Lutezin

Package leaflet: Information for the patient

Lutezin, 50 mg, vaginal tablets
Progesterone
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• 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 other people, 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 Lutezin is and what it is used for
2. Important information before using Lutezin
3. How to use Lutezin
4. Possible side effects
5. How to store Lutezin
6. Contents of the pack and other information

1. What Lutezin is and what it is used for

Lutezin is a medicine containing progesterone, a naturally occurring female sex hormone produced synthetically.
In the body, progesterone acts via specific receptors located, among others, in the uterus, mammary glands, central nervous system, and pituitary gland.
The most important effects of progesterone on reproductive organs include: enabling ovulation, transformation of the endometrium (uterine lining) allowing implantation of the fertilized egg, inhibition of excessive endometrial proliferation caused by estrogens, and cyclic changes in the epithelium of the fallopian tubes, cervix, and vagina. Progesterone and estrogens also act on the mammary gland, stimulating the growth of glands and ductal epithelium and enabling lactation.
Progesterone is a hormone essential for proper preparation of the endometrium for embryo implantation and for maintaining pregnancy throughout its duration: it suppresses spontaneous contractile activity of the pregnant uterus, inhibits the mother's immune response to fetal antigens, serves as a precursor for fetal hormone production, and initiates labor.

Indications for use of Lutezin:

• Conditions associated with endogenous progesterone deficiency, such as menstrual cycle disorders, painful menstruation, anovulatory cycles, premenstrual tension syndrome, and functional uterine bleeding.
• Endometriosis.
• In vitro fertilization.
• Infertility associated with luteal phase deficiency.
• Recurrent and threatened miscarriage.
• Luteal phase deficiency in the perimenopausal period.
• Hormone replacement therapy in postmenopausal women with an intact uterus, to protect the endometrium.

2. Important information before using Lutezin
When not to use Lutezin

• If you are allergic to progesterone or to any of the other ingredients of this medicine (listed in section 6).
• If you have vaginal bleeding of unknown origin.
• If you have severe liver impairment.
• If you have a liver tumor.
• If you have or are suspected of having a tumor of the breast or genital organs.
• If you have active venous thrombosis (e.g., deep vein thrombosis in the limbs or pulmonary embolism), or if you have a history of such thrombotic events.
• If you are at risk of cerebral hemorrhage.
• If you have a rare inherited blood disorder called porphyria.
• If a miscarriage has occurred and there is suspicion that some tissue remains in the uterus, or if pregnancy is developing outside the uterus (ectopic pregnancy).

Warnings and precautions
Before starting this medicine, discuss it with your doctor.
This medicine, when used as directed, does not have contraceptive effects.
Before starting hormone replacement therapy during menopause (and subsequently at annual intervals), you should consult your doctor, who will perform an examination of the breasts and pelvic organs. Inform your doctor if:

• You have a history of venous thrombosis.
• You experience uterine bleeding. You should stop taking this medicine if:
• You develop any visual disturbances (e.g., visual field defects, double vision, retinal vascular lesions).
• You develop blood clots (venous thromboembolic disease or thrombosis).
• You experience severe headaches.
  If menstruation does not occur during treatment, pregnancy should be ruled out. During treatment, the endometrium may undergo excessive growth (endometrial hyperplasia), or existing hyperplasia may worsen. If unexpected bleeding or spotting occurs during or after prolonged treatment and persists, contact your doctor.

If mood changes or worsening of depressive symptoms occur during treatment in patients with a history of depression, contact your doctor immediately.
Your doctor will inform you about the need to report any changes in the breasts.
This medicine should be used with particular caution in patients:

• With mild to moderate liver function impairment.
• With conditions whose symptoms may be exacerbated by fluid retention (e.g., epilepsy, migraine, asthma, heart or kidney dysfunction).
• With diabetes or diagnosed insulin resistance.
• Over 35 years of age, who smoke, or who have risk factors for atherosclerosis.

Children and adolescents
There is insufficient data on the safety and efficacy of Lutezin vaginal tablets in children and adolescents.
Lutezin and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Some medicines may affect the action of Lutezin:

• Barbiturates used for sleep disorders or anxiety.
• Medicines used for epilepsy (carbamazepine, phenytoin).
• Certain antibiotics (ampicillins, tetracyclines, rifampicin).
• Phenylbutazone (an anti-inflammatory medicine).
• Spironolactone (a diuretic).
• Certain antifungal medicines (ketoconazole, griseofulvin).
• Similarly, Lutezin may affect the action of certain medicines used to treat diabetes.
• Herbal products containing St. John's wort ( Hypericum perforatum ) may reduce the effectiveness of Lutezin.
• Lutezin may enhance the effects of cyclosporine.

Pregnancy, breastfeeding, and effects on fertility
Pregnancy

• If you are pregnant, suspect you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Breastfeeding

• Breastfeeding women should not use this medicine.
• Discuss this with your doctor before starting this medicine.

Fertility

• This medicine may be used in women who have difficulty becoming pregnant. Lutezin has no known harmful effects on fertility.
• Discuss this with your doctor before starting this medicine.

