Clindamycin phosphate 2% vaginal cream (Clindesse) for the treatment of bacterial vaginosis
Pharmaceutical Services Division (PSD) requested a systematic review of Clindesse for the treatment of non-pregnant women ≥ 18 years of age with bacterial vaginosis.
Clindesse is a semi-solid white cream containing 2% clindamycin phosphate, which is a water-soluble ester of the semi-synthetic antibiotic produced by a 7 (S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic, lincomycea. The recommended dose is a single intravaginal administration on one day.
Bacterial vaginosis is a common vaginal infection caused by an imbalance in the vaginal flora. In bacterial vaginosis there is suppression of lactobacilli, a rise in pH and overgrowth of other organisms, most commonly Gardnerella vaginalis. The overgrowth of these bacteria causes an increase in pH and a white or grey-like vaginal discharge accompanied by an unpleasant fishy odour.
In clinical practice bacterial vaginosis is diagnosed using the Amsel criteria of which at least three of the four following criteria must be met: thin, white, yellow, homogeneous discharge, clue cells on microscopy, pH of vaginal fluid >4.5, release of a fishy odour on adding alkali. For diagnosis in asymptomatic women and for clinical trials the FDA also requires use of the Nugent score which requires the use of a gram stained vaginal smear where the vaginal flora are examined and graded as: 0–3 normal (lactobacillus predominant), 4–6 intermediate, 7+ indicative of BV.
Once diagnosis is confirmed the mainstay of treatment is antibiotic therapy. Antimicrobials, which include the 5-nitroimidazoles (metronidazole, tinidazole, secnidazole), and the lincosamide clindamycin, inhibit anaerobes that support Gardnerella vaginalis but do not affect lactobacilli, and thus reduce the risk of relapse.
- In double blind randomized controlled trials does clindamycin phosphate 2% vaginal cream provide a therapeutic advantage over other medications used in the treatment of bacterial vaginosis in non-pregnant women ≥ 18 years of age?
- In double blind randomized controlled trials are there any safety or toxicity considerations with respect to clindamycin phosphate 2% vaginal cream compared to other medications used to treat bacterial vaginosis in non-pregnant women ≥18 years of age?
Randomized controlled trials (double blind, single blind or open label) comparing Clindesse to metronidazole or other formulations of clindamycin.
- Non-fatal Serious Adverse Events (SAEs)
- Therapeutic cure, defined as clinical cure: resolution of all 4 Amsel criteria and investigator cure and Nugent score: 0-3 for normal bacterial morphotypes
- Treatment failure, defined as at least three Amsel criteria and Nugent Score 7-10 at seven days after treatment or one to two month follow up (relapse in symptomatic women)
- Relapse rates within 12 months
- Incidence of endometritis; pelvic inflammatory disease, or other infections (fungal, HIV)
- Total adverse events (metallic taste, nausea, diarrhea, hypersensitivity, pseudomembranous colitis)
- Withdrawal due to adverse events
Search strategy and findings: The search included the following electronic databases: Medline (1966-July 2009), Embase (1988-July 2009), Cochrane Database of Systematic Reviews and Cochrane Central Registry of Clinical Studies. Key search words included bacterial vaginosis, clindamycin, Clindesse, metronidazole. The U.S. FDA and EMEA websites were also searched.
One trial (Faro et al 2005) comparing clindamycin single dose (Clindesse) to 7-day clindamycin (Cleocin) met the inclusion criteria for this review. However, because the per protocol analysis in the published trial included less than half of the total randomized population, results from the ITT and modified ITT analyses of the FDA review of Clindesse are presented.
Overall there were no clinically or statistically significant differences in serious morbidity therapeutic cure, withdrawals, treatment failure, incidence of pelvic inflammatory disease, vaginosis, fungal infections, incidence of other infections that were reported (Urinary tract infection), additional treatment required for bacterial vaginosis, total adverse events, and withdrawals due to adverse events for Clindesse versus Cleocin.
Treatment failure or cure in asymptomatic women and incidence of endometritis were not reported. Since the trial follow-up was for 21-30 days from start of treatment there is no data on the incidence of relapse.
Long-term adverse events are unknown.
In a 4-week single-blinded randomized controlled trial there was no significant difference between single dose clindamycin cream (Clindesse) versus clindamycin vaginal cream administered once daily for 7 days (Cleocin).
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