Ciclo-proginova

Package Leaflet: Information for the User

Cyclo-Progynova, 2 mg (white); 2 mg + 0.5 mg (light brown), film-coated tablets
(Estradiol valerate; Estradiol valerate + Norgestrel)

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient

• Keep this package leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Cyclo-Progynova and what is it used for
• 2. Important information before taking Cyclo-Progynova
• 3. How to take Cyclo-Progynova
• 4. Possible side effects
• 5. How to store Cyclo-Progynova
• 6. Contents of the pack and other information

1. What is Cyclo-Progynova and what is it used for

Cyclo-Progynova is a medicine used in Hormone Replacement Therapy (HRT).
It contains two different hormones: estrogen and progestogen. In postmenopausal women, the ovaries stop producing these hormones.

What is Cyclo-Progynova used for

Cyclo-Progynova is used to treat symptoms of estrogen deficiency (such as hot flashes, sleep disturbances, dizziness, vaginal dryness) following natural menopause or hypogonadism, removal of the uterus or primary ovarian failure in women with an intact uterus.
Cyclo-Progynova is used to control irregular menstrual cycles.
Treatment of primary or secondary amenorrhea.
Cyclo-Progynova is not a contraceptive.

2. Important information before taking Cyclo-Progynova

Medical history and regular medical examination

Taking HRT involves risks that need to be considered when deciding to start or continue treatment.
Experience with the treatment of women with premature menopause (due to ovarian failure or surgery) is limited. In women with premature menopause, the risks associated with HRT may be different. In such cases, consult a doctor.
Before starting (or restarting) HRT, the doctor will take a medical history of the patient and her family. The doctor may decide that a medical examination is necessary. The doctor may examine the breasts and (if necessary) perform a gynecological examination.
After starting Cyclo-Progynova, the patient should have regular medical check-ups (at least once a year). During these visits, the benefits and risks associated with continuing Cyclo-Progynova should be discussed with the doctor.
Regular breast examinations should be performed as recommended by the doctor.
Patients with pituitary adenoma require careful observation (including periodic prolactin level tests).

When not to take Cyclo-Progynova

Do not take Cyclo-Progynova if you have any of the following conditions. If you are unsure whether any of these conditions apply to you, consult a doctor before taking Cyclo-Progynova.
Do not take Cyclo-Progynova:

• if you are allergic (hypersensitive) to the active substances or any of the other ingredients of Cyclo-Progynova (listed in section 6);
• if you have breast cancer - diagnosed in the past or suspected;
• if you have estrogen-dependent tumors (e.g. endometrial cancer) or if you suspect you have such a tumor;
• if you have unexplained vaginal bleeding;
• if you have untreated endometrial hyperplasia (thickening of the lining of the uterus);
• if you have a current or past blood clot in a vein (thrombosis), such as in the legs (deep vein thrombosis) or lungs (pulmonary embolism);
• if you have had a disease caused by blood clots in an artery, such as a heart attack, stroke, or angina;
• if you have blood clotting disorders (such as protein C, protein S, or antithrombin deficiency);
• if you have had liver disease in the past and liver function tests have not returned to normal;
• if you are pregnant or breastfeeding;
• increased risk of venous or arterial thromboembolic disease;
• if you have a rare, inherited blood disorder called porphyria.

If any of these conditions occur for the first time while taking Cyclo-Progynova, stop taking the medicine and consult a doctor immediately.

Warnings and precautions

Before starting Cyclo-Progynova, discuss it with your doctor, pharmacist, or nurse.
When to be particularly careful when taking Cyclo-Progynova.

