Pharmacology: Mechanism of Action: Deviry contraceptive injection when administered at the recommended dose in 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.
Pharmacodynamics: No specific pharmacodynamic studies were conducted with Deviry.
Clinical Studies: Contraception: In 5 clinical studies using Deviry, the 12-month failure rate for the group of women treated with Deviry was 0 (no pregnancies reported) to 0.7 by life-table method. The effectiveness of Deviry is dependent on the patient returning every 3 months (13 weeks) for re-injection.
Bone Mineral Density (BMD) Changes in Adult Women: In a controlled, clinical study, adult women using Deviry for up to 5 years showed spine and hip BMD mean decreases of 5-6%, compared to no significant change in BMD in the control group. The decline in BMD was more pronounced during the first 2 years of use, with smaller declines in subsequent years. Mean changes in lumbar spine BMD of -2.86%, -4.11%, -4.89%, -4.93% 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 Deviry (150 mg), there was partial recovery of BMD toward baseline values during the 2-year post-therapy period. Longer duration of treatment was associated with less complete recovery during this 2-year period following the last injection. Table 1 shows the change in BMD in women after 5 years of treatment with Deviry and in women in a control group, as well as the extent of recovery of BMD for the subset of the women for whom 2-year post-treatment data were available.
BMD Changes in Adolescent Females (12-18 years): The impact of Deviry (150 mg) use for up to 240 weeks (4.6 years) was evaluated in an open-label non-randomized clinical study in 389 adolescent females (12-18 years). Use of Deviry was associated with a significant decline from baseline in BMD.
Partway through the trial, drug administration was stopped (at 120 weeks). The mean number of injections per Deviry user was 9.3. The decline in BMD at total hip and femoral neck was greater with longer duration of use. The mean decrease in BMD at 240 weeks was more pronounced at total hip (-6.4%) and femoral neck (-5.4%) compared to lumbar spine (-2.1%).
In general, adolescents increase bone density during the period of growth following menarche, as seen in the untreated cohort. However, the 2 cohorts were not matched at baseline for age, gynecologic age, race, BMD and other factors that influence the rate of acquisition of bone mineral density.
BMD Recovery Post-treatment in Adolescent Women: Longer duration of treatment and smoking were associated with less recovery of BMD following the last injection of Depo-Provera 150. Table 3 shows the extent of recovery of BMD up to 60 months post-treatment for adolescent women who received Deviry for ≤2 years compared to >2 years. Post-treatment follow-up showed that, in women treated for >2 years, only lumbar spine BMD recovered to baseline levels after treatment was discontinued. Subjects treated with Deviry for >2 years did not recover to their baseline BMD level at femoral neck and total hip even up to 60 months post-treatment. Adolescent women in the untreated cohort gained BMD throughout the trial period (data not shown).
Relationship of Fracture Incidence to Use of DMPA 150 mg IM or Non-Use by Women of Reproductive Age: A retrospective cohort study to assess the association between DMPA injection and the incidence of bone fractures was conducted in 312,395 female contraceptive users in the UK. The incidence rates of fracture were compared between DMPA users and contraceptive users who had no recorded use of DMPA. The incident rate ratio (IRR) for any fracture during the follow-up period (mean=5.5 years) was 1.41 (95% CI 1.35, 1.47). It is not known if this is due to DMPA use or to other related lifestyle factors that have a bearing on fracture rate.
In the study, when cumulative exposure to DMPA was calculated, the fracture rate in users who received fewer than 8 injections was higher than that in women who received 8 or more injections. However, it is not clear that cumulative exposure, which may include periods of intermittent use separated by periods of non-use, is a useful measure of risk, as compared to exposure measures based on continuous use.
There were very few osteoporotic fractures (fracture sites known to be related to low BMD) in the study overall, and the incidence of osteoporotic fractures was not found to be higher in DMPA users compared to non-users. Importantly, this study could not determine whether use of DMPA has an effect on fracture rate later in life.
Pharmacokinetics: Absorption: Following a single Deviry mg IM dose in 8 women between 28 and 36 years, MPA concentrations, measured by an extracted radioimmunoassay procedure, increase for approximately 3 weeks to reach peak plasma concentrations of 1-7 ng/mL.
Distribution: Plasma protein binding of MPA averages 86%. MPA binding occurs primarily to serum albumin. No binding of MPA occurs with sex-hormone-binding globulin (SHBG).
Metabolism: MPA is extensively metabolized in the liver by P450 enzymes. Its metabolism primarily involves ring A and/or side-chain reduction, loss of the acetyl group, hydroxylation in the 2-, 6-, and 21-positions or a combination of these positions, resulting in >10 metabolites.
Excretion: The concentrations of MPA decrease exponentially until they become undetectable (<100 pg/mL) between 120-200 days following injection. Using an unextracted radioimmunoassay procedure for the assay of MPA in serum, the apparent half-life for MPA following IM administration of Deviry is approximately 50 days. Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.
Special Population: The effect of hepatic and/or renal disease on the pharmacokinetics of Deviry contraceptive injection is unknown.
