Depo-Provera
Manufacturer
Distributor Contents Indications Dosage & Administration Contraindications Warning Special Precautions Adverse Drug Reactions Drug Interaction Pregnancy Category (US FDA) Caution for usage Storage Description Mechanism of Action MIMS Class ATC Classification Regulatory Classification |
Pfizer
Zuellig Medroxyprogesterone acetate Prevention of pregnancy. Endometriosis. Menopausal vasomotor symptoms. Endometrial or renal carcinoma. Hormone-dependent breast cancer. Recommended Dose: 150 mg every 3 months (13 weeks) administered by deep IM injection in the gluteal or deltoid muscle. The 1-mL vial should be shaken vigorously just before use to ensure that the dose being administered represents a uniform suspension. Endometriosis: 50 mg weekly or 100 mg twice weekly IM for at least 6 months. Menopausal vasomotor symptoms: 150 mg every 3 months IM. Endometrial or renal carcinoma: 400-1000 mg IM per week then maintain at 400 mg/month. Hormone-dependent breast cancer: 500 mg/day IM for 28 days then maintain at 500 mg twice weekly. Known or suspected pregnancy or as a diagnostic test for pregnancy. Undiagnosed vaginal bleeding. Known or suspected malignancy of breast. Active thrombophlebitis, or current or past history of thromboembolic disorders or cerebral vascular disease. Liver dysfunction or disease. Known hypersensitivity to Depo-Provera (medroxyprogesterone acetate) or any of its other ingredients. Use in children: Medroxyprogesterone acetate (MPA) IM is not indicated before menarche. Data are available in adolescent females (12-18 years) (see Precautions). Other than concerns about loss of bone mineral density (BMD), the safety and effectiveness of MPA IM are expected to be the same for postmenarcheal adolescent and adult females. Loss of Bone Mineral Density (BMD): Use of MPA injection reduces serum estrogen levels and is associated with significant loss of BMD as bone metabolism accommodates to a lower estrogen level. This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. Bone loss is greater with increasing duration of use and may not be completely reversible. It is unknown if use of MPA injection by younger women will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. In both adult and adolescent females, the decrease in BMD appears to be at least partially reversible after MPA injection is discontinued and ovarian estrogen production increases. A study to assess the reversibility of loss of BMD in adolescent females is ongoing. MPA injection should only be used as a long-term (eg, >2 years) birth control method if other birth control methods are inadequate. BMD should be evaluated when a female needs to continue to use MPA injection long-term. In adolescent females, interpretation of BMD results should take into account patient age and skeletal maturity. Other birth control methods should be considered in the risk/benefit analysis for the use of MPA injection in women with osteoporotic risk factors. MPA injection can pose an additional risk in patients with risk factors for osteoporosis (eg, metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis or chronic use of drugs that can reduce bone mass eg, anticonvulsants or corticosteroids). It is recommended that all patients have adequate calcium and vitamin D intake. BMD Changes in Adult Women: In a controlled, clinical study, adult women using MPA injection (150 mg IM) for up to 5 years showed spine and hip mean BMD decreases of 5-6%, compared to no significant change in BMD in the control group. The decline in BMD was more pronounced during the 1st 2 years of use, with smaller declines in subsequent years. Mean changes in lumbar spine BMD of -2.86%, -4.11%, -4.89% and -5.38% after 1, 2, 3, 4 and 5 years, respectively, were observed. Mean decreases in BMD of the total hip and femoral neck were similar. After stopping use of MPA injection (150 mg IM), there was partial recovery of BMD toward baseline values during the 2-year post-therapy period. A longer duration of treatment was associated with a slower rate of BMD recovery. BMD Changes in Adolescent Females (12-18 years): Preliminary results from an ongoing, open-label clinical study of MPA injectable (150 mg IM every 12 weeks for up to 5 years) in adolescent females (12-18 years) also showed that MPA IM use was associated with a significant decline in BMD from baseline. The mean decrease in lumbar spine BMD was 4.2% after 5 years; mean decreases for the total hip and femoral neck were 6.9% and 6.1%, respectively. In contrast, most adolescent girls will significantly increase bone density during this period of growth following menarche. Preliminary data from a small number of adolescents have shown partial recovery of BMD during the 2-year follow-up period. Bleeding Irregularities: Most women using Depo-Provera experience disruption of menstrual bleeding patterns. Altered menstrual bleeding patterns include irregular or unpredictable bleeding or spotting, or rarely, heavy or continuous bleeding. If abnormal bleeding persists or is severe, appropriate investigation should be instituted to rule out the possibility of organic pathology, and appropriate treatment should be instituted when necessary. As women continue