionally, erythromycin has been the drug of choice for treatment of cases and prophylaxis in selected contacts. However, its use in neonates is known to carry a risk of infantile hypertrophic pyloric stenosis.1,2 Its propensity to cause QT prolongation and ventricular arrhythmias is also well described.2,3
Both azithromycin and clarithromycin have been recently recommended as suitable alternatives for management of pertussis.2,4 The US Centres for Disease Control now regard azithromycin as the agent of choice for neonates less than 1 month of age.1 There is evidence suggesting azithromycin has less pro-arrhythmic potential than erythromycin or clarithromycin.5,6 Azithromycin does not interact significantly with the hepatic cytochrome P450 system and has less potential for significant drug interactions than other macrolide antibiotics.3,5,6 Azithromycin and clarithromycin also require less frequent administration (1–2 doses per day) and shorter treatment regimens (5–7 days) than erythromycin.
In Australia, roxithromycin is the most widely prescribed macrolide antibiotic. However, there are no clinical studies on its effectiveness in pertussis, and in-vitro sensitivity studies suggest it may be inferior to erythromycin. Thus, roxithromycin cannot be recommended in pertussis.4
Updated versions of Australian antibiotic guidelines to be released later this year will recommend azithromycin for pertussis treatment and prophylaxis. However, access to azithromycin for this purpose in Australia is currently limited by the restrictions placed on prescribing through the Pharmaceutical Benefits Scheme (PBS). Azithromycin is currently approved for Chlamydia trachomatis urethritis, cervicitis and trachoma. Pertussis is an approved indication only for the use of 500 mg tablets under the Repatriation PBS.
This restriction has important implications for the effective and safe management of pertussis in Australia. Widespread use of newer macrolides in the community is not advisable because of the propensity of macrolides to induce antibiotic resistance, and their greater cost. However, for pertussis infection, Australians need to be able to access agents such as azithromycin. PBS restrictions for this indication need to be revised, for both tablet and liquid formulations.
References
- Tiwari T, Murphy TV, Moran J; National Immunization Program, Centers for Disease Control and Prevention. Recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis: 2005 CDC Guidelines. MMWR Recomm Rep 2005; 54 (RR-14): 1-16.
- Allen C, Jeffery H. Pertussis in the neonatal nursery. J Paediatr Child Health 2005; 41: 140-142. 0_i1091578
- Liu B, Juurlink D. Drugs and the QT interval — caveat doctor. N Engl J Med 2004; 351: 1053-1056. 0_i1091580
- Altunaiji S, Kukurozovic R, Curtis N, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database Syst Rev 2005; (1): CD004404. 0_i1091582
- Milberg P, Eckardt L, Bruns HJ, et al. Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes. J Pharmacol Exp Ther 2002; 303: 218-225. 0_i1091584
- Ohtani H, Taninaka C, Hanada E, et al. Comparative pharmacodynamic analysis of Q-T interval prolongation induced by the macrolides clarithromycin, roxithromycin, and azithromycin in rats. Antimicrob Agents Chemother 2000; 44: 2630-2637. 0_i1091588
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