Progeffik

Package leaflet: Information for the patient

Progeffik 100 mg soft capsules for oral and vaginal use, 200 mg soft capsules for oral and vaginal use

progesterone
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. 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 their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Progeffik is and what it is used for

Progeffik belongs to the pharmaceutical category of sex hormones and genital system modulators (progestogens).
Oral use
Progeffik is used for disorders due to progesterone insufficiency, in particular:

• premenstrual syndrome (symptoms occurring before menstruation);
• menstrual cycle disorders due to ovulation disturbances or anovulation (menstrual cycle in which the release of an oocyte from the ovary does not occur);
• benign mastopathies (benign breast nodules);
• premenopause (the period preceding the permanent cessation of menstrual cycles);
• hormone replacement therapy in menopause (in combination with estrogen therapy).

Vaginal use (represents an alternative to oral administration)
Progeffik is used as:

• supplementation in the luteal phase (the final phase of the menstrual cycle, after ovulation) during spontaneous or induced cycles, in cases of subfertility (reproductive capacity below normal) or primary sterility (inability to conceive) or secondary sterility (inability to conceive again after a previous pregnancy), particularly due to primary ovarian insufficiency (ovaries unable to respond to normal stimulation) or secondary ovarian insufficiency (ovaries are normal but insufficiently stimulated), associated with ovulation disorders;
• luteal phase supplementation during in-vitro fertilization cycles or other assisted reproductive techniques, specifically in ovariectomized women (women who have undergone surgical removal of the ovaries);
• in cases of threatened abortion or for prevention of recurrent miscarriages due to luteal insufficiency (inadequate progesterone production by the ovary in the second phase of the menstrual cycle), up to the 12th week of amenorrhea (absence of menstruation);
• prevention of preterm birth in singleton pregnancies with clinically silent shortened cervix (≤15 mm), detected by ultrasound examination during the second trimester of pregnancy.

For all other indications of progesterone, vaginal administration represents an alternative to oral use in cases of:
adverse effects related to progesterone (e.g. drowsiness after oral intake);
contraindications to oral use in case of hepatopathies (liver diseases).

2. What you should know before taking Progeffik

Do not take Progeffik

• if you are allergic to progesterone, to substances closely related chemically, or to any of the other ingredients of this medicine (listed in section 6), or if you are allergic to peanuts or soy;
• if you have severe hepatic insufficiency (severely reduced liver function);
• if you have unexplained vaginal bleeding;
• in case of missed or incomplete abortion;
• if you currently have or have had in the past thromboembolism (blockage of blood vessels caused by blood clots);
• if you have or suspect to have breast or genital carcinoma;
• if you have thrombophlebitis (inflammation of superficial veins);
• if you have had cerebral haemorrhage (rupture of a blood vessel in the brain).

Warnings and precautions
Talk to your doctor or pharmacist before taking this medicine.
The treatment, at the recommended doses, is not contraceptive.
Have a thorough general and gynecological examination (pelvic and breast examination), including a Pap
test, before starting treatment.
Since some progestogens may cause some degree of fluid retention, your doctor should carefully monitor
your condition to closely observe any disorders that could be influenced by this factor:

• if you suffer from epilepsy (a disease causing seizures);
• if you suffer from migraine (unilateral headache);
• if you suffer from asthma;
• if you currently have or have had in the past heart failure (the heart's inability to pump sufficient blood to meet the body's needs);
• if you currently have or have had in the past renal insufficiency (reduced kidney function).

In particular, talk to your doctor if:

• you experience vaginal bleeding, as in cases of metrorrhagia (uterine bleeding outside menstrual periods) of unknown cause, your doctor will first determine the underlying cause;
• you have a history of mental depression; in this case, your doctor should monitor your condition carefully;
• you suffer from diabetes mellitus, as progestogens may induce or worsen fluid retention (water retention) and reduce glucose tolerance. If you undergo a histological examination (analysis of tissue obtained by biopsy), inform your doctor that you are being treated with Progeffik.

