SmPC: Special warnings and precautions

Please see the Senshio Summary of Product Characteristics for full safety information https://www.medicines.org.uk/emc/product/9417

Overview of Senshio Pivotal Trial Safety and Real World Experience

Overview of Senshio Pivotal Trial Safety and Real World Experience

Question 1: Endometrial safety profile after 1 year of treatment

  • No significant change in endometrial histology after 1 year1,3

No statistically significant difference between Senshio and placebo in incidence of endometrial thickness ≥5mm at 1 year1

 - There was <1mm difference in the mean change from baseline in endometrial thickness at 1 year between Senshio and placebo1-3

  • No increase in vaginal bleeding in women with a uterus1-2

No clinically relevant changes in endometrial finding at 1 year1-2

 

  Placebo Senshio
Endometrial hyperplasia/cancer1-2

 

0%

 

0.3% (n=1/317)

(1 patient developed simple hyperplasia without atypical 3 months after discontinuing Senshio therapy)
Uterine polyps2-3

 

0.2% (n=1/570)

Only true polyps confirmed

 0.4% (n=5/1140)

 

If bleeding or spotting course on therapy, or continues after treatment has been discontinued, this should be investigated, which may include an endometrial biopsy to exclude endometrial malignancy.

Question 2: No difference between the incidence rate of venous thromboembolic (VTE) events and cerebrovascular events for Senshio vs. placebo[1-3]

Incidences per 1,000 women years across all placebo-controlled clinical trials of Senshio

 

 

Placebo

(n=958, 273 WY)

Senshio

(n=1,242, 548 WY)
VTE1-3

3.66

95% CI: 0.09-20.41

3.65

95% CI: 0.44-13.9
CV events2,3

3.66

95% CI: 0.09-20.41

1.83

95% CI: 0.05-10.17 

 

Real-world pharmacovigilance experience

Incidence rates for VTE are consistently much lower than the background risks identified [2-year interim data of the Post Approval Safety Study (PASS) from May 2013 to December 2015]2

 

 

Untreated patients with VVA

(n= 161,196)

Senshio

(n= 5,157)

VTE2

Incidence rate per 1000 WY

12.02

95% CI: 11.50-12.57

4.02

95% CI: 1,48-8.75

 

A PASS study analysis published in 2022 found incidence of VTE in the real-world ospemifene cohort consistent with the ospemifene clinical development programme. The ospemifene clinical development programme found an incidence of VTE of 3.65 (95% CI: 0.44–13.90) per 1000 patient years with ospemifene and 3.66 (0.09–20.41) per 1000 patient years with placebo.6

SERM class effects risk: The risk of VTE cannot be excluded with SERMs. Senshio should be discontinued at least 4-6 weeks prior to and during prolonged immobilisation. The risk of CV events is possibly increased with other SERMs. The risk of CV events associated with Senshio cannot be excluded. This should be considered when prescribing Senshio for post-menopausal women with a history of stroke or other significant stroke risk factors.  If VTE develops after initiating therapy, the drug should be discontinued. 

 

VTE (Venous thromboembolic events) |  CV (Cardiovascular)  |  WY (Women years)

Question 3: Senshio can be used in women with a history of breast cancer once their adjuvant treatment is completed[1]

Pre-clinical models

  • Senshio exerts an anti-oestrogenic, anti-proliferative effect in breast tissue1,2

 

Clinical evidence

  • No abnormal breast-related findings identified for Senshio1,3 
  • No clinically significant changes in mammography after 1 year of treatment3 

 

Senshio should be used for the treatment of vaginal atrophy only after the treatment of breast cancer, including adjuvant therapy, has been completed1

Senshio has not been formally studied in women with a prior history of breast cancer.  No data are available on its concomitant use with agents used in the treatment of early or advanced breast cancer.

Question 4: Senshio real world experience

Post-marketing surveillance up to 3.5 years and the 2 year results from the Post-Authorisation Safety Study (PASS) confirm that there has not been an increase in the risk of thrombosis, stroke, vaginal bleeding and cancer or endometrial hyperplasia with Senshio from launch until September 20185

  • 128,995 patient-years of cumulative post-marketing exposure in the USA and EU1 
  • Over 47 million tablets1 
  • None of the 'Important Potential Risks' (incl.VTE) identified in the Senshio RMP has been flagged

The PASS published in 2022 found no increase in risk of VTE or other adverse events with use of ospemifine in post menopausal women. 6

The safety of Senshio has been assessed in over 1,100 women with VVA in phase II/III trials[1]

The most frequently reported adverse reaction was hot flushes (7.5%, n=93/1242), which led to discontinuation in 1% (n=13/1242) of women1,3

  • Frequency of hot flushes declined after 4 weeks of treatment3
  • Senshio did not increase the frequency or worsen the severity of existing hot flushes3

Adverse events (Frequency ≥1/100 to <1/10)1

  • Hot flush
  • Vulvovaginal candidiasis/mycotic infections
  • Muscle spasms
  • Vaginal discharge, genital discharge
  • Headache
  • Rash (includes rash erythematous, rash generalised)

5.7% of women discontinued Senshio because of treatment-emergent adverse events vs. 1.8% with placebo1

References:

  1. Senshio Summary of Product Characteristics.
  2. Palacios S, Cancelo M. International Journal of Women’s Health 2016; 8: 617–626.
  3. Simon J, et al. Journal of Women’s Health 2018; 27(1), 14-23
  4. EPAR. European Medicines Agency. Senshio Public Assessment Report.
  5. Bruyniks N, et al. J Gynecol Women’s Health 2018; 9(3): 555762. DOI: 10.19080/JGWH.2018.09.555762.
  6. Nordstrom B, et al. Therapeutic Advances in Drug Safety 2022;13: 1-13.
PP-UK-OSP-0351 | July 2024