Depo-provera

Package leaflet: Information for the patient

DEPO-PROVERA, 150 mg/ml, suspension for injection
Medroxyprogesteroni acetas
Please read this leaflet carefully before using the medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What DEPO-PROVERA is and what it is used for
2. What you need to know before using DEPO-PROVERA
3. How to use DEPO-PROVERA
4. Possible side effects
5. How to store DEPO-PROVERA
6. Contents of the pack and other information

1. What DEPO-PROVERA is and what it is used for

DEPO-PROVERA is used as a hormonal contraceptive medicine. Medroxyprogesterone acetate, the active substance in this medicine, is a progestagen and a chemical compound similar to the natural hormone progesterone.
DEPO-PROVERA:

• inhibits the secretion of gonadotropins and thereby controls ovarian function,
• prevents the maturation of Graafian follicles and full development of oocytes, thus preventing their release from the ovaries (ovulation) during the menstrual cycle,
• also leads to a reduction in the thickness of the endometrium (uterine lining). An oocyte that has not been released from the ovary cannot be fertilized by spermatozoa, thus preventing pregnancy,
• causes an increase in the viscosity of cervical mucus, which prevents spermatozoa from entering the uterus.

In women of all ages, prolonged use of the medicinal product DEPO-PROVERA may lead to a decrease in bone mineral density (BMD). Therefore, the doctor should consider evaluating the benefit-risk ratio of using this medicine, taking into account also the decrease in BMD occurring during pregnancy and/or lactation.
It should also be considered that return to fertility (ovulation) may be delayed for up to one year.

2. Important information before using DEPO-PROVERA

When not to use DEPO-PROVERA

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• in women who are pregnant or suspect they may be pregnant;
• in women who have experienced unexplained vaginal bleeding until a definitive diagnosis has been made and malignancy of the reproductive organs has been excluded;
• in women diagnosed with or suspected of having hormone-dependent malignant tumours of the breast or reproductive system;
• in women with severe liver insufficiency;
• in women with active thrombophlebitis, or who have had or currently have thromboembolic disorders or cerebrovascular disease;
• if the patient has meningioma or has ever been diagnosed with meningioma (usually a benign tumour of the tissue surrounding the brain and spinal cord).

DEPO-PROVERA should not be used before the onset of the first menstrual period.
Warnings and precautions
Before prescribing DEPO-PROVERA, the doctor should examine the patient. Prior to starting treatment,
this should be discussed with the doctor. The patient should inform the doctor if she has or has had
any of the following conditions. The doctor should discuss with the patient whether DEPO-PROVERA is suitable for her.
DEPO-PROVERA may be used in adolescent women, but only after discussing other contraceptive methods with the patient and determining them to be unsuitable or unacceptable.
The patient should inform the doctor about:

• hypersensitivity to steroids other than medroxyprogesterone acetate;
• vaginal bleeding;
• concomitant medical conditions such as epilepsy, migraine, asthma, or heart or kidney dysfunction, in which weight gain or fluid retention may worsen the health condition (medroxyprogesterone acetate may cause fluid retention);
• history of depression;
• occurrence of symptoms resembling premenstrual dysphoric disorder during treatment with DEPO-PROVERA;
• diabetes, as glucose tolerance may be reduced in individuals receiving DEPO-PROVERA;
• submission of an endometrial or cervical canal mucosal biopsy specimen for histopathological examination;
• DEPO-PROVERA may reduce concentrations of hormonal biomarkers;
• sudden partial or complete loss of vision, proptosis, double vision, or migraine (ophthalmological examination is required; if papilledema or retinal vascular changes are diagnosed, treatment should be discontinued);
• history of thrombotic disorders or thrombotic events occurring during treatment with DEPO-PROVERA; in such cases, the doctor may consider discontinuing the medication;
• risk factors for osteoporosis, such as: excessive alcohol consumption and/or tobacco use, chronic use of medications that may reduce bone mass (e.g. anticonvulsants or corticosteroids), low body mass index or eating disorders (e.g. anorexia nervosa or bulimia), previous low-energy fractures, family history of osteoporosis, because intramuscular administration of DEPO-PROVERA leads to decreased bone mineral density;
• irregular, scanty, heavy, or prolonged menstrual periods;
• weight gain;
• development of jaundice; in such cases, the doctor may consider discontinuing treatment.

