Oxytocin

1007.19

1006.436462

200-048-4

1JQS135EYN

DTXSID8048361

C724

White powder

H - Systemic hormonal preparations, excl. sex hormones and insulins

2937190000

450.13000

-4.26

White lyophilized powder

1.3±0.1 g/cm3

192-194°C

1533.3±65.0 °C at 760 mmHg

881.1±34.3 °C

1.554

soluble in water.

2-8°C

0.0 mm Hg at 25 °C (est)

LD50 oral in rat: > 20520ug/kg

D22 -26.2° (c = 0.53)

303.8 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|294.98 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|298.97 Ų [M-H]- [CCS Type: DT, Method: stepped-field]|297.9 Ų [M-H]-

Shows an activity of 450-500 USP units/mg when compared with USP posterior pituitary reference std|Oxytocin from beef and hog sources shows no difference in amino acid composition|Hydroxyl radical reaction rate constant = 5.3X10-10 cu cm/molec-sec at 25 °C (est)

II

6.1(a)

3249

3

36/37/38

26-36

RS7534000

Xi

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Oxytocin injection appears to be compatible with most iv infusion fluids but is reported to be physically incompatible with fibrinolysin, norepinephrine bitartrate, prochlorperazine edisylate, and warfarin sodium. Oxytocin injection has also been reported to be incompatible with various other drugs, but the compatibility depends on several factors (eg, the concentration of the drugs, resulting pH, temperature). Specialized references should be consulted for more specific compatibility information.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including oxytocin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Oxytocin is included on this list.|Oxytocin may be used as a uterine contractor to precipitate and accelerate normal parturition and postpartum evacuation of uterine debris. In surgery it may be used postoperatively following cesarean section to facilitate involution and resistance to the large inflow of blood. It will contract smooth muscle cells of the mammary gland for milk letdown if the udder is in proper physiological state. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian.

|Danger|H300 (40%): Fatal if swallowed [Danger Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P310, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 49 companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Engineering controls such as exhaust ventilation are recommended.|Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|/Use/ safety goggles or glasses /and/ protect exposed skin.

May cause irritation. Avoid contact. Avoid inhalation. Remove to fresh air.

Severe hypertension has been reported when oxytocin was given 3-4 hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia.|Cyclopropane anesthesia may modify oxytocin's cardiovascular effects, producing less pronounced tachycardia but more severe hypotension than occurs with oxytocin alone; maternal sinus bradycardia with abnormal atrioventricular rhythms has been noted when oxytocin was used concomitantly with cyclopropane anesthesia.|Oxytocin reportedly has delayed induction of thiopental anesthesia by producing venous spasm that caused peripheral pooling of thiopental; however, this interaction has not been conclusively established.

A hormone secreted by the posterior lobe of the pituitary gland. Its chief action is stimulation of the contraction of the smooth muscle of the uterus. It contains eight different amino acids.

Samples of human milk obtained from lactating women in the early postpartum period were assayed for oxytocin concentrations by specific RIA, following extraction procedures with Florisil. Mean oxytocin concentrations in human milk at postpartum day 1 to 5 were 4.5 +/- 1.1, 4.7 +/- 1.1, 4.0 +/- 1.3, 3.2 +/- 0.4, 3.3 +/- 0.6 microunits/mL (+/- SE), respectively. Oxytocin levels in milk were significantly increased by nursing (3.1 +/- 0.6, 5.3 +/- 1.0 microunits/mL, respectively). 3H-oxytocin in human milk was stable even after incubation at 37 degrees C for 2 hours. The dilution curve for milk was parallel to the curve for the standard oxytocin. The chromatographic fraction of immunoreactive oxytocin was identical to that of 3H-oxytocin. 3H-oxytocin was administered to lactating rats. Radioactivity in the neonatal gastric contents and plasma were 12.8% and 4.4% of the counts in the maternal plasma. It was made clear that oxytocin is stable in milk and that oxytocin in maternal blood can be transferred to milk and then to neonates.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 2,515 workers (1,568 of these were female) were potentially exposed to oxytocin in the US(1).