If Progeffik is used in combination with estrogens as part of hormone replacement therapy (HRT),
be alert for the onset of symptoms such as partial or complete vision loss or double vision during treatment;
discontinue treatment at the first signs of thrombotic disorders (blood clot formation) affecting peripheral, cerebral, or pulmonary vessels.
Your doctor will prescribe Progeffik only if you have luteal phase deficiency, as this medicine is not a treatment for all cases of premature spontaneous abortion. The only effect of administering progesterone in cases of spontaneous abortions due to genetic abnormalities would be to delay the evacuation of a nonviable ovum or the termination of a pregnancy that cannot proceed to term anyway.
Specifically regarding use in menopausal disorders in combination with hormone replacement therapy (HRT)
When treating menopausal symptoms, start hormone replacement therapy (HRT) only if symptoms significantly impair your quality of life. In any case, it is advisable to have a thorough assessment of the risks and benefits of the treatment at least once a year, and to continue HRT only as long as the benefits outweigh the risks.
Before starting or resuming HRT, your doctor will ask for information about your personal and family medical history (anamnesis) and will perform a thorough general and gynecological examination (including pelvic and breast examination), based on your anamnesis, contraindications, and warnings for use.
During treatment with HRT, your doctor will schedule periodic check-ups, the nature and frequency of which will be tailored to your individual clinical needs, to carefully evaluate the risks and benefits related to continuing therapy. Undergo examinations according to currently recommended screening programs, including mammography, and report any changes to your doctor.
You will require close monitoring if you have a family history of tumors or if you currently have or have had:

• recurrent cholestasis (blockage of bile excretion) or persistent pruritus during pregnancy;
• impaired liver function;
• renal or heart failure;
• breast nodules of undetermined nature;
• a disease of the ear causing deafness (otospongiosis);
• diabetes mellitus;
• multiple sclerosis;
• an immune system disorder (systemic lupus erythematosus).

Use of Progeffik in menopause in combination with hormone replacement therapy (HRT)
Taking hormone replacement therapy (HRT) slightly to moderately increases the likelihood of being diagnosed with breast cancer in postmenopausal women.
The risk of breast cancer may indeed increase with the duration of treatment. This risk appears to return to baseline levels within five years after stopping HRT. Among women aged 50 to 70 years who do not use HRT, about 45 out of 1000 are diagnosed with breast cancer, with risk increasing with age. Among women who use HRT for at least five years, the number of diagnosed breast cancer cases increases by 2 to 12 per 1000, depending on the age at which treatment is started and its duration.
Your doctor will discuss with you the increased likelihood of breast cancer diagnosis, weighing it against the benefits of HRT.

Use of Progeffik in the prevention of preterm birth
There are no data available on the long-term safety of Progeffik when used to prevent preterm birth, particularly regarding effects on children (at birth and during childhood) born to mothers exposed to Progeffik (see section 3).

Other medicines and Progeffik
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Progesterone may cause amenorrhea (absence or cessation of menstrual periods) and galactorrhea (production of breast milk outside the lactation period), interfering with the action of bromocriptine (a substance used to correct hormonal imbalances). Do not take both medicines at the same time.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Progeffik may be used during pregnancy, preferably via the vaginal route, and under medical supervision.
Administration of micronized progesterone during the second and third trimesters of pregnancy may cause cholestatic jaundice (yellowing of the skin, whites of the eyes, and mucous membranes due to blocked bile excretion) or hepatocellular disease (liver cell disorders).

Breastfeeding
Do not take Progeffik while breastfeeding, as progesterone is excreted in breast milk.

Driving and using machines
Exercise caution when driving or operating machinery, as this medicine may cause drowsiness and dizziness.

Progeffik contains peanut oil and soy lecithin
Do not take this medicine if you are allergic to peanuts or soy.

3. How to take Progeffik

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Always strictly follow the recommended doses.
The dose must not exceed 200 mg per administration, regardless of the indication and
route of administration (oral or vaginal).

Oral use
In cases of progesterone deficiency, the average daily dose is 200 mg–300 mg of micronized progesterone, divided into two administrations.
Take the medicine away from meals.

In luteal phase deficiency (premenstrual syndrome, benign mastopathies, menstrual cycle disorders, perimenopause), the average daily dose is 200 mg–300 mg of progesterone:

• either 200 mg as a single dose in the evening before bedtime (1 capsule of 200 mg or 2 of 100 mg)
• or 300 mg in two doses: 1 capsule of 100 mg + 1 capsule of 200 mg (or 2 of 100 mg), for a 10-day therapeutic cycle, usually from day 17 to day 26 inclusive of the menstrual cycle.

In hormone replacement therapy during menopause, estrogen-only therapy is not recommended (risk of endometrial hyperplasia [thickening of the uterine lining]). Progesterone should be administered at a dose of 200 mg daily:

• either in two 100 mg doses
• or as a single 200 mg dose in the evening before bedtime (1 capsule of 200 mg or 2 of 100 mg), for 12–14 days per month, or during the last two weeks of each therapeutic cycle. Hormone replacement therapy should be interrupted for approximately one week, during which you may experience vaginal bleeding. For these indications, if you have liver disease (hepatic disorders) or experience side effects related to progesterone (such as drowsiness after oral administration), vaginal use should be considered as an alternative to oral use, with the same dosage.

