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    Labor Inducers

    BOXED WARNING

    Abnormal fetal position, cephalopelvic disproportion, cervical cancer, elective induction of labor, fetal distress, fetal prematurity, herpes infection, multiparity, placenta previa, surgery, uterine prolapse, vasa previa

    Parenteral oxytocin should be used only by qualified professional personnel in a setting where intensive care and surgical facilities are immediately available. Furthermore, according to the manufacturer, oxytocin should only be used when induction of labor is necessary for medical reasons. It should not be used for elective induction of labor as available data are insufficient to evaluate the risk-benefit ratio in this indication. During oxytocin administration, uterine contractions, fetal and maternal heart rate, maternal blood pressure, and, if possible, intrauterine pressure should be continuously monitored to avoid complications. If uterine hyperactivity occurs, oxytocin administration should be immediately discontinued; oxytocin-induced stimulation of the uterine contractions usually decreases soon after discontinuance of the drug. The induction or continuance of labor with oxytocin should be avoided when the following conditions or situations are present: evidence of fetal distress, fetal prematurity, abnormal fetal position (including unengaged head), placenta previa, uterine prolapse, vasa previa, cephalopelvic disproportion, cervical cancer, grand multiparity, previous surgery of the uterus or cervix (including 2 or more cesarean deliveries), active genital herpes infection, or in any condition presenting as an obstetric emergency requiring surgical intervention. Use of oxytocin in any of these settings can aggravate the condition or cause unnecessary fetal or maternal distress.

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral hormone with all the naturally occurring actions of endogenous oxytocin released from the posterior pituitary
    Used clinically to induce labor, aid in delivery of the placenta (third stage of labor), and control postpartum bleeding
    Used only in situations where vaginal delivery is acceptable

    COMMON BRAND NAMES

    Pitocin

    HOW SUPPLIED

    Oxytocin/Pitocin Intramuscular Inj Sol: 1mL, 10U
    Oxytocin/Pitocin Intravenous Inj Sol: 1mL, 10U

    DOSAGE & INDICATIONS

    For labor augmentation in patients with a medical necessity for labor induction, at or near to term, when delivery is in the best interests of the mother and the fetus.
    Intravenous dosage (low-dose continuous infusion)
    Adult females

    Start with 0.5 to 2 milliunits/minute via continuous IV infusion. The rate of infusion may be slowly increased (1 to 2 milliunits/minute increments at 15 to 60 minute intervals) until the required contraction pattern is established; the rate of infusion should be slowly decreased (1 to 2 milliunits/minute decrements at 15 to 60 minute intervals) when labor is established and progressed to 5 to 6 cm dilation. Patients with an unfavorable cervix may be more effectively induced using incremental increases of 2 milliunits/minute every 15 minutes. Low- and high-dose infusions, as well as pulsatile administration regimens, are considered acceptable by the ACOG. Low-dose regimens and less frequent increases in dose are associated with decreased uterine hyperstimulation.

    Intravenous dosage (high-dose continuous infusion)
    Adult females

    6 milliunits/minute via continuous IV infusion initially. The rate of infusion may be increased (6 milliunits/minute increments at 15 to 60 minute intervals) until the required contraction pattern is established. In the presence of uterine hyperstimulation, the infusion rate should be decreased to 3 milliunits/minute, and further reduced to 1 milliunits/minute with recurrent hyperstimulation. Low- and high-dose infusions, as well as pulsatile administration regimens, are considered acceptable by the ACOG. High-dose regimens and more frequent dose increases are associated with shorter labor and less frequent cases of chorioamnionitis and cesarian delivery for dystocia, but increased rates of uterine hyperstimulation.

    Intravenous dosage (pulsatile regimen)
    Adult females

    Give 1 milliunit oxytocin by intravenous injection every 8 to 10 minutes. Low- and high-dose infusions, as well as pulsatile administration regimens, are considered acceptable by the ACOG. Pulsatile administration of oxytocin is just as effective as continuous infusions, with a lower total amount of oxytocin being necessary to achieve similar results.

    For reduction and control of postpartum bleeding and to produce uterine contractions during the third stage of labor.
    Intravenous dosage
    Adult females

    10 to 40 units may be added to existing IV infusion (max concentration: 40 units added per 1,000 mL), after delivery of the placenta. The infusion rate must be adjusted to sustain uterine contraction and control uterine atony.

    Intramuscular dosage
    Adult females

    10 units IM after delivery of the placenta.