Oxytocin is indicated for the medical rather than the elective induction of labor. Available data and information are inadequate to define the benefits-to-risks considerations in the use of the drug product for elective induction. Elective induction of labor is defined as the initiation of labor for convenience in an individual with a term pregnancy who is free of medical indications. /Included in US product label/|Oxytocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve early vaginal delivery. It is indicated for induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is indicated... /Included in US product label/|Oxytocin is indicated for stimulation or reinforcement of labor, as in selected cases of uterine inertia... /Included in US product label/|Oxytocin is indicated as adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. /Included in US product label/|For more Therapeutic Uses (Complete) data for Oxytocin (11 total), please visit the HSDB record page.

When oxytocin is administered in excessive dosage, with abortifacients or to sensitive patients, hyperstimulation of the uterus, with strong (hypertonic) and/or prolonged (tetanic) contractions, or a resting uterine tone of 15-20 mm H2O between contractions may occur, possibly resulting in uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, abruptio placentae, impaired uterine blood flow, amniotic fluid embolism, and fetal trauma including intracranial hemorrhage.|Increased uterine motility may cause adverse fetal effects, including sinus bradycardia, tachycardia, premature ventricular complexes and other arrhythmias, permanent CNS or brain damage, and death secondary to asphyxia. Excessive maternal dosage or administration of the drug to sensitive women also can cause uteroplacental hypoperfusion and variable deceleration of fetal heart rate, fetal hypoxia, perinatal hepatic necrosis, and fetal hypercapnia. Rare incidents of pelvic hematoma have been reported, but these were probably also related to the high incidence of operative vaginal deliveries in primiparas, the fragility of engorged pelvic veins (especially if varicosed), and faulty episiotomy repair.|When large amounts of oxytocin are administered, severe decreases in maternal systolic and diastolic blood pressure, increases in heart rate, systemic venous return and cardiac output, and arrhythmia may occur; these effects may be particularly hazardous to patients with valvular heart disease and those receiving spinal and epidural anesthesia.|Postpartum bleeding may be increased by administration of oxytocin; this effect may be related to reports of oxytocin-induced thrombocytopenia, afibrinogenemia, and hypoprothrombinemia. By carefully controlling delivery, the incidence of postpartum bleeding may be minimized.|For more Drug Warnings (Complete) data for Oxytocin (22 total), please visit the HSDB record page.

Drugs that stimulate contraction of the myometrium. They are used to induce LABOR, OBSTETRIC at term, to prevent or control postpartum or postabortion hemorrhage, and to assess fetal status in high risk pregnancies. They may also be used alone or with other drugs to induce abortions (ABORTIFACIENTS). Oxytocics used clinically include the neurohypophyseal hormone OXYTOCIN and certain prostaglandins and ergot alkaloids. (From AMA Drug Evaluations, 1994, p1157) (See all compounds classified as Oxytocics.)

Oxytocin is destroyed by chymotrypsin in the GI tract. Uterine response occurs almost immediately and subsides within 1 hour following iv administration of oxytocin. Following im injection of the drug, uterine response occurs within 3-5 minutes and persists for 2-3 hours. Following intranasal application of 10-20 units of oxytocin (nasal preparations are no longer commercially available in the US), contractions of myoepithelial tissue surrounding the alveoli of the breasts begin within a few minutes and continue for 20 minutes; iv oxytocin produces the same effect with a dose of 100-200 milliunits.|Like vasopressin, oxytocin is distributed throughout the extracellular fluid. Small amounts of oxytocin probably reach the fetal circulation.|It is not known whether this drug is excreted in human milk.|Its rapid removal from plasma is accomplished largely by the kidney and the liver. Only small amounts oxytocin are excreted in the urine unchanged.|For more Absorption, Distribution and Excretion (Complete) data for Oxytocin (7 total), please visit the HSDB record page.

