What is Depo-Provera used for?

SAYANA is indicated as long-term contraception for women. A single subcutaneous injection prevents ovulation and provides contraceptive efficacy for at least 13 weeks (+/- 1 week). It should, however, be borne in mind that the return of fertility (ovulation) may be delayed by up to 1 year (see section 4.4). Because loss of bone mineral density (BMD) may occur in women of various age groups using SAYANA long-term (see section 4.4), the benefit-risk balance should be considered, taking into accoun

What is the active ingredient in Depo-Provera?

Medroxyprogesteroni acetas (Medroxyprogesteroni acetas)

What pharmaceutical form is Depo-Provera available in?

Depo-Provera: Zawiesina do wstrzykiwań 150 mg/ml (domięśniowo)

Is Depo-Provera OTC or prescription only?

Depo-Provera requires a doctor's prescription.

What are the side effects of Depo-Provera?

Reports from clinical studies: The table below lists the adverse reactions to the medicinal product with frequencies based on all-causality data from clinical trials that included 2,053 women receiving DMPA subcutaneously as a contraceptive. The most commonly reported adverse reactions (> 5%) included headache (8.9%), metrorrhagia (7.1%), weight gain (6.9%), amenorrhoea (6.3%) and injection site reactions (of various types, 6.1%). Adverse reactions are listed by the following categories. By freq

Who should NOT take Depo-Provera?

SAYANA is contraindicated in patients with known hypersensitivity to medroxyprogesterone acetate or to any of the excipients listed in section 6.1. SAYANA is contraindicated in pregnant women or in women with suspected pregnancy. SAYANA is contraindicated in women with known or suspected malignancy of the breast or genital organs. SAYANA is contraindicated in patients with meningioma or a history of meningioma. SAYANA is contraindicated in patients with undiagnosed vaginal bleeding. SAYANA is co

Can Depo-Provera be used during pregnancy?

Fertility SAYANA is indicated for the prevention of pregnancy. The return of fertility (conception) in women may be delayed following discontinuation of SAYANA (see section 4.4). Pregnancy SAYANA is contraindicated in pregnant women. Some data suggest an association between in utero exposure to progestins during the first trimester of pregnancy and genital abnormalities in male and female foetuses. If SAYANA is used during pregnancy or if the patient becomes pregnant while receiving this product

What ATC class does Depo-Provera belong to?

Depo-Provera: ATC G03AC06. ATC is the WHO Anatomical Therapeutic Chemical classification — it groups drugs by organ system and pharmacological mechanism.

Depo-Provera

This information is for educational purposes only. It is not intended as medical advice. Always consult a qualified healthcare professional.

