Leaflet: information for the user

COLPOTROFÍN 10 mg/g vaginal cream

Promestrieno

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

-Keep this leaflet, as you may need to read it again.

-If you have any questions, ask your doctor or pharmacist.

-This medicine has been prescribed for you only. Do not give it to others even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What is Colpotrofín 10 mg/g vaginal cream and what it is used for

2.What you need to know before using Colpotrofín 10 mg/g vaginal cream

3.How to use Colpotrofín 10 mg/g vaginal cream

4.Possible side effects

5.Storage of Colpotrofín 10 mg/g vaginal cream

6.Contents of the pack and additional information

Colpotrofin belongs to the group of medications known as estrogens (female sex hormones).

Colpotrofin is used to treat atrophic disorders of the female genital area (vulva, vestibule, and vaginal ring) that appear in situations where there is a decrease in estrogens, such as menopause, castration, use of contraceptives, etc., and that are manifested with dryness, itching, or irritation of the skin and genital mucosa.

No useColpotrofín

• If you are allergic to the active ingredient or any of the other components of this medication (listed in section 6).
• If you are breastfeeding.
• If you have a history, known presence, or suspicion of breast cancer.
• If you have a history or suspicion of estrogen-dependent malignant tumors (e.g., endometrial cancer).
• If you have undiagnosed genital bleeding.
• If you have untreated endometrial hyperplasia.
• If you have or have had venous thromboembolism (deep vein thrombosis, pulmonary embolism).
• If you have known thrombophilic disorders (e.g., protein C, protein S, or antithrombin deficiency, see "Warnings and precautions").
• If you have recent or active arterial thromboembolic disease (e.g., angina pectoris or myocardial infarction).
• If you have acute liver disease or a history of liver disease when liver function values have not returned to normal.
• If you have porphyria (a rare, usually inherited disorder in which a large amount of porphyrin is eliminated in feces and urine).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Colpotrofin.Before initiating or reconstituting treatment, a complete personal and family medical history and periodic controls adapted to each woman, including mammograms, should be performed. Changes in the breasts should be reported to your doctor.

Be especially careful with Colpotrofin:

• If you have or have had vaginal stenosis (vaginal narrowing) or vaginal prolapse.
• If you have or have had a disease characterized by growth of tissue covering the uterus outside of it (endometriosis) or a type of benign tumor of the uterus (uterine fibroid).

For the treatment of postmenopausal symptoms, local estrogen therapy should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful assessment of the risks and benefits should be performed at least annually, and therapy should only be continued if the benefit outweighs the risk.

The data on the risks associated with hormone replacement therapy (HRT) in the treatment of premature menopause is limited. However, due to the low absolute risk in young women, the balance of benefits and risks may be more favorable in young women than in older women.

Situations that require supervision

If any of the following situations affect you, have affected you previously, and/or have worsened during pregnancy or before hormone treatment, inform your doctor immediately, as you will need to be closely monitored. These situations may be recurrent or worsen during treatment with promestrieno, particularly:

• Uterine fibroids or endometriosis.
• Risk factors for thromboembolic disorders.
• Risk factors for estrogen-dependent tumors, for example, hereditary breast cancer of the first degree.
• High blood pressure.
• Liver disorders (e.g., hepatic adenoma).
• Diabetes mellitus with or without vascular involvement.
• Biliary calculi (cholelithiasis).
• Migraine or severe headache.
• Systemic lupus erythematosus (a disease of the immune system that affects connective tissue).
• History of endometrial hyperplasia.
• Epilepsy.
• Asthma.
• Otosclerosis (a disease that affects the tympanic membrane and hearing).

Reasons for immediate discontinuation of treatment

Treatment should be discontinued if a contraindication is discovered and in the following situations:

• Yellowing of the skin or mucous membranes (jaundice) or deterioration of liver function.
• Significant increase in blood pressure.
• New onset of migrainous headache.
• Pregnancy.

Endometrial hyperplasia and carcinoma

The long-term safety of the endometrium (more than one year) or repeated use of estradiols administered locally via the vagina is uncertain. Therefore, if treatment is repeated, it should be reviewed at least annually.

If you have had a hysterectomy (removal of the uterus) due to endometriosis and have residual endometriosis, inform your doctor, as caution is recommended when using this type of medication.

If bleeding or spotting occurs at any time during treatment, inform your doctor, as it should be investigated, and your doctor may perform an endometrial biopsy.

HRT and cancer

The following risks apply to hormone replacement therapy (HRT) that circulates in the blood. However, Colpotrofin is used for local treatment in the vagina, and absorption into the blood is very small. It is less likely that the mentioned disorders will worsen or recur during treatment with Colpotrofin, but you should consult your doctor if you are concerned.

