openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 3 matching rows.
warnings
WARNINGS 1. Loss of Bone Mineral Density Use of Medroxyprogesterone Acetate Injectable Suspension, USP reduces serum estrogen levels and is associated with significant loss of bone mineral density (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. It is unknown if use of Medroxyprogesterone Acetate Injectable Suspension, USP by younger women will reduce peak bone mass and increase the risk for osteoporotic fracture in later life. In both adults and adolescents, the decrease in BMD appears to be at least partially reversible after Medroxyprogesterone Acetate Injectable Suspension, USP is discontinued and ovarian estrogen production increases. A study to assess the reversibility of loss of BMD in adolescents is ongoing. Medroxyprogesterone Acetate Injectable Suspension, USP should be used as a long-term birth control method (e.g. longer than 2 years) only if other birth control methods are inadequate. BMD should be evaluated when a woman needs to continue to use Medroxyprogesterone Acetate Injectable Suspension, USP long term. In adolescents, 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 Medroxyprogesterone Acetate Injectable Suspension, USP in women with osteoporosis risk factors. Medroxyprogesterone Acetate Injectable Suspension, USP can pose an additional risk in patients with risk factors for osteoporosis (e.g., 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 such as anticonvulsants or corticosteroids). Although there are no studies addressing whether calcium and Vitamin D may lessen BMD loss in women using Medroxyprogesterone Acetate Injectable Suspension, USP, all patients should have adequate calcium and Vitamin D intake. BMD Changes in Adult Women In a controlled, clinical study, adult women using Medroxyprogesterone Acetate Injectable Suspension, USP 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 two 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 Medroxyprogesterone Acetate Injectable Suspension, USP (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 2 shows the extent of recovery of BMD for women who completed 5 years of treatment. Table 2. Mean Percent Change from Baseline in BMD in Adults by Skeletal Site and Cohort Time in Study Spine Total Hip Femoral Neck Medroxy-progesterone Acetate The treatment group consisted of women who received Medroxyprogesterone Acetate Injectable Suspension, USP for 5 years and were then followed for 2 years post-use. Control The control group consisted of women who did not use hormonal contraception and were followed for 7 years. Medroxy-progesterone Acetate Control Medroxy-progesterone Acetate Control 5 years n=33 n=105 n=21 n=65 n=34 n=106 -5.38% 0.43% -5.16% 0.19% -6.12% -0.27% 7 years n=12 n=60 n=7 n=39 n=13 n=63 -3.13% 0.53% -1.34% 0.94% -5.38% -0.11% BMD Changes in Adolescent Females (12–18 years of age) Preliminary results from an ongoing, open-label, self-selected, non-randomized clinical study of adolescent females (12–18 years) also showed that Medroxyprogesterone Acetate Injectable Suspension, USP use was associated with a significant decline in BMD from baseline (Table 3). In general, adolescents increase bone density during the period of growth following menarche, as seen in the untreated cohort. However, the two 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, with the result that they differed with respect to these demographic factors. Preliminary data from the small number of adolescents participating in the 2-year post-use observation period demonstrated partial recovery of BMD. Table 3. Mean Percent Change from Baseline in BMD in Adolescents by Skeletal Site and Cohort Duration of Treatment Medroxyprogesterone Acetate Injectable Suspension, USP (150 mg IM) Unmatched, Untreated Cohort N Mean % Change N Mean % Change Total Hip BMD Week 60 (1.2 years) 103 -2.82 171 1.32 Week 144 (2.8 years) 45 -6.16 111 1.74 Week 240 (4.6 years) 9 -6.92 69 1.12 Femoral Neck BMD Week 60 103 -3.05 171 1.87 Week 144 45 -6.01 111 2.54 Week 240 9 -6.06 69 1.45 Lumbar Spine BMD Week 60 104 -2.42 171 3.47 Week 144 46 -2.78 111 5.41 Week 240 9 -4.17 70 5.12 2. Bleeding Irregularities Most women using Medroxyprogesterone Acetate Injectable Suspension, USP 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 Medroxyprogesterone Acetate Injectable Suspension, USP, 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 Medroxyprogesterone Acetate Injectable Suspension, USP. 2 3. Cancer Risks Long-term case-controlled surveillance of users of Medroxyprogesterone Acetate Injectable Suspension, USP found slight or no increased overall risk of breast cancer 3 and no overall increased risk of ovarian, 4 liver, 5 or cervical 6 cancer and a prolonged, protective effect of reducing the risk of endometrial 7 cancer in the population of users. A pooled analysis 14 from two case-control studies, the World Health Organization Study 3 and the New Zealand Study 13 , reported the relative risk (RR) of breast cancer for women who had ever used Medroxyprogesterone Acetate Injectable Suspension, USP as 1.1 (95% confidence interval (CI) 0.97 to 1.4). Overall, there was no increase in risk with increasing duration of use