Oxytocinase, a circulating enzyme produced early in pregnancy, is also capable of inactivating the polypeptide.|During pregnancy ... "oxytocinase" ... is capable of inactivating oxytocin by cleavage of the 1-cysteine to 2-tyrosine peptide bond.

Oxytocin has a plasma half-life of about 3 to 5 minutes.

The pharmacologic and clinical properties of oxytocin are identical with those of naturally occurring oxytocin principle of the posterior lobe of pituitary. Oxytocin exerts a selective action on the smooth musculature of the uterus, particularly toward the end of pregnancy, during labor, and immediately following delivery. Oxytocin stimulates rhythmic contractions of the uterus, increases the frequency of existing contractions, and raises the tone of the uterine musculature.|Oxytocin indirectly stimulates contraction of uterine smooth muscle by increasing the sodium permeability of uterine myofibrils. High estrogen concentrations lower the threshold for uterine response to oxytocin. Uterine response to oxytocin increases with the duration of pregnancy and is greater in patients who are in labor than those not in labor; only very large doses elicit contractions in early pregnancy. Contractions produced in the term uterus by oxytocin are similar to those occurring during spontaneous labor. In the term uterus, oxytocin increases the amplitude and frequency of uterine contractions which in turn tend to decrease cervical activity producing dilation and effacement of the cervix and to transiently impede uterine blood flow.|Oxytocin contracts myoepithelial cells surrounding the alveoli of the breasts, forcing milk from the alveoli into the larger ducts and thus facilitating milk ejection. The drug possesses no galactopoietic properties.|Oxytocin produces vasodilation of vascular smooth muscle, increasing renal, coronary, and cerebral blood flow. Blood pressure is usually unchanged, but following iv administration of very large doses or undiluted solutions, blood pressure may decrease transiently, and tachycardia and an increase in cardiac output may be reflexly induced. Any initial fall in blood pressure is usually followed by a small but sustained increase in blood pressure. In contrast to vasopressin, oxytocin has minimal antidiuretic effects; however, water intoxication may occur when oxytocin is administered with an excessive volume of electrolyte-free iv fluids and/or at too rapid a rate.|For more Mechanism of Action (Complete) data for Oxytocin (15 total), please visit the HSDB record page.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ ... Thirty-eight healthy women scheduled for a surgical suction curettage with general anesthesia were enrolled /in this study/ to assess the effect of oxytocin on QT interval. General anesthesia was induced by propofol and maintained by either propofol (n = 18) or sevoflurane (n = 20). Electrocardiographic recordings were obtained before and at 1, 2, 3, and 5 minutes after a 10-U intravenous bolus of oxytocin. Intravenous oxytocin induced a pronounced QTc interval prolongation of 41 +/- 21 ms ( P < 0.0001), which was maximal 1 minute after administration. The QTc interval returned to control values 3 minutes after oxytocin bolus. Oxytocin bolus also induced an increase in heart rate of 19 +/- 10 beats/min and a significant decrease in systolic arterial pressure of 11 +/- 9 mm Hg (both P < 0.0001). The drug used to maintain anesthesia was not an independent factor of QT interval prolongation in ANOVA analysis. Oxytocin intravenous bolus induced a large and transient QTc interval prolongation, suggesting that it may lead to proarrhythmia in circumstances favoring QTc interval increase.|/HUMAN EXPOSURE STUDIES/ ... In humans, oxytocin has been found to enhance trust and the ability to interpret the emotions of others. It has been suggested that oxytocin may enhance facial processing by increasing focus on the eye region of human faces. In a double-blind, randomized, placebo-controlled, between-subject design, /investigators/ tracked the eye movements of 52 healthy male volunteers who were presented with 24 neutral human faces after intranasal administration of 24 IU oxytocin or placebo. Participants given oxytocin showed an increased number of fixations and total gaze time toward the eye region compared with placebo participants. Oxytocin increases gaze specifically toward the eye region of human faces. This may be one mechanism by which oxytocin enhances emotion recognition, interpersonal communication, and social approach behavior in humans. Findings suggest a possible role for oxytocin in the treatment of disorders characterized by eye-gaze avoidance and facial processing deficits.