If the patient has ever had any of the following conditions, they should inform their doctor before starting treatment, as these conditions may recur or worsen during Cyclo-Progynova treatment. In such cases, more frequent check-ups with the doctor are recommended:

In such cases, more frequent check-ups with the doctor are recommended:

• uterine fibroids;
• endometriosis or endometrial hyperplasia in the past;
• increased risk of blood clots (see below "Blood clots in veins (thrombosis)");
• increased risk of estrogen-dependent tumors, such as breast cancer in the patient's mother, sister, or grandmother;
• high blood pressure;
• liver disease, such as a benign liver tumor;
• diabetes;
• gallstones;
• migraine or severe headaches;
• systemic lupus erythematosus (SLE), an immune system disease that can affect many organs;
• inherited or acquired angioedema;
• epilepsy;
• asthma;
• otosclerosis (a condition affecting the bones of the middle ear);
• very high levels of triglycerides (a type of fat) in the blood;
• fluid retention due to heart or kidney failure;
• chorea minor (a movement disorder).

Stop taking Cyclo-Progynova and consult a doctor immediately

If the patient experiences any of the following symptoms while taking HRT:

• any of the conditions listed in the "When not to take Cyclo-Progynova" section;
• yellowing of the skin or whites of the eyes (jaundice) - this may be a sign of liver disease;
• a significant increase in blood pressure (symptoms may include headache, fatigue, dizziness);
• the onset of migraine-like headaches;
• pregnancy;
• symptoms that may indicate a blood clot, such as:
• painful swelling and redness of the legs;
• sudden chest pain;
• shortness of breath;
• swelling of the face, tongue, and/or throat, and/or difficulty swallowing or hives, accompanied by difficulty breathing, which may indicate angioedema.

Note: Cyclo-Progynova is not a contraceptive. Women who have not had a menstrual period for 12 months or are under 50 years of age may still require additional contraception to prevent pregnancy. Consult a doctor for advice.

HRT and cancer

Endometrial hyperplasia (thickening of the lining of the uterus) and endometrial cancer
(cancer of the lining of the uterus)
Taking only estrogens in HRT increases the risk of endometrial hyperplasia and endometrial cancer.
The progestogen in Cyclo-Progynova protects against this additional risk.
In women who have not had a hysterectomy and are not taking HRT, endometrial cancer is diagnosed in about 5 out of 1000 women between the ages of 50 and 65. Depending on the duration of treatment and the dose of estrogens taken, in women between the ages of 50 and 65 who have not had a hysterectomy and are taking only estrogens in HRT, endometrial cancer is diagnosed in 10 to 60 out of 1000 women (i.e., an additional 5 to 55 cases).
Unusual bleeding
While taking Cyclo-Progynova, monthly bleeding (so-called withdrawal bleeding) will occur. However, if unusual bleeding or spotting occurs between monthly bleedings, which:

• lasts longer than the first 6 months,
• occurs after taking Cyclo-Progynova for more than 6 months,
• continues after stopping HRT,
consult a doctor as soon as possible.

Breast cancer
There is evidence that taking HRT (combined estrogen-progestogen or estrogen-only) increases the risk of breast cancer - this risk is dependent on the duration of treatment. The increased risk becomes apparent after 3 years of HRT. After stopping HRT, the additional risk will decrease over time, but the risk may persist for 10 years or more if HRT lasted more than 5 years.

The patient should regularly examine their breasts. If any of the following changes occur, consult a doctor:

• indentation of the skin;
• changes in the nipple;
• any noticeable or palpable lumps.

In addition, it is recommended to participate in screening mammography if available. When undergoing screening mammography, it is essential to inform the nurse or medical staff performing the X-ray that you are taking HRT, as this medication may increase breast density, which can affect the mammography result.
In areas of increased breast density, mammography may not detect all lumps.
Comparison
In women between the ages of 50 and 54 who are not taking HRT, breast cancer is diagnosed in about 13 to 17 out of 1000 women over a 5-year period.
In women aged 50 who start 5-year estrogen-only HRT, the number of cases will be 16-17 out of 1000 patients (i.e., 0 to 3 additional cases).
In women aged 50 who start 5-year combined estrogen-progestogen HRT, the number of cases will be 21 out of 1000 patients (i.e., 4 to 8 additional cases).
In women between the ages of 50 and 59 who are not taking HRT, breast cancer is diagnosed in about 27 out of 1000 patients over a 10-year period.
In women aged 50 who start 10-year estrogen-only HRT, the number of cases will be 34 out of 1000 patients (i.e., 7 additional cases).
In women aged 50 who start 10-year combined estrogen-progestogen HRT, the number of cases will be 48 out of 1000 patients (i.e., 21 additional cases).
Ovarian cancer
Ovarian cancer is rare - much rarer than breast cancer. Taking HRT that contains only estrogens or a combination of estrogens and progestogens is associated with a slightly increased risk of ovarian cancer.
The risk of ovarian cancer depends on age. For example, in women between the ages of 50 and 54 who are not taking HRT, ovarian cancer is diagnosed in about 2 out of 2000 women over a 5-year period. In women taking HRT for 5 years, ovarian cancer is diagnosed in about 3 out of 2000 women (i.e., about 1 additional case).
Effect of HRT on the heart and circulation

• Blood clots in veins (thrombosis)
  The risk of blood clots in veins is about 1.3 to 3 times higher in women taking HRT, especially in the first year of treatment, than in women not taking HRT.
  Blood clots can be life-threatening, especially if one travels to the lungs, causing chest pain, shortness of breath, fainting, or even death.
  The risk of blood clots increases with age and if any of the following conditions apply to the patient. Inform your doctor:
• if you are unable to walk for a long time due to a major operation, injury, or illness (see also section 3 "Before surgery");
• if you are severely overweight (BMI > 30 kg/m2);
• if you have blood clotting problems that require long-term treatment with medicines to prevent blood clots;
• if your close relatives have had blood clots in their legs, lungs, or other organs in the past;
• if you have systemic lupus erythematosus (SLE);
• if you have had cancer.

Symptoms that may indicate a blood clot are listed in the "Stop taking Cyclo-Progynova and consult a doctor immediately" section
Comparison
In women around the age of 50 who are not taking HRT, it is expected that about 4 to 7 out of 1000 women will develop a blood clot in a vein over a 5-year period.
In women around the age of 50 taking combined estrogen-progestogen HRT for more than 5 years, about 9 to 12 such cases will occur per 1000 patients (i.e., 5 additional cases).
Heart disease (heart attack)
It has not been proven that HRT prevents heart attacks.
In women over 60 years of age taking combined estrogen-progestogen HRT, the risk of heart disease is slightly higher than in women not taking HRT.
Stroke
The risk of stroke in women taking HRT is about 1.5 times higher than in women not taking HRT. The number of additional stroke cases associated with HRT increases with age.
Comparison
In women around the age of 50 who are not taking HRT, it is expected that about 8 out of 1000 women will have a stroke over a 5-year period. In women around the age of 50 taking HRT, this value is 11 cases per 1000 patients over a 5-year period (i.e., 3 additional cases).
Other diseases

• If the patient has kidney or heart disease, they should be monitored, as estrogens may cause fluid retention in the body. In severe kidney failure, the levels of the active substances in Cyclo-Progynova in the blood will be increased.
• If the patient has high levels of triglycerides (a type of fat) in the blood, they should be monitored, as these levels may increase further and lead to pancreatitis.
• If the patient has a history of angioedema, taking Cyclo-Progynova may worsen its symptoms.
• If the patient has a tendency to develop brown spots (chloasma) on the face, they should avoid sun or ultraviolet radiation while taking Cyclo-Progynova.
• HRT does not prevent memory loss. There is some evidence that women who start HRT after the age of 65 may experience greater memory loss. Consult a doctor for more information.

Estrogens increase the levels of total circulating thyroid hormones, corticosteroids, and sex hormones. This fact may be relevant when evaluating laboratory test results.

Cyclo-Progynova and other medicines

Tell your doctor about all medicines you are currently taking or have recently taken, including those obtained without a prescription, herbal medicines, or other natural products.
Certain medicines (listed below) may affect the action of Cyclo-Progynova, which may lead to irregular bleeding:

• medicines used to treat epilepsy (such as barbiturates, phenytoin, primidone, carbamazepine, and possibly oxcarbazepine, topiramate, and felbamate)
• medicines used to treat tuberculosis (such as rifampicin, rifabutin)
• medicines used to treat HIV and hepatitis C virus (protease inhibitors and non-nucleoside reverse transcriptase inhibitors, such as nevirapine, efavirenz, nelfinavir, and ritonavir)
• St. John's wort (Hypericum perforatum)
• medicines used to treat fungal infections (such as griseofulvin, itraconazole, ketoconazole, voriconazole, fluconazole)
• medicines used to treat bacterial infections (such as clarithromycin, erythromycin)
• medicines used to treat certain heart conditions, high blood pressure (such as verapamil, diltiazem)
• grapefruit juice

If the patient is taking paracetamol, the action of Cyclo-Progynova may be enhanced.
HRT may affect the action of other medicines:

• medicines used to treat epilepsy (lamotrigine), as they may increase the frequency of seizures
• medicines used to treat hepatitis C virus (HCV) (such as the treatment regimen using ombitasvir/paritaprevir/ritonavir with or without dasabuvir, and the treatment regimen using glecaprevir/pibrentasvir) may cause increased liver enzyme levels in blood tests in women taking combined hormonal contraceptives containing ethinyl estradiol. Cyclo-Progynova contains estradiol instead of ethinyl estradiol. It is not known whether increased liver enzyme levels may occur when taking Cyclo-Progynova with such a treatment regimen.

Laboratory tests
If laboratory tests are necessary, inform your doctor or laboratory staff that you are taking Cyclo-Progynova, as this medicine may affect the results of some tests.
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, herbal medicines, or other natural products.
Your doctor will provide appropriate guidance.

Pregnancy and breastfeeding

Cyclo-Progynova is intended for postmenopausal women. If pregnancy occurs, stop taking Cyclo-Progynova and consult a doctor immediately.
Small amounts of sex hormones may pass into breast milk. Hormone replacement therapy is not indicated during breastfeeding.

Driving and using machines

No effect on the ability to drive or operate machinery has been observed.

Cyclo-Progynova contains lactose monohydrate and sucrose

The product contains lactose monohydrate and sucrose. If the patient has previously been diagnosed with intolerance to some sugars, they should consult a doctor before taking the medicine.

3. How to take Cyclo-Progynova

Take this medicine always as directed by your doctor. If you are unsure, consult your doctor or pharmacist. The doctor will decide how long you should take Cyclo-Progynova.
If the patient is still menstruating, they should start taking Cyclo-Progynova on the fifth day of menstruation. In all other cases, the attending doctor may recommend starting treatment immediately.
The doctor will prescribe the patient the lowest possible dose for the shortest possible time to alleviate symptoms. If the patient thinks the dose is too high or too low, they should consult a doctor.
Take 1 white tablet daily for the first 11 days, and then 1 light brown tablet daily for the next 10 days, preferably at the same time every day. Swallow the tablets whole with a small amount of liquid.
One pack is enough for 21 days of treatment.
After a 21-day treatment cycle, take a 7-day break.
Withdrawal bleeding usually occurs during the 7-day break, a few days after taking the last tablet.

Use in children and adolescents

Cyclo-Progynova is not intended for use in children and adolescents.

Elderly patients

There is no data on the need to adjust the dose in elderly patients.

Patients with liver disorders

No adequate studies have been conducted on the use of Cyclo-Progynova in patients with liver function disorders. The medicine is contraindicated in women with severe liver disease (see "When not to take Cyclo-Progynova").

Patients with kidney disorders

No adequate studies have been conducted on the use of Cyclo-Progynova in patients with kidney function disorders.

Missed dose of Cyclo-Progynova

If the patient forgets to take a tablet at the usual time and it has been less than 24 hours, they should take the tablet as soon as possible and then take the next tablet at the usual time. However, if more than 24 hours have passed, the missed tablet should be left in the blister pack and the remaining tablets should be taken as usual. If several tablets are missed, bleeding may occur.

Overdose of Cyclo-Progynova

Overdose may cause nausea, vomiting, and irregular bleeding. There is no need for specific treatment, but if you have any doubts, consult a doctor.

Before surgery

If the patient is scheduled for surgery, they should inform the surgeon that they are taking Cyclo-Progynova. It may be necessary to stop taking Cyclo-Progynova about 4-6 weeks before the planned surgery to reduce the risk of blood clots (see section 2 "Blood clots in veins (thrombosis)"). Ask your doctor when you can resume taking Cyclo-Progynova.

4. Possible side effects

Like all medicines, Cyclo-Progynova can cause side effects, although not everybody gets them.

Severe side effects associated with HRT are described in section "Warnings and precautions"

The following diseases are reported more frequently in women taking HRT than in women not taking HRT:

• breast cancer;
• abnormal growth or cancer of the lining of the uterus (endometrial hyperplasia or endometrial cancer);
• ovarian cancer;
• blood clots in the veins of the legs or lungs (venous thromboembolism);
• heart disease;
• stroke;
• possible memory loss, if HRT is started after the age of 65.

Detailed information on these side effects can be found in section 2.
The following symptoms may be related to HRT or may be symptoms of menopause. These symptoms have also been observed in patients taking other HRT products.

Frequent side effects(in 1 to 10 out of 100 patients):

• weight gain or loss,
• abdominal pain, nausea,
• rash, itching,
• vaginal bleeding or spotting.

Uncommon side effects(in 1 to 10 out of 1000 patients):

• allergic reactions,
• depressive mood,
• dizziness,
• vision disturbances,
• rapid heartbeat (palpitations),
• nausea,
• erythema multiforme, hives,
• breast pain, breast tenderness,
• edema.

Rare side effects(in 1 to 10 out of 10,000 patients):

• anxiety,
• decreased or increased libido (sex drive),
• migraine,
• intolerance to contact lenses,
• bloating, vomiting,
• hirsutism (excessive hair growth), acne,
• muscle cramps,
• painful menstruation, vaginal discharge, premenstrual syndrome, breast swelling,
• fatigue.

The following side effects have been reported in patients taking other HRT products:

• gallbladder disease
• various skin disorders: skin discoloration, especially on the face or neck, known as "pregnancy spots" (chloasma); painful red lumps on the skin (erythema nodosum); rash with target-shaped redness or ulcers (erythema multiforme).

Cyclo-Progynova may cause or worsen the symptoms of hereditary angioedema (see section "Warnings and precautions").
If any side effect gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist.
Side effects can be reported directly to the Department of Drug Safety, Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych
Al. Jerozolimskie 181 C
02-222 Warszawa
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Cyclo-Progynova

Do not take this medicine after the expiry date stated on the packaging.
Keep the medicine out of the sight and reach of children.
Storage: No special requirements.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Cyclo-Progynova contains

• The active substances of Cyclo-Progynova are estradiol valerate (Estradioli valeras) and norgestrel (Norgestrelum). Each white film-coated tablet contains 2 mg of estradiol valerate. Each light brown film-coated tablet contains 2 mg of estradiol valerate and 0.5 mg of norgestrel.
• Other ingredients of the medicine are: White tablets: core: lactose monohydrate, corn starch, povidone K25, talc, magnesium stearate; coating: sucrose, povidone K90, macrogol 6000, calcium carbonate, talc, Montana wax.

Light brown tablets:
core: lactose monohydrate, corn starch, povidone K25, talc, magnesium stearate;
coating: sucrose, povidone K90, macrogol 6000, calcium carbonate, talc, glycerol 85%, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), Montana wax.

What Cyclo-Progynova looks like and contents of the pack

Each Cyclo-Progynova blister pack contains 11 white tablets and 10 light brown tablets.
The blister pack contains 21 film-coated tablets.
The pack may contain 1 or 3 blister packs.

Marketing authorization holder and manufacturer

Marketing authorization holder

Bayer AG
Kaiser-Wilhelm-Allee 1
51373 Leverkusen
Germany

Manufacturer

Bayer Weimar GmbH und Co. KG
Döbereinerstrasse 20
99427 Weimar
Germany
To obtain more detailed information, contact the local representative of the marketing authorization holder:
Bayer Sp. z o.o.
Al. Jerozolimskie 158
02-326 Warszawa
phone: (22) 5723500
fax (22) 5723555

Date of last revision of the leaflet: 01/2024