VA Class:GU600
ATC Class:G02AB03
Ergonovine maleate and methylergonovine maleate, which are amine ergot alkaloids, directly stimulate contractions of uterine smooth muscle.
Ergonovine maleate and methylergonovine maleate are used for the prevention and treatment of postpartum hemorrhage caused by uterine atony. The drugs appear to be equally effective for these purposes; however, many clinicians prefer methylergonovine to ergonovine because the former drug may produce hypertension less frequently than does the latter drug. Methylergonovine is a first-line agent for the treatment of postpartum hemorrha methylergonovine usually is given after oxytocin. Administration of parenteral ergot alkaloids during the third stage of labor decreases mean blood loss and the incidence of postpartum blood loss of 500 mL or more. Ergonovine and methylergonovine should not be used for the induction or augmentation of labor.
Ergonovine maleate has been used as a provocative test† for the diagnosis of variant angina. The drug has been used to precipitate coronary artery spasm in patients with suspected variant angina.
Ergonovine maleate or methylergonovine maleate may be administered orally or by IM or IV injection. IV use of methylergonovine should be limited to patients with severe uterine bleeding or other life-threatening emergency situations. IV doses of methylergonovine should be given over a period of not less than 1 minute. Some clinicians recommend diluting the IV dose to a volume of 5 mL with 0.9% sodium chloride injection before administration.
For the prevention and treatment of postpartum hemorrhage, the IM dose of ergonovine maleate is 0.2 mg; the dose can be repeated as necessary. The manufacturer states that it is rarely necessary to administer IM doses more frequently than every 2-4 hours. Following IM administration, the drug can be given orally to minimize late postpartum bleeding. The usual oral dosage of ergonovine maleate to minimize late postpartum bleeding is 0.2-0.4 mg every 6-12 hours until uterine atony has passed (usually 48 hours). Severe uterine cramping may be reduced by decreasing dosage. Ergonovine maleate tablets also may be administered sublingually.
For the prevention and treatment of postpartum hemorrhage, the IM dose of methylergonovine maleate is 0.2 mg; the dose can be repeated as necessary every 2-4 hours. For excessive uterine bleeding or other emergency situations, the same dose may be given IV, but blood pressure and uterine contractions should be carefully monitored. To control uterine bleeding during the puerperium, methylergonovine maleate can be administered orally in a dosage of 0.2 mg 3 or 4 times daily for a maximum of 1 week postpartum.
When used as a provocative test† in the diagnosis of variant angina, ergonovine maleate has been administered IV in a dose of 0.1-0.4 mg.
When administered in correct doses to carefully selected patients who are closely monitored, there is little risk of serious adverse systemic effects in patients receiving ergonovine or methylergonovine. However, IV administration of methylergonovine produces serious adverse effects if the injections are not diluted and administered slowly. The most common adverse effects of the drugs include nausea and vomiting. Dizziness, headache, tinnitus, diaphoresis, palpitation, transient chest pain, dyspnea, thrombophlebitis, hematuria, water intoxication, hallucinations, leg cramps, nasal congestion, diarrhea, foul taste, and allergic phenomena including shock have also been reported.
Hypertension may occur following administration of ergonovine or methylergonovine, especially when administered IV undiluted or too rapidly or when used in conjunction with regional anesthesia or vasoconstrictors; hypertension may occur less frequently with methylergonovine than with ergonovine. Some patients, especially eclamptic or previously hypertensive patients, may be unusually sensitive to the hypertensive effects of the drugs; generalized headaches, severe arrhythmias, seizures, and cerebrovascular accidents have been associated with ergonovine- or methylergonovine-induced hypertension in these patients. Hypotension also has been reported.
Precautions and Contraindications
Since ergonovine or methylergonovine may cause serious adverse cardiovascular effects, some clinicians recommend that the drugs not be used in patients with hypertension, heart disease, venoatrial shunts, mitral valve stenosis, or obliterative vascular disease.
Because prolonged use of ergonovine or methylergonovine may produce ergotism in sensitive individuals, prolonged use of the drugs should be avoided. Ergonovine and methylergonovine should be used with caution in patients with sepsis or with hepatic or renal impairment. The drugs should not be used in cases of threatened spontaneous abortion or in patients who previously displayed a hypersensitivity or idiosyncratic reaction to ergonovine or methylergonovine.
Concomitant use of methylergonovine and inhibitors of cytochrome (CYP) 3A4 may result in vasospasm, cerebral ischemia, and/or ischemia of the extremities. Concomitant use of ergot alkaloids and human immunodeficiency virus (HIV) protease inhibitors, delavirdine, or nevirapine is contraindicated.
Because postpartum hemorrhage due to uterine atony is often managed with methylergonovine, the Perinatal HIV Guidelines Working Group of the Public Health Service Task Force has issued recommendations concerning use of methylergonovine in women receiving certain antiretroviral agents. If a women receiving an HIV protease inhibitor, efavirenz, or delavirdine as part of an antiretroviral regimen experiences uterine atony and excessive postpartum bleeding, methylergonovine should be used for the treatment of hemorrhage only if alternative treatments (i.e., misoprostol, carboprost, oxytocin) cannot be used and the potential benefits of the ergot alkaloid outweigh risks. In this situation, methylergonovine maleate should be used in the lowest dosage and shortest duration possible.