using Depo-Provera, fewer experience irregular bleeding and more experience amenorrhea. By month 12, amenorrhea was reported by 55% of women and by month 24 amenorrhea was reported by 68% of women using Depo-Provera. Cancer Risks: Long-term case controlled surveillance of users of Depo-Provera found slight or no increased overall risk of breast cancer and no overall increased risk of ovarian, liver or cervical cancer and a prolonged protective effect of reducing the risk of endometrial cancer in the population of users. A pooled analysis from 2 case control studies, the World Health Organization (WHO) Study and the New Zealand Study, reported the relative risk (RR) of breast cancer for women who had ever used Depo-Provera as 1.1 (95% confidence interval (CI) 0.97-1.4). Overall, there was no increase in risk with increasing duration of use of Depo-Provera. The RR of breast cancer for women of all ages who had initiated use of Depo-Provera within the previous 5 years was estimated to be 2 (95% CI 1.5-2.8). The WHO Study, a component of the pooled analysis described in the previous section, showed an increased RR of 2.19 (95% CI 1.23-3.89) of breast cancer associated with use of Depo-Provera in women whose first exposure to drug was within the previous 4 years and who were <35 years. However, the overall RR for every user of Depo-Provera was only 1.2 (95% CI 0.96-1.52). [Note: A RR of 1 indicates neither an increased nor a decreased risk of cancer associated with the use of the drug, relative to no use of the drug. In the case of the subpopulation with a RR of 2.19, the 95% CI is fairly wide and does not include the value of 1 thus, inferring an increased risk of breast cancer in the defined subgroup relative to nonusers. The value of 2.19-fold (95% CI 1.23- to 3.89-fold) increased risk of breast cancer relative to nonusers. The National Cancer Institute reports an average annual incidence rate for breast cancer for women in US, all races, 30-34 years of 26.7/100,000 women. A RR of 2.19, thus, increases the possible risk from 26.7-58.5 cases/100,000 women. The attributable risk, thus, is 31.8/100,000 women/year.] A statistically insignificant increase in RR estimates of invasive squamous-cell cervical cancer has been associated with the use of Depo-Provera in women who were first exposed before the age of 35 years (RR 1.22-1.28 and 95% CI 0.93-1.7). The overall, non-significant relative rate of invasive squamous-cell cervical cancer in women who ever used Depo-Provera was estimated to be 1.11 (95% CI 0.96-1.29). No trends in risk with duration of use or times since initial or most recent exposure were observed. Thromboembolic Disorders: The physician should be alert to the earliest manifestation of thrombotic disorders (thrombophlebitis, pulmonary embolism, cerebrovascular disorders and retinal thrombosis). Should any of these occur or be suspected, the drug should not be re-administered. Ocular Disorders: Medication should not be re-administered pending examination if there is a sudden partial or complete loss of vision or if there is a sudden onset of proptosis, diplopia or migraine. If examination reveals papilledema or retinal vascular lesions, medication should not be re-administered. Unexpected Pregnancies, Ectopic Pregnancy, Lactation: See Use in pregnancy and Use in lactation under Precautions. Anaphylaxis and Anaphylactoid Reaction: Anaphylaxis and anaphylactoid reaction have been reported with the use of Depo-Provera. If an anaphylactic reaction occurs, appropriate therapy should be instituted. Serious anaphylactic reactions require emergency medical treatment. Physical Examination: The pre-treatment, annual history and physical examination should include special reference to breast and pelvic organs, as well as a Papanicolau smear. Fluid Retention: Because progestational drugs may cause some degree of fluid retention, conditions that might be influenced by this conditions eg, epilepsy, migraine, asthma, cardiac or renal dysfunction require careful observation. Weight Changes: There is a tendency for women to gain weight while on therapy with Depo-Provera. From an initial average body weight of 136 lbs, women who completed 1 year of therapy with Depo-Provera gained an average of 5.4 lbs. Women who completed 2 years of therapy gained an average of 8.1 lbs. Women who completed 4 years gained an average of 13.8 lbs. Women who completed 6 years gained an average of 16.5 lbs. Two percent of women withdrew from a large-scale clinical trial because of excessive weight gain. Return of Fertility: Depo-Provera has a prolonged contraceptive effect. In a large US study of women who discontinued use of Depo-Provera to become pregnant, data are available for 61% of them. Based on Life-Table analysis of these data, it is expected that 68% of women who do become pregnant may conceive within 12 months, 83% may conceive within 15 months, and 93% may conceive within 18 months from the last injection. The median time to conception for those who do conceive is 10 months, following the last injection with a range of 4-31 months, and is unrelated to the duration of use. No data are available for 39% of the patients who discontinued Depo-Provera to become pregnant