Driving and operating machinery
Lutezin administered vaginally does not affect the ability to drive or operate machinery. However, if side effects such as drowsiness, difficulty concentrating, or dizziness occur, driving and operating machinery are not recommended (see section 4).
3. How to use Lutezin
Always use this medicine exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Dosage
For doses other than 25 and 50 mg, vaginal tablets of 100 mg and 200 mg are available.
Adults

• For menstrual cycle disorders, painful menstruation, premenstrual tension syndrome, and luteal phase deficiency in the perimenopausal period, the recommended dose is 25 to 50 mg (½ to 1 tablet) administered vaginally twice daily during the second phase of the menstrual cycle (natural or induced), for 10–12 days.

• For menstrual cycle disorders, painful menstruation, and premenstrual tension syndrome, treatment should continue for 3–6 consecutive cycles.

• For luteal phase deficiency in the perimenopausal period, treatment should continue until menopause occurs.

• For hormone replacement therapy, 200 mg daily for 12 days per month or 100–200 mg daily in continuous therapy is recommended.

• For a progesterone challenge test in secondary amenorrhea, 50 mg (1 tablet) is administered vaginally twice daily for 5–7 days. Withdrawal bleeding should occur within 7–10 days after stopping the medication.

• For treatment of functional uterine bleeding, 50 mg (1 tablet) is administered vaginally twice daily for 5–7 days. Treatment should continue for the next 2–3 months, with 25 to 50 mg (½ to 1 tablet) administered vaginally twice daily from day 15 to day 25 of the cycle.

• For endometriosis, 50 to 100 mg (1 to 2 tablets) is administered vaginally twice daily in continuous therapy for 6 months.

• For recurrent and threatened miscarriage, anovulatory, and induced cycles, 50 to 150 mg (1 to 3 tablets) is administered vaginally twice daily.

• For recurrent miscarriage, progesterone supplementation should begin in the cycle when pregnancy is planned. Treatment should continue uninterrupted until the 18th–20th week of pregnancy.

• In in vitro fertilization programs, 100 to 200 mg is administered vaginally 2–3 times daily. Treatment should continue until day 77 after embryo transfer. Therapy should be discontinued by gradually reducing the dose.

Use in children and adolescents
There is insufficient data on the safety and efficacy of Lutezin vaginal tablets in children and adolescents.
Instructions for use
The tablet may be divided into equal doses.
Lutezin should be inserted into the vagina.
In pregnant women, due to a softened cervix, it is recommended to insert Lutezin with the index finger.
Overdose
If you take more than the recommended dose, contact your doctor or pharmacist immediately.
Symptoms of overdose may include: dizziness, fatigue, and depression.
These symptoms usually resolve spontaneously after dose reduction. Consult your doctor beforehand.
Missed dose
If you miss a dose, take it as soon as you remember, unless it is almost time for the next dose. Do not take a double dose to make up for a missed dose.
Stopping treatment
Abrupt discontinuation of progesterone may cause increased anxiety, mood swings, and seizures.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine may cause adverse reactions, although not everyone experiences them.
This medicine must be discontinued immediately if the patient experiences any of the
following adverse reactions:

• stroke, blood clots or internal bleeding in the brain,
• blood clots in the veins of limbs or pelvis,
• sudden severe headaches,
• visual disturbances,
• yellowing of the skin or whites of the eyes (jaundice).

The following adverse reactions occur frequently (in 1 out of 10 patients):

• headache
• abdominal bloating
• abdominal pain
• nausea
• uterine cramps

The following adverse reactions occur less frequently (in 1 out of 100 patients):

• dizziness
• drowsiness
• diarrhoea
• constipation
• urticaria (allergic rash)
• rash
• vaginal disorders (e.g. vaginal discomfort, burning sensation, discharge, dryness and bleeding)
• vaginal fungal infection
• nipple disorders (e.g. breast pain, breast swelling, breast tenderness)
• itching in the genital area
• peripheral oedema (swelling due to fluid accumulation)

Frequency of occurrence is unknown (cannot be
determined from available data):

• fatigue
• vomiting
• allergic reactions.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in the leaflet, the patient should inform a doctor or pharmacist.
Adverse reactions can be reported directly to the Department of Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C,
02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website:
https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Lutezin
Store below 25 °C.
Keep out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via the sewage system or household waste. Ask a pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Lutezin contains

• The active substance is progesterone.
• Each tablet contains 50 mg of progesterone.
• The other components are: monohydrate lactose, corn starch, monohydrate citric acid, magnesium stearate, hypromellose (6 mPa·s).

What Lutezin looks like and contents of the pack
White, uncoated, round, biconvex tablets with a score line on one side, 9 mm in diameter.
PVC/PVDC/Aluminium blisters. The blisters are placed in a cardboard box containing 30 vaginal tablets, or 60 vaginal tablets, or 90 vaginal tablets.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
tel. +48 22 732 77 00
Manufacturer:
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5,
95-200 Pabianice