of Medroxyprogesterone Acetate Injectable Suspension, USP. The RR of breast cancer for women of all ages who had initiated use of Medroxyprogesterone Acetate Injectable Suspension, USP within the previous 5 years was estimated to be 2.0 (95% CI 1.5 to 2.8). The World Health Organization Study 3, a component of the pooled analysis 14 described above, showed an increased RR of 2.19 (95% CI 1.23 to 3.89) of breast cancer associated with use of Medroxyprogesterone Acetate Injectable Suspension, USP in women whose first exposure to drug was within the previous 4 years and who were under 35 years of age. However, the overall RR for ever-users of Medroxyprogesterone Acetate Injectable Suspension, USP was only 1.2 (95% CI 0.96 to 1.52). [ NOTE: A RR of 1.0 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 1.0, thus inferring an increased risk of breast cancer in the defined subgroup relative to nonusers. The value of 2.19 means that women whose first exposure to drug was within the previous 4 years and who are under 35 years of age have a 2.19 fold (95% CI 1.23 to 3.89-fold) increased risk of breast cancer relative to nonusers. The National Cancer Institute 8 reports an average annual incidence rate for breast cancer for US women, all races, age 30 to 34 years of 26.7 per 100,000. A RR of 2.19, thus, increases the possible risk from 26.7 to 58.5 cases per 100,000 women. The attributable risk, thus, is 31.8 per 100,000 women per year.] A statistically insignificant increase in RR estimates of invasive squamous-cell cervical cancer has been associated with the use of Medroxyprogesterone Acetate Injectable Suspension, USP in women who were first exposed before the age of 35 years (RR 1.22 to 1.28 and 95% CI 0.93 to 1.70). The overall, nonsignificant relative rate of invasive squamous-cell cervical cancer in women who ever used Medroxyprogesterone Acetate Injectable Suspension, USP was estimated to be 1.11 (95% CI 0.96 to 1.29). No trends in risk with duration of use or times since initial or most recent exposure were observed. 4. Thromboembolic Disorders The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, pulmonary embolism, cerebrovascular disorders, and retinal thrombosis). Should any of these occur or be suspected, the drug should not be readministered. 5. Ocular Disorders Medication should not be readministered 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 readministered. 6. Unexpected Pregnancies To ensure that Medroxyprogesterone Acetate Injectable Suspension, USP is not administered inadvertently to a pregnant woman, the first injection must be given ONLY during the first 5 days of a normal menstrual period; ONLY within the first 5-days postpartum if not breast-feeding, and if exclusively breast-feeding, ONLY at the sixth postpartum week (see DOSAGE AND ADMINISTRATION ). Neonates from unexpected pregnancies that occur 1 to 2 months after injection of Medroxyprogesterone Acetate Injectable Suspension, USP 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. 9,10 A significant increase in incidence of polysyndactyly and chromosomal anomalies was observed among infants of users of Medroxyprogesterone Acetate Injectable Suspension, USP, the former being most pronounced in women under 30 years of age. The unrelated nature of these defects, the lack of confirmation from other studies, the distant preconceptual exposure to Medroxyprogesterone Acetate Injectable Suspension, USP, and the chance effects due to multiple statistical comparisons, make a causal association unlikely. 11 Neonates 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 first trimester of pregnancy and genital abnormalities in male and female fetuses. The risk of hypospadias (five to eight per 1,000 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 first trimester of pregnancy. To ensure that Medroxyprogesterone Acetate Injectable Suspension, USP is not administered inadvertently to a pregnant woman, it is important that the first injection be given only during the first 5 days after the onset of a normal menstrual period within 5 days postpartum if not breast-feeding and if breast-feeding, at the sixth week postpartum (see DOSAGE AND ADMINISTRATION ). 7. Ectopic Pregnancy Health-care providers should be alert to the possibility of an ectopic pregnancy among women using Medroxyprogesterone Acetate Injectable Suspension, USP who become pregnant or complain of severe abdominal pain. 8. Lactation Detectable amounts of drug have been identified in the milk of mothers receiving Medroxyprogesterone Acetate Injectable Suspension, USP. In nursing mothers treated with Medroxyprogesterone Acetate Injectable Suspension, USP, milk composition, quality, and amount are not adversely affected. Neonates and infants exposed to medroxyprogesterone from breast milk have been studied for developmental and behavioral effects through puberty. No adverse effects have been noted. 9. Anaphylaxis and Anaphylactoid Reaction Anaphylaxis and anaphylactoid reaction have been reported with the use of Medroxyprogesterone Acetate Injectable Suspension, USP. If an anaphylactic reaction occurs appropriate therapy should be instituted. Serious anaphylactic reactions require emergency medical treatment.