|/HUMAN EXPOSURE STUDIES/ The aim of the work was to compare labor courses, ways of delivery, condition of the newborns in spontaneous and oxytocin-related labors and to analyse the indications for oxytocin administration. 2198 full-term deliveries (pregnant women qualified for elective caesarean section were excluded from the study) at the Provincial Hospital in Przemys'l, Poland. Labors with the adjunctive oxytocin infusion--1102 women. Spontaneous labors (without oxytocin administration)--1096 women. The analysis of the compatibility of measured traits was carried out by the Chi-squared test (Chi2), p < 0.05 was assumed as statistically significant level. Indications for the oxytocin administration: secondary hypokinetic contractions of the uterus (642 labors--58.25%), premature rupture of membranes (176 labors - 15.97 %). Deliveries by caesarean section: 1. study group--187 women (16.97%). 2. control group--97 women (8.85%). Chi2 = 32.192; df = 1; p = 0.0000. Newborns after vaginal labors scored 7 or below according to the Apgar in the first minute after the delivery. 1. study group--35 newborns (8.7%); 2. control group--18 newborns (1.8%) Chi2 = 5.493; df = 1; p = 0.0190. Newborns hospitalized for over 48 hours: 1. study group--346 (31.39%); 2. control group--216 newborns (19.70%). Chi2 = 39.454; df = 1; p = 0.0000. Hypokinetic uterine contractions were the most frequent indication for oxytocin administration during labor. Oxytocin administration increases twice the risk of delivery by the caesarean section. Newborns after vaginal oxytocin-related labours scored 7 or below on the Apgar score in the first minute after the birth when compared to the newborns after spontaneous labor. Oxytocin administration during parturition elongates the time of newborns hospitalization.|/HUMAN EXPOSURE STUDIES/ Oxytocin (OT) effect on ghrelin-stimulated neuropeptide Y (NPY) secretion was evaluated in 12 normal men. Tests: ghrelin (1 ug/kg B.W. as an intravenous bolus); OT (2 mIU/min infusion); ghrelin plus OT; normal saline. Plasma NPY did not change during saline or OT infusions, whereas it showed a significant 29% increase vs baseline at 15 min after ghrelin injection. When OT was present, ghrelin-induced NPY increment was completely abolished. Results show that oxytocin modulates the NPY response to ghrelin, whereas it is unable to produce direct inhibitions of basal circulating NPY levels.|For more Human Toxicity Excerpts (Complete) data for Oxytocin (21 total), please visit the HSDB record page.

Ocytocin

Oxytocin injection, USP ... contains 10 USP units per mL and may be administered iv or im. All commercial preparations are now synthetic.|... injection, USP

Each mL of posterior pituitary injection NF possesses oxytocic activity equivalent to 10 USP posterior pituitary units (permissible range, 8.5-12 units) ... /Posterior pituitary/|The hypotensive response of the chicken is the basis for the USP bioassay for oxytocin.

Analyte: oxytocin; matrix: chemical identification; procedure: retention time of the peak in the liquid chromatogram with comparison to standards|Analyte: oxytocin; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 220 nm and comparison to standards|Analyte: oxytocin; matrix: pharmaceutical preparation (injection solution; nasal solution); procedure: liquid chromatography with ultraviolet detection at 220 nm and comparison to standards (chemical purity)|USE OF HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY IN THE QUALITY CONTROL OF OXYTOCIN.|ANALYSIS OF OXYTOCIN IN PHARMACEUTICAL DOSAGE FORMS OR IN SYNTHETIC & NATURAL PRODUCTS BY GRADIENT ELUTION HIGH-PRESSURE LIQUID CHROMATOGRAPHY.

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