5AN - - - - - - /Revised: October 2016 change in weight (increase or decrease) pain, irritation, swelling, and/or redness at the injection area yellow discoloration of skin or white eyes skin reactions including rash, hives, itching, and swelling reac allergic) (life-threatening anaphylactoid tion with symptoms that may include a sense of uneasiness or apprehension; flushing; fast, throbbing heartbeat; itching; hives; difficult breathing; swelling of the throat; fainting; nausea; vomiting; or convulsions. If you are allergic to progesterone, proges terone-like drugs, benzyl alcohol or sesame oil/seeds. vaginal bleedingwhich have unusual Ifyou has not been evaluated by your doctor. If you have known or suspected cancer of the breast or genital organs. If you have a miscarriage and your physician suspects some tissue is still in the uterus. If you have or had blood clots in the legs, lungs, eyes, or elsewhere. breast tenderness, discharge from the nipple Patient Information When you do not produce enough proges If you experience sleepiness, do not drive or If you experience sleepiness, do not drive or operate machinery. For intramuscular use only. FOR THE TREATMENT OF AMENORRHEA FOR THE TREATMENT OF AMENORRHEA (ABSENCE OF MENSES IN WOMEN WHO HAVE PREVIOUSLY HAD A MENSTRUAL PERIOD) OR ABNORMAL UTERINE BLEEDING DUE TO HORMONAL IMBALANCE. Please read this information carefully before you start to use Progesterone Injection and each time your prescription is renewed, in case any thing has changed. This leaflet does not take the place of discussions with your doctor. If you still have any questions, ask your doctor or health-care provider. About Progesterone Injection Progesterone Injection is a sterile injectable solution containing the natural female hormone called progesterone. Progesterone Injection is indicated for the treatment of amenorrhea and due to progesterone abnormal uterine bleeding deficiency. Understanding the role of Progesterone Injection in the treatment of your menstrual irregularities. Progesterone is one of the hormones essential has doctor your If periods. menstrual regular for determined your body does not produce enough Injection Progesterone on its own, progesterone may be prescribed to provide the progesterone you need. Injection, USP terone, menstrual irregularities can occur. Pro gesterone Injection can provide you with the progesterone needed during a normal menstrual cycle. Possible side effects of Progesterone Injection reported been have effects side following The with Progesterone Injection. Consult your doc tor if you experience any of the side effects mentioned below, or other side effects. • breakthrough bleeding • spotting • changes in menstrual flow • amenorrhea • • • general swelling • vaginal discharge • • • • acne • hair loss or growth of new • mental depression • fever • insomnia or sleepiness* • nausea • * When you should not use Progesterone Injection • • • If you have liver disease. • • • 45919F Progesterone DESCRIPTION: Metabolism 2. Liver dysfunction or disease. bination treatment. The mechanism of The following adverse reactions have Progesterone injection, a progestin, is Progesterone is metabolized primarily in 3. Known or suspected malignancy of this decrease is obscure. For this rea- been observed in patients receiving a sterile solution of progesterone in a the liver by reduction to pregnanediol, breast or genital organs. son, diabetic patients should be carefully estrogen-progestin combination drugs: suitable vegetable oil available for intra- pregnanetriol and pregnanolone. Subse- 4. Undiagnosed vaginal bleeding. observed while receiving such therapy. Rise in blood pressure in susceptible indi- muscular use. quent conjugation results in the formation 5. Missed abortion. Carcinogenesis, Mutagenesis, Impair- vidual, premenstrual syndrome, changes Progesterone occurs as a white or of glucuronide and sulfate metabolites. 6. Known sensitivity to progesterone ment of Fertility in libido, changes in appetite, cystitis-like creamy white, crystalline powder. It is The mean plasma metabolic clearance injection. Long-term intramuscular administration syndrome, headache, nervousness, odorless and is stable in air. Practically rate in cycling women is 2510 ± 135 WARNINGS: of Medroxy progesterone acetate (MPA) fatigue, backache, hirsutism, loss of scalp insoluble in water, it is soluble in alco- (SEM) L/day. The physician should be alert to the earli- has been shown to produce mammary hair, erythema multiforme, erythema hol, acetone, and dioxane and sparingly nodosum, hemorrhagic eruption, itching, m Excretion est manifestations of thrombotic disor- tumors in beagle dogs. There is no evi- soluble in vegetable oils. ders (thrombophlebitis, cerebrovascular dence of a carcinogenic