    For the adjunctive treatment of inevitable or incomplete abortion.
    Intravenous dosage
    Adult females

    10 to 20 milliunits/minute via continuous IV infusion. Do not exceed 30 units in a 12-hour period. Intravenous oxytocin is usually safe and effective for inducing labor for near term fetal demise, but is less effective remote from term.

    For the evaluation of fetal distress† using an oxytocin-induced contraction stress test (aka, oxytocin challenge test or CST)†.
    Intravenous dosage
    Adult females

    Protocols may vary slightly by institution. Following baseline monitoring for 20 to 30 minutes, initiate at a low dose (e.g., 0.5 to 2.33 milliunits/minute) via continuous IV infusion to the mother. Double the infusion rate every 10 to 30 minutes until the frequency of the contractions are 3 within a 10-minute period (1 contraction every 3 to 4 minutes) and the duration is 40 to 60 seconds. When the desired number of contractions is obtained, record fetal heart rate and contractions until sufficient, then discontinue the infusion. Compare baseline and oxytocin-induced recordings.

    †Indicates off-label use

    MAXIMUM DOSAGE

    No specific maximum dosage limit recommendations are available. Dosage regimens of oxytocin depend upon the patient's age, sex, weight, condition being treated, product chosen, and the prescribing clinician's judgment. Therefore, doses may vary widely and must be carefully individualized.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Injectable Administration

    Administer by intravenous infusion or intramuscular injection.
    Prior to administration, an IV infusion of 0.9% Sodium Chloride should be already running for use in case of adverse reactions.
    Magnesium sulfate should be readily available if relaxation of the myometrium is necessary.
    Visually inspect parenteral product for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Intravenous infusion:
    Induction of labor: Dilute 1 mL (10 units) in 1,000 mL of a compatible IV infusion solution. Rotate infusion bottle for thorough mixing. The resultant infusion should contain 10 milliunits/mL.
    Control of postpartum uterine bleeding: Dilute 10 to 40 units in a compatible IV solution or to an already infusing compatible IV solution. The maximum concentration is 40 units in 1,000 mL of solution.
    Incomplete, inevitable, or elective abortion: Dilute 10 units in 500 mL of a compatible IV solution.
    Administer using an infusion pump to ensure accurate dosing.

    Intramuscular Administration

    Intramuscular injection:
    Inject into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel.

    STORAGE

    Pitocin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Pregnancy

    Oxytocin is indicated during pregnancy to induce labor; it precipitates uterine contractions and abortion.

    Breast-feeding

    Endogenous oxytocin is involved in the process of lactation and therefore, oxytocin has been used in mothers having difficulty with engorgement and breast-feeding. Because several small studies have failed to show a beneficial effect, oxytocin is not used for this indication. Oxytocin is excreted in the breast-milk, but is not expected to have adverse effects in the infant.

    Abnormal fetal position, cephalopelvic disproportion, cervical cancer, elective induction of labor, fetal distress, fetal prematurity, herpes infection, multiparity, placenta previa, surgery, uterine prolapse, vasa previa

    Parenteral oxytocin should be used only by qualified professional personnel in a setting where intensive care and surgical facilities are immediately available. Furthermore, according to the manufacturer, oxytocin should only be used when induction of labor is necessary for medical reasons. It should not be used for elective induction of labor as available data are insufficient to evaluate the risk-benefit ratio in this indication. During oxytocin administration, uterine contractions, fetal and maternal heart rate, maternal blood pressure, and, if possible, intrauterine pressure should be continuously monitored to avoid complications. If uterine hyperactivity occurs, oxytocin administration should be immediately discontinued; oxytocin-induced stimulation of the uterine contractions usually decreases soon after discontinuance of the drug. The induction or continuance of labor with oxytocin should be avoided when the following conditions or situations are present: evidence of fetal distress, fetal prematurity, abnormal fetal position (including unengaged head), placenta previa, uterine prolapse, vasa previa, cephalopelvic disproportion, cervical cancer, grand multiparity, previous surgery of the uterus or cervix (including 2 or more cesarean deliveries), active genital herpes infection, or in any condition presenting as an obstetric emergency requiring surgical intervention. Use of oxytocin in any of these settings can aggravate the condition or cause unnecessary fetal or maternal distress.

    Eclampsia, uterine atony

    Oxytocin may possess antidiuretic effects, and prolonged use can increase the possibility of an antidiuretic effect. Prolonged use of oxytocin and administration in large volumes of low-sodium infusion fluids are not recommended, particularly in patients with eclampsia or who have unresponsive uterine atony. Antidiuretic effects have the potential to lead to water intoxication and convulsive episodes due to hypertension.