and who were lost to follow-up or changed their mind. CNS Disorders and Convulsions: Patients who have a history of psychic depression should be carefully observed and the drug not be re-administered if the depression recurs. There have been a few reported cases of convulsions in patients who were treated with Depo-Provera. Association with drug use or preexisting conditions is not clear. Carbohydrate Metabolism: A decrease in glucose tolerance has been observed in some patients on Depo-Provera treatment. The mechanism of this decrease is obscure. For this reason, diabetic patients should be carefully observed while receiving Depo-Provera. Liver Function: If jaundice develops, consideration should be given to not re-administering the drug. Protection Against Sexually Transmitted Diseases: Patients should be counseled that Depo-Provera does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Information for the Patient: It is recommended that physicians or other health care providers responsible for those patients advise them at the beginning of treatment that their menstrual cycle may be disrupted and that irregular and unpredictable bleeding or spotting may result and that this usually decreases to the point of amenorrhea as treatment with Depo-Provera continues, without other therapy being required. Use in pregnancy: Pregnancy Category X. Unexpected Pregnancies: To ensure that Depo-Provera is not administered inadvertently to a pregnant woman, the 1st injection must be given only whithin the first 5 days of a normal menstrual period; only within the first 5 days postpartum if not breastfeeding, and if exclusively breastfeeding, only at the 6th postpartum week (see Cautions for Usage). Infants from unexpected pregnancies that occur 1-2 months after injection of Depo-Provera may be at an increased risk of low birth weight, which, in turn, is associated with an increased risk of neonatal death. The attributable risk is low because such pregnancies are uncommon. A significant increase in incidence of polysyndactyly and chromosomal anomalies was observed among infants of users of Depo-Provera, the former being most pronounced in women <30 years. The unrelated nature of these defects, the lack of confirmation from other studies, the distant preconception exposure of Depo-Provera and the chance effects due to multiple statistical comparisons, make a causal association unlikely. Children exposed to medroxyprogesterone acetate in utero and followed to adolescence, showed no evidence of any adverse effects on their health including their physical, intellectual, sexual or social development. Several reports suggest an association between intrauterine exposure to progestational drugs in the 1st trimester of pregnancy and genital abnormalities in male and female fetuses. The risk of hypospadias (5-8 per 1000 male births in the general population) may be approximately doubled with exposure to these drugs. There are insufficient data to quantify the risk to exposed female fetuses, but because some of these drugs induce mild virilization of the external genitalia of the female fetus and because of the increased association of hypospadias in the male fetus, it is prudent to avoid the use of these drugs during the 1st trimester of pregnancy. Ectopic Pregnancy: Health care providers should be alert to the possibility of an ectopic pregnancy among women using Depo-Provera who become pregnant or complain of severe abdominal pain. Use in lactation: Detectable amounts of drug have been identified in the milk of mothers receiving Depo-Provera. In nursing mothers treated with Depo-Provera, milk composition, quality and amount are not adversely affected. Infants exposed to medroxyprogesterone from breast milk have been studied for developmental and behavioral effects through puberty. No adverse effects have been noted. In the largest clinical trial with Depo-Provera, >3900 women, who were treated for up to 7 years, reported the following adverse reactions, which may or may not be related to the use of Depo-Provera. The following adverse reactions were reported by >5% of subjects: Menstrual irregularities (bleeding or amenorrhea or both), weight changes, headache, nervousness, abdominal pain or discomfort, dizziness and asthenia (weakness or fatigue). Adverse reactions reported by 1-5% of subjects using Depo-Provera were: Decreased libido or anorgasmia, backache, leg cramps, depression, nausea, insomnia, leukorrhea, acne, arthralgia, vaginitis, pelvic pain, breast pain, no hair growth or alopecia, bloating, rash, edema and hot flashes. Events reported by <1 % of subjects included: Galactorrhea, melasma, chloasma, convulsions, changes in appetite, gastrointestinal disturbances, jaundice, genitourinary infections, vaginal cysts, dyspareunia, paresthesia, chest pain, pulmonary embolus, allergic reactions, anemia, drowsiness, syncope, dyspnea and asthma, tachycardia, fever, excessive sweating and body odor, dry skin, chills, increased libido, excessive thirst, hoarseness, pain at injection site, blood dyscrasia, rectal bleeding, changes in breast size, breast lumps or nipple bleeding, axillary swelling, breast cancer, prevention of lactation, sensation of pregnancy, lack of return