DEPO-PROVERA- medroxyprogesterone acetate injection ...

1 [3/7/2017 11:39:49 AM] depo - provera - medroxyprogesterone acetate injection , suspension Pharmacia and Upjohn Company LLC----------HIGHLIGHTS OF PRESCRIBING INFORMATIONT hese highlights do not include all the information needed to useDEPO- provera CI safely and effectively. See full prescribinginformation for depo - provera CI ( medroxyprogesterone acetate ) injectablesuspension, for intramuscular useInitial Approval: 1959 WARNING: LOSS OF BONE MINERAL DENSITYSee full prescribing information for complete who use depo - provera Contraceptive injection ( depo - provera CI) may lose significant bone mineraldensity. Bone loss is greater with increasing duration ofuse and may not be completely reversible. ( )It is unknown if use of depo - provera ContraceptiveInjection during adolescence or early adulthood, acritical period of bone accretion, will reduce peak bonemass and increase the risk for osteoporotic fracture inlater life. ( ) depo - provera Contraceptive injection should not beused as a long-term birth control method ( , longerthan 2 years) unless other birth control methods areconsidered inadequate.

2 ( )RECENT MAJOR CHANGESD osage and Administration, Prevention of Pregnancy ( )11/2016 Warnings and Precautions, injection Site Reactions ( )11/2016 INDICATIONS AND USAGEDepo- provera CI is a progestin indicated only for the prevention ofpregnancy. (1)DOSAGE AND ADMINISTRATIONThe recommended dose is 150 mg of depo - provera CI every 3months (13 weeks) administered by deep, intramuscular (IM) injection in the gluteal or deltoid muscle. ( )DOSAGE FORMS AND STRENGTHSV ials containing sterile aqueous suspension: 150 mg per mL (3)Prefilled syringes: prefilled syringes are available packaged with22-gauge 1 1/2 inch Terumo SurGuard Needles or with 22gauge 1 1/2 inch BD SafetyGlide Needles. (3)CONTRAINDICATIONSK nown or suspected pregnancy or as a diagnostic test forpregnancy. (4)Active thrombophlebitis, or current or past history ofthromboembolic disorders, or cerebral vascular disease. (4)Known or suspected malignancy of breast. (4)Known hypersensitivity to depo - provera CI( medroxyprogesterone acetate or any of its other ingredients).

3 (4)Significant liver disease. (4)Undiagnosed vaginal bleeding. (4)WARNINGS AND PRECAUTIONST hromboembolic Disorders: Discontinue depo - provera CI inpatients who develop thrombosis. ( )Cancer Risks: Monitor women with a strong family history ofbreast cancer carefully. ( )Ectopic Pregnancy: Consider ectopic pregnancy if a woman usingDepo- provera CI becomes pregnant or complains of severeabdominal pain. ( )Anaphylaxis and Anaphylactoid Reactions: Provide emergencymedical treatment. ( )Liver Function: Discontinue depo - provera CI if jaundice ordisturbances of liver function develop. ( )Carbohydrate Metabolism: Monitor diabetic patients carefully.( )ADVERSE REACTIONSMost common adverse reactions (incidence >5%) are: menstrualirregularities (bleeding or spotting) 57% at 12 months, 32% at 24months, abdominal pain/discomfort 11%, weight gain > 10 lbs at 24months 38%, dizziness 6%, headache 17%, nervousness 11%,decreased libido 6%. ( )To report SUSPECTED ADVERSE REACTIONS, contact PfizerInc.

4 At 1-800-438-1985 or FDA at 1-800-FDA-1088 INTERACTIONSD rugs or herbal products that induce certain enzymes, includingCYP3A4, may decrease the effectiveness of contraceptive drugproducts. Counsel patients to use a back-up method or alternativemethod of contraception when enzyme inducers are used with depo - provera CI. ( )USE IN SPECIFIC POPULATIONSN ursing Mothers: Detectable amounts of drug have been identifiedin the milk of mothers receiving depo - provera CI. ( )Pediatric Patients: depo - provera CI is not indicated beforemenarche. ( )See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient : 1/2017 [3/7/2017 11:39:49 AM]FULL PRESCRIBING INFORMATION:CONTENTS*WARNING: LOSS OF BONE MINERAL DENSITY1 INDICATIONS AND USAGE2 DOSAGE AND Prevention of Switching from other Methods of Contraception3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND Loss of Bone Mineral Thromboembolic Cancer Ectopic Anaphylaxis and Anaphylactoid injection Site Liver Bleeding Weight Carbohydrate Fluid Return of Sexually Transmitted Interference with Laboratory Tests6 ADVERSE Clinical Trials Post-marketing Experience7 DRUG Changes in Contraceptive EffectivenessAssociated with Co-Administration of Other Laboratory Test Interactions8 USE IN SPECIFIC Nursing Pediatric Geriatric Renal Hepatic Impairment11 DESCRIPTION12 CLINICAL Mechanism of Pharmacokinetics13 NONCLINICAL Carcinogenesis, Mutagenesis, Impairment ofFertility14 CLINICAL Bone Mineral Density (BMD) Changes in Bone Mineral Density Changes in AdolescentFemales (12 18 years of age)

