Prometrium

Package leaflet: Information for the patient

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

Progesterone
Please read all of 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 other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4. Contents of this leaflet:
  1. What Prometrium is and what it is used for
  2. What you need to know before taking Prometrium
  3. How to take Prometrium
  4. Possible side effects
  5. How to store Prometrium
  6. Contents of the pack and other information

1. What Prometrium is and what it is used for

Prometrium belongs to the pharmaceutical category of sex hormones and genital system regulators (progestogens).
Oral use
Prometrium is used for disorders due to insufficient production of the hormone progesterone (progestogenic insufficiency), particularly in the following cases:

• symptoms occurring before menstruation (premenstrual syndrome),
• menstrual cycle disturbances,
• benign breast nodules (benign mastopathy),
• menstrual irregularities occurring in the period preceding the permanent cessation of menstruation (premenopause),
• hormone replacement therapy in menopause (in association with estrogen hormone therapy).

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

• a supplementary progestogenic hormone during the final phase of the menstrual cycle, after ovulation (luteal phase), during spontaneous or induced cycles, in cases of reduced fertility (subfertility) or inadequate ovarian response to normal stimulation (primary or secondary ovarian insufficiency).
• in cases of threatened miscarriage or for the prevention of recurrent miscarriages due to confirmed insufficient progesterone production by the ovary during the luteal phase of the menstrual cycle (luteal phase deficiency), up to the 12th week of amenorrhea.

2. What you should know before taking Prometrium

Do not take Prometrium

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

Warnings and precautions
Talk to your doctor or pharmacist before taking this medicine.
The treatment, at the recommended doses, is not contraceptive (it does not prevent pregnancy).

Before starting treatment, you should undergo a thorough general and gynaecological examination (pelvic and breast examination), including a Pap test.
Since progesterone may cause fluid retention, your doctor should closely monitor you if you have any of the following conditions, as they could be influenced by this factor:

• a neurological condition characterized by overactivity of certain nerve cells causing loss of consciousness and seizures (epilepsy),
• headache usually on one side (migraine),
• inflammatory disease characterized by narrowing, generally reversible, of the lower airways (asthma),
• inability of the heart to pump adequate amounts of blood (heart failure),
• reduced kidney function (renal insufficiency).

Talk to your doctor especially if:

• you experience vaginal bleeding, since in cases of unexplained uterine bleeding outside menstrual periods (metrorrhagia), your doctor will determine the cause before treatment;
• you have a history of depression; in this case your doctor should carefully monitor your condition during treatment;
• you suffer from diabetes, as progestogens may cause or worsen fluid retention and reduce glucose tolerance;
• you experience symptoms of partial or complete loss of vision or double vision during treatment;
• you need to undergo a tissue examination via biopsy (histological examination); your doctor must know that you are taking Prometrium.
  If you are premenopausal, keep in mind that progestogenic treatment may mask the onset of menopause.
  Following treatment with progesterone, changes in tests assessing glandular systems or liver function may occur.

Stop treatment at the first signs of disorders caused by blood clot formation (thrombi) in peripheral, cerebral, or pulmonary vessels.
Your doctor will prescribe Prometrium only in case of insufficient progesterone production by the ovary during the second half of the menstrual cycle (luteal insufficiency), since this medicine is not a treatment for spontaneous abortion.
Indeed, administration of progesterone in cases of spontaneous abortion—usually due to genetic complications, infectious diseases, or mechanical disorders—would only delay the evacuation of a nonviable ovum or the termination of a pregnancy that cannot proceed to term.

Regarding the use of Prometrium for menopausal disorders in combination with hormone replacement therapy (HRT), consider the following:
Before starting or resuming hormone replacement therapy (HRT), your doctor will ask about your personal and family medical history (anamnesis) and will perform a thorough general and gynaecological examination (including pelvic and breast examination), based on your anamnesis, contraindications, and usage warnings.
During HRT treatment, you will need periodic medical check-ups, the nature and frequency of which will be tailored to your individual needs, to accurately assess the risks and benefits of continuing therapy. You should undergo clinical investigations, including mammography, in accordance with currently accepted screening programmes, and inform your doctor of any changes.
If you are postmenopausal, HRT slightly to moderately increases the likelihood of being diagnosed with breast cancer. This may be due to earlier diagnosis, a real effect of HRT, or a combination of both.
The likelihood of a breast cancer diagnosis increases with the duration of treatment and appears to return to baseline levels within five years after stopping HRT. Breast cancer diagnosed in women currently or recently using HRT seems to be less invasive than that found in untreated women.
In women aged between 50 and 70 years who do not use HRT, breast cancer is diagnosed in approximately 45 out of 1000 women, with risk increasing with age. It has been estimated that among women using HRT for at least five years, the number of additional breast cancer diagnoses will range between 2 and 12 per 1000 women, depending on the age at which treatment is started and its duration.
Your doctor will discuss with you the increased risk of breast cancer diagnosis associated with long-term therapy, weighing it against the benefits of HRT.
You will require close monitoring if you have a family history of cancer or if you currently have or have previously had:

• recurrent bile excretion blockage (cholestasis) or persistent pruritus during pregnancy;
• liver function abnormalities;
• renal or cardiac insufficiency;
• breast nodules or widespread nodularity in both breasts (fibrocystic mastopathy);
• epilepsy;
• asthma;
• a disease of the ear causing hearing loss (otospongiosis);
• diabetes mellitus;
• an autoimmune disease affecting the central nervous system (multiple sclerosis);
• an immune system disorder (systemic lupus erythematosus).