effect associated and dizziness. It has the following structural formula: The glucuronide and sulfate conjugates The following laboratory results may be of pregnanediol and pregnanolone are disorders, pulmonary embolism, and with the oral administration of MPA to rats retinal thrombosis). Should any of these altered by the use of estrogen-progestin CH excreted in the urine and bile. Progester- and mice. 3 occur or be suspected, the drug should Medroxyprogesterone acetate was not combination drugs: increased sulfobro- one metabolites which are excreted in the mophthalein retention and other hepatic CO bile may undergo enterohepatic recycling be discontinued immediately. mutagenic in a battery of in vitro or in vivo Medication should be discontinued function tests; coagulation tests: increase CH3 or may be excreted in the feces. genetic toxicity assays. H pending examination if there is a sud- Progesterone at high doses is an anti- in prothrombin factors VII, VIII, IX, and X; The pharmacokinetic data was deter- metyrapone test; pregnanediol determi- mined in a small number of patients, lim- den partial or complete loss of vision, or if fertility drug and high doses would be there is a sudden onset of proptosis, dip- expected to impair fertility until the ces- nations; thyroid function: increase in PBI, CH H iting the precision in which population 3 lopia or migraine. If examination reveals sation of treatment. and butanol extractable protein bound values may be estimated. iodine and decrease in T3 papilledema or retinal vascular lesions, Geriatric Use uptake values. Special Populations medication should be withdrawn. H H The safety and effectiveness in geriat- DOSAGE AND ADMINISTRATION: Renal Insufficiency PRECAUTIONS: ric patients (over age 65) have not been Progesterone is administered by intra- O The safety and effectiveness in patients General established. muscular injection. It differs from other with renal insufficiency have not been The pretreatment physical examination Pediatric Use commonly used steroids in that it is irritat- C21H30O2 M.W. 314.47 established. Since progesterone metabo- should include special reference to breast ing at the place of injection. lites are excreted mainly by the kidneys, Safety and effectiveness in pediatric Pregn-4-ene-3, 20-dione and pelvic organs, as well as a Papanico- Amenorrhea progesterone should be administered patients have not been established. laou smear. Five to 10 mg are given for six to eight 45918F/Revised: October 2016 with caution and careful monitoring in this Nursing Mothers Each mL contains: Progesterone 50 mg, Because progestational drugs may consecutive days. If there has been suf- patient population (see PRECAUTIONS). Detectable amounts of drug have been benzyl alcohol 10% as preservative in cause some degree of fluid retention, ficient ovarian activity to produce a pro- sesame oil q.s. conditions which might be influenced by identified in the milk of mothers receiv- Progesterone Hepatic Insufficiency ing progestational drugs. The effect of liferative endometrium, one can expect The safety and effectiveness in patients this condition, such as epilepsy, migraine, withdrawal bleeding 48 to 72 hours after Injection, USP CLINICAL PHARMACOLOGY: asthma, cardiac, or renal dysfunction, this on the nursing infant has not been IN SESAME OIL with hepatic insufficiency have not been determined. the last injection. This may be followed Transforms proliferative endometrium into established. Since progesterone is require careful observation. by spontaneous normal cycles. secretory endometrium. metabolized by the liver, use in patients In cases of breakthrough bleeding, ADVERSE REACTIONS: Inhibits (at the usual dose range) the as in all cases of irregular bleeding per Breakthrough bleeding; spotting; change Functional Uterine Bleeding with liver dysfunction or disease is contra- Five to 10 mg are given daily for six secretion of pituitary gonadotropins, indicated (see CONTRAINDICATIONS). vaginum, nonfunctional causes should be in menstrual flow; amenorrhea; edema; which in turn prevents follic ular matura- borne in mind, and adequate diagnostic change in weight (increase or decrease); doses. Bleeding may be expected to tion and ovulation. Drug Interactions measures undertaken. changes in cervical erosion and cervical cease within six days. When estrogen The metabolism of progesterone by Patients who have a history of psychic secretions; cholestatic jaundice; breast is given as well, the administration of Pharmacokinetics and Metabolism human liver microsomes was inhibited depression should be carefully observed tenderness and galactorrhea; pain, irri- progesterone is begun after two weeks of estro gen therapy. If menstrual flow Absorption by ketoconazole (IC50 < 01