Psychiatric disorders
Some women using hormonal contraceptives, including DEPO-PROVERA, have reported depression or depressed mood. Depression can be severe and may sometimes lead to suicidal thoughts. If mood changes or symptoms of depression occur, the patient should contact her doctor as soon as possible for further medical advice.
Meningioma
The use of medroxyprogesterone acetate has been associated with the development of usually benign tumours of the tissue surrounding the brain and spinal cord (meningiomas). This risk increases especially with long-term use (several years). If meningioma is diagnosed, the doctor will discontinue treatment with DEPO-PROVERA (see section "When not to use DEPO-PROVERA"). If the patient experiences any of the following symptoms—visual disturbances (e.g. double or blurred vision), hearing loss or tinnitus, loss of smell, progressively worsening headaches, memory loss, seizures, or weakness in arms or legs—she should immediately inform her doctor.
The use of DEPO-PROVERA is associated with a significant decrease in bone mineral density due to the known effect of estrogen deficiency on bone remodelling. The extent of bone loss increases with longer duration of DEPO-PROVERA use, while bone mineral density increases after discontinuation of the drug.
The reduction in bone mineral density is of particular significance during adolescence and early adulthood—life stages critical for bone mass accrual.
It is not known whether the use of DEPO-PROVERA in young women reduces peak bone mass and increases the risk of fractures later in life, i.e. after menopause.
The doctor may recommend calcium and vitamin D supplementation and periodic assessment of bone mineral density.
DEPO-PROVERA does not protect against HIV infection, including AIDS, or against other
sexually transmitted infections (STIs).
Safe sexual practices, including correct and consistent use of condoms, reduce the risk of contracting STIs, including HIV infection.
The patient should consult a healthcare professional for information on ways to reduce the risk of contracting STIs, including HIV infection.
DEPO-PROVERA and other medicines
The patient should inform the doctor about all medicines currently or recently taken, as well as any medicines she plans to take.
Before starting any new medicine together with DEPO-PROVERA, the patient should inform her doctor.
Concomitant administration of aminoglutethimide may reduce plasma concentrations of medroxyprogesterone acetate and thereby reduce the contraceptive efficacy of DEPO-PROVERA.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning a pregnancy, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
Use of this medicine during pregnancy is contraindicated.
In newborns born from unintended pregnancies occurring between the first and second month after administration of the contraceptive injection DEPO-PROVERA, low birth weight may occur, which in turn is associated with an increased risk of neonatal death. This risk is very low, as such pregnancies are extremely rare.
However, data suggest an association between the use of progestogen-type drugs during the first trimester of pregnancy and the occurrence of developmental disorders of the genital system in fetuses of both sexes.
The patient should be informed of the potential risk to the fetus if DEPO-PROVERA is used during pregnancy or if pregnancy occurs during treatment with the drug.
Breastfeeding
Medroxyprogesterone acetate and its metabolites pass into human milk. There are insufficient data to suggest that their presence may pose a risk to the infant; however, breastfeeding is not recommended during treatment.
Driving and using machines
The effect of DEPO-PROVERA on the ability to drive and operate machinery has not been studied.
DEPO-PROVERA contains methyl parahydroxybenzoate (E 218) and propyl
parahydroxybenzoate (E 216)
This medicine may cause allergic reactions (delayed-type reactions are possible).
DEPO-PROVERA contains polysorbate 80
This medicine contains 2.4 mg of polysorbate 80 per ml, equivalent to 2.4 mg of polysorbate 80 per dose of Depo-Provera.
Polysorbates may cause allergic reactions. The patient should inform the doctor if she has known allergic reactions.
DEPO-PROVERA contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per vial or pre-filled syringe, meaning the medicine is considered "sodium-free".
3. How to use DEPO-PROVERA
This medicine should always be used exactly as directed by the doctor or pharmacist. If in doubt, consult the doctor or pharmacist.
Route and method of administration
The recommended dose is 150 mg every 3 months.
DEPO-PROVERA is administered as deep intramuscular injections into the gluteal or deltoid muscle. Injections should be given as long as directed by the doctor. The medicine should be shaken vigorously before administration to obtain a uniform suspension.
Administration of the first dose of DEPO-PROVERA
To ensure the patient is not pregnant at the time of the first dose, the injection must be given ONLY within the first five days of a normal menstrual cycle.
If DEPO-PROVERA is to be administered after childbirth, the first dose MUST be given within five days after delivery, provided the patient is not breastfeeding.
DEPO-PROVERA is administered at six weeks postpartum if the mother is breastfeeding.
DEPO-PROVERA is effective only if injections are administered regularly and exactly on schedule.
Subsequent doses
Subsequent doses of DEPO-PROVERA should be administered every 12 weeks. If the interval between injections exceeds 89 days, pregnancy must be ruled out before administration, and the patient should use additional (e.g. mechanical) contraceptive methods for 14 days after the next injection.
Switching from other contraceptive methods to DEPO-PROVERA
When switching from other contraceptive methods to DEPO-PROVERA, the first dose should be administered in a way that ensures continuous contraceptive protection, taking into account the mechanism of action of both methods (e.g. in patients who have previously used oral contraceptives, the first DEPO-PROVERA injection should be given within 7 days after taking the last contraceptive pill). It is very important that subsequent injections are administered exactly on schedule.
Use of this medicine is not recommended before the onset of the first menstrual period. Use of DEPO-PROVERA in adolescents aged between 12 and 18 years is associated with a statistically significant reduction in bone mineral density.
Data are available on the use of DEPO-PROVERA in adolescent women (aged 12 to 18 years). In addition to concerns regarding reduced bone mineral density, the safety and efficacy of DEPO-PROVERA in adolescent women after menarche and in adult women are expected to be similar.
Use of a higher than recommended dose of DEPO-PROVERA
Do not use more medicine than prescribed by the doctor. If a higher dose of DEPO-PROVERA than recommended has been administered, contact the doctor immediately.
Missed dose of DEPO-PROVERA
If a dose of DEPO-PROVERA is missed or if the interval between two consecutive injections exceeds 12 weeks, there is a risk of pregnancy. Therefore, the patient should consult her doctor to determine whether the next dose of DEPO-PROVERA can be administered.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.

Very common (may affect more than 1 in 10 people):

• nervousness
• headache
• increased body weight, decreased body weight

Common (may affect up to 1 in 10 people):

• depression, decreased libido
• dizziness
• varicose veins
• abdominal pain, discomfort in the upper abdomen, nausea, bloating
• acne, hair loss, rash
• back pain
• hot flushes, breast tenderness, painful menstruation
• fatigue, fluid retention

Uncommon (may affect up to 1 in 100 people):

• infections of the urogenital tract
• hypersensitivity to the medicine
• increased appetite, decreased appetite
• insomnia
• seizures, somnolence
• increased heart rate (tachycardia)
• hot flushes
• shortness of breath
• liver function disorders
• excessive hair growth, itching, skin pigmentation on the face (chloasma), urticaria
• abnormal uterine bleeding (irregular, excessively heavy, too light, menstrual spotting), pain during intercourse, pelvic pain, galactorrhea, absence of lactation
• chest pain

Rare (may affect up to 1 in 1,000 people):

• endometritis, abscess at injection site
• breast cancer
• anaemia, blood disorders
• sudden, severe allergic or non-allergic reaction which may lead to death
• prolonged anovulation
• inability to achieve orgasm despite sexual arousal in women, emotional disturbances, psychiatric disorders, hyperexcitability, anxiety
• migraine, paralysis, fainting, paraesthesia
• dizziness
• hypertension, thrombophlebitis, embolism and thromboembolic disorders, deep vein thrombosis, pulmonary embolism
• hoarseness
• gastrointestinal disorders
• jaundice
• skin and mucous membrane disease characterized by localized swelling (angioedema), skin inflammation, petechiae, striae, atrophy or impaired structure of fatty tissue (acquired lipodystrophy)
• muscle cramps, joint pain, limb pain, osteoporosis, osteoporotic fractures, swelling in the armpit area, excessive and pathological skin fibrosis (morphea)
• absence of menstruation, breast pain, uterine haemorrhage, heavy irregular menstruation, menstrual bleeding, dryness of the vulva and vagina, changes in breast gland size, ovarian cysts, premenstrual syndrome, endometrial hyperplasia, breast lumps, bleeding from nipple glands, vaginal cysts, subjective symptoms of pregnancy, vaginal infections
• reactions at injection site, pain and tenderness at injection site, persistent atrophy and depression at injection site, nodule at injection site, fever, feeling of fatigue, swelling, increased thirst
• decreased bone mineral density, impaired glucose tolerance (prediabetes), abnormal liver function tests, abnormal cervical smear

Frequency not known (cannot be estimated from the available data):

• usually benign tumour of the tissue surrounding the brain and spinal cord (meningioma) (see section 2 "Warnings and precautions").

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +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 authorisation holder or its representative.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store DEPO-PROVERA medicine

Keep this medicine out of the sight and reach of children.
Store below 25°C.
Do not use this medicine after the expiry date stated on the packaging after: EXP.
The expiry date refers to the last day of the stated month.
Any unused medicine or waste material should be disposed of appropriately. Medicines must 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 DEPO-PROVERA contains

• The active substance is medroxyprogesterone acetate. Each vial contains 150 mg of medroxyprogesterone acetate in 1 ml of injection solution. The pre-filled syringe contains 150 mg of medroxyprogesterone acetate in 1 ml of injection solution.
• The other ingredients are: sodium chloride (see section 2 "DEPO-PROVERA contains sodium"), methyl parahydroxybenzoate (E 218), propyl parahydroxybenzoate (E 216) [see section 2 "DEPO-PROVERA contains methyl parahydroxybenzoate (E 218) and propyl parahydroxybenzoate (E 216)"], polysorbate 80 (see section 2 "DEPO-PROVERA contains polysorbate 80"), macrogol 3350, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), water for injections.

What DEPO-PROVERA looks like and contents of the pack
White suspension.
Pack contents:
1 vial of 1 ml
10 vials of 1 ml
1 pre-filled syringe of 1 ml
Vial made of colourless glass closed with a rubber stopper, packed in a cardboard box.
Pre-filled syringe with a sterile needle, packed in a cardboard box.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Pfizer Manufacturing Belgium NV
Rijksweg 12
2870 Puurs-Sint-Amands
Belgium

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Pfizer Polska Sp. z o.o.
tel. 22 335 61 00