Depo-Provera - instructions for use, dose, side effects, contraindications

Excipients: sodium chloride (8.6 mg), methylparahydroxybenzoate 1.35 mg, propyl parahydroxybenzoate 0.15 mg, polysorbate 80 2.4 mg, macrogol 3350 28.5 mg, sodium hydroxide (pH adjusted), hydrochloric acid (for pH adjustment), water for injections up to 1 ml.

Description:FROMwhite color.

Pharmacotherapeutic group:Gestagen

ATX: & nbsp

L.02.A.B.02 Medroxyprogesterone

L.02.A.B Progestogens

Pharmacodynamics:

Medroxyprogesterone acetate (MPA) refers to progestins (progestins) and is a progesterone derivative (gestagenic agent) that does not possess estrogenic activity. On the other hand, its androgenic activity is considered to be minimal. MPA in appropriate doses suppresses the secretion of pituitary gonadotropins, which in turn prevents the maturation of follicles, causing anovulation in women of childbearing age.This action can also be explained by the ability of the drug to reduce the severity of vasomotor symptoms in women menopuazalnom period. IPA also causes typical gestagen preparations changes in cervical mucus: increases the viscosity of the cervical mucus, thereby impeding the penetration of sperm.

Possible manifestation of anabolic effect. The anti-inflammatory effect of MPA was noted. In large doses has glucocorticosteroid activity.

Pharmacokinetics:

After intramuscular (IM) administration of MPA it release occurs slowly, which ensures the creation of low, but constant concentrations of MPA in the blood plasma. Immediately after the on / IM injection of 150 mg / ml IPA concentration in blood plasma was 1.7 ± 0.3 nmol / l, and after 2 weeks - 6.8 ± 0.8 nmol / l. The time to reach maximum concentration in the / th injection is about 4-20 days, then the IPA concentration is gradually reduced and stored at approximately 1 ng / ml for 2-3 months. However, MPA can be detected in the blood plasma even 7-9 months after the IM injection. About 90-95% of MPA are in the blood plasma in a protein-related condition. The volume of distribution is 20 ± 3 liters.MPA penetrates through the blood-brain barrier, placental barrier and into breast milk. The half-life period after the / m administration is 6 weeks. MPA is metabolized in the liver and is excreted primarily by biliary secretion through the intestine. Approximately 44% of MPA in unchanged form is excreted by the kidneys. Currently, more than 10 metabolites of MPA that are excreted in the urine are described, most of them in the form of conjugates.

Indications:

1) Contraception (suppression of ovulation).

2) Endometriosis (treatment).

3) Vasomotor symptoms in the menopoiasis period.

Contraindications:

- Pregnancy and the period of breastfeeding (during the first 6 weeks of the postpartum period);

- tovaginal discharge from an unknown origin;

- theestablished or suspected cancer of the breast and genital organs (with the exception of endometrial cancer);

- tsevere liver function disorder;

- theincreased sensitivity to MPA or any component of the drug;

- aboutthrombosis and thromboembolism at present (including deep vein thrombosis, pulmonary embolism);

- mplayfulness (see section "Special instructions").

Carefully:

Thrombophlebitis, thromboembolism or stroke (increased risk of developing or in anamnesis), epilepsy, bronchial asthma, cardiac, renal failure, diabetes, depressive states.

Since women who have been using the drug for a long time can decrease bone density (PCT) before the onset of menopause, the risk / benefit ratio should be assessed when prescribing the drug.

Pregnancy and lactation:

MPA is contraindicated in pregnancy.

There are reports that, under certain conditions, there is a correlation between the use of progestogens during the first trimester of pregnancy and the developmental disorders of the genitals in the fetus.

Newborns, in the case of an unplanned pregnancy occurring within 1-2 months after the injection of MPA, have a greater risk of developing hypotrophy, which in turn increases the risk of intrapartum and neonatal mortality. The risk of developing such complications is relatively low, since pregnancy with the use of MPA is rare.

In the event that pregnancy has developed against the background of the use of MPA, the patient should be warned about the possible risk to the fetus.

MPA is excreted in breast milk.There is no evidence that this may cause any harm to the newborn breastfed. However, the use of MPA in the first six weeks of the postpartum period is not recommended.

