Progesterone 45918F/Revised: October2016

Rx only For intramuscularuseonly. IN SESAMEOIL Injection, USP Progesterone 45918F/Revised: October2016

45919F/Revised: October 2016

Patient Information Progesterone Injection, USP For intramuscular use only. FOR THE TREATMENT OF AMENORRHEA (ABSENCE OF MENSES IN WOMEN WHO maximum plasmaconcentration(C resulted ingeometricmeanvaluesfor tion. Injectionof10,25,and50mg baseline for about 24 hours after injec plasma concentrations remained above mately 8hours after injection and 7 ng/mL)werereachedwithinapproxi concentrations (geometric mean of of progesterone in oil maximum plasma After intramuscularadministrationof10mg Absorption Pharmacokinetics andMetabolism to 48%). to 54%)andcortisol-bindingprotein(43 plasma proteins,primarily albumin (50 Progesterone isextensivelyboundto Distribution 7, 28,and50ng/mL,respectively. CLINICAL PHARMACOLOGY: C DESCRIPTION: tion andovulation. which inturnprevents secretion ofpituitarygonadotropins, secretory endometrium. Transforms proliferativeendometriuminto soluble in hol, acetone,anddioxanesparingly insoluble inwater,itissolublealco odorless andisstablein air.Practically creamy white, crystalline powder. It is muscular use. suitable vegetableoilavailableforintra a sterile Progesterone injection,aprogestin,is benzyl sesame oilq.s. HAVE PREVIOUSLY HAD A MENSTRUAL 21 O It hasthefollowingstructuralformula: Each mL contains: Progesterone 50 mg, Each mLcontains:Progesterone50mg, Inhibits (at the usual dose range) the Progesterone occursasawhiteor H

30 PERIOD) OR ABNORMAL UTERINE BLEEDING O

2 DUE TO HORMONAL IMBALANCE.

alcohol 10%aspreservativein

solution of progesterone in a Pregn-4-ene-3, 20-dione

vegetable oils. Please read this information carefully before you

CH start to use Progesterone Injection and each

3 time your prescription is renewed, in case any-

H thing has changed. This leaflet does not take the place of discussions with your doctor. If H follic you still have any questions, ask your doctor CH

H or health-care provider. ular matura 3 M.W. 314.47 CO CH About Progesterone Injection 3

max Progesterone Injection is a sterile injectable

H solution containing the natural female hormone ) of ) of - - - - - called progesterone. Progesterone Injection is

indicated for the treatment of amenorrhea and by ketoconazole (IC human livermicrosomeswasinhibited The metabolismofprogesteroneby Drug Interactions indicated (see with liverdysfunctionordiseaseiscontra metabolized bytheliver,useinpatients established. Sinceprogesteroneis with hepaticinsufficiencyhavenotbeen The safetyandeffectivenessinpatients Hepatic Insufficiency evance ofthe ability ofprogesterone.Theclinicalrel of thisenzymemayincreasethebioavail ketoconazole orotherknowninhibitors P450 3A4andthesedatasuggestthat azole isaknowninhibitorofcytochrome patient population(see with caution and careful monitoringin this progesterone shouldbeadministered lites areexcretedmainlybythekidneys, established. Sinceprogesteronemetabo with renal insufficiency have not been The safetyandeffectivenessinpatients Renal Insufficiency Special Populations values maybeestimated. iting theprecisioninwhichpopulation mined inasmallnumberofpatients,lim or maybeexcretedinthefeces. bile mayundergoenterohepaticrecycling one metaboliteswhichareexcretedinthe excreted intheurineandbile.Progester of pregnanediolandpregnanoloneare The glucuronideandsulfateconjugates Excretion (SEM) L/day. rate in cycling women is 2510 ± 135 The meanplasmametabolicclearance of glucuronide and sulfate metabolites. quent conjugationresultsintheformation pregnanetriol and pregnanolone. Subse the liverbyreductiontopregnanediol, Progesterone ismetabolizedprimarilyin Metabolism CONTRAINDICATIONS: INDICATIONS ANDUSAGE: 1. fibroids oruterinecancer. organic pathology, such as submucous hormonal imbalanceintheabsenceof and abnormaluterinebleedingdueto This drugisindicatedinamenorrhea abnormal uterine bleeding due to progesterone The pharmacokineticdatawasdeter or cerebralapoplexy. phlebitis, thromboembolicdisorders, Current or past history of thrombo deficiency. Understanding the role of Progesterone Injection in the treatment of your menstrual irregularities. in vitrofindingsisunknown. CONTRAINDICATIONS). Progesterone is one of the hormones essential for regular menstrual periods. If your doctor has 50

<01 μM). Ketocon determined your body does not produce enough PRECAUTIONS progesterone on its own, Progesterone Injection may be prescribed to provide the progesterone you need. When you do not produce enough proges-

terone, menstrual irregularities can occur. Pro- 5AN ). ------gesterone Injection can provide you with the progesterone needed during a normal menstrual PRECAUTIONS: WARNINGS: of patientsonestrogen-progestincom been observedinasmallpercentage mizing theseadverseeffects. dosage used may be important in mini carbohydrate andlipidmetabolism.The treatment, including adverse effects on be associatedwiththeuseofprogestin mens aresubmitted. pro of the ment withprogestinmaymasktheonset 4. absolute sion recurstoaseriousdegree. and thedrugdiscontinuedifdepres depression shouldbecarefullyobserved measures undertaken. borne inmind,andadequatediagnostic vaginum, as inallcasesofirregularbleeding require carefulobservation. asthma, cardiac,orrenaldysfunction, this condition,suchasepilepsy,migraine, conditions whichmightbeinfluencedby cause somedegreeoffluidretention, laou smear. and pelvicorgans,as well as a Papanico should includespecialreferencetobreast The pretreatmentphysicalexamination General papilledema or lopia or migraine. If examination reveals there isasuddenonsetofproptosis,dip den partialorcompletelossofvision,if pending examination ifthereisa sud be occur orbe retinal thrombosis).Shouldanyofthese disorders, pulmonaryembolism, and ders (thrombophlebitis, cerebrovascular est manifestationsofthromboticdisor The physicianshouldbealerttotheearli 6. Knownsensitivitytoprogesterone 5. 3. 2. medication shouldbewithdrawn. cycle. A decreaseinglucosetolerancehas There are possible risks which may The pathologistshouldbeadvisedof The age of the patient constitutes no Patients whohaveahistoryofpsychic In casesofbreakthroughbleeding, Because progestationaldrugsmay Medication should be discontinued injection. Missed abortion. Undiagnosed vaginalbleeding. breast or Known orsuspectedmalignancyof Liver dysfunctionordisease. discontinued immediately. gestin Possible side effects of Progesterone Injection

climacteric. The following side effects have been reported

nonfunctional causes should be nonfunctional causesshouldbe with Progesterone Injection. Consult your doc-

limiting factoralthoughtreat therapy whenrelevantspeci

genital organs. tor if you experience any of the side effects suspected, thedrugshould mentioned below, or other side effects. retinal • breakthrough bleeding • spotting

vascular lesions, • changes in menstrual flow • amenorrhea • change in weight (increase or decrease) • pain, irritation, swelling, and/or redness at the injection area

per • general swelling ------• vaginal discharge • yellow discoloration of skin or white of eyes determined. this onthenursinginfanthasnotbeen ing progestationaldrugs.Theeffectof identified inthemilkofmothersreceiv Detectable amountsofdrughavebeen Nursing Mothers patients havenotbeenestablished. Safety andeffectivenessinpediatric Pediatric Use established. ric patients(overage65)havenotbeen The safety and effectiveness in geriat Geriatric Use ADVERSE REACTIONS: sation oftreatment. expected toimpair fertility drugandhighdoseswouldbe genetic mutagenic inabatteryof and mice. with theoraladministrationofMPA to rats dence ofacarcinogeniceffectassociated of Medroxy Long-term intramuscularadministration tumors in beagle dogs. There is no evi has beenshown toproduce mammary ment of Carcinogenesis, Mutagenesis,Impair observed whilereceivingsuch son, diabeticpatientsshouldbecarefully this decreaseisobscure.Forrea bination treatment. The mechanism of tenderness andgalactorrhea;pain,irri secretions; cholestatic jaundice; breast changes incervicalerosionand change inweight(increaseordecrease); in menstrualflow;amenorrhea;edema; Breakthrough bleeding;spotting;change bosis andopticneuritis. neuro-ocular lesions,e.g., retinalthrom dence suggestiveofanassociationwith be carefully observed. There is also evi son patientsonpro thrombosis and embolism. For this rea and pulmonaryembolismcerebral estrogen-progestin combination drugs has been demonstrated between use of somnolence. sion; pyrexia;insomnia;nausea;and anaphylactoid reactions;mentaldepres- rash (allergic) with and without pruritus; ized rash;acne,alopeciaandhirsutism; of urticaria,pruritus,edemaandgeneral area; skinsensitivityreactionsconsisting tation, and/or redness at the injection • breast tenderness, discharge from the nipple Progesterone athighdosesisananti Medroxyprogesterone acetatewasnot A statisticallysignificantassociation • skin reactions including rash, hives, itching, and swelling toxicity assays.