Toxicology: Carcinogenicity, Mutagenicity & Impairment of Fertility: See Cancer Risks, Return of Fertility and Pregnancy under Precautions.
A nurse or other trained health professional will give you Deviry in a hospital or clinic. Deviry is given as a shot into one of your muscles (usually in the buttocks or upper arm).
If you are using Depo-Provera®: Deviry is initially given on a weekly basis, but the frequency may be less often over time.
If you are using Depo-Provera CI® (contraceptive injection):
Call your doctor or pharmacist for instructions.
You must have your shot of Depo-Provera CI® (contraceptive injection) every 12 to 14 weeks to prevent pregnancy. If you do not get another shot after 14 weeks, talk with your doctor. You may need to use another form of birth control and wait until your next menstrual period before starting the shots again.
IM: Depo-Provera Contraceptive: Administer first dose during the first 5 days of menstrual period, or within the first 5 days postpartum if not breastfeeding, or at the sixth week postpartum if breastfeeding exclusively. Shake vigorously prior to administration. Administer by deep IM injection in the gluteal or deltoid muscle. Rotate administration site with each injection. Injection must be administered by a health care professional only.
When switching from combined hormonal contraceptives (estrogen plus progestin), the first injection should be on the day after the last active tablet or (at the latest) the day after the final inactive tablet. When switching from other contraceptive methods, ensure continuous contraceptive coverage.
SubQ: Depo-subQ Provera 104: Administer first dose during the first 5 days of menstrual period, or at the sixth week postpartum if breastfeeding. Shake vigorously for at least 1 minute prior to administration. Administer by SubQ injection in the upper anterior thigh or abdomen; avoid boney areas and the umbilicus. Administer slowly over 5 to 7 seconds. Do not rub the injection area. Rotate administration site with each injection. Injection must be administered by a health care professional only.
When switching from oral combined hormonal contraceptives (estrogen plus progestin), the first injection should be within 7 days after the last active pill. When switching from a vaginal ring or transdermal patch, administer the first injection on the day the patient would have inserted the next ring or applied the next patch. When switching from an implant, administer the first injection on the day the implant is removed. When switching from an intrauterine device/system (IUD/IUS), administer the first injection on the day the IUD/IUS is removed; if IUD/IUS not removed on the first day of the menstrual cycle, use a nonhormonal back-up method of contraception for the first 7 days following the injection. When switching from the IM to SubQ formulation, the next dose should be given 12 to 14 weeks after the last IM injection.
IM, SubQ: Additional contraceptive considerations: Available guidelines note the first injection may be given at any time in the menstrual cycle once it is determined that the woman is not pregnant. Back-up contraception is not needed if given within 7 days of onset of menstruation, immediately postpartum, or immediately after a spontaneous or induced abortion. Additional contraception is needed for 7 days unless the injection is given at the time of a surgical abortion. If the injection is given >7 days after menstrual bleeding started, an additional form of contraception must be used for 7 days unless the woman abstains from sexual intercourse. When switching from an IUD to the injection in women who have had sexual intercourse since the start of their last menstrual cycle, consider postponing removal of the IUD for 7 days after the initial injection, instruct the woman to use a nonhormonal method of contraception or abstain from intercourse for 7 days before the first injection, or consider emergency contraception at the time of IUD removal. When contraception will be continued, repeat injections should be given every 13 weeks but may be given early if needed. Injections may be given up to 2 weeks late, however pregnancy should be ruled out and additional contraceptive measures are required for 7 days if the repeat dose is >15 weeks from the last injection (Curtis 2016a).
MPA Injectable Suspension, USP, 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.
No specific pharmacodynamic studies were conducted with MPA Injectable Suspension, USP.
Following a single 150 mg IM dose of MPA Injectable Suspension, USP in eight women between the ages of 28 and 36 years old, MPA concentrations, measured by an extracted radioimmunoassay procedure, increase for approximately 3 weeks to reach peak plasma concentrations of 1 to 7 ng/mL.
Plasma protein binding of MPA averages 86%. MPA binding occurs primarily to serum albumin. No binding of MPA occurs with sex-hormone-binding globulin (SHBG).
MPA is extensively metabolized in the liver by P450 enzymes. Its metabolism primarily involves ring A and/or side-chain reduction, loss of the acetyl group, hydroxylation in the 2-, 6-, and 21-positions or a combination of these positions, resulting in more than 10 metabolites.
The concentrations of Deviry decrease exponentially until they become undetectable (<100 pg/mL) between 120 to 200 days following injection. Using an unextracted radioimmunoassay procedure for the assay of Deviry in serum, the apparent half-life for Deviry following IM administration of MPA Injectable Suspension, USP is approximately 50 days. Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.
The effect of hepatic and/or renal impairment on the pharmacokinetics of MPA Injectable Suspension, USP is unknown.
|With a meal||1||33.3%|
There are no reviews yet. Be the first to write one!
Information checked by Dr. Sachin Kumar, MD Pharmacology