    ADVERSE REACTIONS

    Severe

    uterine rupture / Early / Incidence not known
    cervical laceration / Early / Incidence not known
    postpartum hemorrhage / Early / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    afibrinogenemia / Delayed / Incidence not known
    retinal hemorrhage / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    pulmonary edema / Early / Incidence not known
    coma / Early / Incidence not known
    water intoxication / Delayed / Incidence not known
    ocular hemorrhage / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    uterine contractions / Early / Incidence not known
    hematoma / Early / Incidence not known
    bleeding / Early / Incidence not known
    hypertension / Early / Incidence not known
    fetal bradycardia / Delayed / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known
    blurred vision / Early / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known

    Mild

    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Articaine; Epinephrine: (Major) Simultaneous use of epinephrine with oxytocics can cause severe, prolonged hypertension.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carbetapentane; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carbinoxamine; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Carboprost Tromethamine: (Major) Carboprost tromethamine may augment the activity of other oxytocics. Augmentation can result in uterine hypertonus with subsequent uterine rupture, particularly in the absence of adequate cervical dilation. The concurrent use of carboprost tromethamine and other oxytocic drugs is not recommended.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Chlorpheniramine; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Codeine; Phenylephrine; Promethazine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Diclofenac; Misoprostol: (Major) In certain cases, oxytocin can be used in combination with other oxytocics for therapeutic purposes. However, in the augmentation of labor, oxytocin administration is usually withheld until after the last dose of intravaginal misoprostol. There is a risk of severe uterine hypertony occurring, with possible uterine rupture or cervical laceration when misoprostol and oxytocin are used at the same time. These products should be used concomitantly only under adequate supervision, with particular attention to ensure adequate cervical dilation has occurred.
    Dinoprostone, Prostaglandin E2: (Major) In certain cases, oxytocin can be used in combination with other oxytocics for therapeutic purposes. There is a risk, however, of severe uterine hypertony occurring, with possible uterine rupture or cervical laceration. The concurrent use of dinoprostone, prostaglandin E2 and oxytocin is not recommended; following the removal of the dinoprostone vaginal insert, an interval of at least 30 minutes is recommended prior to the use of another oxytocic agent. These products should be used sequentially only under adequate obstetric supervision.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Diphenhydramine; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Dopamine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjuction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Ephedrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjuction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Epinephrine: (Major) Simultaneous use of epinephrine with oxytocics can cause severe, prolonged hypertension.
    Ergonovine: (Major) Ergonovine and oxytocin both control uterine atony, and if used in combination there may be a risk of severe uterine hypertony, with possible uterine rupture or cervical laceration.
    General anesthetics: (Major) Adverse cardiovascular effects can develop as a result of concomitant administration of oxytocin with general anesthetics, especially in those with preexisting valvular heart disease. Cyclopropane, when administered with or without oxytocin, has been implicated in producing maternal sinus bradycardia, abnormal atrioventricular rhythms, hypotension, and increases in heart rate, cardiac output, and systemic venous return. In addition, halogenated anesthetics decrease uterine responsiveness to oxytocics (e.g., oxytocin) and, in high doses, can abolish it, increasing the risk of uterine hemorrhage. Halothane is a potent uterine relaxant. Enflurane displaces the myometrial response curve to oxytocin so that at lower concentrations of enflurane oxytocin will restore uterine contractions. However, as the dose of enflurane progresses (somewhere between 1.5 to 3% delivered enflurane) the response to oxytocin is inhibited. It is not clear if other halogenated anesthetics would interact with oxytocics in this manner.
    Guaifenesin; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Hydrocodone; Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Methohexital: (Major) Adverse cardiovascular effects can develop as a result of concomitant administration of oxytocin with general anesthetics.
    Methylergonovine: (Major) Methylergonovine and oxytocin both control uterine atony, and if used in combination there may be a risk of severe uterine hypertony, with possible uterine rupture or cervical laceration.
    Midodrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjuction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Misoprostol: (Major) In certain cases, oxytocin can be used in combination with other oxytocics for therapeutic purposes. However, in the augmentation of labor, oxytocin administration is usually withheld until after the last dose of intravaginal misoprostol. There is a risk of severe uterine hypertony occurring, with possible uterine rupture or cervical laceration when misoprostol and oxytocin are used at the same time. These products should be used concomitantly only under adequate supervision, with particular attention to ensure adequate cervical dilation has occurred.
    Norepinephrine: (Moderate) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Phenylephrine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Phenylephrine; Promethazine: (Major) The administration of prophylactic vasopressors with oxytocin can cause severe, persistent hypertension, as the 2 drugs may have a synergistic and additive vasoconstrictive effect. This interaction was noted when oxytocin was given 3 to 4 hours after prophylactic vasoconstrictor in conjunction with caudal anesthesia. The incidence of such an interaction may be decreased if vasopressors are not administered prior to oxytocin.
    Prilocaine; Epinephrine: (Major) Simultaneous use of epinephrine with oxytocics can cause severe, prolonged hypertension.
    Thiopental: (Major) Adverse cardiovascular effects can develop as a result of concomitant administration of oxytocin with general anesthetics.