Fertility • acne

progesterone acetate(MPA) • hair loss or growth of new hair • mental depression • fever gestin therapy should gestin therapyshould

fertility untiltheces • insomnia or sleepiness* • nausea

in vitro • anaphylactoid (life-threatening allergic) reaction with symptoms that may include a sense

therapy. of uneasiness or apprehension; flushing; fast, or

in vivo in vivo throbbing heartbeat; itching; hives; difficult breathing; swelling of the throat; fainting; ------nausea; vomiting; or convulsions. * If you experience sleepiness, do not drive or DOSAGE ANDADMINISTRATION: iodine and decrease in T and butanol extractable protein bound nations; thyroidfunction:increaseinPBI, metyrapone test;pregnanedioldetermi in prothrombin factors VII, VIII, IX,andX; function tests; coagulation tests: increase mophthalein retentionandotherhepatic combination drugs:increasedsulfobro altered bytheuseofestrogen-progestin and dizziness. nodosum, hemorrhagiceruption,itching, hair, fatigue, backache,hirsutism,lossofscalp syndrome, headache, in libido,changesappetite,cystitis-like vidual, premenstrualsyndrome,changes Rise in blood pressure in susceptible indi Rise inbloodpressuresusceptible estrogen-progestin combinationdrugs: been observed in patients receiving 260110 No. Product HOW SUPPLIED: mit. whenever the solution and and discolorationpriortoadministration inspected of progesterone,theyaredis begins duringthecourseofinjections of estro progesteroneis begun aftertwoweeks is givenaswell,theadministrationof cease within sixdays. Whenestrogen doses. Bleedingmaybeexpectedto Five to 10 mg are given daily for six Functional UterineBleeding by spontaneous the last withdrawal bleeding48to72hoursafter liferative endometrium, one can expect ficient ovarian activity to produce a pro consecutive days. If there has been suf Five to10mgaregivenforsixeight Amenorrhea ing attheplaceofinjection. commonly usedsteroidsinthatitisirritat muscular Progesterone isadministeredbyintra operate machinery. The following laboratory results may be The followinglaboratoryresultsmaybe The followingadversereactionshave Parenteral drugproductsshouldbe When you should not use Progesterone erythema multiforme, Injection gen injection. Thismaybefollowed 63323-261-10 No. NDC • If you are allergic to progesterone, proges- injection. It differs from other

visually forparticulatematter terone-like drugs, benzyl alcohol or sesame therapy.Ifmenstrualflow oil/seeds.

normal cycles. • If you have unusual vaginal bleeding which has not been evaluated by your doctor.

individually. packaged multiple dosevial, (50 mgpermL) 500 mgper10mL, Injection, USP, Progesterone • If you have liver disease. 3 uptake values. nervousness, • If you have known or suspected cancer of the container per

continued. breast or genital organs. • If you have a miscarriage and your physician suspects some tissue is still in the uterus. • If you have or have had blood clots in the legs,

------lungs, eyes, or elsewhere.

CrossTech–79920–Proof A1 Form M01 Fresenius Kabi USA, LLC P.O. No. 4500201837–Job No. 45918F, 45919F 10/11/16–hc–O–Indd6 m Fonts: Helvetica (A) Typesmiths Pi Font Rx only For intramuscularuseonly. IN SESAMEOIL Injection, USP Progesterone 45918F/Revised: October2016

45919F/Revised: October 2016

Patient Information Progesterone Injection, USP For intramuscular use only. FOR THE TREATMENT OF AMENORRHEA (ABSENCE OF MENSES IN WOMEN WHO maximum plasmaconcentration(C resulted ingeometricmeanvaluesfor tion. Injectionof10,25,and50mg baseline for about 24 hours after injec plasma concentrations remained above mately 8hours after injection and 7 ng/mL)werereachedwithinapproxi concentrations (geometric mean of of progesterone in oil maximum plasma After intramuscularadministrationof10mg Absorption Pharmacokinetics andMetabolism to 48%). to 54%)andcortisol-bindingprotein(43 plasma proteins,primarily albumin (50 Progesterone isextensivelyboundto Distribution 7, 28,and50ng/mL,respectively. CLINICAL PHARMACOLOGY: C DESCRIPTION: tion andovulation. which inturnprevents secretion ofpituitarygonadotropins, secretory endometrium. Transforms proliferativeendometriuminto soluble in hol, acetone,anddioxanesparingly insoluble inwater,itissolublealco odorless andisstablein air.Practically creamy white, crystalline powder. It is muscular use. suitable vegetableoilavailableforintra a sterile Progesterone injection,aprogestin,is sesame oilq.s. benzyl HAVE PREVIOUSLY HAD A MENSTRUAL 21 O It hasthefollowingstructuralformula: Each mL contains: Progesterone 50 mg, Each mLcontains:Progesterone50mg, Inhibits (at the usual dose range) the Progesterone occursasawhiteor H

30 PERIOD) OR ABNORMAL UTERINE BLEEDING O

2 DUE TO HORMONAL IMBALANCE.

alcohol 10%aspreservativein

solution of progesterone in a Pregn-4-ene-3, 20-dione

vegetable oils. Please read this information carefully before you

CH start to use Progesterone Injection and each

3 time your prescription is renewed, in case any-

H thing has changed. This leaflet does not take the place of discussions with your doctor. If H follic you still have any questions, ask your doctor CH

H or health-care provider. ular matura 3 M.W. 314.47 CO CH About Progesterone Injection 3

max Progesterone Injection is a sterile injectable

H solution containing the natural female hormone ) of ) of - - - - - called progesterone. Progesterone Injection is

indicated for the treatment of amenorrhea and by ketoconazole (IC human livermicrosomeswasinhibited The metabolismofprogesteroneby Drug Interactions indicated (see with liverdysfunctionordiseaseiscontra metabolized bytheliver,useinpatients established. Sinceprogesteroneis with hepaticinsufficiencyhavenotbeen The safetyandeffectivenessinpatients Hepatic Insufficiency evance ofthe ability ofprogesterone.Theclinicalrel of thisenzymemayincreasethebioavail ketoconazole orotherknowninhibitors P450 3A4andthesedatasuggestthat azole isaknowninhibitorofcytochrome CONTRAINDICATIONS: INDICATIONS ANDUSAGE: patient population(see with caution and careful monitoringin this progesterone shouldbeadministered lites areexcretedmainlybythekidneys, established. Sinceprogesteronemetabo with renal insufficiency have not been The safetyandeffectivenessinpatients Renal Insufficiency Special Populations values maybeestimated. iting theprecisioninwhichpopulation mined inasmallnumberofpatients,lim or maybeexcretedinthefeces. bile mayundergoenterohepaticrecycling one metaboliteswhichareexcretedinthe excreted intheurineandbile.Progester of pregnanediolandpregnanoloneare The glucuronideandsulfateconjugates Excretion (SEM) L/day. rate in cycling women is 2510 ± 135 The meanplasmametabolicclearance of glucuronide and sulfate metabolites. quent conjugationresultsintheformation pregnanetriol and pregnanolone. Subse the liverbyreductiontopregnanediol, Progesterone ismetabolizedprimarilyin Metabolism 1. fibroids oruterinecancer. organic pathology, such as submucous hormonal imbalanceintheabsenceof and abnormaluterinebleedingdueto This drugisindicatedinamenorrhea abnormal uterine bleeding due to progesterone The pharmacokineticdatawasdeter or cerebralapoplexy. phlebitis, thromboembolicdisorders, Current or past history of thrombo deficiency. Understanding the role of Progesterone Injection in the treatment of your menstrual irregularities. in vitrofindingsisunknown. CONTRAINDICATIONS). Progesterone is one of the hormones essential for regular menstrual periods. If your doctor has 50