Breast cancer

The available data indicate that using Colpotrofin does not increase the risk of breast cancer in women who have not had breast cancer in the past. It is not known if Colpotrofin can be used safely in women who have had breast cancer in the past.

Ovarian cancer

Ovarian cancer is much rarer than breast cancer.

Epidemiological data suggest a slight increase in risk in women taking systemic estrogen-only hormone replacement therapy (HRT), which becomes apparent within 5 years of use and decreases over time after treatment is stopped.

Venous thromboembolism

Systemic hormone replacement therapy (HRT) is associated with a 1.3-3 times higher 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 hormone replacement therapy (HRT) than after (see section 4).

Generally, patients with known thromboembolic states have a higher risk of VTE, and hormone replacement therapy (HRT) may increase this risk. Therefore, hormone replacement therapy (HRT) is contraindicated in these patients (see section 2 "Do not use Colpotrofin").

If prolonged immobilization is required after optional surgery, it is recommended to temporarily discontinue hormone replacement therapy (HRT) for 4-6 weeks. Treatment should not be resumed until you can move completely.

Women without personal history of VTE but with a family member with a history of thrombosis at a young age should be carefully evaluated.

Hormone replacement therapy (HRT) is contraindicated if a thrombophilic defect that has caused thrombosis in family members is identified or if the defect is severe (e.g., antithrombin, protein S, or protein C deficiency or a combination of defects).

Women already on chronic anticoagulant therapy require careful consideration of the benefit-risk of using hormone replacement therapy (HRT).

If VTE occurs after starting treatment, the medication should be discontinued. You should contact your doctor immediately if you detect any potential thromboembolic symptoms (e.g., painful swelling of a leg, sudden chest pain, shortness of breath).

Coronary artery disease (CAD)

Studies have not increased the risk of CAD in women who have undergone hysterectomy and used systemic estrogen-only hormone replacement therapy.

Ischemic stroke

Systemic estrogen-only hormone replacement therapy is associated with a 1.5 times higher risk of ischemic stroke.

This relative risk is not dependent on age or duration of use, but as the baseline risk is strongly dependent on age, the overall risk of stroke in women using hormone replacement therapy (HRT) will increase with age (see section 4).

Other situations

Estradiols can cause fluid retention, and patients with heart or kidney dysfunction should be closely monitored.

If you have pre-existing hypertriglyceridemia, your doctor will closely monitor you during estrogen substitution or hormone replacement therapy (HRT), as rare cases of significant increases in plasma triglycerides have been reported, leading to pancreatitis with estrogen therapy in this condition.

There is some evidence of an increased risk of probable dementia in women who start using continuous combined hormone replacement therapy or estrogen-only hormone replacement therapy after the age of 65.

Use of Colpotrofin with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Due to the intravaginal administration of promestrieno and its minimal systemic absorption, it is unlikely that clinically significant interactions will occur with promestrieno. However, interactions with other locally applied vaginal treatments should be considered.

It is not recommended to use this medication with spermicides (substances that alter or kill sperm).

Pregnancy and lactation

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

There is insufficient information on the use of promestrieno in pregnant women. Promestrieno is not indicated during pregnancy. If you become pregnant during treatment with promestrieno, discontinue it immediately.

The results of most current epidemiological studies on accidental fetal exposure to estradiols indicate that there are no teratogenic or fetotoxic effects.

Lactation

It is not recommended to use this medication during lactation, as the medication may pass into breast milk.

Driving and operating machinery

Not applicable.

Colpotrofin contains parahydroxybenzoate methyl ester, sodium salt (E-219) and parahydroxybenzoate propyl ester, sodium salt (E-217)

This medication may cause allergic reactions (possibly delayed) because it contains parahydroxybenzoate methyl ester, sodium salt (E-219) and parahydroxybenzoate propyl ester, sodium salt (E-217).

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will prescribe the lowest dose to treat your symptoms for the shortest time possible. Consult your doctor if you think the dose is too strong or too weak.

This medication is administered via the vaginal route.

The recommended dose is:

• One or two applications per day of the amount of cream necessary to cover the treated area, followed by gentle massage.
• In cases where it is considered convenient to apply the cream intravaginally, this will be done 1-2 times per day, with one of the doses being recommended to be administered at night, before going to bed, equivalent to a dose of 10-20 mg of promestriene per day.

Your doctor may adjust the dose based on the observed improvement.

The treatment should last an average of 3 weeks.

If the underlying condition persists (menopause, castration, contraceptive treatments with estrogen-progestogen) or if the iatrogenic effect (due to medical intervention) is lasting (irradiations), it may be necessary to perform maintenance treatments.

Intravaginal application mode:

• For the intravaginal application of the cream, a special applicator included in the packaging will be used, loading it directly from the tube, up to the signal that appears on the applicator and corresponds to1 gramof cream (Figure 1).

• Once loaded, it will be inserted into the vagina to the desired depth, injecting the dose by pressing the plunger (Figure 2).

• The application is easier in a lying position with the legs flexed and slightly separated (Figure 3).

Once the applicator has been used, it should be washed with warm water for its best conservation and subsequent use.

If you need to undergo surgery

If you are to undergo surgery, inform the surgeon that you are using Colpotrofin. You may need to stop using Colpotrofin for 4 to 6 weeks before the operation to reduce the risk of a blood clot (see section 2). Ask your doctor when you can start using Colpotrofin again.

If you use more Colpotrofín than you should

Given the application route, it is unlikely that an overdose will occur.

However, excessive use may lead to the exacerbation of local side effects such as irritation, pruritus, and burning sensation in the vulvar area.

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicological Information Service, phone91 562 04 20, indicating the medication and the amount used.

If you forgot to use Colpotrofín

Do not use a double dose to compensate for the missed doses.

If you forgot to use this medication when it was due, apply the cream as soon as you remember and continue with your regular treatment regimen.

If you have any other doubts about the use of this product, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Very rare (may affect up to 1 in 10,000 people): allergic reactions (e.g., hives, eczema, severe allergic reaction).

Very rare (may affect up to 1 in 10,000 people): vaginal/vulvar itching.

Frequency not known (the frequency cannot be estimated from the available data): vaginal bleeding.

Frequency not known (the frequency cannot be estimated from the available data): burning sensation in the vagina/vulva, vaginal discomfort, vaginal pain, vaginal discharge.

Class effects associated with systemic hormone replacement therapy (HRT)

The following risks have been associated with systemic hormone replacement therapy (HRT)and apply to a lesser degree to estrogen products for vaginal application, of which systemic exposure to estrogens remains within the normal postmenopausal range.

The following diseases are observed more frequently in women using systemic HRT medications compared to women not using HRT. These risks are less related to treatments administered vaginally, such as Colpotrofin.

Ovarian cancer

The use ofsystemic hormone replacement therapy (HRT)has been associated with a slight increase in the risk of diagnosed ovarian cancer (see section 2).

Increased risk of venous thromboembolism

Systemic hormone replacement therapy (HRT)has been associated with an increased risk of 1.3-3 times more of developing venous thromboembolism (VTE), i.e., deep vein thrombosis or pulmonary embolism. The incidence of such an event is more likely in the first year of use of hormone therapy (see section 2).

Increased risk of stroke

The use ofsystemic hormone replacement therapy (HRT)is associated with an increased risk of up to 1.5 times more of stroke. The risk of hemorrhagic stroke does not increase during the use of hormone replacement therapy (HRT).

This relative risk is not dependent on age or duration of use, but as the baseline risk is strongly dependent on age, the overall risk of stroke in women using hormone replacement therapy (HRT)will increase with age, see section 2.

Other adverse reactions have been reported in association with systemic estrogen/progestogen treatment:Estimates of risk were based on systemic exposure to estrogens and it is not known how these may be extrapolated to local treatment:

• Gallbladder disease
• Skin and subcutaneous tissue disorders: yellow-brown skin discoloration, particularly on the face (melasma), red lesions on the extremities and interior of the mouth (erythema multiforme), inflammation in the form of nodules under the skin (erythema nodosum), red or purple discoloration of the skin and/or mucous membranes (purpura).
• Probable dementia above 65 years of age (see section 2).

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

This medicationdoes not require special conditions for conservation.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box after CAD. The expiration date is the last day of the month indicated.

Medicines should not be thrown down the drains or in the trash. Dispose of the containers and medicines you no longer need at the SIGRE collection pointof the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. By doing so, you will help protect the environment.

Composition of Colpotrofín

• The active principle is promestriene. Each gram of cream contains 10 mg of promestriene.
• The other components (excipients) are monoestearate of glycerol, decylo oleate, medium-chain triglycerides, glycerol (E-422), eumulgine, methyl parahydroxybenzoate, sodium salt (E-219), propyl parahydroxybenzoate, sodium salt (E-217), and purified water.

Appearance of the product and contents of the packaging

Colpotrofín is a white, greasy cream.

It is presented in an aluminum tube with a polypropylene screw cap and an applicator containing 15 g or 30 g of cream.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Theramex Ireland Limited

3rd Floor, Kilmore House,

Park Lane, Spencer Dock,

Dublin 1

D01 YE64

Ireland

Responsible for manufacturing

Laboratoires CHEMINEAU

93 route de Monnaie

37210 Vouvray

France

Local Representative

Theramex Healthcare Spain, S.L.

Calle Martínez Villergas 52, Edificio C, planta 2ª izquierda.

28027 Madrid

Spain

Last review date of this leaflet: March 2022

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/