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NDC 0703-6271-01 only , USP Synthetic 10 units/1 mL 1 mL Single Dose Vial IV Infusion or IM Dosage: See Package Insert Note: Oversized Vial Sterile sicor™ SICOR Pharmaceuticals, Inc. Irvine, CA 92618

00335A

Product Name: Oxytocin Injection, USP Part Number: Y29-003-35A Catalog Number: 6271-01 Labeling Component: Vial Label Drawing Specification Number: C-PK-LBL-2327, Rev. 1 Comments: Create labeling for new product.

Initiated By: Robert Herndon Department: Regulatory Affairs

Supercedes part number : New Label

Labeling Approvals Signature Date Regulatory Affairs Mirabelle Pao Packaging Engineering Pete Montalvo Quality Assurance Kristina McIntyre Marketing

Product Development

Research and Development

Other Approval

Store at controlled room NDC 0703-6275-03 only For intravenous infusion or . temperature 15°-30°C Oxytocin Each mL contains: Oxytocin activity equivalent to 10 USP (59°-86°F). Oxytocin Units; 5.25 mg Chlorobutanol, NF (hemihydrate); Do not permit to freeze. Injection, USP Water for Synthetic Injection q.s. 100 units/10 mL Acetic acid may LOT/EXP CODE (10 units/mL) have been added PLACE HOLDER for pH adjustment. (NO TEXT) 10 mL Multiple Dose Vial Sterile IMPRINTED ON-LINE sicor™ IV Infusion or IM Usual Dosage: SICOR Pharmaceuticals, Inc. 10 Vials See Package Irvine, CA 92618 Insert. 00338A PROOFING COPY

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Store at controlled For intravenous infusion or intramuscular room temperature NDC 0703-6275-01 only injection. 15°-30°C (59°-86°F). Oxytocin Each mL contains: Oxytocin activity Do not permit to equivalent to 10 USP Oxytocin Units; freeze. Injection, USP 5.25 mg Chlorobutanol, NF Synthetic (hemihydrate); Water for Injection q.s. Acetic acid may have been 100 units/10 mL added for pH (10 units/mL) adjustment. Sterile 10 mL Multiple Dose Vial Usual IV Infusion or IM Dosage: sicor™ See Package SICOR Pharmaceuticals, Inc., Irvine, CA 92618 Insert. 00336A

Product Name: Oxytocin Injection, USP Part Number: Y29-003-36A Catalog Number: 6275-01 Labeling Component: Vial Label Drawing Specification Number: C-PK-LBL-2322, Rev. 1 Comments: Revised Temp pee FDA letter.

Initiated By: Robert Herndon Department: Regulatory Affairs

Supercedes part number : New Label

Labeling Approvals Signature Date Regulatory Affairs Mirabelle Pao Packaging Engineering Pete Montalvo Quality Assurance Kristina McIntyre Marketing

Product Development

Research and Development

Other Approval Package Insert only Postpartum Oxytocin has been shown to have an intrinsic antidiuretic Oxytocin injection (synthetic) is indicated to produce effect, acting to increase water reabsorption from the glomerular filtrate. Consideration should, therefore, Oxytocin uterine contractions during the third stage of labor and to control or hemorrhage. be given to the possibility of water intoxication, Injection, USP particularly when oxytocin is administered continuously (Synthetic) CONTRAINDICATIONS by infusion and the patient is receiving fluids by FOR INTRAVENOUS INFUSION OR INTRAMUSCULAR USE mouth. Oxytocin injection (synthetic) is contraindicated in DESCRIPTION any of the following conditions: Drug Interactions Each mL of oxytocin injection, USP (synthetic), • Significant cephalopelvic disproportion; Severe has been reported when oxytocin intended for intravenous infusion or intramuscular was given three to four hours following prophylactic injection, possesses an oxytocic activity equivalent • Unfavorable fetal positions or presentations which administration of a vasoconstrictor in conjunction to 10 USP oxytocin units and contains 5.25 mg are undeliverable without conversion prior to with caudal block anesthesia. Cyclopropane Chlorobutanol, NF (hemihydrate). This product delivery, i.e., transverse lies; anesthesia may modify oxytocin’s cardiovascular may contain up to 12.5% decomposition products/ • In obstetrical emergencies where the benefit-to- effects, so as to produce unexpected results such impurities. Oxytocin injection (synthetic) is a sterile, risk ratio for either the or the mother favors as hypotension. Maternal sinus bradycardia with clear, colorless solution of oxytocin in Water for surgical intervention; abnormal atrioventricular rhythms has also been Injection prepared by synthesis. Acetic acid may noted when oxytocin was used concomitantly with • In cases of where delivery is not have been added for pH adjustment (pH 3.0-5.0) The cyclopropane anesthesia. structural formula is: imminent; Carcinogenesis, Mutagenesis, Impairment of • Prolonged use in uterine inertia or severe toxemia; H-Cys-Tyr-lle-Glu (NH2)-Asp(NH2)-Cys-Pro-Leu-Gly-NH2 Fertility • Hypertonic uterine patterns; 1 2 3 4 5 6 7 8 9 There are no animal or human studies on the • Patients with hypersensitivity to the drug; carcinogenicity and mutagenicity of this drug, nor is CLINICAL PHARMACOLOGY • Induction or augmentation of labor in those cases there any information on its effect on fertility. Oxytocin injection (synthetic) acts on the smooth where vaginal delivery is contraindicated, such Pregnancy Category C muscle of the uterus to stimulate contractions; as cord presentation or prolapse, total placenta There are no known indications for use in the first response depends on the uterine threshold of previa, and vasa previa. excitability. It exerts a selective action on the smooth and second trimester of pregnancy other than in musculature of the uterus, particularly toward the WARNINGS relation to spontaneous or induced abortion. Based end of the pregnancy, during labor and immediately on the wide experience with this drug and its following delivery. Oxytocin stimulates rhythmic Oxytocin injection (synthetic), when given for chemical structure and pharmacological properties, contractions of the uterus, increases the frequency induction of labor or stimulation of labor, must be it would not be expected to present a risk of fetal of existing contractions and raises the tone of the administered only by the intravenous route and with abnormalities when used as indicated. adequate medical supervision in a hospital. uterine musculature. Synthetic oxytocin does not Nonteratogenic Effects possess the cardiovascular effects, such as elevation PRECAUTIONS of blood pressure, as exhibited by found See ADVERSE REACTIONS in the fetus or . in posterior pituitary injection. General Labor and Delivery All patients receiving intravenous oxytocin must be INDICATIONS AND USAGE See INDICATIONS AND USAGE section. under continuous observation by trained personnel Nursing Mothers IMPORTANT NOTICE with a thorough knowledge of the drug and qualified Oxytocin injection, USP (synthetic) is indicated to identify complications. A physician qualified to It is not known whether this drug is excreted in for the medical rather than the elective induction manage any complications should be immediately human milk. Because many drugs are excreted of labor. Available data and information are available. in human milk, caution should be exercised when inadequate to define the benefits to risks When properly administered, oxytocin should stimulate oxytocin is administered to a nursing woman. considerations in the use of the drug product for uterine contractions similar to those seen in normal ADVERSE REACTIONS elective induction. Elective induction of labor is labor. Overstimulation of the uterus by improper defined as the initiation of labor for convenience administration can be hazardous to both mother and The following adverse reactions have been reported in an individual with term pregnancy who is free of fetus. Even with proper administration and adequate in the mother: medical indications. supervision, hypertonic contractions can occur in Anaphylactic reaction patients whose uteri are hypersensitive to oxytocin. Postpartum hemorrhage Except in unusual circumstances, oxytocin should Antepartum not be administered in the following conditions: Cardiac Premature ventricular Oxytocin injection (synthetic) is indicated for the prematurity, borderline cephalopelvic disproportion, contractions initiation or improvement of uterine contractions, previous major surgery on the cervix or uterus including where this is desirable and considered suitable, in Fatal afibrinogenemia Pelvic hematoma , overdistension of the uterus, grand order to achieve early vaginal delivery for fetal or multiparity or invasive cervical . Because of Excessive dosage or hypersensitivity to the drug maternal reasons. It is indicated for (1) induction of the variability of the combinations of factors which may result in uterine hypertonicity, spasm, tetanic labor in patients with a medical indication for the may be present in the conditions listed above, the contraction, or rupture of the uterus. initiation of labor, such as Rh problems, maternal definition of “unusual circumstances” must be left to The possibility of increased blood loss and diabetes, preeclampsia at or near term, when the judgment of the physician. The decision can only afibrinogenemia should be kept in mind when delivery is in the best interests of mother and fetus be made by carefully weighing the potential benefits administering the drug. or when membranes are prematurely ruptured and which oxytocin can provide in a given case against delivery is indicated; (2) stimulation or reinforcement Severe water intoxication with convulsions and coma rare but definite potential for the drug to produce of labor, as in selected cases of uterine inertia; (3) as has occurred, and is associated with a slow oxytocin hypertonicity or tetanic spasm. adjunctive therapy in the management of incomplete infusion over a 24-hour period. Maternal due or inevitable abortion. In the first trimester, curettage Maternal due to hypertensive episodes, to oxytocin-induced water intoxication has been is generally considered primary therapy. In second , rupture of the uterus, and reported. trimester abortion, oxytocin infusion will often be fetal deaths due to various causes have been reported successful in emptying the uterus. Other means of associated with the use of parenteral oxytocic drugs therapy, however, may be required in such cases. for induction of labor and for augmentation in the first and second stages of labor. ™ only  sicor

Y36-001-19A Oxytocin Injection, USP (Synthetic) The following adverse reactions have been reported fetal distress. Oxygen should be administered to the in the fetus or infant: mother. The mother and fetus must be evaluated by Due to induced Due to use of oxytocin the responsible physician. uterine mobility: in the mother: Control of Postpartum Uterine Bleeding Intravenous infusion (drip method) Bradycardia Neonatal retinal hemorrhage To control postpartum bleeding, 10 to 40 units of oxytocin may be added to 1,000 mL of a nonhydrating Premature ventricular Low Apgar scores diluent and run at a rate necessary to control uterine contractions and at five minutes atony. other Intramuscular administration Permanent CNS or Neonatal jaundice 1 mL (10 units) of oxytocin can be given after the delivery of the placenta. Fetal death Treatment of Incomplete or Inevitable Abortion OVERDOSAGE Intravenous infusion with physiologic saline solution, Overdosage with oxytocin injection (synthetic) 500 mL, or 5% dextrose in physiologic saline solution depends essentially on uterine hyperactivity to which 10 units of oxytocin have been added should whether or not due to hypersensitivity to this be infused at a rate of 20 to 40 drops/minute. agent. Hyperstimulation with strong (hypertonic) or Parenteral drug products should be inspected prolonged (tetanic) contractions, or a resting tone of visually for particulate matter and discoloration prior 15 to 20 mm H20 or more between contractions can to administration, whenever solution and container lead to tumultuous labor, , cervical permit. and vaginal lacerations, postpartum hemorrhage, uteroplacental hypoperfusion, and variable HOW SUPPLIED deceleration of fetal heart, fetal hypoxia, hypercapnia or death. Water intoxication with convulsions, which Oxytocin Injection, USP (Synthetic) is available as is caused by the inherent antidiuretic effect of follows: oxytocin, is a serious complication that may occur if NDC Number Oxytocin Injection, USP large doses (40 to 50 milliunits/minute) are infused 0703-6271-04 1 mL single dose vials packaged for long periods. Management consists of immediate 25 per shelf pack discontinuation of oxytocin, and symptomatic and supportive therapy. 0703-6275-03 10 mL multiple dose vials packaged 10 per shelf pack DOSAGE AND ADMINISTRATION Discard unused portion. Dosage of oxytocin is determined by uterine response. Use only if solution is clear & seal intact. The following dosage information is based upon various regimens and indications in general use. STORAGE Induction or Stimulation of Labor Store at controlled room tempertature 15°-30°C Intravenous infusion (drip method) is the only (59°-86°F). acceptable method of administration for the Do not permit to freeze. induction or stimulation of labor. Accurate control of the rate of infusion flow is Issued: February 2006 essential. An infusion pump or other such device sicor™ and frequent monitoring of strength of contractions SICOR Pharmaceuticals, Inc. and fetal are necessary for the safe Irvine, CA 92618 administration of oxytocin for the induction or stimulation of labor. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane. An intravenous infusion of a non-oxytocin containing solution should be started. Physiologic electrolyte solutions should be used except under unusual circumstances. To prepare the usual solution for the intraveneous infusion-one mL (10 units) is combined aseptically with 1,000 mL of a non-hydrating diluent. The combined solution, rotated in the infusion bottle to insure thorough mixing, contains 10 mU/mL. Add the container with dilute oxytocic solution to the system through the use of a constant infusion pump or other such device to control accurately the rate of infusion. The inital dose should be no more than 1 to 2 mU/min. The dose may be gradually increased in increments of no more than 1 to 2 mU/min., until a contraction pattern has been established which is similar to normal labor. The fetal heart rate, resting uterine tone, and the frequency, duration, and force of contractions should be monitored. The oxytocin infusion should be discontinued immediately in the event of uterine hyperactivity or

Store at controlled NDC 0703-6271-04 only For intravenous infusion or intramuscular injection. room temperature Each mL contains: Oxytocin activity equivalent to 10 USP 15°-30°C (59°-86°F). Oxytocin Oxytocin Units; 5.25 mg Chlorobutanol, NF (hemihydrate); Do not permit to freeze. Injection, USP Water for Injection q.s. Acetic acid may have been added for pH Synthetic adjustment. 10 units/1 mL Sterile Usual 1 mL Single Dose Vial Dosage: IV Infusion or IM See Package Insert. sicor™ Note: Oversized Vial SICOR Pharmaceuticals, Inc. 25 Vials Irvine, CA 92618 00337A