Intrarosa

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ANNEX I 

 
SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Intrarosa 6.5 mg pessary. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pessary contains 6.5 mg of prasterone. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Pessary. 
 
White to off-white, bullet-shaped pessary approximately 28 mm long and 9 mm in diameter at its 
widest end. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Intrarosa is indicated for the treatment of vulvar and vaginal atrophy in postmenopausal women 
having moderate to severe symptoms.  
 
4.2 Posology and method of administration 
 
Posology 
The recommended dose is 6.5 mg prasterone (one pessary) administered once daily, at bedtime. 
 
For the treatment of postmenopausal symptoms, Intrarosa should only be initiated for symptoms that 
adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be 
reassessed at least every 6 months and Intrarosa should only be continued as long as the benefit 
outweighs the risk. 
 
If a dose is forgotten, it should be taken as soon as the patient remembers. However, if the next dose is 
due in less than 8 hours, the patient should skip the missed pessary. Two pessaries should not be used 
to make up for a forgotten dose. 
 
Special populations 
 
Elderly 
No dose adjustment is considered necessary in elderly women. 
 
Patients with renal and/or hepatic impairment 
Since Intrarosa acts locally in the vagina, no dosage adjustment is needed for postmenopausal women 
having renal or hepatic impairment or any other systemic anomaly or disease. 
 



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Paediatric population 
There is no relevant use of Intrarosa in female children of any age group for the indication of vulvar 
and vaginal atrophy due to menopause. 
 
Method of administration  
 
Vaginal use. 
 
Intrarosa can be inserted in the vagina with the finger or with an applicator provided within the 
identified pack. 
 
The pessary should be inserted in the vagina as far as it can comfortably go without force. 
 
If inserted with an applicator, the following steps should be followed: 
 
1. The applicator should be activated (by pulling back the plunger) before use. 
2. The flat end of the pessary should be placed into the open end of the activated applicator. 
3. The applicator should be inserted into the vagina as far as it can comfortably go without force. 
4. The plunger of the applicator should be pressed to release the pessary. 
5. The applicator should then be withdrawn and disassembled, and the two pieces of the applicator 

should be rinsed for 30 seconds under running water before wiping with paper towel and 
reassembled. The applicator should be kept in a clean place until next use. 

6. Each applicator should be discarded after one week of usage (two extra applicators are 
provided). 

 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to the excipient listed in section 6.1; 
• Undiagnosed genital bleeding; 
• Known, past or suspected breast cancer; 
• Known or suspected oestrogen-dependent malignant tumours (e.g endometrial cancer); 
• Untreated endometrial hyperplasia; 
• Acute liver disease, or a history of liver disease as long as liver function tests have failed to 

return to normal 
• Previous or current venous thromboembolism (deep vein thrombosis, pulmonary embolism); 
• Known thrombophilic disorders (e.g. protein C, protein S, or antithrombin deficiency, see 

section 4.4); 
• Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction); 
• Porphyria. 
 
4.4 Special warnings and precautions for use 
 
For the treatment of postmenopausal symptoms, Intrarosa should only be initiated for symptoms that 
adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be 
reassessed at least every 6 months and Intrarosa should only be continued as long as the benefit 
outweighs the risk following discussions with their doctor. 
 
Before initiating Intrarosa, a complete personal and family medical history should be taken. Physical 
(including pelvic and breast) examination should be guided by this and by the contraindications and 
special warnings and precautions for use according to the decision of their doctor. During treatment, 
periodic check-ups are recommended of a frequency and nature adapted to the individual woman. 
Women should be advised what changes in their breasts should be reported to their doctor or nurse 
(see ‘Breast cancer’ below). Investigations, including Pap smears and blood pressure measurements 
should be carried out in accordance with currently accepted screening practices, modified to the 
clinical needs of the individual.  
 



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Conditions which need supervision 
• If any of the following conditions are present, have occurred previously, and/or have been 

aggravated during pregnancy or previous hormone treatment, the patient should be closely 
supervised.  It should be taken into account that these conditions may recur or be aggravated 
during treatment with Intrarosa, in particular: 
– Leiomyoma (uterine fibroids) or endometriosis 
– Risk factors for thromboembolic disorders (see below) 
– Risk factors for oestrogen dependent tumours, e.g. 1st degree heredity for breast cancer 
– Hypertension 
– Liver disorders (e.g. liver adenoma) 
– Diabetes mellitus with or without vascular involvement 
– Cholelithiasis 
– Migraine or (severe) headache 
– Systemic lupus erythematosus. 
– A history of endometrial hyperplasia (see below) 
– Epilepsy 
– Asthma 
– Otosclerosis 

 
Reasons for immediate withdrawal of therapy 
Therapy should be discontinued in case a contraindication is discovered and in the following situation: 
– Jaundice or deterioration in liver function 
– Significant increase in blood pressure  
– New onset of migraine-type headache 
– Pregnancy. 
 
Endometrial hyperplasia and carcinoma 
• Estrogen is a metabolite of prasterone. In women with an intact uterus, the risk of endometrial 

hyperplasia and carcinoma is increased when exogenous oestrogens are administered for 
prolonged periods. No cases of endometrial hyperplasia have been reported in women treated 
for 52 weeks during the clinical studies. Intrarosa has not been studied in women with 
endometrial hyperplasia.  

• For oestrogen products for vaginal application of which the systemic exposure to oestrogen 
remains within the normal postmenopausal range, it is not recommended to add a progestagen. 

• Endometrial safety of long-term of local vaginally administered prasterone has not been studied 
for more than one year. Therefore, if repeated, treatment should be reviewed at least annually.  

• If bleeding or spotting appears at any time on therapy, the reason should be investigated, which 
may include endometrial biopsy to exclude endometrial malignancy. 