terone, menstrual irregularities can occur. Pro- 5AN ). ------gesterone Injection can provide you with the progesterone needed during a normal menstrual PRECAUTIONS: WARNINGS: pro of patientsonestrogen-progestincom been observedinasmallpercentage mizing theseadverseeffects. dosage used may be important in mini carbohydrate andlipidmetabolism.The treatment, including adverse effects on be associatedwiththeuseofprogestin mens aresubmitted. 6. Knownsensitivitytoprogesterone 5. 4. of the ment withprogestinmaymasktheonset absolute sion recurstoaseriousdegree. and thedrugdiscontinuedifdepres depression shouldbecarefullyobserved measures undertaken. borne inmind,andadequatediagnostic vaginum, as inallcasesofirregularbleeding require carefulobservation. asthma, cardiac,orrenaldysfunction, this condition,suchasepilepsy,migraine, conditions whichmightbeinfluencedby cause somedegreeoffluidretention, laou smear. and pelvicorgans,as well as a Papanico should includespecialreferencetobreast The pretreatmentphysicalexamination General medication shouldbewithdrawn. papilledema or lopia or migraine. If examination reveals there isasuddenonsetofproptosis,dip den partialorcompletelossofvision,if pending examination ifthereisa sud be occur orbe retinal thrombosis).Shouldanyofthese disorders, pulmonaryembolism, and ders (thrombophlebitis, cerebrovascular est manifestationsofthromboticdisor The physicianshouldbealerttotheearli 3. 2. cycle. The pathologistshouldbeadvisedof A decreaseinglucosetolerancehas There are possible risks which may The age of the patient constitutes no Patients whohaveahistoryofpsychic In casesofbreakthroughbleeding, Because progestationaldrugsmay Medication should be discontinued injection. Missed abortion. Undiagnosed vaginalbleeding. breast or Known orsuspectedmalignancyof Liver dysfunctionordisease. discontinued immediately. gestin Possible side effects of Progesterone Injection

climacteric. The following side effects have been reported

nonfunctional causes should be nonfunctional causesshouldbe with Progesterone Injection. Consult your doc-

limiting factoralthoughtreat therapy whenrelevantspeci

genital organs. tor if you experience any of the side effects suspected, thedrugshould mentioned below, or other side effects. retinal • breakthrough bleeding • spotting

vascular lesions, • changes in menstrual flow • amenorrhea • change in weight (increase or decrease) • pain, irritation, swelling, and/or redness at the injection area

per • general swelling ------• vaginal discharge • yellow discoloration of skin or white of eyes determined. this onthenursinginfanthasnotbeen ing progestationaldrugs.Theeffectof identified inthemilkofmothersreceiv Detectable amountsofdrughavebeen Nursing Mothers patients havenotbeenestablished. Safety andeffectivenessinpediatric Pediatric Use established. ric patients(overage65)havenotbeen The safety and effectiveness in geriat Geriatric Use ADVERSE REACTIONS: sation oftreatment. mutagenic inabatteryof and mice. with theoraladministrationofMPA to rats dence ofacarcinogeniceffectassociated tumors in beagle dogs. There is no evi has beenshown toproduce mammary of Medroxy Long-term intramuscularadministration ment of Carcinogenesis, Mutagenesis,Impair observed whilereceivingsuch son, diabeticpatientsshouldbecarefully this decreaseisobscure.Forrea bination treatment. The mechanism of expected toimpair fertility drugandhighdoseswouldbe genetic bosis andopticneuritis. neuro-ocular lesions,e.g., retinalthrom dence suggestiveofanassociationwith be carefully observed. There is also evi son patientsonpro thrombosis and embolism. For this rea and pulmonaryembolismcerebral estrogen-progestin combination drugs has been demonstrated between use of somnolence. sion; pyrexia;insomnia;nausea;and anaphylactoid reactions;mentaldepres- rash (allergic) with and without pruritus; ized rash;acne,alopeciaandhirsutism; of urticaria,pruritus,edemaandgeneral area; skinsensitivityreactionsconsisting tation, and/or redness at the injection tenderness andgalactorrhea;pain,irri secretions; cholestatic jaundice; breast changes incervicalerosionand change inweight(increaseordecrease); in menstrualflow;amenorrhea;edema; Breakthrough bleeding;spotting;change • breast tenderness, discharge from the nipple Medroxyprogesterone acetatewasnot Progesterone athighdosesisananti A statisticallysignificantassociation • skin reactions including rash, hives, itching, and swelling toxicity assays.

Fertility • acne

progesterone acetate(MPA) • hair loss or growth of new hair • mental depression • fever gestin therapy should gestin therapyshould

fertility untiltheces • insomnia or sleepiness* • nausea

in vitro • anaphylactoid (life-threatening allergic) reaction with symptoms that may include a sense

therapy. of uneasiness or apprehension; flushing; fast, or

in vivo in vivo throbbing heartbeat; itching; hives; difficult breathing; swelling of the throat; fainting; ------nausea; vomiting; or convulsions. * If you experience sleepiness, do not drive or DOSAGE ANDADMINISTRATION: iodine and decrease in T and butanol extractable protein bound nations; thyroidfunction:increaseinPBI, metyrapone test;pregnanedioldetermi in prothrombin factors VII, VIII, IX,andX; function tests; coagulation tests: increase mophthalein retentionandotherhepatic combination drugs:increasedsulfobro altered bytheuseofestrogen-progestin and dizziness. nodosum, hemorrhagiceruption,itching, hair, fatigue, backache,hirsutism,lossofscalp syndrome, headache, in libido,changesappetite,cystitis-like vidual, premenstrualsyndrome,changes indi Rise inbloodpressuresusceptible estrogen-progestin combinationdrugs: been observed in patients receiving muscular Progesterone isadministeredbyintra the last withdrawal bleeding48to72hoursafter liferative endometrium, one can expect ficient ovarian activity to produce a pro consecutive days. If there has been suf Five to10mgaregivenforsixeight Amenorrhea ing attheplaceofinjection. commonly usedsteroidsinthatitisirritat 260110 No. Product HOW SUPPLIED: mit. whenever the solution and and discolorationpriortoadministration of progesterone,theyaredis begins duringthecourseofinjections of estro progesteroneis begun aftertwoweeks is givenaswell,theadministrationof cease within sixdays. Whenestrogen doses. Bleedingmaybeexpectedto Five to 10 mg are given daily for six Functional UterineBleeding by spontaneous inspected operate machinery. The following laboratory results may be The followinglaboratoryresultsmaybe The followingadversereactionshave Parenteral drugproductsshouldbe When you should not use Progesterone erythema multiforme, Injection gen injection. Thismaybefollowed 63323-261-10 No. NDC • If you are allergic to progesterone, proges- injection. It differs from other

visually forparticulatematter terone-like drugs, benzyl alcohol or sesame therapy.Ifmenstrualflow oil/seeds.

normal cycles. • If you have unusual vaginal bleeding which has not been evaluated by your doctor.

continued. breast or genital organs. • If you have a miscarriage and your physician suspects some tissue is still in the uterus. • If you have or have had blood clots in the legs,

------lungs, eyes, or elsewhere.

CrossTech–79920–Proof A1 Form M01 Fresenius Kabi USA, LLC P.O. No. 4500201837–Job No. 45918F, 45919F 10/11/16–hc–O–Indd6 m Fonts: Helvetica (A) Typesmiths Pi Font 5AN Lake Zurich, IL 60047 Revised: October 2016 45919F www.fresenius-kabi.us expiration date which is printed on the vial label. Do not use Progesterone Injection after the or health-care provider. about product administration, ask your doctor instructions closely. If you have any questions tion should be injected. Follow your doctor’s the dose and manner in which the medica Your doctor will provide instructions regarding you by a health-care provider or your caregiver. Progesterone Injection will be administered to How to use Progesterone Injection 3. 2. 1. Other information the bloodstream. lowing injection, the medication is absorbed into istration by injection into a muscle mass. Fol Progesterone Injection is intended for admin How Progesterone Injection works • • • • • terone Injection, call your doctor immediately: symptoms) happen while you are using Proges of these warning signals (or any other unusual Be alert for unusual signs and symptoms. If any Precautions • Risks of Progesterone Injection indicating possible liver problems. Yellowing of the skin and/or white eyes your breasts monthly.) care provider to show you how examine breast cancer. (Ask your doctor or health- with fibrocystic disorders, fibroadenoma, or Breast lumps, which could be associated possible clots in the brain or eye. ness or numbness of an arm leg indicating ness, or changes in vision speech, weak Severe headache or vomiting, dizziness, faint possible clots in the legs, heart, or lungs. ness of breath or coughing blood indicating Pains in the calves or chest, a sudden short Abnormal bleeding from the vagina. or she may advise you to stop using this drug. suspect you have any of these conditions. He disability. Call your doctor immediately if you tions may cause death or serious long-term lungs), or other problems. Any of these condi embolus (by cutting off blood to part of the off blood to part of the heart), a pulmonary part of the brain), a heart attack (by cutting may include a stroke (by cutting off blood to causing serious problems. These problems can cut off the blood supply to vital organs, blood clots do form in your bloodstream, they gestational drugs (alone or in combination). If estrogens and pro reported with the use of Abnormal blood clotting. Blood clots have been children. Keep this and all drugs out of the reach for another condition. particular medical condition. Do not use it This medication was prescribed for your anyone else. you and alone. Do not give this drug to Your doctor has prescribed this drug for ------

The container closure is not made with • pain, irritation, swelling, and/or redness conditions. He or she may advise you natural rubber latex. at the injection area to stop using this drug. Store at 20° to 25°C (68° to 77°F) [see • general swelling Precautions USP Controlled Room Temperature]. • vaginal discharge Be alert for unusual signs and symptoms. • yellow discoloration of skin or white PATIENT INFORMATION: If any of these warning signals (or any of eyes other unusual symptoms) happen while PROGESTERONE INJECTION, USP • breast tenderness, discharge from the you are using Progesterone Injection, call For Intramuscular Use Only nipple your doctor immediately: FOR THE TREATMENT OF AMENOR- • skin reactions including rash, hives, • Abnormal bleeding from the vagina.