    PREGNANCY AND LACTATION

    Pregnancy

    Oxytocin is indicated during pregnancy to induce labor; it precipitates uterine contractions and abortion.

    Endogenous oxytocin is involved in the process of lactation and therefore, oxytocin has been used in mothers having difficulty with engorgement and breast-feeding. Because several small studies have failed to show a beneficial effect, oxytocin is not used for this indication. Oxytocin is excreted in the breast-milk, but is not expected to have adverse effects in the infant.

    MECHANISM OF ACTION

    Synthetic oxytocin elicits the same pharmacological response produced by endogenous oxytocin, with cervical dilation, parity, and gestational age as predictors of the dose response to oxytocin administration for labor stimulation. Oxytocin increases the sodium permeability of uterine myofibrils, indirectly stimulating contraction of the uterine smooth muscle. The uterus responds to oxytocin more readily in the presence of high estrogen concentrations and with the increased duration of pregnancy. There is a gradual increase in uterine response to oxytocin for 20 to 30 weeks gestation, followed by a plateau from 34 weeks of gestation until term, when sensitivity increases. Women who are in labor have a greater response to oxytocin compared to women who are not in labor; only very large doses will elicit contractions in early pregnancy. In the term uterus, contractions produced by exogenous oxytocin are similar to those that would occur during spontaneous labor. Oxytocin increases the amplitude and frequency of uterine contractions, which transiently impede uterine blood flow and decrease cervical activity, causing dilation and effacement of the cervix.
     
    Oxytocin causes contraction of the myoepithelial cells surrounding the alveolar ducts of the of the breast. This forces milk from the alveolar channels into the larger sinuses, and thus facilitates milk ejection. While oxytocin possesses no galactopoietic properties, if it is absent the milk-ejection reflex in the breast fails.
     
    Oxytocin causes dilation of vascular smooth muscle, thus increasing renal, coronary, and cerebral blood flow. Blood pressure usually remains unaffected, but with the administration of very large doses or high concentration solutions blood pressure may decrease transiently. This transient decrease in blood pressure leads to reflex tachycardia and an increase in cardiac output; any fall in blood pressure is usually followed by a small, but sustained, increase in blood pressure.
     
    Oxytocin does possess antidiuretic effects, but they are minimal. If oxytocin is administered with an excessive volume of electrolyte-free IV solution and/or at too rapid a rate, the antidiuretic effects are more apparent and water intoxication can result.
     
    Oxytocin appears to have important roles in sexual function and bonding responses in both males and females.

    PHARMACOKINETICS

    Oxytocin administered effectively by parenteral injection or nasal inhalation. Steady state, following parenteral administration, is usually achieved in plasma by 40 minutes. Oxytocin's plasma half-life is between 1 and 6 minutes. The drug distributes throughout the extracellular fluid, with minimal amounts reaching the fetus.
     
    Oxytocinase, a glycoprotein aminopeptidase that is capable of degrading oxytocin, is produced during pregnancy and is present in the plasma. Enzyme activity increases gradually until term approaches, when there is a sharp rise in plasma levels and activity is high in the plasma, placenta and uterus. After delivery enzyme activity declines. Oxytocinase most likely originates from the placenta and regulates the amount of oxytocin in the uterus; there is little or no degradation of oxytocin in men, nonpregnant women, or cord blood. Oxytocin is rapidly removed from plasma by the liver and the kidneys, with only small amounts being excreted unchanged in the urine. Oxytocin is metabolized in the lactating mammary gland and is distributed into breast-milk.

    Oral Route

    Chymotrypsin, present in the GI tract, destroys oxytocin, rendering oral administration ineffective.

    Intravenous Route

    When administered by IV infusion, the uterus responds almost immediately to oxytocin, with response subsiding in about an hour.

    Intramuscular Route

    When oxytocin is administered by IM injection, the uterus responds within 3—5 minutes, with response subsiding in approximately 2—3 hours.

    Topical Route

    Following intranasal use of oxytocin, contractions of the myoepithelial tissue surrounding the alveoli of the breasts begin within minutes and persist for about 20 minutes.