Depo-Provera — Description, Dosage, Side Effects | PillsCard

ATC code: G03AC06 Medroxyprogesterone acetate is an analogue of 17α-hydroxyprogesterone with antiestrogenic, antiandrogenic and antigonadotropic activity. DMPA s.c. suppresses the secretion of pituitary gonadotropins, thereby preventing follicular maturation and the subsequent ovulation, and produces thickening of the cervical mucus, which prevents the passage of sperm into the uterus. These effects account for its contraceptive action. Changes in bone mineral density (BMD) in adult women In a study comparing changes in BMD in women receiving DMPA s.c. with those receiving DMPA i.m., no significant differences in BMD loss were demonstrated between the two groups after two years of treatment. The mean percentage changes in BMD in women receiving DMPA s.c. are shown in Table 1. Table 1. Mean change in BMD (95% CI) from baseline in adult women receiving DMPA s.c. by skeletal site Duration of treatment Lumbar spine Total hip Femoral neck n Mean change (%) (95% CI) n Mean change (%) (95% CI) n Mean change (%) (95% CI) 1 year 166 -2.7 166 -1.7 166 -1.9 (-3.1 to -2.3) (-2.1 to -1.3) (-2.5 to -1.4) 2 years 106 -4.1 106 -3.5 106 -3.5 (-4.6 to -3.5) (-4.2 to -2.7) (-4.3 to -2.6) CI = Confidence Interval In another controlled clinical study, adult women receiving DMPA i.m. for at least 5 years showed a mean decrease in BMD at the spine and hip of approximately 5 to 6% compared with a control group, in which no significant change occurred. The decline in BMD was most pronounced during the first two years of use, with smaller declines in subsequent years. Mean changes at the lumbar spine were -2.9%, -4.1%, -4.9%, -4.9% and -5.4% after 1, 2, 3, 4 and 5 years, respectively. Mean decreases at the total hip and femoral neck were similar. See Table 2 for further details. After discontinuation of DMPA i.m., BMD increased towards baseline values. A longer duration of treatment was associated with slower recovery of BMD. In the same clinical study, a limited number of women who had received DMPA i.m. for 5 years were followed for 2 years after discontinuation of treatment with DMPA i.m. During the two-year post-treatment period, BMD rose toward baseline values. Two years after the last DMPA injection, mean BMD had increased at all 3 skeletal sites, although deficits remained (see Table 2 below). Table 2. Mean change (95% CI) in BMD from baseline in adults by skeletal site and cohort after 5 years of DMPA i.m. treatment and after 2 years post-treatment or 7 years of observation (control group) Time in study Spine Total hip Femoral neck DMPA Control DMPA Control DMPA Control 5 years* n 33 105 21 65 34 106 Mean (SD) 95% CI -5.4% (3.57) -6.65; -4.11 0.4% (3.27) -0.20; 1.06 -5.2% (3.60) -6.80; -3.52 0.2% (3.18) -0.60; 0.98 -6.1% (4.68) -7.75; -4.49 -0.3% (5.22) -1.27; 0.73 7 years** n 12 60 7 39 13 63 Mean (SD) 95% CI -3.1% (3.15) -5.13; -1.13 0.5% (3.65) -0.39; 1.49 -1.3% (4.95) -5.92; 3.23 0.9% (3.81) -0.29; 2.17 -5.4% (2.73) -7.03; -3.73 0.0% (5.88) -1.51; 1.45 *The treatment group consisted of women who had received DMPA i.m. for 5 years and the control group consisted of women who had not used hormonal contraception during that time. **The treatment group consisted of women who had received DMPA i.m. for 5 years and were then followed for 2 years post-treatment, and the control group consisted of women who had not used hormonal contraception for 7 years. SD = Standard Deviation; CI = Confidence Interval Changes in BMD in adolescent girls (12 to 18 years) Results from an open-label, non-randomised clinical study of DMPA i.m. (150 mg i.m. every 12 weeks for up to 240 weeks (4.6 years)), with post-treatment follow-up in adolescent girls (12 to 18 years), also showed that medroxyprogesterone acetate i.m. was associated with a significant decline in BMD from baseline. Among subjects who received ≥ 4 injections/60 weeks, the mean decline in BMD at the lumbar spine was -2.1% at 240 weeks (4.6 years); the mean decline at the total hip was -6.4% and at the femoral neck -5.4% (see Table 3). In contrast, a non-comparable cohort of untreated subjects with differing baseline bone parameter values showed mean increases in BMD at week 240 of 6.4% at the lumbar spine, 1.7% at the total hip and 1.9% at the femoral neck. Table 3. Mean change (95% CI) in BMD from baseline in adolescents receiving ≥ 4 injections per 60 weeks, by skeletal site Duration of treatment DMPA i.m. n Mean change (95% CI) Total hip BMD Week 60 (1.2 years) 113 -2.7 [-3.27; -2.12] Week 120 (2.3 years) 73 -5.4 [-6.16; -4.64] Week 180 (3.5 years) 45 -6.4 [-7.38; -5.37] Week 240 (4.6 years) 28 -6.4 [-8.56; -4.24] Femoral neck BMD Week 60 113 -2.9 [-3.72; -2.15] Week 120 73 -5.3 [-6.23; -4.37] Week 180 45 -6.0 [-7.31; -4.59] Week 240 28 -5.4 [-7.81; -3.00] Lumbar spine BMD Week 60 114 -2.5 [-2.95; -1.98] Week 120 73 -2.7 [-3.57; -1.91] Week 180 44 -2.7 [-3.99; -1.35] Week 240 27 -2.1 [-4.16; -0.07] CI = Confidence Interval Post-treatment follow-up of adolescent participants in the same study who had received at least 1 injection of DMPA and had at least 1 BMD measurement following discontinuation of DMPA i.m. is presented in Table 4. The median number of injections administered during the treatment phase in this cohort was 9. At the time of the last DMPA injection, mean BMD changes (%) from baseline in this cohort were -2.7% for the spine, -4.1% for the total hip and -3.9% for the femoral neck. Following discontinuation of DMPA i.m., these deficits gradually recovered fully to baseline values. Full recovery required 1.2 years at the lumbar spine, 4.6 years at the total hip and 4.6 years at the femoral neck. It is important to note, however, that a large number of subjects discontinued from the study, so these results are based on a small number of subjects, and some subjects still had BMD deficits at the total hip at 240 weeks. Longer treatment duration and smoking were associated with slower recovery of BMD. See Table 4 below. Table 4. Mean change (95% CI) in BMD from baseline in adolescents following discontinuation of DMPA Weeks following discontinuation of DMPA n Median number of injections Mean change (% SE) from baseline at end of treatment 95% CI Mean change (% SE) from baseline at the post-discontinuation visit 95% CI Total hip BMD 0 98 9 -4.1 (0.43) [-4.95; -3.25] N/A 24 74 9 -4.1 (0.53) [-5.15; -3.04] -4.0 (0.61) [-5.25; -2.80] 60 71 8 -3.6 (0.46) [-4.48; -2.66] -2.8 (0.56) [-3.97; -1.72] 120 52 10 -4.3 (0.64) [-5.56; -2.98] -1.7 (0.72) [-3.14; -0.26] 180 39 7 -4.1 (0.72) [-5.55; -2.63] -1.2 (0.85) [-2.96; 0.46] 240 25 9 -3.4 (0.67) [-4.73; -1.98] 0.1 (0.98) [-1.95; 2.11] Femoral neck BMD 0 98 9 -3.9 (0.50) [-4.92; -2.92] N/A 24 74 9 -3.8 (0.60) [-5.01; -2.62] -4.0 (0.71) [-5.40; -2.55] 60 71 8 -3.3 (0.56) [-4.41; -2.18] -3.6 (0.70) [-4.99; -2.18] 120 52 10 -3.8 (0.74) [-5.25; -2.28] -1.8 (0.82) [-3.43; -0.13] 180 39 7 -3.9 (0.85) [-5.62; -2.17] -1.0 (0.98) [-3.00; 0.97] 240 25 9 -3.4 (0.80) [-5.07; -1.78] -0.7 (1.19) [-3.20; 1.72] Lumbar spine BMD 0 98 9 -2.7 (0.39) [-3.45; -1.91] N/A 24 74 9 -2.6 (0.43) [-3.42; -1.69] -2.5 (0.51) [-3.52; -1.48] 60 70 8 -2.8 (0.43) [-3.66; -1.96] -0.2 (0.60) [-1.41; 1.01] 120 52 10 -2.7 (0.61) [-3.96; -1.50] 2.2 (0.73) [0.74; 3.67] 180 39 7 -3.0 (0.67) [-4.35; -1.66] 2.8 (0.79) [1.16; 4.35] 240 25 9 -2.6 (0.80) [-4.28; -0.99] 4.5 (1.03) [2.35; 6.61] SE = Standard Error; CI = Confidence Interval Relationship between fracture incidence and use of DMPA i.m. (150 mg) in women of reproductive age A large retrospective cohort study analysing data from the General Practice Research Database (GPRD) included N = 41,876 women using DMPA as a contraceptive for whom data were available for 6 to 24 months prior to the first administration of DMPA and for up to 15 years (mean 5.5 years) following the first DMPA injection. A higher fracture risk was observed in the cohort of DMPA users compared with women who had never used DMPA, both "before" and "after" DMPA use. The fracture risk was compared in women "after" and "before" the first DMPA injection: incidence rate ratio = 1.01 (95% CI: 0.92, 1.11), indicating that DMPA does not increase the risk of bone fractures. The longest follow-up in this study was 15 years; the possible effects of DMPA beyond 15 years of follow-up therefore cannot be determined. Importantly, this study cannot determine whether the use of DMPA influences fracture incidence later in life, i.e. after the menopause. Based on the results of a French case-control epidemiological study, an association was observed between medroxyprogesterone acetate and meningioma. This study was based on data from the French national health data system (SNDS – Système National des Données de Santé) and included a population of 18,061 women who had undergone intracranial surgery for meningioma and 90,305 women without meningioma. Exposure to medroxyprogesterone acetate 150 mg/3 ml (injectable) was compared between women who had undergone intracranial surgery for meningioma and women without meningioma. The analyses demonstrated an increased risk of meningioma with the use of medroxyprogesterone acetate 150 mg/3 ml (9/18,061 (0.05%) versus 11/90,305 (0.01%); OR 5.55 (95% CI 2.27 to 13.56)). This increased risk appears to be primarily attributable to long-term (≥ 3 years) use of medroxyprogesterone acetate.

⚠️ Warnings

Loss of bone mineral density (BMD) The use of depot medroxyprogesterone acetate subcutaneously (DMPA s.c.) reduces serum estrogen levels and is associated with a significant loss of bone mineral density as bone metabolism adapts to the lower estrogen levels. Bone loss is greater with longer duration of use, but BMD appears to increase once DMPA s.c. is discontinued and ovarian estrogen production rises. Bone loss is particularly concerning during adolescence and early adulthood, a critical period of bone mass accretion. It is not known whether the use of DMPA s.c. by younger women reduces peak bone mass and thereby increases the risk of fractures later in life, i.e. after the menopause. A study evaluating the effects of DMPA i.m. (Depo-Provera) on bone mineral density in adolescent women showed that its administration was associated with a statistically significant decrease in bone mineral density from baseline. Following discontinuation of DMPA i.m. in adolescents, however, the return of mean BMD to baseline values required 1.2 years at the lumbar spine, 4.6 years at the total hip and 4.6 years at the femoral neck (see section 5.1). In some participants, BMD did not fully return to baseline during follow-up, and the long-term outcomes of this group are unknown. In adolescents, SAYANA may be used, but only after other contraceptive methods have been discussed with the patient and have been found inadequate or unsuitable. A large observational study in predominantly adult contraceptive users demonstrated that the use of DMPA i.m. does not increase the risk of bone fractures. Importantly, this study could not determine whether DMPA use affects fracture incidence later in life (see section 5.1 – Relationship between fracture incidence and use of DMPA i.m. in women of reproductive age). In a woman of any age, if long-term use of medroxyprogesterone acetate for more than 2 years is required, the benefit-risk balance of treatment should be carefully reassessed. In particular, in women with medical risk factors for osteoporosis, other contraceptive methods should be considered before using SAYANA. Significant risk factors for osteoporosis are: Alcohol and/or tobacco use Chronic use of medicinal products that reduce bone mass, e.g. anticonvulsants or corticosteroids Low BMI or eating disorders, e.g. anorexia or bulimia Previous spontaneous fracture Family history of osteoporosis Further information on changes in bone mineral density in both adult and adolescent women is provided in section 5.1. Adequate intake of calcium and vitamin D, whether from diet or supplements, is important for bone health in women of all ages. Irregular menstrual cycle Most women using SAYANA reported menstrual cycle disturbances. Patients should be appropriately counselled regarding the possibility of menstrual cycle disturbances and possible prolongation of anovulation. With increasing duration of SAYANA use, fewer patients report irregular bleeding and more report amenorrhoea. After the fourth dose, 39% of women reported amenorrhoea during the sixth month. At the twelfth month, 56.5% of women reported amenorrhoea. Changes in menstrual cycle across three contraceptive efficacy studies are shown in Figures 1 and 2. Figure 1 shows the increasing percentage of women experiencing amenorrhoea during the 12-month study. Figure 2 shows the percentage of women with spotting only, bleeding only, and bleeding plus spotting during the same period. In addition to amenorrhoea, menstrual cycle changes included irregular uterine bleeding, menorrhagia and metrorrhagia. If abnormal bleeding associated with the use of SAYANA is persistent or severe, appropriate investigation should be performed and treatment instituted. 100 90 80 70 60 62.0 58.7 % 53.2 56.5 50.9 51.7 50 40 30 20 10 0 39.1 40.5 39.0 22.4 26.5 4.0 1 2 3 4 5 Ns: 1831 1854 1840 1729 1717 6 7 8 9 10 11 12 1689 1544 1550 1520 1413 1404 1273 Amenorrhoea Figure 1. Percentage of women with amenorrhoea lasting 30 days in the month under observation who received SAYANA in contraceptive efficacy studies (ITT population, n = 2,053) Figure 2. Percentage of women with amenorrhoea lasting 30 days in the month under observation who received SAYANA in contraceptive efficacy studies (ITT population, n = 2,053) 100 90 80 % 70 60 50 40 30 20 10 0 1 Ns: 1831 2 1854 3 1840 4 1729 5 1717 6 1689 7 1544 8 1550 9 1520 10 1413 11 1404 12 1273 Month Risk of cancer Spotting only Bleeding only Bleeding and spotting Long-term follow-up of patients receiving DMPA i.m. 150 mg has not shown any increase in the overall risk of ovarian, hepatic or cervical cancers and has demonstrated a persistent protective effect reducing the risk of endometrial carcinoma. Breast cancer is rare in women under 40 years of age, whether they are using hormonal contraception or not. The results of some epidemiological studies suggest a small difference in the risk of being diagnosed with breast cancer in women who are using or have used hormonal contraception compared with those who have never used it. The risk in current and recent DMPA users is small relative to the overall risk of breast cancer, particularly in young women (see below), and is no longer apparent 10 years after last use. The duration of use does not appear to be significant. Estimated number of additional cases of breast cancer diagnosed up to 10 years after discontinuation of injectable progestogens+ Age at last MPA injection Number of cases per 10,000 women who have never used MPA Estimated number of additional cases per 10,000 MPA users 20 Less than 1 Considerably less than 1 30 44 2-3 40 160 10 +with 5 years of use Meningioma Cases of meningioma (both single and multiple) have been reported in patients treated with medroxyprogesterone acetate for a prolonged period (several years). Patients treated with SAYANA should be monitored for signs and symptoms of meningioma in accordance with clinical practice. If a patient is diagnosed with meningioma, treatment with SAYANA must be discontinued as a precautionary measure. In some cases, regression of the meningioma has been observed following discontinuation of treatment with depot medroxyprogesterone acetate. Thromboembolic disorders Although medroxyprogesterone acetate has no causal relationship with the induction of thrombotic or thromboembolic disorders, it should not be readministered to any patient using SAYANA who experiences such an event, e.g. pulmonary embolism, cerebrovascular accident, retinal thrombosis or deep vein thrombosis. Women with a previous history of thromboembolic disorders have not been studied in clinical trials, and no information is available to support the safety of administering SAYANA to this population. Anaphylaxis and anaphylactic reactions If an anaphylactic reaction occurs, appropriate treatment should be instituted immediately. Severe anaphylactic reactions require immediate treatment. Eye disorders If partial or complete loss of vision, sudden onset of proptosis, diplopia or migraine occurs, further administration of the product should be withheld pending ophthalmological evaluation. If the examination reveals papilloedema or retinal vascular lesions, the product should not be administered further. Changes in body weight Changes in body weight are common but unpredictable. In phase 3 studies, body weight was monitored over 12 months. Half (50%) of the women remained within 2.2 kg of their original weight. 12% of women lost more than 2.2 kg, and 38% gained more than 2.3 kg. Fluid retention There is evidence that progestogens may produce some degree of fluid retention. The product should therefore be used with caution in patients whose pre-existing conditions could be adversely affected by weight gain or fluid retention. Cessation of anovulation After a single dose of SAYANA, the cumulative incidence of cessation of anovulation as measured by plasma progesterone level was 97.4% (38/39 patients) within one year of administration. After a 14-week therapeutic interval, the earliest return of ovulation was observed at one week, with a mean time to ovulation of 30 weeks. Women should be informed that there is a possibility of a delayed return of ovulation following use of the method, regardless of the duration of use. It should be noted, however, that amenorrhoea and/or irregular menstruation following discontinuation of hormonal contraception may be caused by an underlying condition associated with irregular menstruation, particularly polycystic ovary syndrome. Psychiatric disorders Depressed mood and depression are well-known adverse reactions to the use of hormonal contraception (see section 4.8). Depression can be severe and is a known risk factor for suicidal behaviour and suicide. Women should be advised to contact their physician in the event of mood changes and symptoms of depression, including shortly after starting treatment. Protection against sexually transmitted infections Women should be informed that SAYANA does not provide protection against sexually transmitted infections (STIs), including HIV infection (AIDS); however, the DMPA injection is sterile, so when administered correctly it will not expose them to STIs. Safer sex practices, including the correct and consistent use of condoms, reduce the risk of sexual transmission of STIs, including HIV. The benefits and risks of each method of contraception must be evaluated individually for each woman. Carbohydrates/metabolism In some patients treated with progestins, glucose tolerance may decrease. Patients with diabetes should be carefully monitored during such treatment. Hepatic function If jaundice develops in a patient receiving SAYANA, discontinuation of the product should be considered (see section 4.3). Hypertension and lipid metabolism disorders Only limited data suggest that in patients with hypertension or lipid metabolism disorders who have received progesterone injections there is a slightly increased risk of cardiovascular events. If hypertension is recorded during treatment with SAYANA and/or progression of hypertension cannot be adequately controlled with antihypertensive therapy, treatment with SAYANA must be discontinued. Other risk factors for arterial thrombotic disorders include: hypertension, smoking, age, lipid metabolism disorders, migraine, obesity, positive family history, valvular heart disease and atrial fibrillation. SAYANA should be used with caution in patients with 1 or more risk factors. Other conditions During pregnancy and during the use of sex steroids, the following conditions have been reported, although a relationship with the use of progestogens has not been established: jaundice and/or pruritus due to cholestasis, gallstone formation, porphyria, systemic lupus erythematosus, haemolytic uraemic syndrome, Sydenham's chorea, herpes gestationis, hearing loss due to otosclerosis. If any of the conditions/risk factors mentioned above is present, the benefits of SAYANA should be weighed against the possible risks individually for each woman and discussed with her before deciding to initiate use of the product. In the event of worsening or initial onset of any of these conditions or risk factors, the woman should contact her physician. The physician will then decide whether use of SAYANA should be discontinued. Laboratory tests When sending samples for pathological examination, the pathologist should be informed of treatment with progestins. The physician should be informed that certain endocrine tests and tests of hepatic and blood components may be affected by treatment with progestins: Plasma/urinary steroid levels are decreased (e.g. progesterone, estradiol, pregnanediol, testosterone, cortisol) Plasma and urinary gonadotropin levels are decreased (e.g. LH, FSH) Concentrations of sex hormone–binding globulin (SHBG) are decreased. As the product contains methylparaben and propylparaben, it may cause allergic reactions (including delayed reactions) and, exceptionally, bronchospasm. This medicinal product contains less than 1 mmol sodium (23 mg) per 104 mg/0.65 ml, i.e. it is essentially "sodium-free".

Depo-Provera

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