RHEA (ABSENCE OF MENSES IN itching, and swelling • Pains in the calves or chest, a sudden m WOMEN WHO HAVE PREVIOUSLY • acne shortness of breath or coughing blood HAD A MENSTRUAL PERIOD) OR • hair loss or growth of new hair indicating possible clots in the legs, ABNORMAL UTERINE BLEEDING DUE • mental depression heart, or lungs. TO HORMONAL IMBALANCE. • fever • Severe headache or vomiting, dizzi- • insomnia or sleepiness* ness, faintness, or changes in vision or Please read this information carefully • nausea before you start to use Progesterone speech, weakness or numbness of an • anaphylactoid (life-threatening aller- arm or leg indicating possible clots in Injection and each time your prescrip- gic) reaction with symptoms that may tion is renewed, in case anything has the brain or eye. include a sense of uneasiness or appre- • Breast lumps, which could be associ- changed. This leaflet does not take the hension; flushing; fast, throbbing heart- place of discussions with your doctor. ated with fibrocystic disorders, fibroade- beat; itching; hives; difficult breathing; noma, or breast cancer. (Ask your doc- If you still have any questions, ask your swelling of the throat; fainting; nausea; doctor or health-care provider. tor or health-care provider to show you vomiting; or convulsions. how to examine your breasts monthly.) About Progesterone Injection * If you experience sleepiness, do not • Yellowing of the skin and/or white of the Progesterone Injection is a sterile inject- drive or operate machinery. eyes indicating possible liver problems. able solution containing the natural How Progesterone Injection works female hormone called progesterone. When you should not use Progesterone Progesterone Injection is intended for Progesterone Injection is indicated for Injection administration by injection into a muscle the treatment of amenorrhea and abnor- • If you are allergic to progesterone, pro- mass. Following injection, the medication mal uterine bleeding due to progesterone gesterone-like drugs, benzyl alcohol or is absorbed into the bloodstream. deficiency. sesame oil/seeds. Other information Understanding the role of Progester- • If you have unusual vaginal bleeding 1. Your doctor has prescribed this drug one Injection in the treatment of your which has not been evaluated by your for you and you alone. Do not give this menstrual irregularities. doctor. drug to anyone else. Progesterone is one of the hormones • If you have liver disease. 2. This medication was prescribed for your essential for regular menstrual periods. • If you have known or suspected cancer particular medical condition. Do not use If your doctor has determined your body of the breast or genital organs. it for another condition. does not produce enough progesterone • If you have a miscarriage and your phy- 3. Keep this and all drugs out of the reach on its own, Progesterone Injection may be sician suspects some tissue is still in of children. prescribed to provide the progesterone the uterus. you need. • If you have or have had blood clots in How to use Progesterone Injection When you do not produce enough pro- the legs, lungs, eyes, or elsewhere. Progesterone Injection will be administered to you by a health-care provider or gesterone, menstrual irregularities can Risks of Progesterone Injection your caregiver. Your doctor will provide occur. Progesterone Injection can provide • Abnormal blood clotting. Blood clots instructions regarding the dose and man- you with the progesterone needed during have been reported with the use of ner in which the medication should be a normal menstrual cycle. estrogens and progestational drugs injected. Follow your doctor’s instructions Possible side effects of Progesterone (alone or in combination). If blood clots closely. If you have any questions about Injection do form in your bloodstream, they can product administration, ask your doctor The following side effects have been cut off the blood supply to vital organs,

or health-care provider. reported with Progesterone Injection. causing serious problems. These prob- Consult your doctor if you experience lems may include a stroke (by cutting any of the side effects mentioned below, off blood to part of the brain), a heart or other side effects. attack (by cutting off blood to part of • breakthrough bleeding the heart), a pulmonary embolus (by • spotting cutting off blood to part of the lungs), or Lake Zurich, IL 60047 • changes in menstrual flow other problems. Any of these conditions • amenorrhea may cause death or serious long-term www.fresenius-kabi.us • change in weight (increase or disability. Call your doctor immediately 45918F decrease) if you suspect you have any of these Revised: October 2016 Typesmiths Pi Font Typesmiths Helvetica (A) P.O. No. 4500201837–Job No. 45918F, 45919F P.O. No. 10/10/16–hc–O–Indd6 CrossTech–79920–Proof 1 CrossTech–79920–Proof M02 Form Fresenius Kabi USA, LLC Fonts: Rx only For intramuscular use only. IN SESAME OIL Injection, USP Progesterone 45918F /Revised: October 2016

45919F/Revised: October 2016

Patient Information Progesterone Injection, USP For intramuscular use only. FOR THE TREATMENT OF AMENORRHEA (ABSENCE OF MENSES IN WOMEN WHO of progesterone in oil maximum plasma After intramuscular administration of 10 mg Absorption Pharmacokinetics and Metabolism maximum plasma concentration (C resulted in geometric mean values for tion. Injection of 10, 25, and 50 mg baseline for about 24 hours after injec plasma concentrations remained above mately 8 hours after injection and 7 ng/mL) were reached within approxi concentrations (geometric mean of to 48%). to 54%) and cortisol-binding protein (43 plasma proteins, primarily albumin (50 Progesterone is extensively bound to Distribution 7, 28, and 50 ng/mL, respectively. CLINICAL PHARMACOLOGY: C DESCRIPTION: tion and ovulation. which in turn prevents secretion of pituitary gonadotropins, secretory endometrium. Transforms proliferative endometrium into soluble in hol, acetone, and dioxane sparingly insoluble in water, it is soluble alco odorless and is stable in air. Practically creamy white, crystalline powder. It is muscular use. suitable vegetable oil available for intra a sterile Progesterone injection, a progestin, is benzyl sesame oil q.s. HAVE PREVIOUSLY HAD A MENSTRUAL 21 O It has the following structural formula: Each mL contains: Progesterone 50 mg, Each mL contains: Progesterone 50 mg, Inhibits (at the usual dose range) the Progesterone occurs as a white or H

30 PERIOD) OR ABNORMAL UTERINE BLEEDING O

2 DUE TO HORMONAL IMBALANCE. alcohol 10% as preservative in

solution of progesterone in a Pregn-4-ene-3, 20-dione

vegetable oils. Please read this information carefully before you

CH start to use Progesterone Injection and each

3 time your prescription is renewed, in case any-

H thing has changed. This leaflet does not take the place of discussions with your doctor. If H follic you still have any questions, ask your doctor CH

H or health-care provider. ular matura 3 M.W. 314.47 CO CH About Progesterone Injection 3 max Progesterone Injection is a sterile injectable