Other medicines and Prometrium
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Progesterone may affect the action of a substance used to correct hormonal imbalances (bromocriptine).

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.
You may use Prometrium only during the first trimester of pregnancy and only via the vaginal route.

Prometrium is not a treatment for inducing preterm labour.
If you take micronized progesterone during the second and third trimesters of pregnancy, you may develop yellowish discoloration of the skin, whites of the eyes, and mucous membranes due to impaired bile excretion (cholestatic jaundice), or liver cell disorders.

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

3. How to take Prometrium

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

Oral use
On average, for insufficient production of the hormone progesterone (progestin deficiency), the daily dose is 200–300 mg of progesterone.
It is recommended to take the medicine away from meals.

In cases of insufficient progesterone production by the ovary during the second half of the menstrual cycle (luteal phase deficiency), particularly in premenstrual syndrome, diffuse nodular breast changes (benign mastopathy), menstrual cycle irregularities, and perimenopause, the daily dose is 200–300 mg of progesterone, administered in a 10-day treatment cycle, usually from day 17 to day 26 inclusive of the menstrual cycle.

In hormone replacement therapy (HRT) during menopause, estrogen monotherapy is not recommended due to the risk of thickening of the uterine lining (endometrial hyperplasia). Progesterone should be administered at a dose of 200 mg daily for 12–14 days per month, or during the last two weeks of each treatment cycle.
HRT should be interrupted for approximately one week, during which vaginal bleeding may occur.

For these indications, in cases of liver disease (hepatopathies) or side effects due to progesterone (e.g. drowsiness after oral administration), vaginal administration should be used as an alternative to oral administration, using the same doses.

Vaginal use
Insert each capsule deeply into the vagina.

As a supplement during the second half of the menstrual cycle (luteal phase), either in spontaneous or induced cycles, in cases of reduced fertility or primary or secondary infertility, particularly in cases of ovulation disorders, the recommended daily dose is 200–300 mg daily, starting on day 17 of the cycle for 10 consecutive days. The treatment should be repeated as soon as possible if absence of menstruation (amenorrhea) and confirmed pregnancy occur.

In cases of threatened miscarriage or prevention of recurrent miscarriages due to insufficient progesterone production during the luteal phase, the recommended daily dose is 200–400 mg.

If you take more Prometrium than you should
If you accidentally ingest/absorb an excessive dose of Prometrium, contact your doctor immediately or go to the nearest hospital.

If you forget to take Prometrium
Do not take a double dose to make up for the missed dose.

If you have any 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.
The following may occur occasionally:

• drowsiness and dizziness for up to three hours after oral administration of Prometrium. In such cases, the dose should be reduced or adjusted (for example: 1 capsule of 200 mg or 2 capsules of 100 mg taken at bedtime, for 12–14 days per cycle). Vaginal administration may also be used. The following effects have also been reported:

• reduction of menstrual cycle or uterine bleeding outside menstrual periods (metrorrhagia). In these cases, it is advisable to delay treatment by a few days (for example, starting treatment on day 19 of the cycle instead of day 17). The following adverse reactions have been reported with progestogen administration in general:

• intermenstrual bleeding,

• changes in menstrual flow,

• absence of menstruation (amenorrhoea),

• alteration of cervical mucus,

• breast tenderness (mastodynia),

• change in body weight (increase or decrease),

• yellowish discoloration of the skin, whites of the eyes and mucous membranes due to impaired bile excretion (cholestatic jaundice),

• severe allergic reaction (anaphylaxis or anaphylactoid reactions),

• skin reactions (cutaneous rash with or without itching), appearance of yellowish-brown facial spots during pregnancy (chloasma),

• fever,

• insomnia,

• nervousness,

• depression,

• headache (cephalalgia).

• Following the instructions provided in this leaflet reduces the risk of adverse reactions.
  Reporting of adverse reactions
  If you experience any adverse reaction, including those not listed in this leaflet, please contact your doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at the following website:

https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store Prometrium

Keep this medicine out of the sight and reach of children.
No special storage instructions are required.
Do not use this medicine after the expiry date stated on the pack after EXP. The expiry date refers to the last day of that month. The expiry date applies to the product in its original, unopened packaging and properly stored.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Prometrium contains
Soft capsule 100 mg:

• The active substance is micronized progesterone. Each capsule contains 100 mg of micronized progesterone.
• The other components are: sunflower seed oil, soy lecithin.
• Capsule shell components: gelatin, glycerol, titanium dioxide, purified water.

Soft capsule 200 mg:

• The active substance is micronized progesterone. Each capsule contains 200 mg of micronized progesterone.
• The other components are: sunflower seed oil, soy lecithin.
• Capsule shell components: gelatin, glycerol, titanium dioxide, purified water.

Description of the appearance of Prometrium and contents of the pack
Soft capsules for oral or vaginal use.
Prometrium 100 mg: box of 30 capsules.
Prometrium 200 mg: box of 15 or 30 capsules.

Marketing Authorization Holder
BESINS HEALTHCARE IRELAND LIMITED
Plaza 4, Level 4 Custom House Plaza
Harbourmaster Place, IFSC
Dublin 1, D01 A9N3
Ireland

Manufacturer
CYNDEA PHARMA S.L.
Poligono Industrial Emiliano Revilla Sanz
Avenida de Agreda, 31, Olvega
42110 (Soria)
Spain

BESINS MANUFACTURING BELGIUM
Groot-Bijgaardenstraat, 128
1620 Drogenbos
Belgium

BESINS MANUFACTURING ESPAÑA
Polígono Industrial El Pitarco, parcela nr. 4
50450 Muel (Zaragoza)
Spain