The principal manifestations of severe ergonovine overdosage are seizures and gangrene; other manifestations include vomiting, diarrhea, dizziness, increase or decrease in blood pressure, weak pulse, dyspnea, loss of consciousness, numbness and coldness of the extremities, tingling, chest pain, hypercoagulability, and gangrene of the fingers and toes. In two reports of accidental administration of 0.2 mg of oral ergonovine maleate or of 0.5 mg of IM ergonovine maleate to neonates, peripheral cyanosis and threatening gangrene, apnea, myoclonic movements, purpuric manifestations, and mild jaundice were noted. Treatment was mainly supportive; IV chlorpromazine controlled myoclonic movements. One death was reported in an infant who received 0.2 mg of oral ergonovine maleate.
In acute oral ergonovine overdosage, the stomach should be emptied immediately by inducing emesis or by gastric lavage, followed by administration of activated charcoal and catharsis. If the patient is comatose, having seizures, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of vomitus. Supportive and symptomatic treatment should be initiated. Seizures should be treated with anticonvulsants. Hypercoagulability should be controlled by administration of heparin. A vasodilator may be administered, with dosage adjusted according to heart rate and blood pressure. Gangrene may require surgical amputation.
Ergonovine maleate and methylergonovine maleate are pharmacologically similar. Both drugs directly stimulate contractions of uterine and vascular smooth muscle.
Following administration of usual therapeutic doses of ergonovine or methylergonovine, intense contractions of the uterus are produced and are usually followed by periods of relaxation. Larger doses of the drugs, however, produce sustained, forceful contractions followed by only short or no periods of relaxation. The drugs increase the amplitude and frequency of uterine contractions and uterine tone which in turn impede uterine blood flow. Ergonovine and methylergonovine also increase contractions of the cervix.
Ergonovine and methylergonovine produce vasoconstriction, mainly of capacitance vessels; increased central venous pressure, elevated blood pressure, and, rarely, peripheral ischemia and gangrene may result. Methylergonovine reportedly may interfere with prolactin secretion, but this effect has not been definitely established.
Ergonovine maleate and methylergonovine maleate are rapidly absorbed after oral or IM administration. About 60% of a single oral dose of methylergonovine is absorbed from the GI tract. In one study in fasting, healthy males given a single 0.25-mg oral dose of methylergonovine, peak plasma drug concentrations of about 3 ng/mL occurred within 30 minutes. In another study in postpartum patients receiving oral doses of 0.25 mg of methylergonovine, similar peak plasma drug concentrations were attained but were delayed, occurring about 3 hours after a dose. Methylergonovine does not accumulate in plasma following multiple oral doses.
Uterine contractions are usually initiated within 5-15 minutes following oral administration, within 2-5 minutes after IM injection, and immediately following IV injection of ergonovine or methylergonovine. Uterine contractions persist for 3 hours or longer after oral or IM administration and for 45 minutes after IV injection of either drug.
Distribution of ergonovine or methylergonovine has not been fully characterized. Following IV administration, methylergonovine is rapidly and mainly distributed into plasma and extracellular fluid; the drug appears to be rapidly distributed into tissues. Methylergonovine has been detected in the milk of lactating women, but apparently not in quantities sufficient to affect nursing infants.
Plasma concentrations of methylergonovine appear to decline in a biphasic manner. Following IV administration of methylergonovine to adults with normal renal function, the half-life of the drug in the initial phase (t½α) reportedly ranges from about 1-5 minutes and the half-life in the terminal phase (t½β) ranges from about 0.5-2 hours. Following IV administration of ergonovine to adults, the half-life of the drug in the initial phase (t½α) reportedly is about 10 minutes and the half-life in the terminal phase (t½β) is about 2 hours.
Little is known about the elimination of ergonovine or methylergonovine. It has been suggested that the drugs are principally eliminated by nonrenal mechanisms (i.e., metabolism in the liver, excretion in feces). It appears that only a very small amount of methylergonovine is excreted in urine. Elimination of the drugs may be prolonged in neonates.
Ergonovine maleate and methylergonovine maleate are amine ergot alkaloids. Ergonovine maleate occurs as a white to grayish-white or faintly yellow, odorless, microcrystalline powder and is sparingly soluble in water and slightly soluble in alcohol. Methylergonovine maleate, which differs structurally from ergonovine maleate by the addition of a methylene group on the alkyl side chain, occurs as a white to pinkish-tan, odorless, microcrystalline powder having a bitter taste and is slightly soluble in water and in alcohol.
Ergonovine maleate darkens with age and on exposure to light. Injections of ergonovine maleate and methylergonovine maleate should preferably be stored at temperatures below 8°C and protected from light; however, the manufacturer of ergonovine maleate injection (Ergotrate®) states that it may be stored at room temperature for up to 60 days. Ergonovine and methylergonovine tablets and injections should be stored in light-resistant containers.
Ergonovine maleate and methylergonovine maleate injections are reportedly incompatible with various drugs, but the compatibility depends on several factors (e.g., concentration of the drugs, resulting pH, temperature). Specialized references should be consulted for more specific compatibility information.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 0.2 mg | ||
Parenteral | Injection | 0.2 mg/mL | Ergotrate® | Pharmacist Pharmaceutical |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 0.2 mg | ||
Parenteral | Injection | 0.2 mg/mL | Methergine® | Novartis |