st 21 Expert Committee on Selection and Use of Essential Medicines

STI ANTIBIOTICS REVIEW

(1) Have all important studies/evidence of which you are aware been included in the application? YES

(2) For each of the STIs reviewed in the application, and noting the corresponding updated WHO treatment guidelines, please comment in the table below on the application’s proposal for antibiotics to be included on the EML STI ANTIBIOTICS USED IN WHO AND RECOGNIZED GUIDELINES

Chlamydia trachomatis

UNCOMPLICATED GENITAL CHLAMYDIA AZITHROMYCIN 1g DOXYCYCLINE 100mg TETRACYCLINE 500mg ERYTHROMYCIN 500mg OFLOXACIN 200mg ANORECTAL CHLAMYDIAL INFECTION

DOXYCYCLINE 100mg AZITHROMYCIN 1g GENITAL CHLAMYDIAL INFECTION IN PREGNANT WOMEN

AZITHROMYCIN 1g AMOXYCILLIN 500mg ERYTHROMYCIN 500mg LYMPHOGRANULOMA VENEREUM (LGV)

DOXYCYCLINE 100mg AZITHROMYCIN 1g OPHTHALMIA NEONATORUM

AZITHROMYCIN SUSPENSION ERYTHROMYCIN SUSPENSIONS FOR OCULAR PROPHYLAXIS TETRACYCLINE HYDROCHLORIDE 1% EYE OINTMENT ERYTHROMYCIN 0.5% EYE OINTMENT POVIDONE IODINE 2.5% SOLUTION (water-based) SILVER NITRATE 1% SOLUTION CHLORAMPHENICOL 1% EYE OINTMENT.

Neisseria gonorrhoeae GENITAL AND ANORECTAL GONOCOCCAL INFECTIONS CEFTRIAXONE 250 MG IM + AZITHROMYCIN 1g CEFIXIME 400 MG + AZITHROMYCIN 1g SPECTINOMYCIN 2 G IM ou CEFTRIAXONE 250 MG IM ou CEFIXIME 400 MG OROPHARYNGEAL GONOCOCCAL INFECTIONS CEFTRIAXONE 250 MG IM + AZITHROMYCIN 1g CEFIXIME 400 MG + AZITHROMYCIN 1g CEFTRIAXONE 250 MG IM RETREATMENT IN CASE OF FAILURE CEFTRIAXONE 500 mg IM + AZITHROMYCIN 2g CEFIXIME 800 mg + AZITHROMYCIN 2g SPECTINOMYCIN 2 G IM + AZITHROMYCIN 2g GENTAMICIN 240 MG IM + AZITHROMYCIN 2g OPHTALMIA NEONATORUM

CEFTRIAXONE 50 MG/KG IM (MAXIMUM 150 MG) KANAMYCIN 25 MG/KG IM (MAXIMUM 75 MG) SPECTINOMYCIN 25 MG/KG IM (MAXIMUM 75 MG) FOR OCULAR PROPHYLAXIS, TETRACYCLINE HYDROCHLORIDE 1% EYE OINTMENT ERYTHROMYCIN 0.5% EYE OINTMENT POVIDONE IODINE 2.5% SOLUTION (water-based) SILVER NITRATE 1% SOLUTION CHLORAMPHENICOL 1% EYE OINTMENT.

Treponema pallidum (SYPHILIS)

EARLY SYPHILIS (PRIMARY, SECONDARY AND EARLY LATENT SYPHILIS OF NOT MORE THAN TWO YEARS DURATION) BENZATHINE PENICILLIN G 2.4 MILLION UNITS or PROCAINE PENICILLIN G 1.2 MILLION UNITS IF ALLERGY

DOXYCYCLINE 100mg or CEFTRIAXONE 1g IM or AZITHROMYCIN 2g PREGNANT WOMEN BENZATHINE PENICILLIN G 2.4 MILLION UNITS or PROCAINE PENICILLIN G 1.2 MILLION UNITS IF ALLERGY ERYTHROMYCIN 500mg or CEFTRIAXONE 1g IM or AZITHROMYCIN 2g LATE SYPHILIS (INFECTION OF MORE THAN TWO YEARS DURATION WITHOUT EVIDENCE OF TREPONEMAL INFECTION) BENZATHINE PENICILLIN G 2.4 MILLION UNITS or PROCAINE PENICILLIN G 1.2 MILLION UNITS DOXYCYCLINE 100mg PREGNANT WOMEN BENZATHINE PENICILLIN G 2.4 MILLION UNITS or PROCAINE PENICILLIN G 1.2 MILLION UNITS ERYTHROMYCIN 500mg INFANTS WITH CONFIRMED CONGENITAL SYPHILIS

AQUEOUS BENZYL PENICILLIN 100 000–150 000 U/ KG/DAY IV PROCAINE PENICILLIN 50 000 U/KG/DAY IM 201 (3) Please frame the decisions and recommendations that the Expert Committee could make.

All the antibiotics listed in the above table are already in the 19 th WHO Model List of Essential Medicines except TETRACYCLINE and OFLOXACIN as such while AZITHROMYCIN is only listed for single‐ dose treatment of genital Chlamydia trachomatis and of trachoma.

I propose to add Neisseria gonorrhoeae and syphilis among the indications of AZITHROMYCIN ( see also the yaws application where AZITHROMYCIN is also indicated in order to achieve eradication).

Although, levofloxacin and ofloxacin are effective treatment alternatives, they are more expensive and offer no advantage in the dosage regimen. Other quinolones either are not reliably effective against chlamydial infection or have not been evaluated adequately. I do not recommend to add the quinolones for Chlamydia trachomatis.

I also do not recommend to add TETRACYCLINE for Chlamydia trachomatis.

I propose to add ERYTHROMYCIN 0.5% EYE OINTMENT in the list of: “21. OPHTHALMOLOGICAL PREPARATIONS 21.1 Anti-infective agents”

I do not recommend to add SILVER NITRATE 1% SOLUTION and CHLORAMPHENICOL 1% EYE OINTMENT

(4) References

1) 30 August 2016: WHO has today launched new treatment guidelines WHO guidelines for the treatment of Neisseria gonorrhoeae WHO guidelines for the treatment of Treponema pallidum (syphilis) WHO guidelines for the treatment of Chlamydia trachomatis

2) Sexually Transmitted Diseases Treatment Guidelines, 2015 Morbidity and Mortality Weekly Report Vol. 64 / No. 3 June 5, 2015