Dosing and Administration:

CONTRACEPTION: 150 mg once every 3 months deep in the / m in the gluteus or deltoid muscle. The first injection should be performed within the first 5 days after the start of regular regular menstruation; if the patient does not breast-feed the baby; or 6 weeks after delivery if the patient is breastfeeding. To ensure reliable contraception, subsequent injections should be carried out at intervals of 12 weeks (but not more than 89 days).

ENDOMETRIOSIS: IM 50 mg once a week, or 100 mg once every 2 weeks for at least 6 months. Due to prolonged action, the recovery of the menstrual cycle after such therapy may occur after a while.

VAZOMETRIC SYMPTOMS IN WOMEN IN THE MENOPOASAL PERIOD: in / m by 150 mg one time in 12 weeks.

Immediately before use, shake the contents of the vial or syringe until a uniform suspension is obtained.

Disposable syringe

1. Remove the protective cap from the syringe.

2. Observing sterility, put the needle on the syringe.

3. Remove the protective cap from the needle. Now the syringe is ready for use.

Side effects:

The frequency of unwanted reactions is represented by the following classification:

Very Frequent		≥10%
Frequent		≥1% and <10%
Infrequent		≥0.1% and <1%
Rare		≥0.01% and <0.1%
Very rare		<0,01%
Frequency unknown		It is impossible to determine from the available data
From the genitals of the breast and glands
Very Frequent	dysfunctional uterine bleeding (irregular, abundant, meager), amenorrhea.
Frequent	dysmenorrhea, leukorrhea, tenderness of the mammary glands, vaginitis.
From the nervous system
Very Frequent	headache.
Frequent	dizziness.
From the gastrointestinal tract
Very Frequent	pain and discomfort in the abdomen.
Frequent	flatulence, bloating, nausea.
From the skin and subcutaneous tissues
Frequent	acne, alopecia, rash, itching, urticaria.
From the musculoskeletal and connective tissue
Frequent	pain in the back and joints, cramps calf muscles.
Disorders of the psyche
Very Frequent	nervousness.
Frequent	asthenia / fatigue, depression, insomnia, decreased libido or anorgasmia.
Other
Very Frequent	increase in body weight by more than 4.5 kg after 24 months, bleeding.
Frequent	edema / fluid retention in the body, "hot flushes".

Side effects identified during post-marketing studies and the frequency of which is not specified:

From the side of the cardiovascular system	syncope, tachycardia, thromboembolic disorders (including pulmonary embolism, deep vein thrombosis of the lower extremities), thrombophlebitis, varicose veins.
From the gastrointestinal tract	change appetite, disorders gastrointestinal tract, impaired liver function, increased activity of "liver" transaminases, jaundice, including cholestatic, bleeding from the rectum.
On the part of the blood and lymphatic system	anemia, pathological changes in blood cells or blood clotting elements.
From the side of skeletal-muscular and connective tissue	osteoporosis, in rare cases with osteoporotic and fractures.
From the nervous system	paralysis, paralysis of the facial nerve, paresthesia, drowsiness.
From the respiratory side systems	Shortness of breath and exacerbation of bronchial asthma.
From the skin and subcutaneous tissues	hirsutism, increased sweating, dry skin, scleroderma, hyperpigmentation on the face and body (melasma, chloasma)
From the genitals and breast	cervical cancer, breast cancer, lack of fertility recovery, unplanned pregnancy, decreased lactation, breast engorgement, breast compressions or bleeding from the nipples, galactorrhea, uterine hyperplasia, urogenital infections, vaginal cysts, abdominal pains, vaginal discharge , erosion of the cervix, prolonged anovulation, mastodynia, hypersensitivity of the nipples of the mammary glands, dyspareunia.
Violations psyche	increased libido.
Other	reactions hypersensitivity (eg, anaphylaxis and anaphylactoid reactions, angioneurotic edema), fever, reactions at the injection site (pain, compression at the injection site, skin discoloration at the injection site, "sterile" abscess), chills, swelling in the armpits, decreased glucose tolerance, thirst, hoarseness.

Overdose:

The use of very high doses of the drug can cause a number of symptoms, including weight gain (with some fluid retention in the body),increased fatigue, and in some cases, the effects of glucocorticosteroids are observed.

The drug should be discontinued. Specific treatment is not required.

Interaction:

When combined aminoglutethimide can significantly reduce the concentration of MPA in the blood plasma and thereby reduce its effectiveness.

IPA in vitro metabolized predominantly by hydroxylation via the CYP3A4 isoenzyme. Special studies of the effect of inhibitors or inducers of the isoenzyme CYP3A4 on the pharmacokinetics of MPA have not been conducted. In connection with the high probability of such interaction, it is theoretically possible to assume the effect on the efficiency of MPA. However, the clinical effects of simultaneous use of inhibitors or inducers of the isoenzyme CYP3A4 and MPA are unknown.

Special instructions:

Use strictly according to the doctor's prescription to avoid complications.

- Before the start of therapy, cervical erosion should be treated. With continued erosion, careful medical supervision. It is necessary to exclude genital cancers and other organic lesions.It is also necessary to conduct a thorough medical examination (including cervical cytology), paying special attention to such indicators as blood pressure, mammary glands, gastrointestinal tract and pelvic organs.

- If dysfunctional uterine bleeding occurs during the period of MPA application, a patient should be examined to exclude malignant neoplasms.

- If the interval between the first and the subsequent injection of the drug DEPO-PROVUER® is more than 13 weeks, then before the next injection it is necessary to exclude the occurrence of pregnancy.

- The transition from other methods of contraception to the use of the drug DEPO-PROVERA® should be carried out taking into account the mechanisms of action of both methods so that the contraceptive effect is not interrupted (for example, when switching from oral contraceptives, the first injection of MPA should be performed within 7 days after taking the last pill) .

- In postmenopausal women, estrogen-progestational therapy should be used at the lowest effective doses and at the shortest possible rate, depending on the purpose of the therapy.In addition, a regular evaluation of this therapy should be made in accordance with the individual characteristics of the patient.

- Contraindicated in the use of MPA in patients with a deleted uterus. Exception is made by patients who have previously been diagnosed with endometriosis.

- MPA can cause fluid retention in the body. Therefore, care must be taken when treating patients whose condition may be adversely affected fluid retention in the body.

- During the period of therapy with the drug DEPO-PROVERE®, it is necessary to carefully monitor the condition of patients who were previously treated for depression.

- When used in patients with diabetes should take into account the ability of MPA to reduce glucose tolerance.

- If it is necessary to cytologic or histological study of the endometrium or cervix, the pathologist should be warned about the therapy with DEPO-PROVERA®.

- When conducting laboratory studies, it should be borne in mind that the use of MPA can alter the concentrations of the following endocrine biomarkers:

a) Steroids in blood plasma and urine (cortisol, estrogens, pregnanediol, progesterone, testosterone);

b) gonadotropins in blood plasma and in urine (luteinizing hormone (LH) and follicle-stimulating hormone (FSH));

c) globulin, which binds the sex hormones.

- It is necessary to interrupt the use of the drug and to conduct a test with sudden partial or complete loss of vision, or with acute development of exophthalmos, double vision, migraine attacks. When revealing damage to the vessels of the retina or edema of the optic nerve disc, treatment with the drug should be discontinued.

- Despite the fact that there was no causal relationship between the use of MPA and the development of thromboembolic disorders, in patients with a history of thromboembolic complications or when they occur against the background of treatment, the use of the drug DEPO-PROVERE® is not recommended.

- In most women, with the use of the drug DEPO-PROVERE® (both after a single dose and after repeated administration of the drug), prolonged anovulation with amenorrhea and menstrual irregularities (eg, acyclic bleeding / hemorrhage, rare, profuse or prolonged bleeding). If patients continue to use the drug, the frequency of irregular bleeding decreases, and the incidence of amenorrhea increases.

- The use of the drug leads to a decrease in the concentration of estrogens in the blood plasma and is associated with a significant decrease in PCT, as the metabolism of bone tissue depends on the concentration of estrogens. After long-term use (up to 5 years) for contraception of 150 mg in adult women, the PCT of the bones of the spine and femurs decreased by an average of 5-6%. With an increase in the duration of the drug, the decrease in PCT increases, with the greatest decrease observed in the first 2 years of the drug. The PCT of the femoral neck is reduced to the same extent as that of the entire femur. Within 2 years after drug discontinuation, partial restoration of PCT and an increase in the synthesis of estrogens in the ovaries were observed, and the longer the drug was used, the slower the recovery of PCT. The above should be taken into account especially in young women during the period of increasing bone mass. It is unknown whether the use of the drug in young women reduces the peak mass of bone tissue and increases the risk of osteoporotic fractures in subsequent years of life.