5 Relationship of fracture incidence to use ofDMPA 150 mg IM or non-use by women ofreproductive age15 REFERENCES16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION*FULL PRESCRIBING INFORMATIONWARNING: LOSS OF BONE MINERAL DENSITYW omen who use depo - provera Contraceptive injection may lose significant bone mineral density. Boneloss is greater with increasing duration of use and may not be completely is unknown if use of depo - provera Contraceptive injection during adolescence or early adulthood, acritical period of bone accretion, will reduce peak bone mass and increase the risk for osteoporoticfracture in later Contraceptive injection should not be used as a long-term birth control method ( ,longer than 2 years) unless other birth control methods are considered inadequate [see Warnings andPrecautions ( )].Sections or subsections omitted from the full prescribinginformation are not [3/7/2017 11:39:49 AM]1 INDICATIONS AND USAGEDepo- provera CI is indicated only for the prevention of pregnancy.

6 The loss of bone mineral density (BMD) inwomen of all ages and the impact on peak bone mass in adolescents should be considered, along with the decrease inBMD that occurs during pregnancy and/or lactation, in the risk/benefit assessment for women who use depo -ProveraCI long-term [see Warnings and Precautions ( )].2 DOSAGE AND Prevention of PregnancyBoth the 1 mL vial and the 1 mL prefilled syringe of depo - provera CI should be vigorously shaken just before use toensure that the dose being administered represents a uniform recommended dose is 150 mg of depo - provera CI every 3 months (13 weeks) administered by deepintramuscular (IM) injection using strict aseptic technique in the gluteal or deltoid muscle, rotating the sites withevery injection . As with any IM injection , to avoid an inadvertent subcutaneous injection , body habitus should beassessed prior to each injection to determine if a longer needle is necessary particularly for gluteal IM CI should not be used as a long-term birth control method ( longer than 2 years) unless other birthcontrol methods are considered inadequate.

7 Dosage does not need to be adjusted for body weight [see Clinical Studies( )].To ensure the patient is not pregnant at the time of the first injection , the first injection should be given ONLY duringthe first 5 days of a normal menstrual period; ONLY within the first 5-days postpartum if not breast-feeding; and ifexclusively breast-feeding, ONLY at the sixth postpartum week. If the time interval between injections is greater than13 weeks, the physician should determine that the patient is not pregnant before administering the drug. The efficacyof depo - provera CI depends on adherence to the dosage schedule of Switching from other Methods of ContraceptionWhen switching from other contraceptive methods, depo - provera CI should be given in a manner that ensurescontinuous contraceptive coverage based upon the mechanism of action of both methods, ( , patients switchingfrom oral contraceptives should have their first injection of depo - provera CI on the day after the last active tablet orat the latest, on the day following the final inactive tablet).

8 3 DOSAGE FORMS AND STRENGTHSS terile Aqueous suspension: 150mg/mlPrefilled syringes are available packaged with 22-gauge 1 1/2 inch Terumo SurGuard Needles or with 22 gauge 1 1/2 inch BD SafetyGlide CONTRAINDICATIONSThe use of depo - provera CI is contraindicated in the following conditions:Known or suspected pregnancy or as a diagnostic test for thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease [ [3/7/2017 11:39:49 AM]Warnings and Precautions ( )].Known or suspected malignancy of breast [see Warnings and Precautions ( )].Known hypersensitivity to depo - provera CI ( medroxyprogesterone acetate ) or any of its other ingredients [seeWarnings and Precautions ( )].Significant liver disease [see Warnings and Precautions ( )].Undiagnosed vaginal bleeding [see Warnings and Precautions ( )].5 WARNINGS AND Loss of Bone Mineral DensityUse of depo - provera CI reduces serum estrogen levels and is associated with significant loss of bone mineral density(BMD).

9 This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of boneaccretion. It is unknown if use of depo - provera CI by younger women will reduce peak bone mass and increase therisk for osteoporotic fracture in later discontinuing depo - provera CI in adolescents, mean BMD loss at total hip and femoral neck did not fullyrecover by 60 months (240 weeks) post-treatment [see Clinical Studies ( )]. Similarly, in adults, there was onlypartial recovery of mean BMD at total hip, femoral neck and lumbar spine towards baseline by 24 months post-treatment. [See Clinical Studies ( ).] depo - provera CI should not be used as a long-term birth control method ( , longer than 2 years) unless other birthcontrol methods are considered inadequate. BMD should be evaluated when a woman needs to continue to use depo - provera CI long-term. In adolescents, interpretation of BMD results should take into account patient age and birth control methods should be considered in the risk/benefit analysis for the use of depo - provera CI inwomen with osteoporosis risk factors.

10 depo - provera CI can pose an additional risk in patients with risk factors forosteoporosis ( , metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong familyhistory 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 usingDepo- provera CI, all patients should have adequate calcium and Vitamin D Thromboembolic DisordersThere have been reports of serious thrombotic events in women using depo - provera CI (150 mg). However, depo - provera CI has not been causally associated with the induction of thrombotic or thromboembolic disorders. Anypatient who develops thrombosis while undergoing therapy with depo - provera CI should discontinue treatmentunless she has no other acceptable options for birth not re-administer depo - provera CI pending examination if there is a sudden partial or complete loss of vision or ifthere is a sudden onset of proptosis, diplopia, or migraine.