Vaginal use
Insert each capsule deeply into the vagina.
Supplement in the luteal phase during spontaneous or induced cycles, in cases of hypofertility or primary or secondary infertility, particularly in cases of ovulation disorders: the recommended daily dose is 200 mg (in two 100 mg doses), or 300 mg in two doses: 1 capsule of 100 mg + 1 capsule of 200 mg (or 2 of 100 mg), starting on day 17 of the cycle for 10 consecutive days. If amenorrhea or confirmed pregnancy occurs, resume treatment as soon as possible and continue until week 12 of pregnancy.
Threatened miscarriage or prevention of recurrent miscarriages due to luteal insufficiency: the recommended daily dose is 200 mg (in two 100 mg doses), or 400 mg (in two 200 mg doses: 1 capsule of 200 mg or 2 of 100 mg), up to week 12 of pregnancy.
Prevention of preterm birth in singleton pregnancies with a shortened cervix (≤15 mm), clinically silent, detected by ultrasound examination performed during the second trimester of pregnancy: the recommended daily dose is 200 mg (two capsules of 100 mg or one capsule of 200 mg) up to week 34 of pregnancy.

Long-term safety data, especially in children (at birth and during childhood) born from mothers exposed to Progeffik, are not available (see section 2).

If you take more Progeffik than you should
If you accidentally ingest/overdose on Progeffik, contact your doctor immediately or go to the nearest hospital.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everybody experiences them.
The following list includes adverse effects associated with the use of Progeffik:

System organ classification | Adverse effects
---|---
Nervous system | Somnolence and dizziness*, headache**.
Skin and subcutaneous tissue disorders | Skin reactions (urticaria, rash with or without pruritus)**,
| appearance of yellowish-brown facial spots during pregnancy (chloasma**).
Reproductive and breast disorders | Reduced menstrual cycle or metrorrhagia***,
| intermenstrual bleeding**,
| changes in menstrual flow**,
| amenorrhoea**,
| alteration of cervical mucus**,
| breast pain**.
Psychiatric disorders | Depression**, insomnia**, nervousness**.
Metabolism and nutrition disorders | Weight changes (increase or decrease)**.
Hepatobiliary disorders | Yellowish discoloration of the skin, whites of the eyes, and mucous membranes
| caused by impaired bile excretion (cholestatic jaundice**).

(*) Somnolence and dizziness may occasionally occur up to three hours after oral administration of Progeffik. In such cases, the dose should be reduced or adjusted, for example, to a daily dose of 200 mg administered as a single dose taken away from meals (1 capsule of 200 mg or 2 of 100 mg), before bedtime for 12–14 days per cycle). Vaginal administration may also be used.

(***) In case of shortened menstrual cycle or metrorrhagia, it is advisable to delay treatment by a few days (for example, start treatment on day 19 of the cycle instead of day 17).

(**) All other adverse effects listed have been reported following administration of progestogens in general.

Following the instructions provided in this leaflet reduces the risk of adverse effects.

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, please contact your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at: http://www.agenziafarmaco.gov.it/it/responsabili. By reporting adverse effects, you can help provide further information on the safety of this medicine.

5. How to store Progeffik

Keep this medicine out of the sight and reach of children.
Store below 30°C.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month. The expiry date applies to the product in its original, unopened packaging stored under the recommended conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Progeffik contains
100 mg soft capsule:

• The active substance is micronized progesterone. Each capsule contains 100 mg of micronized progesterone.
• The other components are: peanut oil, soy lecithin (E322).
• Capsule shell components are: gelatin, glycerol, titanium dioxide (E171).

200 mg soft capsule:

• The active substance is micronized progesterone. Each capsule contains 200 mg of micronized progesterone.
• The other components are: peanut oil, soy lecithin (E322).
• Capsule shell components are: gelatin, glycerol, titanium dioxide (E171).

Description of Progeffik's appearance and contents
Soft capsules for oral or vaginal use.
Progeffik 100 mg: pack containing 30 capsules.
Progeffik 200 mg: pack containing 15 capsules.
Marketing Authorization Holder
EFFIK ITALIA SpA
Via Lincoln 7/A
20092 Cinisello Balsamo (MI)
Manufacturer
Laboratoires EFFIK
Parc Tertiaire de Meudon, Immeuble Le Newton, 9/11 rue Jeanne Braconnier,
F-92 366 MEUDON LA FORET CEDEX, France
Leon Farma
C/ La Vallina, s/n, Poligono Industrial Navatejera, 24008 Villaquilambre – Leon – Spain