H solution containing the natural female hormone ) of ) of - - - - - called progesterone. Progesterone Injection is

indicated for the treatment of amenorrhea and by ketoconazole (IC human liver microsomes was inhibited The metabolism of progesterone by Drug Interactions indicated (see with liver dysfunction or disease is contra metabolized by the liver, use in patients established. Since progesterone is with hepatic insufficiency have not been The safety and effectiveness in patients Hepatic Insufficiency evance of the ability of progesterone. The clinical rel of this enzyme may increase the bioavail ketoconazole or other known inhibitors P450 3A4 and these data suggest that azole is a known inhibitor of cytochrome CONTRAINDICATIONS: INDICATIONS AND USAGE: patient population (see with caution and careful monitoringin this progesterone should be administered lites are excreted mainly by the kidneys, established. Since progesterone metabo with renal insufficiency have not been The safety and effectiveness in patients Renal Insufficiency Special Populations values may be estimated. iting the precision in which population mined in a small number of patients, lim or may be excreted in the feces. bile may undergo enterohepatic recycling one metabolites which are excreted in the excreted in the urine and bile. Progester of pregnanediol and pregnanolone are The glucuronide and sulfate conjugates Excretion (SEM) L/day. rate in cycling women is 2510 ± 135 The mean plasma metabolic clearance of glucuronide and sulfate metabolites. quent conjugation results in the formation pregnanetriol and pregnanolone. Subse the liver by reduction to pregnanediol, Progesterone is metabolized primarily in Metabolism 1. fibroids or uterine cancer. organic pathology, such as submucous hormonal imbalance in the absence of and abnormal uterine bleeding due to This drug is indicated in amenorrhea abnormal uterine bleeding due to progesterone The pharmacokinetic data was deter or cerebral apoplexy. phlebitis, thromboembolic disorders, Current or past history of thrombo deficiency. Understanding the role of Progesterone Injection in the treatment of your menstrual irregularities. in vitro findings is unknown. CONTRAINDICATIONS ). Progesterone is one of the hormones essential for regular menstrual periods. If your doctor has 50

< 01 μM). Ketocon determined your body does not produce enough PRECAUTIONS progesterone on its own, Progesterone Injection may be prescribed to provide the progesterone you need. When you do not produce enough proges-

terone, menstrual irregularities can occur. Pro- 5AN ). ------gesterone Injection can provide you with the progesterone needed during a normal menstrual PRECAUTIONS: WARNINGS: of patients on estrogen-progestin com been observed in a small percentage mizing these adverse effects. dosage used may be important in mini carbohydrate and lipid metabolism. The treatment, including adverse effects on be associated with the use of progestin mens are submitted. pro of the ment with progestin may mask the onset absolute sion recurs to a serious degree. and the drug discontinued if depres depression should be carefully observed measures undertaken. borne in mind, and adequate diagnostic vaginum, as in all cases of irregular bleeding require careful observation. asthma, cardiac, or renal dysfunction, this condition, such as epilepsy, migraine, conditions which might be influenced by cause some degree of fluid retention, laou smear. and pelvic organs, as well as a Papanico should include special reference to breast The pretreatment physical examination General medication should be withdrawn. papilledema or lopia or migraine. If examination reveals there is a sudden onset of proptosis, dip den partial or complete loss of vision, if pending examination if there is a sud be occur or be retinal thrombosis). Should any of these disorders, pulmonary embolism, and ders (thrombophlebitis, cerebrovascular est manifestations of thrombotic disor The physician should be alert to the earli 6. Known sensitivity to progesterone 5. 4. 3. 2. cycle. A decrease in glucose tolerance has There are possible risks which may The pathologist should be advised of The age of the patient constitutes no Patients who have a history of psychic In cases of breakthrough bleeding, Because progestational drugs may Medication should be discontinued injection. Missed abortion. Undiagnosed vaginal bleeding. breast or Known or suspected malignancy of Liver dysfunction or disease. discontinued immediately. gestin Possible side effects of Progesterone Injection

climacteric. The following side effects have been reported

nonfunctional causes should be nonfunctional causes should be with Progesterone Injection. Consult your doc- limiting factor although treat therapy when relevant speci

genital organs. tor if you experience any of the side effects suspected, the drug should mentioned below, or other side effects. retinal • breakthrough bleeding • spotting

vascular lesions, • changes in menstrual flow • amenorrhea • change in weight (increase or decrease) • pain, irritation, swelling, and/or redness at the injection area

per • general swelling ------• vaginal discharge • yellow discoloration of skin or white of eyes The safety and effectiveness in geriat Geriatric Use determined. this on the nursing infant has not been ing progestational drugs. The effect of identified in the milk of mothers receiv Detectable amounts of drug have been Nursing Mothers patients have not been established. Safety and effectiveness in pediatric Pediatric Use established. ric patients (over age 65) have not been ADVERSE REACTIONS: sation of treatment. expected to impair fertility drug and high doses would be genetic mutagenic in a battery of and mice. with the oral administration of MPA to rats dence of a carcinogenic effect associated tumors in beagle dogs. There is no evi has been shown to produce mammary ment of Carcinogenesis, Mutagenesis, Impair observed while receiving such son, diabetic patients should be carefully of Medroxy Long-term intramuscular administration this decrease is obscure. For rea bination treatment. The mechanism of bosis and optic neuritis. neuro-ocular lesions, e.g., retinal throm dence suggestive of an association with be carefully observed. There is also evi son patients on pro thrombosis and embolism. For this rea and pulmonary embolism cerebral estrogen-progestin combination drugs has been demonstrated between use of somnolence. sion; pyrexia; insomnia; nausea; and anaphylactoid reactions; mental depres - rash (allergic) with and without pruritus; ized rash; acne, alopecia and hirsutism; of urticaria, pruritus, edema and general area; skin sensitivity reactions consisting tation, and/or redness at the injection tenderness and galactorrhea; pain, irri secretions; cholestatic jaundice; breast changes in cervical erosion and change in weight (increase or decrease); in menstrual flow; amenorrhea; edema; Breakthrough bleeding; spotting; change • breast tenderness, discharge from the nipple Medroxyprogesterone acetate was not Progesterone at high doses is an anti A statistically significant association • skin reactions including rash, hives, itching, and swelling toxicity assays.

Fertility • acne

progesterone acetate (MPA) • hair loss or growth of new hair • mental depression • fever gestin therapy should gestin therapy should

fertility until the ces • insomnia or sleepiness* • nausea

in vitro • anaphylactoid (life-threatening allergic) reaction with symptoms that may include a sense

therapy. of uneasiness or apprehension; flushing; fast, or

in vivo in vivo throbbing heartbeat; itching; hives; difficult breathing; swelling of the throat; fainting; ------nausea; vomiting; or convulsions. * If you experience sleepiness, do not drive or DOSAGE AND ADMINISTRATION: the last withdrawal bleeding 48 to 72 hours after liferative endometrium, one can expect ficient ovarian activity to produce a pro consecutive days. If there has been suf Five to 10 mg are given for six eight Amenorrhea ing at the place of injection. commonly used steroids in that it is irritat muscular Progesterone is administered by intra syndrome, headache, in libido, changes appetite, cystitis-like vidual, premenstrual syndrome, changes indi Rise in blood pressure susceptible estrogen-progestin combination drugs: been observed in patients receiving 260110 No. whenever the solution and and discoloration prior to administration of progesterone, they are dis begins during the course of injections of estro progesterone is begun after two weeks is given as well, the administration of cease within six days. When estrogen doses. Bleeding may be expected to Five to 10 mg are given daily for six Functional Uterine Bleeding by spontaneous combination drugs: increased sulfobro altered by the use of estrogen-progestin and dizziness. nodosum, hemorrhagic eruption, itching, hair, fatigue, backache, hirsutism, loss of scalp Product HOW SUPPLIED: mit. inspected iodine and decrease in T and butanol extractable protein bound nations; thyroid function: increase in PBI, metyrapone test; pregnanediol determi in prothrombin factors VII, VIII, IX, and X; function tests; coagulation tests: increase mophthalein retention and other hepatic operate machinery. The following adverse reactions have The following laboratory results may be The following laboratory results may be Parenteral drug products should be When you should not use Progesterone erythema multiforme, Injection gen injection. This may be followed 63323-261-10 No. NDC • If you are allergic to progesterone, proges- injection. It differs from other

visually for particulate matter terone-like drugs, benzyl alcohol or sesame therapy. If menstrual flow oil/seeds. normal cycles. • If you have unusual vaginal bleeding which has not been evaluated by your doctor. multiple dose vial, multiple dose vial, (50 mg per mL) 500 mg per 10 mL, Injection, USP, Progesterone individually. packaged • If you have liver disease. 3 uptake values. nervousness, • If you have known or suspected cancer of the container per

continued. breast or genital organs. • If you have a miscarriage and your physician suspects some tissue is still in the uterus. • If you have or have had blood clots in the legs,

------lungs, eyes, or elsewhere.

