FDA Approves Secnidazole: Single-Dose Oral Treatment for BV

SUMMARY: 

• The FDA has approved a single-dose oral therapy, secnidazole, for the treatment of bacterial vaginosis (BV) 
  • Available first quarter 2018
• Secnidazole is a 5-nitroimidazole with a longer half-life than metronidazole that has been available in Europe and Asia 
• Dosage regimen
  • Administer a single 2-gram packet of granules once orally, without regard to the timing of meals
  • Sprinkle entire contents of packet onto applesauce, yogurt or pudding and consume all of the mixture within 30 minutes without chewing or crunching the granules
  • A glass of water may be taken after the administration of secnidazole to aid in swallowing
  • Not intended to be dissolved in any liquid
• Primary side effect is vulvo-vaginal candidiasis
• Pregnancy (as per FDA)

Limited available data with SOLOSEC use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, there were no adverse developmental outcomes when secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose.

• Lactation (as per FDA)

Breastfeeding is not recommended. Discontinue breastfeeding for 96 hours after administration

EVIDENCE:

• A European study by Bohbot et al (Infectious Diseases in Obstetrics and Gynecology, 2010) demonstrated that secnidazole was comparable to metronidazole in effectiveness and safety
• Hillier et al. (Obstetrics & Gynecology, 2017) assessed the efficacy of secnidazole as a one-dose treatment for BV in a US population 

METHODS 

• 3-arm, phase 2, double-blind, randomized placebo-controlled study  
• Subjects were categorized into 3 arms: 
  • 1 g Secnidazole group 
  • 2 g Secnidazole group  
  • Placebo group (bittering agent added so no difference in taste) 
• Randomization took in to account number of BV episodes within past year (≤ 3 vs ≥ 4) 
• Inclusion criteria 
  • Non-pregnant 
  • ≥ 18 years of age 
  • Met all 4 Amsel criteria (discharge; pH ≥ 4.7; ≥ 20% clue cells; positive whiff test)  
  • Agree to abstain from sexual activity for 1 week after treatment 
• Exclusion criteria 
  • Allergy to metronidazole 
  • Pregnancy 
  • Vaginal bleeding 
  • Refusal to abstain from alcohol for 3 days post treatment 
  • Concomitant or recent antimicrobial medications 
• Primary outcome was clinical cure for BV 21-30 days following treatment (1998 FDA guidance)  
  • Normal vaginal discharge 
  • Negative 10% potassium hydroxide whiff test 
  • Clue cells less than 20% of total epithelial cells on microscopic examination of the vaginal wet mount using saline at the test of cure visit 
• Secondary outcomes were  
  • Microbiologic cure (Nugent score 0-3) 
  • Therapeutic cure meeting both microbiological and clinical cure 

RESULTS 

• In modified intent-to-treat group (all randomized patients who met all study selection criteria), clinical, microbiological, and therapeutic cure rates were (n= 188): 
  • 2g secnidazole group: 67.7%, 40.3%, and 40.3%  
  • 1g secnidazole group: 51.6%, 23.4%, and 21.9%  
  • Placebo group: 17.7%, 6.5%, and 6.5% in placebo group 
• All treatment-emergent adverse events were mild or moderate 
  • Majority were related to infections and equal across all groups 
  • Yeast infections were unusual (only 7 women, 5 having received the medication) 
  • Only 1/144 women randomized to secnidazole had nausea  
    • Consistent with well established safety profile outside the US 

CONCLUSION 

• 1 or 2 grams of secnidazole was significantly (P<0.001) better than placebo in treating BV  
  • 2g secnidazole: Clinical cure 68%; microbiologic cure 40% 
• For comparison (using new FDA criteria of only needing resolution of 3 of 4 Amsel criteria) 
  • 500 mg oral metronidazole twice daily for 7 days or 7 day clindamycin cream: Clinical cure 58% 
  • Oral tinidazole  
    • 2 day regimen: Clinical cure 46%  
    • 5 day regimen: Clinical cure 64%  
  • FDA single-dose intravaginal 
    • Clindamycin: Clinical cure 64%; microbiologic cure 57% 
    • Metronidazole 1.3% gel clinical cure 37%; microbiologic cure 18%   

Learn More – Primary Sources:  

Hillier et al: Secnidazole Treatment of Bacterial Vaginosis – A Randomized Controlled Trial 

Bohbot et al: Treatment of bacterial vaginosis – a multicenter, double-blind, double-dummy, randomised phase III study comparing secnidazole and metronidazole

FDA: Highlights of Prescribing Information for Solosec