• Unopposed oestrogen stimulation may lead to premalignant or malignant transformation in the 
residual foci of endometriosis. Therefore caution is advised when using this product in women 
who have undergone hysterectomy because of endometriosis, especially if they are known to 
have residual endometriosis since intravaginal prasterone has not been studied in women with 
endometriosis.  

 
Prasterone is metabolised into estrogenic compounds. The following risks have been associated with 
systemic HRT and apply to a lesser extent for oestrogen products for vaginal application of which the 
systemic exposure to the oestrogen remains within the normal postmenopausal range. However, they 
should be considered in case of long term or repeated use of this product. 
 
Breast cancer 
The overall evidence suggests an increased risk of breast cancer in women taking combined oestrogen-
progestagen and possibly also oestrogen-only systemic HRT, that is dependent on the duration of 
taking HRT. The excess risk becomes apparent within a few years of use but returns to baseline within 
a few (at most five) years after stopping treatment. 
 



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Intrarosa has not been studied in women with active or past breast cancer. One case of breast cancer at 
week 52 has been reported on 1196 women who have been exposed with the 6.5 mg dose which is 
below the incidence rate observed in the normal population of the same age.  
 
Ovarian cancer 
Ovarian cancer is much rarer than breast cancer. 
Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women 
taking oestrogen-only systemic HRT, which becomes apparent within 5 years of use and diminishes 
over time after stopping. 
 
Intrarosa has not been studied in women with active or past ovarian cancer. One Case of ovarian 
cancer has been reported on 1196 women who have been exposed with the 6.5 mg dose which is 
above the incidence rate observed in the normal population of the same age. Of note, this case was 
present before start of treatment and was bearing a BRCA1 mutation.  
 
Abnormal Pap smear 
Intrarosa has not been studied in women with abnormal Pap smears (Atypical Squamous Cells of 
Undetermined Significance (ASCUS)) or worse. Cases of abnormal Pap smears corresponding to 
ASCUS or Low Grade Squamous Intraepithelial Lesion (LSIL) have been reported in women treated 
with the 6.5 mg dose (common frequency).  
 
Venous thromboembolism 
Intrarosa has not been studied in women with current or previous venous thromboembolic disease.  
• Systemic HRT is associated with a 1.3-3 fold risk of developing venous thromboembolism (VTE), 

i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely 
in the first year of HRT than later (see section 4.8). 

• Patients with known thrombophilic states have an increased risk of VTE and HRT may add to this 
risk. HRT is therefore contraindicated in these patients (see section 4.3). 

• Generally recognised risk factors for VTE include, use of oestrogens, older age, major surgery, 
prolonged immobilisation, obesity (BMI > 30 kg/m2), pregnancy/postpartum period, systemic 
lupus erythematosus (SLE), and cancer. There is no consensus about the possible role of varicose 
veins in VTE. 
As in all postoperative patients, prophylactic measures need be considered to prevent VTE 
following surgery. If prolonged immobilisation is to follow elective surgery temporarily stopping 
HRT 4 to 6 weeks earlier is recommended. Treatment should not be restarted until the woman is 
completely mobilised. 

• In women with no personal history of VTE but with a first degree relative with a history of 
thrombosis at young age, screening may be offered after careful counselling regarding its 
limitations (only a proportion of thrombophilic defects are identified by screening). 
If a thrombophilic defect is identified which segregates with thrombosis in family members or if 
the defect is ‘severe’ (e.g, antithrombin, protein S, or protein C deficiencies or a combination of 
defects) HRT is contraindicated. 

• Women already on chronic anticoagulant treatment require careful consideration of the benefit-
risk of use of HRT. 

• If VTE develops after initiating therapy, the drug should be discontinued. Patients should be told 
to contact their doctors immediately when they are aware of a potential thromboembolic symptom 
(e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea). 
 

One case of pulmonary embolism has been reported in the 6.5 mg group and one in the placebo group 
during clinical trials.  
 
Coronary artery disease (CAD)/ Hypertension  
Intrarosa has not been studied in women with uncontrolled hypertension (blood pressure above 
140/90 mmHg) and cardiovascular disease. Cases of hypertension have been reported in clinical trials 
with an uncommon frequency and similar incidence rates were observed in both groups (6.5 mg 
prasterone and placebo). No case of coronary artery disease has been reported during clinical trials.  
 



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Ischaemic stroke 
Systemic oestrogen-only therapy is associated with an up to 1.5-fold increase in risk of ischaemic 
stroke. The relative risk does not change with age or time since menopause. However, as the baseline 
risk of stroke is strongly age-dependent, the overall risk of stroke in women who use HRT will 
increase with age (see section 4.8). 
Intrarosa has not been studied in women with current or previous arterial thromboembolic disease. 
No cases of arterial thromboembolic disease have been reported during clinical trials. 
 
Other conditions observed with HRT 
• Oestrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction 

should be carefully observed. 
• Women with pre-existing hypertriglyceridaemia should be followed closely during oestrogen 

replacement or hormone replacement therapy, since rare cases of large increases of plasma 
triglycerides leading to pancreatitis have been reported with oestrogen therapy in this condition. 

• Oestrogens increase thyroid binding globulin (TBG), leading to increased circulating total 
thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radio-
immunoassay) or T3 levels (by radio-immunoassay). T3 resin uptake is decreased, reflecting the 
elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be 
elevated in serum, i.e. corticoid binding globulin (CBG), sex-hormone-binding globulin 
(SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or 
biological active hormone concentrations are unchanged. Other plasma proteins may be 
increased (angiotensinogen/renin substrate, alpha-I-antitrypsin, ceruloplasmin). 

• HRT use does not improve cognitive function.  There is some evidence of increased risk of 
probable dementia in women who start using continuous combined or oestrogen-only HRT after 
the age of 65. 

 
None of these conditions has been observed with Intrarosa during the clinical trials. 
Women with vaginal infection should be treated with appropriate antimicrobial therapy before starting 
Intrarosa. 
 
Due to melting of the hard fat base added to an expected increase in vaginal secretions due to 
treatment, vaginal discharge can occur although it does not require to stop the medication (see 
section 4.8). 
 
Use of Intrarosa with condoms, diaphragms or cervical caps made of latex must be avoided since the 
rubber may be damaged by the preparation. 
 
Intrarosa has not been studied in women with a current hormonal treatment: hormone replacement 
therapy (oestrogens alone or combined with progestogens) or androgens treatment.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Concomitant use with systemic hormone replacement therapy (oestrogen-only or oestrogen-
progestagen combination or androgen treatment) or vaginal oestrogens has not been investigated and 
is therefore not recommended. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Intrarosa is not indicated in pre-menopausal women of child-bearing age, including pregnancy.  
 
If pregnancy occurs during treatment with Intrarosa, the treatment should be withdrawn immediately. 
There are no data on the use of Intrarosa in pregnant women. 
 
No studies in animals were performed with regard to the reproductive toxicity (see section 5.3). The 
potential risk in humans is unknown. 
 



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Breast-feeding 
Intrarosa is not indicated during breast-feeding. 
 
Fertility 
Intrarosa is not indicated in fertile women. 
 
4.7 Effects on ability to drive and use machines 
 
Intrarosa has no influence in the ability to drive and use machines. 
 
4.8 Undesirable effects 

Summary of safety profile 
The most frequently observed adverse reaction was vaginal discharge. This is due to melting of the hard 
fat used as vehicle, added to the expected increase in vaginal secretions due to treatment. It is not 
required to stop Intrarosa if vaginal discharge occurs (see section 4.4).  
 
Tabulated list of adverse reactions 
The adverse reaction observed with prasterone 6.5 mg pessaries obtained from clinical studies is 
tabulated below. 

MedDRA System Organ Class Common 
(≥ 1/100 to < 1/10) 

Uncommon 
(≥ 1/1,000 to < 1/100) 

General disorders and 
administration site conditions 

Application site discharge  

Reproductive system and 
breast disorders  

Abnormal Pap smear (mostly 
ASCUS or LGSIL) 
 

Cervical/ uterine polyps 
 
Breast mass (benign)  

Investigations  Weight fluctuation  
 
Breast cancer risk 
• An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking 

combined oestrogen-progestagen therapy for more than 5 years.  
• Any increased risk in users of oestrogen-only therapy is substantially lower than that seen in 

users of oestrogen-progestagen combinations.  
• The level of risk is dependent on the duration of use (see section 4.4).  
• Results of the largest randomised placebo-controlled trial (WHI-study) and largest 

epidemiological study (MWS) are presented. 
 
Million Women study– Estimated additional risk of breast cancer after 5 years’ use  

Age 
range 

(years) 

Additional 
cases per 1000 
never-users of 
HRT over a 5 
year period*1 

Risk ratio & 
95%CI#  

Additional cases per 1000 HRT users over 5 years 
(95%CI)  

 Oestrogen only HRT 

50-65 9-12 1.2 1-2 (0-3) 

#Overall risk ratio.  The risk ratio is not constant but will increase with increasing duration on use 

Note: Since the background incidence of breast cancer differs by EU country, the number of additional 
cases of breast cancer will also change proportionately. 

 

                                                      
1 *Taken from baseline incidence rates in developed countries 



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US WHI studies - additional risk of breast cancer after 5 years’ use 

Age range 
(yrs) 

Incidence per 1000 women 
in placebo arm over 
5 years 

Risk ratio & 95%CI  Additional cases per 1000 HRT users over 5 years (95%CI) 

 CEE oestrogen-only 
50-79 21 0.8 (0.7 – 1.0) -4 (-6 – 0)*2 

 
Ovarian cancer 
Use of oestrogen-only or combined oestrogen-progestagen HRT has been associated with a slightly 
increased risk of having ovarian cancer diagnosed (see section 4.4).  
A meta-analysis from 52 epidemiological studies reported an increased risk of ovarian cancer in 
women currently using HRT compared to women who have never used HRT (RR 1.43, 95% CI 1.31-
1.56). For women aged 50 to 54 years taking 5 years of HRT, this results in about 1 extra case per 
2000 users. In women aged 50 to 54 who are not taking HRT, about 2 women in 2000 will be 
diagnosed with ovarian cancer over a 5-year period. 
 
Risk of venous thromboembolism 
HRT is associated with a 1.3-3-fold increased relative risk of developing venous thromboembolism 
(VTE), i.e. deep vein thrombosis or pulmonary embolism.  The occurrence of such an event is more 
likely in the first year of using HT (see section 4.4).  Results of the WHI studies are presented: 
 
WHI Studies - Additional risk of VTE over 5 years’ use 

 
Risk of coronary artery disease 
 
• The risk of coronary artery disease is slightly increased in users of combined oestrogen-progestagen 

HRT over the age of 60 (see section 4.4). 
 
Risk of ischaemic stroke 
 
• The use of oestrogen-only and oestrogen + progestagen therapy is associated with an up to 1.5 

fold increased relative risk of ischaemic stroke. The risk of haemorrhagic stroke is not increased 
during use of HRT. 

• This relative risk is not dependent on age or on duration of use, but as the baseline risk is 
strongly age-dependent, the overall risk of stroke in women who use HRT will increase with 
age, see section 4.4. 
 

WHI studies combined - Additional risk of ischaemic stroke*4 over 5 years’ use 

Age range (years) 
Incidence 
per 1000 women in 
placebo arm over 5 years 

Risk ratio and 
95%CI 

Additional cases per 1000 
HRT users over 5 years 

50-59 8 1.3 (1.1-1.6) 3 (1-5) 
 

Other adverse reactions have been reported in association with oestrogen/progestagen treatment:  
 
– Gall bladder disease. 

                                                      
2 *WHI study in women with no uterus, which did not show an increase in risk of breast cancer 
3 *Study in women with no uterus 
4 *no differentiation was made between ischaemic and haemorrhagic stroke. 

Age range (years) Incidence 
per 1000 women in 
placebo arm over 5 years 

Risk ratio and 
95%CI 

Additional cases per 1000 
HRT users 

Oral oestrogen-only*3 
50-59 7 1.2 (0.6 - 2.4) 1 (-3 – 10) 



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– Skin and subcutaneous disorders: chloasma, erythema multiforme, erythema nodosum, vascular 
purpura. 

– Probable dementia over the age of 65 (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
In the event of overdose, vaginal douching is recommended.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other sex hormones and modulators of the genital system, 
ATC code: G03XX01. 
 
Mechanism of action 
Intrarosa contains the active ingredient prasterone, i.e. dehydroepiandrosterone (DHEA), which is 
biochemically and biologically identical to the endogenous human DHEA, a precursor steroid which is 
inactive by itself and it is converted into oestrogens and androgens. Intrarosa is thus different from the 
oestrogens preparations since it delivers also androgen metabolites.  
 
An oestrogen-mediated increase in the number of superficial and intermediate cells and decrease in the 
number of parabasal cells in the vaginal mucosa is noted. In addition, the vaginal pH decreased 
towards the normal range, thus facilitating the growth of the normal bacterial flora. 
 
Clinical efficacy 
Physiological responses (objective measures) 
Efficacy data were obtained from two US and Canadian randomised, double-blind, placebo-controlled, 
multicentre, pivotal phase III trials (ERC-231/Trial 1 and ERC-238/Trial 2) performed in 
postmenopausal women aged 40 to 80 years (mean age = 58.6 years in Trial 1 and 59.5 years in 
Trial 2) with vulvar and vaginal atrophy (VVA ). At baseline, women had ≤ 5.0% superficial cells in 
the vaginal smear, a vaginal pH ˃ 5.0 and they had identified dyspareunia (moderate to severe) as their 
most bothersome symptom (MBS) of VVA. After 12 weeks of daily treatment with a prasterone 
6.5 mg pessary (n=81 in Trial 1 and n=325 in Trial 2), the change from baseline, in comparison with 
placebo treatment (n=77 in Trial 1 and n=157 in Trial 2), demonstrated significant improvements of 
the 3 co-primary endpoints compared to placebo in both studies, namely increase of the percentage of 
superficial cells (p<0.0001), decrease of the percentage of parabasal cells (p<0.0001), and decrease in 
the vaginal pH (p<0.0001).  
 
Symptoms (subjective measures) 
The most bothersome symptom (MBS) dyspareunia (co-primary endpoint) was assessed at baseline 
and 12 weeks with the severity scored as follows: None=0, Mild=1, Moderate=2, Severe=3. 
Table 1 shows the mean change in severity score in MBS dyspareunia after 12 weeks with associated 
statistical testing for the difference vs. placebo for Trial 1 (ERC-231) and Trial 2 (ERC-238). 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Table 1: Primary Efficacy Analysis – Change from Baseline to Week 12 in the Most 
Bothersome Symptom Dyspareunia (ITT Population; LOCF) 

 
Study Dyspareunia 

Intrarosa 6.5 mg  Placebo p-value 

Trial 1  -1.27 -0.87 0.0132 

Trial 2  -1.42 -1.06 0.0002 
 
Table 2 shows the percentage of subjects who reported a change from baseline in their MBS 
dyspareunia at week 12. “Improvement” was defined as a reduction in the severity score of 1 or more. 
“Relief” was defined as no or only mild symptoms at week 12. “Substantial improvement” was 
restricted to patients who had moderate or severe MBS at baseline and changed from severe to mild or 
severe or moderate to none. 
 
Table 2:  Percentage of Patients with Improvement, Relief or Substantial Improvement of 

MBS Dyspareunia after 12 Weeks on Intrarosa vs. Placebo (ITT, LOCF) 
 

 
Improvement Relief Substantial  improvement 

 Intrarosa Placebo Intrarosa Placebo Intrarosa Placebo 

Trial 1 
(Intrarosa: n= 81) 
(Placebo: n= 77) 

72.8% 
(p=0.0565) 

58.4% 58.0% 
(p=0.0813) 

44.2% 43.2% 
(p=0.0821) 

29.9% 

Trial 2 
(Intrarosa: n= 325) 
(Placebo: n= 157) 

80.3% 
(p=0.0003) 

65.0% 68.6% 
(p=0.0003) 

51.6% 47.1% 
(p=0.0179) 

35.7% 

 
Clinical safety 
Apart from the main two 12-week phase III clinical studies, the safety data of Intrarosa has also been 
obtained from one non comparative open-label safety study of one year.  
 
Cases of breast and ovarian cancer have been reported in women treated with 6.5 mg of prasterone for 
52 weeks (see section 4.4). 
 
Cases of abnormal Pap smears either Atypical Squamous Cells of Undetermined Significance 
(ASCUS) or Low Grade Squamous Intraepithelial Lesion (LSIL) have been reported with a common 
frequency in women treated with Intrarosa for 52 weeks (see section 4.4). 
 
Endometrial safety 
On the 389 evaluable end-of-study endometrial biopsies performed after 52 weeks of treatment with 
Intrarosa, no histological abnormalities were reported on the biopsies.  
 
Paediatric population 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Intrarosa in all subsets of the paediatric population.  
 
5.2 Pharmacokinetic properties 
 
Absorption 
Prasterone administered in the vagina is an inactive precursor that enters the vaginal cells and is 
converted intracellularly into cell-specific small amounts of both oestrogens and androgens depending 
upon the level of enzymes expressed in each cell type. The beneficial effects on the symptoms and 



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signs of vulvar and vaginal atrophy are exerted through activation of the vaginal oestrogen and 
androgen receptors. 
In a study conducted in postmenopausal women, administration of the Intrarosa pessary once daily for 
7 days resulted in a mean prasterone Cmax and area under the curve from 0 to 24 hours (AUC0-24) at 
day 7 of 4.4 ng/mL and 56.2 ng h/mL, respectively, which were significantly higher than those in the 
group treated with placebo (Table 3; Figure 1). The Cmax and AUC0-24 of the metabolites testosterone 
and estradiol were also slightly higher in women treated with the Intrarosa pessary compared to those 
receiving placebo but all remained within normal values of postmenopausal women 
(< 10 pg estradiol/mL; < 0.26 ng testosterone/mL) as measured by validated mass spectrometry-based 
assays for both the study samples and reference values.  
 

Table 3: Cmax and AUC0-24 of Prasterone, Testosterone, and Estradiol on Day 7 Following Daily 
Administration of Placebo or Intrarosa (mean ± S.D.) 

  Placebo (N=9) INTRAROSA (N=10) 

Prasterone 
Cmax (ng/mL) 1.60 (±0.95) 4.42 (±1.49) 

AUC0-24 (ng⋅h/mL) 24.82 (±14.31) 56.17 (±28.27) 

Testosterone 
Cmax (ng/mL) 0.12 (±0.04)1 0.15 (±0.05) 

AUC0-24 (ng⋅h/mL) 2.58 (±0.94)1 2.79 (±0.94) 

Estradiol 
Cmax (pg/mL) 3.33 (±1.31) 5.04 (±2.68) 

AUC0-24 (pg⋅h/mL) 66.49 (±20.70) 96.93 (±52.06) 
1 : N=8 

 

 

 
Figure 1: Serum Concentrations of Prasterone (A), Testosterone (B), and Estradiol (C) Measured 
Over a 24h Period on Day 7 Following Daily Administration of Placebo or Intrarosa (mean ± S.D.) 

 

Distribution 
The distribution of intravaginal (exogenous) prasterone is mainly local but some increase in systemic 
exposure is observed especially for the metabolites but within normal values.  
 
Biotransformation 
Exogenous prasterone is metabolized in the same manner as endogenous prasterone. Systemic 
metabolism has not been studied in this application. 
 



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Elimination 
Systemic elimination has not been studied specifically for this application. 
 
5.3 Preclinical safety data 
 
Prasterone was not mutagenic or clastogenic in a standard battery of in vitro and in vivo studies. 
 
Carcinogenic and reproductive and development toxicity studies were not performed. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Hard fat (adeps solidus). 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Store below 30 °C.  
 
Do not freeze.  
 
6.5 Nature and contents of container  
 
Blister composed of an outer layer of PVC and an inner layer of LDPE. 
 
Applicator made of LDPE and 1% colorant (Titanium dioxide). 
 
28 pessaries are packed in a carton with 6 applicators. 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Endoceutics S.A. 
Rue Belliard 40 
1040 Brussels 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1255/001 
 
 



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9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 08 january 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
  

http://www.ema.europa.eu/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 



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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) responsible for batch release 

Basic Pharma Manufacturing B.V. 
Burgemeester Lemmensstraat 352 
6163 JT Geleen 
THE NETHERLANDS 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to medical prescription. 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

• Periodic safety update reports  
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

• Risk Management Plan (RMP) 
The MAH shall perform the required  pharmacovigilance activities and interventions detailed in the  
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed  subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 

• Obligation to conduct post-authorisation measures  
The MAH shall complete, within the stated timeframe, the below measures: 
Description Due date 

Non-interventional PASS - Drug Utilisation Study (DUS) to describe the baseline 
characteristics, utilisation patterns of EU postmenopausal women initiating treatment 
with Intrarosa and to assess whether EU prescribers abide by the contraindications stated 
in the EU SmPC. 

Final study report 
by Q4 2021 

  



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 

  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Intrarosa 6.5 mg pessary 
prasterone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pessary contains 6.5 mg of prasterone. 
 
 
3. LIST OF EXCIPIENTS 
 
Hard fat (adeps solidus). 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Pessary 
 
28 pessaries and 6 applicators. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Vaginal use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 30 °C. 
 



19 

Do not freeze. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Endoceutics S.A. 
Rue Belliard 40 
1040 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1255/001 
 
 
13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot.  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Intrarosa 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 
  



20 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Intrarosa 6,5 mg pessary 
prasterone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Endoceutics  
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
5. OTHER 
 
 
 
  



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
INNER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Intrarosa 6.5 mg pessary  
prasterone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pessary contains 6.5 mg of prasterone. 
 
 
3. LIST OF EXCIPIENTS 
 
Hard fat (adeps solidus). 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Pessary.  
 
28 pessaries. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Vaginal use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 30 °C. 
 
Do not freeze. 



22 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Endoceutics S.A. 
Rue Belliard 40 
1040 Brussels 
Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1255/001 
 
 
13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot.  
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



24 

Package leaflet: Information for the user 
 

 
Intrarosa 6.5 mg pessary 

prasterone 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Intrarosa is and what it is used for  
2. What you need to know before you use Intrarosa 
3. How to use Intrarosa  
4. Possible side effects  
5. How to store Intrarosa 
6. Contents of the pack and other information 
 
 
1. What Intrarosa is and what it is used for 
 
Intrarosa contains the active substance prasterone.  
 
What Intrarosa is used for 
Intrarosa is used to treat postmenopausal women having moderate to severe symptoms of vulvar and 
vaginal atrophy. It is used to relieve menopausal symptoms in the vagina such as dryness or irritation. 
It is caused by a drop in the levels of oestrogen in your body. This happens naturally after the 
menopause. 
 
How Intrarosa works 
Prasterone corrects the symptoms and signs of vulvar and vaginal atrophy by replacing the oestrogens 
which are normally produced before menopause by the ovaries of women. It is inserted into your vagina, 
so the hormone is released where it is needed. This may relieve discomfort in the vagina. 
 
 
2. What you need to know before you use Intrarosa  
 
The use of HRT carries risks which need to be considered when deciding whether to start taking it, or 
whether to carry on taking it.  
 
The experience in treating women with a premature menopause (due to ovarian failure or surgery) is 
limited. If you have a premature menopause the risks of using HRT may be different. Please talk to 
your doctor.  
 
Before you start (or restart) HRT, your doctor will ask about your own and your family’s medical 
history. Your doctor may decide to perform a physical examination. This may include an examination 
of your breasts and/or an internal examination, if necessary.  



25 

 
Once you have started on Intrarosa you should see your doctor for regular check-ups (at least every 
6 months). At these check-ups, discuss with your doctor the benefits and risks of continuing with 
Intrarosa. 
 
Go for regular breast screening, as recommended by your doctor. 
 
Do not take Intrarosa 
if any of the following applies to you. If you are not sure about any of the points below, talk to your 
doctor before taking Intrarosa, 
• If you have or have ever had breast cancer, or if you are suspected of having it; 
• If you have cancer which is sensitive to oestrogens, such as cancer of the womb lining 

(endometrium), or if you are suspected of having it; 
• If you have any unexplained vaginal bleeding; 
• If you have excessive thickening of the womb lining (endometrial hyperplasia ) that is not 

being treated; 
• If you have or have ever had a blood clot in a vein (thrombosis), such as in the legs (deep 

venous thrombosis) or the lungs (pulmonary embolism); 
• If you have a blood clotting disorder (such as protein C, protein S, or antithrombin deficiency); 
• If you have or recently have had a disease caused by blood clots in the arteries, such as a heart 

attack, stroke or angina; 
• If you have or have ever had a liver disease and your liver function tests have not returned to 

normal; 
• If you have a rare blood problem called “porphyria” which is passed down in families 

(inherited); 
• If you are allergic (hypersensitive) to prasterone or any of the other ingredients of Intrarosa 

(listed in section 6 Further information). 
 
If any of the above conditions appears for the first time while taking Intrarosa, stop taking it at once 
and consult your doctor immediately. 
 
Warnings and precautions 
 
When to take special care with Intrarosa 
Tell your doctor if you have ever had any of the following problems, before you start the treatment, as 
these may return or become worse during treatment with Intrarosa. If so, you should see your doctor 
more often for check-ups: 
 

• fibroids inside your womb;  
• growth of womb lining outside your womb (endometriosis) or a history of excessive growth of 

the womb lining (endometrial hyperplasia); 
• increased risk of developing blood clots (see “Blood clots in a vein (thrombosis)”);  
• increased risk of getting a oestrogen-sensitive cancer (such as having a mother, sister or 

grandmother who has had breast cancer); 
• high blood pressure; 
• a liver disorder, such as a benign liver tumour; 
• diabetes; 
• gallstones;  
• migraine or severe headaches; 
• a disease of the immune system that affects many organs of the body (systemic lupus 

erythematosus, SLE); 
• epilepsy; 
• asthma; 
• a disease affecting the eardrum and hearing (otosclerosis); 
• a very high level of fat in your blood (triglycerides); 
• fluid retention due to cardiac or kidney problems. 



26 

 
Stop taking Intrarosa and see a doctor immediately  
If you notice any of the following when taking HRT: 

• any of the conditions mentioned in the ‘DO NOT take Intrarosa’ section; 
• yellowing of your skin or the whites of your eyes (jaundice). These may be signs of a liver 

disease; 
• if you become pregnant; 
• a large rise in your blood pressure (symptoms may be headache, tiredness, dizziness); 
• migraine-like headaches which happen for the first time; 
• if you notice signs of a blood clot, such as: 

- painful swelling and redness of the legs; 
- sudden chest pain; 
- difficulty in breathing. 

For more information, see ‘Blood clots in a vein (thrombosis)’ 
 
Note: Intrarosa is not a contraceptive. If it is less than 12 months since your last menstrual period or 
you are under 50 years old, you may still need to use additional contraception to prevent pregnancy. 
Speak to your doctor for advice. 
 
HRT and cancer 
Intrarosa has not been studied in women with current or history of cancers.  

Excessive thickening of the lining of the womb (endometrial hyperplasia) and cancer of the lining 
of the womb (endometrial cancer) 
Taking oestrogen-only HRT tablets for a long time can increase the risk of developing cancer of the 
womb lining (the endometrium). Intrarosa does not stimulate the endometrium as shown by atrophy of 
the lining of the womb in all women treated with Intrarosa for one year during the clinical trials. 
 
It is uncertain whether a  risk exists with Intrarosa used for long term (more than one year) treatments.  
However, Intrarosa has been shown to have very low absorption into the blood, therefore the addition 
of a progestagen is not necessary. 
 
If you get bleeding or spotting, it’s usually nothing to worry about, but you should make an 
appointment to see your doctor. It could be a sign that your endometrium has become thicker. 
 
The following risks apply to HRT medicines which circulate in the blood. However Intrarosa is for 
local treatment in the vagina and the absorption into the blood is very low. It is less likely that the 
conditions mentioned below will get worse or come back during treatment with Intrarosa, but you 
should see your doctor if you are concerned. 
 
Breast cancer 
Evidence suggests that taking combined oestrogen-progestogen and possibly also oestrogen-only HRT 
increases the risk of breast cancer. The extra risk depends on how long you take HRT. The additional 
risk becomes clear within a few years. However, it returns to normal within a few years (at most 5) 
after stopping treatment.  
 
• Regularly check your breasts. See your doctor if you notice any changes such as: 

 • dimpling of the skin; 
 • changes in the nipple; 
 • any lumps you can see or feel. 
 

Additionally, you are advised to join mammography screening programs when offered to you. 
 
Ovarian cancer 
Ovarian cancer is rare - much rarer than breast cancer. The use of oestrogen-only HRT has been 
associated with a slightly increased risk of ovarian cancer.  
 



27 

The risk of ovarian cancer varies with age. For example, in women aged 50 to 54 who are not taking 
HRT, about 2 women in 2000 will be diagnosed with ovarian cancer over a 5-year period. For women 
who have been taking HRT for 5 years, there will be about 3 cases per 2000 users (i.e. about 1 extra 
case). 
Cases of ovarian and breast cancer have rarely been reported in women treated with 6.5 mg of 
prasterone for 52 weeks. 
 
Effect of HRT on heart and circulation 
Intrarosa has not been studied in women with history of thromboembolic diseases, uncontrolled 
hypertension or heart disease.  
 
Blood clots in a vein (thrombosis) 
The risk of blood clots in the veins is about 1.3 to 3-times higher in HRT users than in non-users, 
especially during the first year of taking it.  
 
Blood clots can be serious, and if one travels to the lungs, it can cause chest pain, breathlessness, 
fainting or even death.  
 
You are more likely to get a blood clot in your veins as you get older and if any of the following 
applies to you. Inform your doctor if any of these situations applies to you: 

• you are unable to walk for a long time because of major surgery, injury or illness (see also 
section 3, If you need to have surgery); 

• you are seriously overweight (BMI >30 kg/m2); 
• you have any blood clotting problem that needs long-term treatment with a medicine used to 

prevent blood clots; 
• if any of your close relatives has ever had a blood clot in the leg, lung or another organ; 
• you have systemic lupus erythematosus (SLE); 
• you have cancer. 

 
For signs of a blood clot, see “Stop taking Intrarosa and see a doctor immediately”. 
In clinical trials, no deep vein thrombosis has been observed with intravaginal prasterone while one 
case of pulmonary embolism which corresponds to an incidence lower with Intrarosa than in the 
placebo group. 
 
Compare 
Looking at women in their 50s who are not taking HRT, on average, over a 5-year period, 4 to 7 in 1000 
would be expected to get a blood clot in a vein.  
 
Heart disease (heart attack) / Hypertension 
For women taking oestrogen-only therapy there is no increased risk of developing a heart disease. 
 
Stroke 
The risk of getting stroke is about 1.5 times higher in HRT users than in non-users. The number of 
extra cases of stroke due to use of HRT will increase with age.  
No case of stroke has been observed with Intrarosa during clinical trials. 
 
Compare 
Looking at women in their 50s who are not taking HRT, on average, 8 in 1000 would be expected to 
have a stroke over a 5-year period. For women in their 50s who are taking HRT, there will be 11 cases 
in 1000 users, over 5 years (i.e. an extra 3 cases). 
 
Other conditions 
• HRT will not prevent memory loss. There is some evidence of a higher risk of memory loss in 

women who start using HRT after the age of 65. Speak to your doctor for advice; 
• You may have vaginal discharge due to melting of the ‘hard fat base’ which adds to increased 

vaginal secretions due to treatment. If vaginal discharge occurs, it is not required to stop 
Intrarosa.  



28 

• Intrarosa may weaken condoms, diaphragms and cervical caps made of latex. 
• If you have a vaginal infection you will need a course of antibiotics before taking Intrarosa. 
 
Children and adolescents 
 
Intrarosa is only used in adult women.  
 
Other medicines and Intrarosa  
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
No data on efficacy and safety are available in women currently treated with hormonal therapy such 
as: androgens, hormone replacement therapy (oestrogen alone or combined with progestogens).  
 
The use of Intraorsa in combination with hormone replacement therapy (oestrogen-only or oestrogen-
progestagen combination or androgen treatment) or vaginal oestrogens is not recommended. 
 
Pregnancy, breast feeding and fertility 
 
Pregnancy and breast feeding  
Intrarosa is for use in postmenopausal women only. If you become pregnant, stop taking Intrarosa and 
contact your doctor. 
 
Fertility 
Intrarosa is not meant for women with child-bearing potential. It is not known if this medicine affects 
fertility. 
 
Driving and using machines 
 
Intrarosa does not affect your ability to drive and use machines. 
 
 
3. How to use Intrarosa 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
Your doctor will aim to prescribe the lowest dose to treat your symptom for as short as necessary. 
Speak to your doctor if you think this dose is too strong or not strong enough. 
 
How much to use 
Use one pessary once a day, at bedtime. 
 
How to use 
Insert the pessary into the vagina with your finger or with an applicator provided in the pack. 
 
Read the instructions on how to use Intrarosa at the end of the leaflet carefully before using this 
medicine. 
 
How long to use 
After initial use, see your doctor at least every 6 months to check if you need to keep using Intrarosa. 
 
If you use more Intrarosa than you should 
 
Vaginal douching is recommended. 
 
 



29 

If you forget to use Intrarosa 
 
If you forget to use a pessary, insert one as soon as you remember. However, if the next dose is due in 
less than 8 hours, skip the missed pessary. 
 
Do not use two pessaries to make up for a forgotten dose. 
 
If you need to have surgery  
 
If you are going to have surgery, tell the surgeon that you are taking Intrarosa. You may need to stop 
taking Intrarosa about 4 to 6 weeks before the operation to reduce the risk of a blood clot (see 
section 2, Blood clots in a vein). Ask your doctor when you can start taking Intrarosa again. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The following diseases are reported more often in women using HRT medicines which circulate in the 
blood compared to women not using HRT. These risks apply less to vaginally administered oestrogen 
treatments: 

• breast cancer; 
• ovarian cancer; 
• blood clots in the veins of the legs or lungs (venous thromboembolism);  
• stroke; 
• probable memory loss if HRT is started over the age of 65. 

For more information about these side effects, see section 2. 
 
The side effect the most frequently reported in the clinical studies was vaginal discharge. This is likely 
due to melting of the hard fat added to an expected increase in vaginal secretions due to treatment. 
Vaginal discharge does not require to stop Intrarosa. 
 
The following adverse effects were also reported: 
− with a common frequency (may affect up to 1 in 10 people): abnormal Pap smear (mostly 

ASCUS or LGSIL), weight fluctuations (either increase or decrease); 
− with a uncommon frequency (may affect up to 1 in 100 people): benign cervical or uterine 

polyps, benign breast mass.  
 
The following side effects have been reported with HRT containing estrogens but not with Intrarosa 
during clinical trials: 
• gall bladder disease 
• various skin disorders: 

- discoloration of the skin especially of the face or neck known as “pregnancy patches” 
(chloasma); 

- painful reddish skin nodules (erythema nodosum); 
- rash with target-shaped reddening or sores (erythema multiforme). 

 
Reporting of side effects 
 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


30 

5. How to store Intrarosa 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and blisters after EXP. The 
expiry date refers to the last day of that month. 
 
Store below 30 °C. 
 
Do not freeze. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Intrarosa contains  
- The active substance is prasterone. Each pessary contains 6.5 mg of prasterone. 
- The only other ingredient is the hard fat (adeps solidus).  
 
What Intrarosa looks like and contents of the pack 
 
Intrarosa is a white to off-white, bullet-shaped pessary approximately 28 mm long and 9 mm in 
diameter at its widest end. 
 
The applicator is made of LDPE and 1% colorant (Titanium dioxide). 
 
It is available in blister packs of 28 pessaries with 6 applicators. 
 
Marketing Authorisation Holder 
 
Endoceutics S.A. 
Rue Belliard 40 
1040 Brussels 
Belgium 
 
Manufacturer 
 
Basic Pharma Manufacturing B.V. 
Burgemeester Lemmensstraat 352 
6163 JT Geleen 
The Netherlands 
 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien, Luxembourg/Luxemburg, Nederland 
Theramex Belgium BVBA 
Tél/Tel: + 32 (0) 28088080 
INTRAROSA.Enquiries@theramex.com 
  
Deutschland, Österreich 
Theramex Germany GmbH 
Tel: + 49 (0) 3088789684 
INTRAROSA.Enquiries@theramex.com 

  

mailto:INTRAROSA.Enquiries@theramex.com
mailto:INTRAROSA.Enquiries@theramex.com


31 

  
España 
Lacer S.A. 
Tel: + 34 934 46 53 00 

 

  
France 
Theramex France S.A.S. 
Tél: + 33 (0) 800100350 
INTRAROSA.Enquiries@theramex.com 

 

  
Italia 
Theramex Italy S.r.l. 
Tel: + 39 (0) 687500626 
INTRAROSA.Enquiries@theramex.com 

 

  
Polska 
Theramex Poland sp. z o.o. 
Tel.: + 48 (0) 22 30 77 166 
INTRAROSA.Enquiries@theramex.com 

 

  
Portugal 
Tecnimede - Sociedade Técnico-Medicinal, S.A. 
Tel: + 351 210 414 100 
dmed.fv@tecnimede.pt  

 

  
United Kingdom, Ireland, Malta 
Theramex UK Limited 
Tel: + 44 (0) 3330096795 
INTRAROSA.Enquiries@theramex.com 

 

  
Danmark, Ísland, Norge, Suomi/Finland, Sverige  
Avia Pharma AB 
Sverige/Svíþjóð/Ruosti 
Tlf/Sími/Tlf/Puh/Tel: + 46 (0) 8 544 900 22 

 

  
България, Česká republika, Eesti, Ελλάδα, Hrvatska, Κύπρο, Latvija, Lietuva, 
Magyarország,  România, Slovenija, Slovenská republika 
Theramex Ireland Limited 
Tel/Teл./Τηλ: + 353 (0) 15138855 
INTRAROSA.Enquiries@theramex.com 

 
 
This leaflet was last revised in MM/YYYY. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. 
 

mailto:INTRAROSA.Enquiries@theramex.com
mailto:INTRAROSA.Enquiries@theramex.com
mailto:INTRAROSA.Enquiries@theramex.com
mailto:dmed.fv@tecnimede.pt
mailto:INTRAROSA.Enquiries@theramex.com
mailto:INTRAROSA.Enquiries@theramex.com


32 

Instructions on how to use Intrarosa 
How should I use Intrarosa 

• Insert one prasterone pessary in your vagina once a day at bedtime with an applicator or your finger.
Before you start 

• Empty your bladder and wash your hands before handling the pessary and applicator.
• Tear off one wrapped pessary from the 7-pessary strip.

A. Using the applicator 

STEP 1 
• 1A. Remove 1 applicator

from the package.
• 1B. Pull back on the plunger

until it stops to activate the
applicator. The applicator
must be activated before
use. Place the applicator on
a clean surface.

STEP 5 
• Select the position for

insertion of the pessary that is
most comfortable for you.

5a. Lying position 

STEP 2 
• Slowly pull the plastic tabs

on the pessary away from
each other while keeping the 
pessary still between your
fingers.

• Carefully remove the
pessary from the plastic
wrap.

• If a pessary falls on an
unsanitary surface, replace it
with a new one.

5b. Standing position 

STEP 3 
• Place the flat end of the

pessary into the open end
of the activated applicator
as shown. You are now
ready to insert the pessary
into your vagina.

STEP 6 
• Gently slide the pessary end

of the applicator into your
vagina as far as it will
comfortably go.

Do not use force. 

STEP 4 

• Hold the applicator
between your thumb and
middle finger.

• Leave your index (pointer)
finger free to press the
applicator plunger after the
applicator is inserted into
your vagina.

STEP 7 

• Press the applicator plunger
with your index (pointer)
finger to release the pessary.

• Remove the applicator. Wash
it or throw it away after using
for one week (two extra
applicators are provided).

• To wash the applicator:
− Take it to pieces;
− Rinse the 2 pieces for 30

seconds under running 
water; 

− Wipe with a paper towel 
and reassemble. 

Keep it in a clean place. 



33 

B. Using the finger 
Follow the above instructions of Step 2, and then insert the pessary into the vagina with your finger as far as it can 
comfortably go.   Do not use force. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET