Lutenyl

Package leaflet: Information for the patient

Lutenyl
Nomegestrol acetate
5 mg, tablets

• Please read this leaflet carefully before taking this medicine, as it contains important information for you.
• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

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

1. What Lutenyl is and what it is used for
Nomegestrol, the active substance in Lutenyl, is a 19-norprogesterone derivative used to correct progesterone deficiency. The affinity of nomegestrol for progesterone receptors is 2.5 times greater than that of the natural hormone.
When administered from day 5 to day 25 of the cycle at a dose of 5 mg per day, Lutenyl inhibits ovulation, reduces gonadotropin secretion, lowers circulating estrogen levels, and prevents the secretion of natural progesterone. Pharmacoclinical studies have not demonstrated complete anti-gonadotropic effects in all patients.
Nomegestrol acetate is rapidly absorbed, with maximum concentration occurring 2 hours after administration. The half-life is approximately 40 hours. It is primarily excreted via the intestines and partially via urine.

Indications
In premenopausal women: menstrual disorders associated with reduced or absent progesterone secretion:

• Menstrual disorders: scanty or infrequent menstruation, excessively frequent menstruation, absence of menstruation
• Functional genital tract bleeding: uterine hemorrhage, menstrual hemorrhage, including bleeding associated with fibroids
• Symptoms preceding or related to menstruation: primary dysmenorrhea, premenstrual syndrome, cyclical breast pain

In postmenopausal women: Lutenyl is used in combination with estrogens (artificially induced cycles) in hormone replacement therapy (HRT)

2. Important information before taking Lutenyl

When not to take Lutenyl:

• If you are allergic to nomegestrol or any of the other ingredients of this medicine (listed in section 6)
• If you have undiagnosed vaginal bleeding
• If you have a history of idiopathic venous thrombosis or active venous thromboembolic disease (deep vein thrombosis, pulmonary embolism)
• If you have active or a history of arterial thromboembolic diseases (e.g., myocardial infarction)
• If you currently have or have had severe liver dysfunction
• If you have meningioma or have ever been diagnosed with meningioma (usually a benign tumor of the tissue layer between the brain and skull)

If in doubt, consult your doctor.
If any of the above conditions occur for the first time during treatment with Lutenyl, stop taking the medicine immediately and contact your doctor without delay.

Warnings and precautions
Discuss with your doctor or pharmacist before starting Lutenyl.

• Clinical studies have not demonstrated complete anti-gonadotropic effects in all patients
• Before starting treatment for certain indications, particularly painful menstruation, uterine hemorrhage, or amenorrhea, your doctor must determine whether the condition is functional
• Before initiating treatment, exclude the presence of tumors of the breast and uterus (cervix and endometrium)
• Discontinue the medicine if any of the following occur: visual disturbances (double vision, acute visual impairment, retinal vessel damage), development of thrombosis or embolism, severe or unusual headache
• Exercise caution if you have cardiovascular diseases, unstable hypertension, diabetes, or porphyria

Special precautions
You should have regular check-ups.
If you notice any changes in your breasts during treatment, inform your doctor immediately.
If any of the following conditions are currently present, have occurred in the past, and/or worsened during pregnancy or previous hormonal treatment, you should remain under close medical supervision. Consider that these conditions may recur or worsen during treatment with Lutenyl, particularly:

• Uterine fibroids
• Endometriosis (endometrial tissue growth outside the uterine cavity) or previous cases of excessive endometrial proliferation (endometrial hyperplasia)
• History of thromboembolic disorders or presence of risk factors increasing their likelihood (see below)
• Risk factors for estrogen-dependent tumors, e.g., first-degree relative with breast cancer
• Hypertension
• Liver dysfunction (e.g., hepatic adenoma)
• Diabetes, with or without vascular complications
• Gallstones
• Migraine or severe headaches
• Autoimmune disease affecting multiple organs (systemic lupus erythematosus)
• Epilepsy
• Asthma
• Otosclerosis (ear disease leading to hearing loss)

Your doctor will decide whether to discontinue treatment if contraindications arise, or in the following situations:

• Yellowing of the skin or whites of the eyes (jaundice) or worsening liver function
• Marked increase in blood pressure
• New onset of migraine-type headache
• Pregnancy

HRT and malignant tumors
Endometrial hyperplasia and endometrial cancer
Unopposed estrogen-only HRT increases the risk of endometrial hyperplasia and endometrial cancer. Adding a progestogen for at least 12 days per cycle protects against this increased risk.
In women aged 50–65 with an intact uterus who do not use HRT, endometrial cancer is diagnosed in an average of 5 per 1,000 women.
In women aged 50–65 with an intact uterus using estrogen-only HRT, endometrial cancer is diagnosed in 10–60 per 1,000 women (i.e., 5 to 55 additional cases), depending on dose and duration of treatment.

Breast cancer
Studies indicate that combined estrogen-progestogen HRT, and possibly estrogen-only HRT, increases the risk of breast cancer. The additional risk depends on the duration of HRT use. This increased risk becomes apparent within a few years but returns to baseline within a few years (at most 5) after stopping treatment.
In women who used estrogen-only HRT for 5 years, no or only a slight increase in breast cancer risk has been observed.

Comparison
Among women aged 50–79 not using HRT, an average of 16 per 1,000 will be diagnosed with invasive breast cancer over 5 years. Among women aged 50–79 using combined estrogen-progestogen HRT for 5 years, 16 to 25 cases per 1,000 women will occur (i.e., 0 to 9 additional cases).

Regularly examine your breasts. Contact your doctor if you notice changes such as:

• Skin dimpling
• Changes in the nipple
• Any visible or palpable lumps

Ovarian cancer
According to some epidemiological studies, long-term (at least 5–10 years) use of estrogen alone in women after hysterectomy increases the risk of ovarian cancer. The risk associated with long-term use of combined estrogen-progestogen therapy is unknown.

Meningioma
The use of nomegestrol acetate has been associated with the development of usually benign tumors of the tissue layer between the brain and skull (meningioma). This risk increases especially with prolonged use (several months or years). If you are diagnosed with meningioma, your doctor will discontinue treatment with Lutenyl (see section "Do not take..."). If you experience any symptoms such as visual disturbances (e.g., double or blurred vision), hearing loss or tinnitus, loss of smell, headaches that worsen over time, memory loss, seizures, or weakness in the arms or legs, inform your doctor immediately.

Effects of HRT on the heart and circulation
Venous thrombosis (blood clots)
The risk of venous thrombosis is approximately 2–3 times higher in women using HRT, especially during the first year of treatment, compared to women not using HRT. If a clot reaches the lungs, it may cause chest pain, shortness of breath, fainting, or even death.
The likelihood of venous thrombosis increases with age and in the presence of the following factors. Inform your doctor if any of the following apply:

• You are unable to walk for prolonged periods due to major surgery, injury, or illness
• You are obese (Body Mass Index, BMI >30 kg/m²)
• You have blood clotting disorders requiring long-term anticoagulant therapy
• You or a close relative have had a blood clot in the leg, lung, or another organ
• You are pregnant and/or in the postpartum period
• You have systemic lupus erythematosus (SLE)

Coronary heart disease
There is no scientific evidence supporting a beneficial effect of HRT on the cardiovascular system. Two large clinical trials on combined (estrogen and progestogen) therapy suggest a possible increased risk of cardiovascular disease during the first year of treatment and no overall benefit. There is limited data on the effects of other HRT medications on cardiovascular disease incidence and mortality.

Stroke
The risk of ischemic stroke is higher in women using HRT than in those who do not. The number of additional stroke cases due to HRT increases with age.

Comparison
Among women aged 50–59 not using HRT, stroke occurs in an average of 3 per 1,000 over 5 years. Among women aged 50–59 using HRT, there are 0 to 3 additional cases per 1,000 women over 5 years.

Other conditions
Due to fluid retention caused by estrogens, women with kidney or heart dysfunction require special monitoring. Women with severe renal impairment require close observation due to the potential for increased nomegestrol concentration in the blood. Women with previously diagnosed hypertriglyceridemia undergoing HRT require special monitoring. There are isolated reports suggesting possible pancreatitis following marked increases in triglyceride levels in women treated with estrogen alone.
Estrogens increase the levels of thyroid-binding globulin (TBG), leading to increased total circulating thyroxine. Levels of other binding proteins in the blood may also increase, such as corticosteroid-binding globulin and sex hormone-binding globulin, resulting in increased circulating levels of corticosteroids and sex hormones, respectively. Levels of free or biologically active hormones remain unchanged. Other plasma proteins may also increase (angiotensinogen/renin substrate, alpha-1 antitrypsin, ceruloplasmin).
HRT does not improve cognitive function (memory loss, perceptual disturbances, attention disorders). Evidence suggests an increased risk of dementia in women who start HRT after age 65.

Lutenyl and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, and any you plan to take.
This includes the following medicines:

• Medicines used to treat epilepsy (e.g., phenobarbital, phenytoin, carbamazepine)
• Medicines used to treat tuberculosis (e.g., rifampicin, rifabutin)

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, suspect you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.
Lutenyl must not be used during pregnancy or while breastfeeding.

Driving and operating machinery
This medicine may cause visual disturbances (see sections 2 and 4).

Lutenyl contains lactose
This medicine should not be used in patients with rare hereditary intolerance to galactose, Lapp-type lactase deficiency, or glucose-galactose malabsorption syndrome.

3. How to use Lutenyl

This medicine should always be used as directed by the physician. If in doubt, consult a doctor or pharmacist.
Recommended dose
The usual daily dose is 5 mg (1 tablet).
In premenopausal women, treatment typically lasts 10 days, from day 16 to day 25 of the cycle.
In postmenopausal women, the dosage depends on the type of hormone replacement therapy used.
In continuous combined hormone replacement therapy, Lutenyl is administered for 12 to 14 days each cycle.
The dose and duration of treatment may be adjusted according to the indication and the patient's response to the medicine.
Taking more Lutenyl than recommended
There have been no reported cases of overdose so far.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The frequency of occurrence is defined according to the following classification:
very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known (frequency cannot be determined from available data).

Metabolism and nutrition disorders
Not known frequency: weight gain

Psychiatric disorders
Not known frequency: insomnia

Eye disorders
Not known frequency: visual disturbances

Vascular disorders
Not known frequency: worsening of venous insufficiency of the lower limbs; occurrence of venous thromboembolism

Gastrointestinal disorders
Not known frequency: gastrointestinal disturbances

Skin and subcutaneous tissue disorders
Not known frequency: skin allergies, excessive hair growth

Reproductive system and breast disorders
Not known frequency: menstrual disorders, absence of menstruation, intermenstrual bleeding

General disorders and administration site conditions
Not known frequency: fever

The use of nomegestrol acetate has been associated with the development of usually benign tumours of the membrane between the brain and the skull (meningioma), particularly at high doses and with long-term use (several months or years), with a frequency of "rare" (see section 2 "Warnings and precautions").

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 4921301, Fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store the medicine Lutenyl

• Do not use this medicine after the expiry date stated on the blister and the carton after EXP. The expiry date refers to the last day of the specified month.
• The batch number on the packaging is marked as "Lot".
• Store the medicine below 25°C.
• Keep the medicine out of sight and reach of children.

6. Contents of the pack and other information

What Lutenyl contains
1 tablet contains:
active substance: 5 mg nomegestrol acetate
other ingredients: lactose, microcrystalline cellulose, glycerol palmitostearate,
anhydrous colloidal silicon dioxide

What Lutenyl looks like and contents of the pack
Lutenyl is in the form of elongated tablets, scored on one side.
The pack contains 10 tablets.

Marketing Authorisation Holder
Theramex Ireland Limited
3rd Floor, Kilmore House,
Park Lane, Spencer Dock,
Dublin 1
D01 YE64
Ireland
(logo of the marketing authorisation holder)

Manufacturer
Laboratoires MACORS
22 Rue des Caillottes
89000 Auxerre
France

For further information, please contact the local representative of the marketing authorisation holder on telephone number: 22 307 71 66.