CrossTech–79920–Proof A1 Form M01 Fresenius Kabi USA, LLC P.O. No. 4500201837–Job No. 45918F, 45919F 10/11/16–hc–O–Indd6 m Fonts: Helvetica (A) Typesmiths Pi Font Rx only For intramuscular use only. IN SESAME OIL Injection, USP Progesterone 45918F /Revised: October 2016

45919F/Revised: October 2016

Patient Information Progesterone Injection, USP For intramuscular use only. FOR THE TREATMENT OF AMENORRHEA (ABSENCE OF MENSES IN WOMEN WHO maximum plasma concentration (C resulted in geometric mean values for tion. Injection of 10, 25, and 50 mg baseline for about 24 hours after injec plasma concentrations remained above mately 8 hours after injection and 7 ng/mL) were reached within approxi concentrations (geometric mean of of progesterone in oil maximum plasma After intramuscular administration of 10 mg Absorption Pharmacokinetics and Metabolism to 48%). to 54%) and cortisol-binding protein (43 plasma proteins, primarily albumin (50 Progesterone is extensively bound to Distribution 7, 28, and 50 ng/mL, respectively. CLINICAL PHARMACOLOGY: C DESCRIPTION: tion and ovulation. which in turn prevents secretion of pituitary gonadotropins, secretory endometrium. Transforms proliferative endometrium into soluble in hol, acetone, and dioxane sparingly insoluble in water, it is soluble alco odorless and is stable in air. Practically creamy white, crystalline powder. It is muscular use. suitable vegetable oil available for intra a sterile Progesterone injection, a progestin, is sesame oil q.s. benzyl HAVE PREVIOUSLY HAD A MENSTRUAL 21 O It has the following structural formula: Each mL contains: Progesterone 50 mg, Each mL contains: Progesterone 50 mg, Inhibits (at the usual dose range) the Progesterone occurs as a white or H

30 PERIOD) OR ABNORMAL UTERINE BLEEDING O

2 DUE TO HORMONAL IMBALANCE. alcohol 10% as preservative in

solution of progesterone in a Pregn-4-ene-3, 20-dione

vegetable oils. Please read this information carefully before you

CH start to use Progesterone Injection and each

3 time your prescription is renewed, in case any-

H thing has changed. This leaflet does not take the place of discussions with your doctor. If H follic you still have any questions, ask your doctor CH

H or health-care provider. ular matura 3 M.W. 314.47 CO CH About Progesterone Injection 3 max Progesterone Injection is a sterile injectable

H solution containing the natural female hormone ) of ) of - - - - - called progesterone. Progesterone Injection is

indicated for the treatment of amenorrhea and by ketoconazole (IC human liver microsomes was inhibited The metabolism of progesterone by Drug Interactions indicated (see with liver dysfunction or disease is contra metabolized by the liver, use in patients established. Since progesterone is with hepatic insufficiency have not been The safety and effectiveness in patients Hepatic Insufficiency CONTRAINDICATIONS: INDICATIONS AND USAGE: patient population (see with caution and careful monitoringin this progesterone should be administered lites are excreted mainly by the kidneys, established. Since progesterone metabo with renal insufficiency have not been The safety and effectiveness in patients Renal Insufficiency Special Populations values may be estimated. iting the precision in which population mined in a small number of patients, lim or may be excreted in the feces. bile may undergo enterohepatic recycling one metabolites which are excreted in the excreted in the urine and bile. Progester of pregnanediol and pregnanolone are The glucuronide and sulfate conjugates Excretion (SEM) L/day. rate in cycling women is 2510 ± 135 The mean plasma metabolic clearance of glucuronide and sulfate metabolites. quent conjugation results in the formation pregnanetriol and pregnanolone. Subse the liver by reduction to pregnanediol, Progesterone is metabolized primarily in Metabolism evance of the ability of progesterone. The clinical rel of this enzyme may increase the bioavail ketoconazole or other known inhibitors P450 3A4 and these data suggest that azole is a known inhibitor of cytochrome 1. fibroids or uterine cancer. organic pathology, such as submucous hormonal imbalance in the absence of and abnormal uterine bleeding due to This drug is indicated in amenorrhea abnormal uterine bleeding due to progesterone The pharmacokinetic data was deter or cerebral apoplexy. phlebitis, thromboembolic disorders, Current or past history of thrombo deficiency. Understanding the role of Progesterone Injection in the treatment of your menstrual irregularities. in vitro findings is unknown. CONTRAINDICATIONS ). Progesterone is one of the hormones essential for regular menstrual periods. If your doctor has 50

< 01 μM). Ketocon determined your body does not produce enough PRECAUTIONS progesterone on its own, Progesterone Injection may be prescribed to provide the progesterone you need. When you do not produce enough proges-

terone, menstrual irregularities can occur. Pro- 5AN ). ------gesterone Injection can provide you with the progesterone needed during a normal menstrual PRECAUTIONS: WARNINGS: of patients on estrogen-progestin com been observed in a small percentage mizing these adverse effects. dosage used may be important in mini carbohydrate and lipid metabolism. The treatment, including adverse effects on be associated with the use of progestin mens are submitted. pro 6. Known sensitivity to progesterone 5. 4. 3. 2. of the ment with progestin may mask the onset absolute sion recurs to a serious degree. and the drug discontinued if depres depression should be carefully observed measures undertaken. borne in mind, and adequate diagnostic vaginum, as in all cases of irregular bleeding require careful observation. asthma, cardiac, or renal dysfunction, this condition, such as epilepsy, migraine, conditions which might be influenced by cause some degree of fluid retention, laou smear. and pelvic organs, as well as a Papanico should include special reference to breast The pretreatment physical examination General medication should be withdrawn. papilledema or lopia or migraine. If examination reveals there is a sudden onset of proptosis, dip den partial or complete loss of vision, if pending examination if there is a sud be occur or be retinal thrombosis). Should any of these disorders, pulmonary embolism, and ders (thrombophlebitis, cerebrovascular est manifestations of thrombotic disor The physician should be alert to the earli cycle. A decrease in glucose tolerance has There are possible risks which may The pathologist should be advised of The age of the patient constitutes no Patients who have a history of psychic In cases of breakthrough bleeding, Because progestational drugs may Medication should be discontinued injection. Missed abortion. Undiagnosed vaginal bleeding. breast or Known or suspected malignancy of Liver dysfunction or disease. discontinued immediately. gestin Possible side effects of Progesterone Injection

climacteric. The following side effects have been reported

nonfunctional causes should be nonfunctional causes should be with Progesterone Injection. Consult your doc- limiting factor although treat therapy when relevant speci

genital organs. tor if you experience any of the side effects suspected, the drug should mentioned below, or other side effects. retinal • breakthrough bleeding • spotting

vascular lesions, • changes in menstrual flow • amenorrhea • change in weight (increase or decrease) • pain, irritation, swelling, and/or redness at the injection area

per • general swelling ------• vaginal discharge • yellow discoloration of skin or white of eyes The safety and effectiveness in geriat Geriatric Use determined. this on the nursing infant has not been ing progestational drugs. The effect of identified in the milk of mothers receiv Detectable amounts of drug have been Nursing Mothers patients have not been established. Safety and effectiveness in pediatric Pediatric Use established. ric patients (over age 65) have not been ADVERSE REACTIONS: sation of treatment. expected to impair fertility drug and high doses would be mutagenic in a battery of and mice. with the oral administration of MPA to rats dence of a carcinogenic effect associated tumors in beagle dogs. There is no evi has been shown to produce mammary of Medroxy Long-term intramuscular administration ment of Carcinogenesis, Mutagenesis, Impair observed while receiving such son, diabetic patients should be carefully genetic this decrease is obscure. For rea bination treatment. The mechanism of bosis and optic neuritis. neuro-ocular lesions, e.g., retinal throm dence suggestive of an association with be carefully observed. There is also evi son patients on pro thrombosis and embolism. For this rea and pulmonary embolism cerebral estrogen-progestin combination drugs has been demonstrated between use of somnolence. sion; pyrexia; insomnia; nausea; and anaphylactoid reactions; mental depres - rash (allergic) with and without pruritus; ized rash; acne, alopecia and hirsutism; of urticaria, pruritus, edema and general area; skin sensitivity reactions consisting tation, and/or redness at the injection tenderness and galactorrhea; pain, irri secretions; cholestatic jaundice; breast changes in cervical erosion and change in weight (increase or decrease); in menstrual flow; amenorrhea; edema; Breakthrough bleeding; spotting; change • breast tenderness, discharge from the nipple Medroxyprogesterone acetate was not Progesterone at high doses is an anti A statistically significant association • skin reactions including rash, hives, itching, and swelling toxicity assays.