- DEPO-PROVER® should be used as a contraceptive and for treatmentendometriosis for a long period of time (more than 2 years) only if other methods are not applicable, and it is necessary to determine PCT. In the presence of risk factors for the development of osteoporosis (metabolic bone disease, chronic alcoholism and / or tobacco smoking, low body mass index, neurogenic anorexia or bulimia, osteoporosis in family history, constant use of drugs that reduce bone mass, such as anticonvulsants and corticosteroids) , the possibility of using other methods of contraception and the treatment of endometriosis should be considered, since with the use of the drug DEPO-PROVERE®, an additional risk of osteoporosis.

- Patients using the drug DEPO-PROVERA® are recommended to take calcium and vitamin preparations D.

- Long-term follow-up of patients using DEPO-PROVERA ® revealed either a low risk or no increased risk of developing breast cancer, however, this risk increases with an increase in the duration of hormone replacement therapy with conjugated estrogens in combination with the DEPO-PROVER ® drug.Also, with the simultaneous use of estrogens and progestin on a mammogram, changes can occur. A relative increase in risk was found in patients who recently or a few years before the study received such therapy. Based on the available data, it is impossible to determine whether this increase is associated with increased surveillance of patients currently receiving therapy, the biological effects of injectable progestogens, or a combination of these causes.

- No increased risk of cancer of the ovaries, liver, cervix, and found that the use of the drug has a long protective effect and reduces the risk of developing endometrial cancer.

- DEPO-PROVUER® has a prolonged contraceptive effect. On average, the ability to conceive is restored 10 months after the last injection of the drug, the interval can be from 4 to 31 months, regardless of the duration of use.

- When using MPA is possible weight gain patient.

- When developing jaundice it is necessary to stop using the drug.

- The patient should be informed that the use of the drug DEPO-PROVERE® does not protect against sexually transmitted infections, including human immunodeficiency virus (AIDS).

- Estrogens in combination with or without progestins should not be used to prevent cardiovascular disease. It was found that the use of this combination in women during the postmenopause leads to an increased risk of cardiovascular complications, such as myocardial infarction, coronary heart disease, stroke and venous thromboembolism. Clinical studies have shown that the use of estrogen in combination with MPA increases the risk of cardiovascular mortality during the first year of taking medications and lack of benefit. An increased risk of venous thromboembolism (including deep vein thromboembolism and pulmonary artery), stroke was observed for one year and persisted throughout the observation period. The risk of venous thromboembolism increases twofold.

- It was found that the use of MPA in combination with conjugated estrogens leads to an increased risk of possible dementia in patients in the postmenopausal period at the age of 65 years and older. In addition, it was found that combination therapy does not prevent the development of mild cognitive disorders in such patients.It is not recommended the use of hormone therapy to prevent the development of dementia in patients aged 65 years and older.

- It was found that when using estrogen or estrogen in combination with progestin derivatives for 5 or more years, postmenopausal women were associated with an increased risk of developing ovarian cancer. Patients who received such therapy earlier and have stopped treatment at the moment have not experienced an increase in this risk.

Effect on the ability to drive transp. cf. and fur:

The effect of the drug on the ability to drive vehicles and mechanisms has not been studied, but it must be taken into account that DEPO-PROVERE® can cause dizziness and other disturbances from the nervous system, so, when taking the drug, care should be taken when performing the above actions.

Form release / dosage:Suspension for intramuscular injection, 150 mg / ml.

Packaging:

Primary packaging: on 150 mg of active substance in bottles of transparent glass class I (Hebrew Pharm.) 1 ml; on 150 mg of active substance in disposable syringes from transparent glass of class I (Hebrew Farm.) on 1 ml.

Secondary packaging: 1 bottle with instruction for use is placed in a cardboard box pack; 1 syringe complete with a needle (0.7 x 40 mm) is placed in a PVC contour mesh package;

Tertiary packaging for syringes: 1 PVC contour pack with instructions for use is placed in a cardboard box.

Storage conditions:

At a temperature of 20-25 ° C, out of reach of children.

The vials should not be stored upside down.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N008862 / 01

Date of registration:20.07.2010 / 06.06.2016

Expiration Date:Unlimited

The owner of the registration certificate:Pfizer IFG Belgium N.V.Pfizer IFG Belgium N.V. Belgium

Manufacturer: & nbsp

PFIZER MFG. BELGIUM, N.V. Belgium

Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation

Information update date: & nbsp23.04.2017

Illustrated instructions

Instructions

Depo-Provera® (Depo-Provera)