to fertility, paralysis, facial palsy, scleroderma, osteoporosis, uterine hyperplasia, cervical cancer, varicose veins, dysmenorrhea, hirsutism, unexpected pregnancy, thrombophlebitis and deep vein thrombosis. Additional Adverse Events Reported During Post-Marketing Experience: There have been rare cases of osteoporosis including osteoporotic fractures reported in patients taking MPA IM. Aminoglutethimide administered concomitantly with Depo-Provera may significantly depress the serum concentrations of medroxyprogesterone acetate. Users of Depo-Provera should be warned of the possibility of decreased efficacy. Laboratory Tests: The pathologist should be advised of progestin therapy when relevant specimens are submitted. The following laboratory test results may be affected by progestins including, Depo-Provera: Plasma and urinary steroid levels are decreased (eg, progesterone, estradiol, pregnanediol, testosterone, cortisol); gonadotropin levels are decreased; sex hormone-binding globulin concentrations are decreased; protein-bound iodine and butanol extractable protein-bound iodine may increase; T3-uptake values may decrease; coagulation test values for prothrombin (Factor II) and Factors VII, VIII, IX and X may increase; sulfobromophthalein and other liver function test values may be increased; the effects of medroxyprogesterone acetate on lipid metabolism are inconsistent; both increases and decreases in total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol have been observed in studies. Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. To ensure that Depo-Provera is not administered inadvertently to a pregnant woman, the 1st injection must be given only within the 1st 5 days of a normal menstrual period; only within the 1st 5-days postpartum if not breastfeeding, and if exclusively breastfeeding, only at or after the 6-weeks postpartum. If the time interval between injections is >13 weeks, the physician should determine if the patient is not pregnant before administering the drug. The efficacy of Depo-Provera depends on adherence to the recommended dosage schedule of administration (see Dosage & Administration). It is a long-term contraceptive in women when administered at 3-month (13-week) intervals. Dosage does not need to be adjusted based on body weight. Store at temperature not exceeding 25°C. Protect from freezing. Each mL contains medroxyprogesterone acetate 150 mg, polyethylene glycol 3350 28.9 mg, polysorbate 80 2.41 mg, sodium chloride 8.68 mg, methylparaben 1.37 mg, propylparaben 0.15 mg and enough water for injection to make 1 mL of solution. When necessary, pH is adjusted with sodium hydroxide or hydrochloric acid, or both. Medroxyprogesterone acetate or pregn-4-ene-3,20-dione, 17-(acetyloxy)-6-methyl-,(6α), a derivative of progesterone, is active by the parenteral and oral routes of administration. It is a white to off-white, odorless crystalline powder that is stable in air and melts between 200°C and 210°C. It is freely soluble in chloroform, soluble in acetone and dioxane, sparingly soluble in alcohol and methanol, slightly soluble in ether and insoluble in water. Pharmacology: Depo-Provera, when administered at the recommended dose to women every 3 months, inhibits the secretion of gonadotropins which, in turn, prevents follicular maturation and ovulation and results in endometrial thinning. These actions produce its contraceptive effect. Following a single 150-mg IM dose of Depo-Provera, medroxyprogesterone acetate concentrations measured by an extracted radioimmunoassay procedure increase for approximately 3 weeks to reach peak plasma concentrations of 1-7 mL. The levels then decrease exponentially until they become undetectable (<100 mcg/mL) between 120-200 days following injection. Using an unextracted radioimmunoassay procedure for the assay of medroxyprogesterone acetate in serum, the apparent half-life for medroxyprogesterone acetate following IM administration of Depo-Provera is approximately 50 days. Women with lower body weights conceive sooner than women with higher body weights after discontinuing Depo-Provera. The effect of hepatic and/or renal disease on the pharmacokinetics of Depo-Provera is unknown. In 5 clinical studies using Depo-Provera, the 12-month failure rate for the group of women treated with Depo-Provera was zero (no pregnancies reported) to 0.7 by Life-Table method. Pregnancy rates with contraceptive measures are typically reported for only the 1st year as shown in the table. Except for intrauterine devices (IUD), implants sterilization and Depo-Provera, the efficacy of these contraceptive measures depends in part on the reliability of use. The effectiveness of Depo-Provera is dependent on the patient returning every 3 months (13 weeks) for reinjection. Since loss of bone mineral density (BMD) may occur in females of all ages who use MPA injection long-term, a risk/benefit assessment, which also takes into consideration the decrease in BMD that occurs during pregnancy and/or lactation, should be considered. Oestrogens, Progesterones & Related Synthetic Drugs / Depot Contraceptives G03AC06 - medroxyprogesterone ; Belongs to the class of progestogens. Used as systemic contraceptives. Rx |