Fertility • acne

progesterone acetate (MPA) • hair loss or growth of new hair • mental depression • fever gestin therapy should gestin therapy should

fertility until the ces • insomnia or sleepiness* • nausea

in vitro • anaphylactoid (life-threatening allergic) reaction with symptoms that may include a sense

therapy. of uneasiness or apprehension; flushing; fast, or

in vivo in vivo throbbing heartbeat; itching; hives; difficult breathing; swelling of the throat; fainting; ------nausea; vomiting; or convulsions. * If you experience sleepiness, do not drive or DOSAGE AND ADMINISTRATION: hair, fatigue, backache, hirsutism, loss of scalp syndrome, headache, in libido, changes appetite, cystitis-like vidual, premenstrual syndrome, changes indi Rise in blood pressure susceptible estrogen-progestin combination drugs: been observed in patients receiving 260110 No. Product HOW SUPPLIED: mit. whenever the solution and and discoloration prior to administration inspected of progesterone, they are dis begins during the course of injections of estro progesterone is begun after two weeks is given as well, the administration of cease within six days. When estrogen doses. Bleeding may be expected to Five to 10 mg are given daily for six Functional Uterine Bleeding by spontaneous the last withdrawal bleeding 48 to 72 hours after liferative endometrium, one can expect ficient ovarian activity to produce a pro consecutive days. If there has been suf Five to 10 mg are given for six eight Amenorrhea ing at the place of injection. commonly used steroids in that it is irritat muscular Progesterone is administered by intra iodine and decrease in T and butanol extractable protein bound nations; thyroid function: increase in PBI, metyrapone test; pregnanediol determi in prothrombin factors VII, VIII, IX, and X; function tests; coagulation tests: increase mophthalein retention and other hepatic combination drugs: increased sulfobro altered by the use of estrogen-progestin and dizziness. nodosum, hemorrhagic eruption, itching, operate machinery. The following adverse reactions have Parenteral drug products should be The following laboratory results may be When you should not use Progesterone erythema multiforme, Injection gen injection. This may be followed 63323-261-10 No. NDC • If you are allergic to progesterone, proges- injection. It differs from other

individually. packaged multiple dose vial, (50 mg per mL) 500 mg per 10 mL, Injection, USP, Progesterone • If you have liver disease. 3 uptake values. nervousness, • If you have known or suspected cancer of the container per

continued. breast or genital organs. • If you have a miscarriage and your physician suspects some tissue is still in the uterus. • If you have or have had blood clots in the legs,

------lungs, eyes, or elsewhere.

CrossTech–79920–Proof A1 Form M01 Fresenius Kabi USA, LLC P.O. No. 4500201837–Job No. 45918F, 45919F 10/11/16–hc–O–Indd6 m Fonts: Helvetica (A) Typesmiths Pi Font 5AN 5AN Lake Zurich,IL60047 Lake Zurich,IL60047 Revised: October2016 45919F www.fresenius-kabi.us Revised: October2016 45919F www.fresenius-kabi.us expiration date which isprinted on theviallabel. Do notuseProgesteroneInjectionafterthe or health-careprovider. about productadministration,askyourdoctor instructions closely. Ifyouhaveanyquestions tion shouldbeinjected.Followyourdoctor’s the dose and manner in which the medica Your doctorwillprovideinstructionsregarding you byahealth-careprovideroryourcaregiver. Progesterone Injectionwillbeadministeredto How touseProgesteroneInjection 3. 2. 1. Other information the bloodstream. lowing injection,themedicationisabsorbedinto istration byinjectionintoamusclemass.Fol expiration date which isprinted on theviallabel. Progesterone Injectionisintendedforadmin Do notuseProgesteroneInjectionafterthe How ProgesteroneInjectionworks or health-careprovider. about productadministration,askyourdoctor • instructions closely. Ifyouhaveanyquestions tion shouldbeinjected.Followyourdoctor’s the dose and manner in which the medica Your doctorwillprovideinstructionsregarding you byahealth-careprovideroryourcaregiver. • Progesterone Injectionwillbeadministeredto How touseProgesteroneInjection 3. • 2. • • terone Injection,callyourdoctorimmediately: 1. symptoms) happenwhileyouareusingProges Other information of thesewarningsignals(oranyotherunusual the bloodstream. Be alertforunusualsignsandsymptoms.Ifany lowing injection,themedicationisabsorbedinto Precautions istration byinjectionintoamusclemass.Fol Progesterone Injectionisintendedforadmin How ProgesteroneInjectionworks • • • • Risks ofProgesteroneInjection • • terone Injection,callyourdoctorimmediately: symptoms) happenwhileyouareusingProges of thesewarningsignals(oranyotherunusual Be alertforunusualsignsandsymptoms.Ifany Precautions • Risks ofProgesteroneInjection indicating possibleliverproblems. Yellowing oftheskinand/orwhiteeyes your breastsmonthly.) care providertoshowyouhowexamine breast cancer.(Askyourdoctororhealth- with fibrocysticdisorders,fibroadenoma,or Breast lumps,whichcouldbeassociated possible clotsinthebrainoreye. ness ornumbnessofanarmlegindicating ness, orchangesinvisionspeech,weak Severe headacheorvomiting,dizziness,faint possible clotsinthelegs,heart,orlungs. ness ofbreathorcoughingbloodindicating Pains inthecalvesorchest,asuddenshort Abnormal bleedingfromthevagina. or she may advise you to stop using this drug. suspect youhaveanyoftheseconditions.He disability. Callyourdoctorimmediatelyifyou indicating possibleliverproblems. tions maycausedeathorseriouslong-term Yellowing oftheskinand/orwhiteeyes lungs), orotherproblems.Anyofthesecondi your breastsmonthly.) embolus (bycuttingoffbloodtopartofthe care providertoshowyouhowexamine off bloodtopartoftheheart),apulmonary breast cancer.(Askyourdoctororhealth- part ofthebrain),aheartattack(bycutting with fibrocysticdisorders,fibroadenoma,or may include a stroke (by cutting off blood to Breast lumps,whichcouldbeassociatedcausing seriousproblems.Theseproblems possible clotsinthebrainoreye. can cutoffthebloodsupplytovitalorgans, ness ornumbnessofanarmlegindicating blood clotsdoforminyourbloodstream,they ness, orchangesinvisionspeech,weak gestational drugs (alone or in combination). If Severe headacheorvomiting,dizziness,faint estrogensandpro reported withtheuseof possible clotsinthelegs,heart,orlungs. Abnormal bloodclotting.Bloodclotshavebeen ness ofbreathorcoughingbloodindicating Pains inthecalvesorchest,asuddenshort Abnormal bleedingfromthevagina. or she may advise you to stop using this drug. suspect youhaveanyoftheseconditions.He disability. Callyourdoctorimmediatelyifyou tions maycausedeathorseriouslong-term lungs), orotherproblems.Anyofthesecondi embolus (bycuttingoffbloodtopartofthe off bloodtopartoftheheart),apulmonary part ofthebrain),aheartattack(bycutting may include a stroke (by cutting off blood to causing seriousproblems.Theseproblems can cutoffthebloodsupplytovitalorgans, blood clotsdoforminyourbloodstream,they gestational drugs (alone or in combination). If estrogensandpro reported withtheuseof Abnormal bloodclotting.Bloodclotshavebeen children. Keep thisandalldrugsoutofthereach for anothercondition. particular medicalcondition.Donotuseit This medicationwasprescribedforyour anyone else. you andalone.Donotgivethisdrugto Your doctor has prescribed this drug for children. Keep thisandalldrugsoutofthereach for anothercondition. particular medicalcondition.Donotuseit This medicationwasprescribedforyour anyone else. you andalone.Donotgivethisdrugto Your doctor has prescribed this drug for ------

The container closure is not made with • pain, irritation, swelling,The container and/or redness closure is notconditions. made with He or •she pain, may irritation, advise swelling,you and/or redness conditions. He or she may advise you natural rubber latex. at the injection areanatural rubber latex. to stop using this drug.at the injection area to stop using this drug. Store at 20° to 25°C (68° to 77°F) [see • general swelling Store at 20° to 25°C (68°Precautions to 77°F) [see • general swelling Precautions USP Controlled Room Temperature]. • vaginal discharge USP Controlled Room Temperature].Be alert for unusual signs• vaginal and symptoms.discharge Be alert for unusual signs and symptoms. • yellow discoloration of skin or white • yellow discoloration of skin or white PATIENT INFORMATION: PATIENT INFORMATION:If any of these warning signals (or any If any of these warning signals (or any of eyes other unusual symptoms)of eyes happen while other unusual symptoms) happen while PROGESTERONE INJECTION, USP • breast tenderness,PROGESTERONE discharge from the INJECTION, you are USPusing Progesterone• breast Injection, tenderness, call discharge from the you are using Progesterone Injection, call For Intramuscular Use Only nipple For Intramuscular Use Onlyyour doctor immediately:nipple your doctor immediately: FOR THE TREATMENT OF AMENOR- • skin reactions includingFOR THE rash, TREATMENT hives, •OF Abnormal AMENOR bleeding- • from skin reactionsthe vagina. including rash, hives, • Abnormal bleeding from the vagina. m RHEA (ABSENCE OF MENSES IN itching, and swellingRHEA (ABSENCE OF •MENSES Pains in the IN calves oritching, chest, and a sudden swelling • Pains in the calves or chest, a sudden m WOMEN WHO HAVE PREVIOUSLY • acne WOMEN WHO HAVE PREVIOUSLYshortness of breath • acneor coughing blood shortness of breath or coughing blood

