Methylergonovine

Pronunciation

(meth il er goe NOE veen)


U.S. Brand Names

Methergine®



Synonyms

Methylergometrine Maleate; Methylergonovine Maleate



Generic Available

No



Canadian Brand Names

Methergine®



Use

Prevention and treatment of postpartum and postabortion hemorrhage caused by uterine atony or subinvolution



Pregnancy Risk Factor

C



Pregnancy Implications

Prolonged constriction of the uterine vessels and/or increased myometrial tone may lead to reduced placental blood flow. This has contributed to fetal growth retardation in animals. Methylergonovine is intended for use after delivery of the infant.



Lactation

Enters breast milk/use caution



Contraindications

Hypersensitivity to methylergonovine or any component of the formulation; ergot alkaloids are contraindicated with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics); hypertension; toxemia; pregnancy



Warnings/Precautions

Use caution in patients with sepsis, obliterative vascular disease, hepatic, or renal involvement, or second stage of labor; administer with extreme caution if using intravenously. Pleural and peritoneal fibrosis have been reported with prolonged daily use. Cardiac valvular fibrosis has also been associated with ergot alkaloids.



Adverse Reactions

Frequency not defined.

Cardiovascular: Acute MI, hypertension, temporary chest pain, palpitation

Central nervous system: Hallucinations, dizziness, seizure, headache

Endocrine & metabolic: Water intoxication

Gastrointestinal: Nausea, vomiting, diarrhea, foul taste

Local: Thrombophlebitis

Neuromuscular & skeletal: Leg cramps

Otic: Tinnitus

Renal: Hematuria

Respiratory: Dyspnea, nasal congestion

Miscellaneous: Diaphoresis

Overdosage/Toxicology

Symptoms of overdose include prolonged gangrene, numbness in extremities, acute nausea, vomiting, abdominal pain, respiratory depression, hypotension, and seizures. Treatment is symptomatic and supportive.



Drug Interactions

of CYP3A4 (major)

Substrate

Antifungals, azole derivatives (itraconazole, ketoconazole) increase levels of ergot alkaloids by inhibiting CYP3A4 metabolism, resulting in toxicity; concomitant use is contraindicated.

Antipsychotics: May diminish the effects of methylergonovine (due to dopamine antagonism); these combinations should generally be avoided.

Beta blockers: severe peripheral vasoconstriction has been reported with concomitant use of beta blockers and ergot derivatives. Monitor.

CYP3A4 inhibitors: May increase the levels/effects of methylergonovine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Macrolide antibiotics: Erythromycin, clarithromycin, and troleandomycin may increase levels of ergot alkaloids by inhibiting CYP3A4 metabolism, resulting in toxicity (ischemia, vasospasm); concomitant use is contraindicated.

MAO inhibitors: The serotonergic effects of ergot derivatives may be increased by MAO inhibitors. Monitor for signs and symptoms of serotonin syndrome.

Metoclopramide: May diminish the effects of methylergonovine (due to dopamine antagonism); concurrent therapy should generally be avoided.

Protease inhibitors (ritonavir, amprenavir, atazanavir, indinavir, nelfinavir, and saquinavir) increase blood levels of ergot alkaloids by inhibiting CYP3A4 metabolism, acute ergot toxicity has been reported; concomitant use is contraindicated.

Serotonin agonists: Concurrent use with methylergonovine may increase the risk of serotonin syndrome (includes buspirone, SSRIs, TCAs, nefazodone, sumatriptan, and trazodone).

Sibutramine: May cause serotonin syndrome; concurrent use with ergot alkaloids is contraindicated.

Sumatriptan and other serotonin 5-HT1 receptor agonists: Prolong vasospastic reactions; do not use sumatriptan or ergot-containing drugs within 24 hours of each other.

Vasoconstrictors: Concomitant use with peripheral vasoconstrictors may cause synergistic elevation of blood pressure; use is contraindicated.

Stability

Ampul: Store under refrigeration at 2°C to 8°C (36°F to 46°F); protect from light

Tablet: Store below 25°C (77°F)

Compatibility

Stable in NS

Y-site administration: Compatible: Heparin, hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C

Mechanism of Action

Similar smooth muscle actions as seen with ergotamine; however, it affects primarily uterine smooth muscles producing sustained contractions and thereby shortens the third stage of labor



Pharmacodynamics/Kinetics

Onset of action: Oxytocic: Oral: 5-10 minutes; I.M.: 2-5 minutes; I.V.: Immediately

Duration: Oral: ~3 hours; I.M.: ~3 hours; I.V.: 45 minutes

Absorption: Rapid

Distribution: Vd: 39-73 L

Rapid; primarily to plasma and extracellular fluid following I.V. administration; tissues

Metabolism: Hepatic

Bioavailability: Oral: 60%; I.M.: 78%

Half-life elimination: Biphasic: Initial: 1-5 minutes; Terminal: 0.5-2 hours

Time to peak, serum: Oral: 0.3-2 hours; I.M.: 0.2-0.6 hours

Excretion: Urine and feces

Dosage

Adults:

Oral: 0.2 mg 3-4 times/day for 2-7 days

I.M., I.V.: 0.2 mg after delivery of anterior shoulder, after delivery of placenta, or during puerperium; may be repeated as required at intervals of 2-4 hours

Administration

Administer over 60 seconds. Should not be routinely administered I.V. because of possibility of inducing sudden hypertension and cerebrovascular accident.



Patient Education

This drug will generally not be needed for more than a week. May cause nausea and vomiting (small, frequent meals may help), dizziness, headache, or ringing in the ears (will reverse when drug is discontinued). Report immediately any chest pain or tightness, jaw, shoulder or mid-back pain; difficulty breathing; acute headache; numb, cold, or cramping extremities; or severe abdominal cramping. Consult prescriber if breast-feeding.

Breast-feeding precaution:

Anesthesia and Critical Care Concerns/Other Considerations

This drug should be used extremely carefully because of it's potent vasoconstrictor action. I.V. use may induce sudden hypertension and cerebrovascular accidents. As a last resort, give I.V. slowly over several minutes and monitor blood pressure closely.



Cardiovascular Considerations

This drug should be used extremely carefully because of its potent vasoconstrictor action. Administration may elicit marked increases in blood pressure and intracranial hemorrhage. Use should be avoided in patients with cardiovascular disease, including hypertension, coronary artery disease and peripheral vascular disease.



Dental Health: Effects on Dental Treatment

No significant effects or complications reported



Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions



Mental Health: Effects on Mental Status

May rarely cause dizziness or hallucinations



Mental Health: Effects on Psychiatric Treatment

None reported



Dosage Forms

Injection, solution, as maleate: 0.2 mg/mL (1 mL)

Tablet, as maleate: 0.2 mg

References

de Groot AN, van Dongen PW, Vree TB, et al, "Ergot Alkaloids. Current Status and Review of Clinical Pharmacology and Therapeutic Use Compared With Other Oxytocics in Obstetrics and Gynaecology,"Drugs, 1998, 56(4):523-35.

International Brand Names

Methergine® (CA)



Review Date: 1969-12-31 Reviewed By: Keywords: ,
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