BACKGROUND AND PURPOSE:

• Ospemifene, a SERM, is an oral medication used to treat postmenopausal moderate/severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA)  
• Simon et al., (Journal of Women’s Health) sought to evaluate the safety of ospemifene

METHODS:

• Post hoc analysis of safety data pooled from six phase 2 and 3 RCTs  
  • Placebo-controlled, double blinded studies  
  • Treatment-emergent adverse events [TEAEs]) with focus on breast, cardiovascular system, and bone  
  • Majority of women received FDA approved 60 mg dose per day  
  • Duration of medication use ranged between 6 to 52 weeks  
• Participants 
  • Postmenopausal women 40-80 years 
  • ≤5% vaginal superficial cells on a vaginal smear 
  • At least 1 self-reported, most bothersome (moderate-to-severe) symptom of VVA (dyspareunia or vaginal dryness)  
• Study assessed TEAEs and in addition 
  • Serious AEs (SAEs), deaths | Discontinuations due to AEs | Specific breast and cardiovascular safety assessments 

RESULTS:

• Total 2200 randomized 
  • 1242 received 60 mg ospemifene  
• Median exposure similar  
  • Ospemifene 86 days | Placebo 84 days  
• Most common treatment-related TEAEs with ospemifene 60 mg  
  • Hot flush (7.5% vs. 2.6% for placebo) 
  • Vaginal discharge (3.8% vs. 0.3%) 
  • Muscle spasms (3.2% vs. 0.9%) 
  • Headache (2.4% vs. 2.4%) 
• TEAEs leading to discontinuation  
  • Ospemifene: 7.6 vs 3.8% with placebo 
  • Most common TEAE causing discontinuation was hot flash (1% vs 0.3%)  
• SAEs 
  • 2.6% for ospemifene 60 mg vs 1.8% for placebo 
  • Most unrelated to treatment  
  • Treatment-related SAEs included  
    • Simple endometrial hyperplasia (n=1) | CVA (n = 1, possibly related) | Ovarian cyst (n = 1, possibly related) | DVT (n = 1, probably related and n = 1, possibly related) | Global amnesia (n = 1, possibly related) | Nausea (n = 1, possibly related) in the ospemifene 60 mg group 
• Breast: Breast cancer and other breast-related TEAEs incidences were comparable between groups  
• Cardiovascular: TEAE incidence, including DVT, were low with both ospemifene (0.3%) and placebo (0.1%) 
• Bone: Vertebral and other fracture-related TEAEs were comparable between ospemifene (1.2%) and placebo (1.5% 
• No deaths reported  

CONCLUSION:

• Ospemifine was generally well tolerated, with no unexpected safety signals for breast, cardiovascular or breast disease  
• Hot flashes were the most common reason for discontinuation 
• Authors report that hot flashes were most frequently experienced in the first 4 weeks and decline with ongoing use  
• There remains an FDA boxed warning regarding risk for endometrial cancer, DVT and stroke 

Learn More – Primary Sources:

Overall Safety of Ospemifene in Postmenopausal Women from Placebo-Controlled Phase 2 and 3 Trials

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