HAD A MENSTRUAL PERIOD) OR • hair loss or growthHAD of new A hairMENSTRUAL PERIOD)indicating OR possible • hair clots loss in orthe growth legs, of new hair indicating possible clots in the legs, ABNORMAL UTERINE BLEEDING DUE • mental depressionABNORMAL UTERINE BLEEDINGheart, or DUE lungs. • mental depression heart, or lungs. TO HORMONAL IMBALANCE. • fever TO HORMONAL IMBALANCE.• Severe headache• orfever vomiting, dizzi- • Severe headache or vomiting, dizzi- • insomnia or sleepiness* ness, faintness, or• changes insomnia in or vision sleepiness* or ness, faintness, or changes in vision or Please read this information carefully • nausea Please read this information carefully • nausea before you start to use Progesterone before you start to use Progesteronespeech, weakness or numbness of an speech, weakness or numbness of an • anaphylactoid (life-threatening aller- arm or leg indicating• anaphylactoid possible clots (life-threatening in aller- arm or leg indicating possible clots in Injection and each time your prescrip- gic) reaction with Injectionsymptoms and that each may time your prescrip- gic) reaction with symptoms that may tion is renewed, in case anything has tion is renewed, in case anythingthe brain hasor eye. the brain or eye. include a sense of uneasiness or appre- • Breast lumps, whichinclude could abe sense associ of -uneasiness or appre- • Breast lumps, which could be associ- changed. This leaflet does not take the hension; flushing; changed.fast, throbbing This heartleaflet- does not take the hension; flushing; fast, throbbing heart- place of discussions with your doctor. place of discussions with atedyour withdoctor. fibrocystic disorders, fibroade- ated with fibrocystic disorders, fibroade- beat; itching; hives; difficult breathing; noma, or breast cancer.beat; (Ask itching; your hives;doc- difficult breathing; noma, or breast cancer. (Ask your doc- If you still have any questions, ask your swelling of the throat;If you fainting; still have nausea; any questions, ask your swelling of the throat; fainting; nausea; doctor or health-care provider. doctor or health-care provider.tor or health-care provider to show you tor or health-care provider to show you vomiting; or convulsions. how to examine yourvomiting; breasts monthly.)or convulsions. how to examine your breasts monthly.) About Progesterone Injection * If you experience Aboutsleepiness, Progesterone do not Injection• Yellowing of the skin* If and/oryou experience white of the sleepiness, do not • Yellowing of the skin and/or white of the Progesterone Injection is a sterile inject- drive or operate machinery.Progesterone Injection is a eyessterile indicating inject- possibledrive liveror operate problems. machinery. eyes indicating possible liver problems. able solution containing the natural able solution containing the natural How Progesterone Injection works How Progesterone Injection works female hormone called progesterone. When you should notfemale use Progesterone hormone called progesterone. When you should not use Progesterone Progesterone Injection is intended for Progesterone Injection is intended for Progesterone Injection is indicated for Injection Progesterone Injection is indicated for Injection administration by injection into a muscle administration by injection into a muscle the treatment of amenorrhea and abnor- • If you are allergic tothe progesterone, treatment of proamenorrhea- and abnor- • If you are allergic to progesterone, pro- mass. Following injection, the medication mass. Following injection, the medication mal uterine bleeding due to progesterone gesterone-like drugs,mal benzyluterine alcohol bleeding or due to progesterone gesterone-like drugs, benzyl alcohol or is absorbed into the bloodstream. is absorbed into the bloodstream. deficiency. sesame oil/seeds.deficiency. sesame oil/seeds. Other information Other information Understanding the role of Progester- • If you have unusualUnderstanding vaginal bleeding the role of Progester- • If you have unusual vaginal bleeding 1. Your doctor has prescribed this drug 1. Your doctor has prescribed this drug one Injection in the treatment of your which has not beenone evaluated Injection by in your the treatment of your which has not been evaluated by your for you and you alone. Do not give this for you and you alone. Do not give this menstrual irregularities. doctor. menstrual irregularities. doctor. drug to anyone else. drug to anyone else. Progesterone is one of the hormones • If you have liver disease.Progesterone is one of the hormones • If you have liver disease. 2. This medication was prescribed for your 2. This medication was prescribed for your essential for regular menstrual periods. • If you have known essentialor suspected for regular cancer menstrual periods. • If you have known or suspected cancer particular medical condition. Do not use particular medical condition. Do not use If your doctor has determined your body of the breast or genitalIf your organs. doctor has determined your body of the breast or genital organs. it for another condition. it for another condition. does not produce enough progesterone • If you have a miscarriagedoes not and produce your phy enough- progesterone • If you have a miscarriage and your phy- 3. Keep this and all drugs out of the reach 3. Keep this and all drugs out of the reach on its own, Progesterone Injection may be sician suspects someon its tissueown, Progesterone is still in Injection may be sician suspects some tissue is still in of children. of children. prescribed to provide the progesterone the uterus. prescribed to provide the progesterone the uterus. you need. • If you have or haveyou had need. blood clots in How to use Progesterone• If you Injectionhave or have had blood clots in How to use Progesterone Injection When you do not produce enough pro- the legs, lungs, eyes,When or elsewhere. you do not produceProgesterone enough pro -Injectionthe will legs, be lungs, adminis eyes,- or elsewhere. Progesterone Injection will be administered to you by a health-care provider or tered to you by a health-care provider or gesterone, menstrual irregularities can Risks of Progesteronegesterone, Injection menstrual irregularities can Risks of Progesterone Injection your caregiver. Your doctor will provide your caregiver. Your doctor will provide occur. Progesterone Injection can provide • Abnormal blood clotting.occur. Progesterone Blood clots Injection can provide • Abnormal blood clotting. Blood clots instructions regarding the dose and man- instructions regarding the dose and man- you with the progesterone needed during have been reportedyou withwith the the progesterone use of needed during have been reported with the use of ner in which the medication should be ner in which the medication should be a normal menstrual cycle. estrogens and progestationala normal menstrual drugs cycle. estrogens and progestational drugs injected. Follow your doctor’s instructions injected. Follow your doctor’s instructions Possible side effects of Progesterone (alone or in combination).Possible If bloodside effects clots of Progesterone (alone or in combination). If blood clots closely. If you have any questions about closely. If you have any questions about Injection do form in your bloodstream,Injection they can do form in your bloodstream, they can product administration, ask your doctor product administration, ask your doctor The following side effects have been cut off the blood supplyThe following to vital organs, side effects have been cut off the blood supply to vital organs,

or health-care provider. or health-care provider. reported with Progesterone Injection. causing serious problems.reported These with Progesteroneprob- Injection. causing serious problems. These prob- Consult your doctor if you experience lems may includeConsult a stroke your (by cuttingdoctor if you experience lems may include a stroke (by cutting any of the side effects mentioned below, off blood to part ofany the of brain), the side a effectsheart mentioned below, off blood to part of the brain), a heart or other side effects. attack (by cuttingor off other blood side to effects.part of attack (by cutting off blood to part of • breakthrough bleeding the heart), a pulmonary• breakthrough embolus bleeding (by the heart), a pulmonary embolus (by • spotting cutting off blood to• part spotting of the lungs), or cutting off blood to part of the lungs), or Lake Zurich, IL 60047 Lake Zurich, IL 60047

• changes in menstrual flow other problems. Any• changesof these conditions in menstrual flow other problems. Any of these conditions • amenorrhea may cause death •or amenorrhea serious long-term www.fresenius-kabi.us may cause death or serious long-term www.fresenius-kabi.us • change in weight (increase or disability. Call your• doctor change immediately in weight (increase 45918F or disability. Call your doctor immediately 45918F decrease) if you suspect you decrease)have any of these Revised: October 2016 if you suspect you have any of these Revised: October 2016 Typesmiths Pi Font Typesmiths Typesmiths Pi Font Typesmiths Helvetica (A) Helvetica (A) CrossTech–79920–Proof 1 CrossTech–79920–Proof M02 Form Fresenius Kabi USA, LLC 4500201837–Job No. 45918F, 45919F P.O. No. 10/10/16–hc–O–Indd6 Fonts: CrossTech–79920–Proof 1 CrossTech–79920–Proof M02 Form Fresenius Kabi USA, LLC 4500201837–Job No. 45918F, 45919F P.O. No. 10/10/16–hc–O–Indd6 Fonts: