DrugindexOnline^{2nd edition}

Pronouncation: (METH-ill-err-go-NO-veen MAL-ee-ate)
Class: Uterine stimulants

Trade Names:
Methergine
- Tablets 0.2 mg
- Injection 0.2 mg/mL

Mechanism of Action

Pharmacology

Acts directly on smooth muscle of the uterus and increases tone, rate, and amplitude of rhythmic contractions, thereby inducing a rapid and sustained tetanic uterotonic effect that shortens the third stage of labor and reduces blood loss.

Pharmacokinetics

Absorption

Oral

Bioavailability is about 60% with no accumulation after repeated doses. C _max is 3,243 pg/mL within 1.12 h.

IM

Bioavailability is about 78%. C _max is 5,918 pg/mL observed at 0.41 h. Decreased bioavailability following oral administration is probably caused by first-pass metabolism in liver.

Distribution

Vd about 56.1 L.

IV

Rapidly distributed to peripheral tissues within 3 min or less.

Metabolism

Plasma Cl about 14.4 L/h. Hepatic metabolism.

Elimination

Hepatic excretion. The decline in plasma concentration is biphasic with a mean elimination t _½ of 3.39 h.

Indications and Usage

Management after delivery of placenta; postpartum atony and hemorrhage; subinvolution; under full obstetric supervision, may be given in second stage of labor following delivery of the anterior shoulder.

Contraindications

Because of the risk of vasospasm leading to cerebral ischemia and ischemia of the extremities, do not use potent CYP3A4 inhibitors (eg, azole antifungal agents, macrolide antibiotics, protease inhibitors) concurrently; hypertension; toxemia; pregnancy; hypersensitivity to any component of product.

Dosage and Administration

Adults

IM/IV 0.2 mg after delivery of anterior shoulder, after delivery of placenta, or during puerperium. May repeat as required at intervals of 2 to 4 h. IV route should not be used routinely (see Precautions).

PO 0.2 mg tid or qid in puerperium for a max of 1 wk.

Storage/Stability

Store tablets below 77°F. Store ampules in refrigerator (36° to 46°F). Protect from light.

Drug Interactions

Less potent CYP3A4 inhibitors (eg, clotrimazole, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, nefazodone, saquinavir, zileuton)

Because of the increased risk of side effects, including vasospasm, use these agents with caution when administering with methylergonovine.

Potent CYP3A4 inhibitors (eg, azole antifungal agents [eg, itraconazole, ketoconazole, voriconazole], macrolide antibiotics [eg, clarithromycin, erythromycin, troleandomycin]), protease inhibitors [eg, delavirdine, indinavir, nelfinavir, ritonavir])

Because of the risk of vasospasm, leading to cerebral ischemia and ischemia of the extremities, use of these agents is contraindicated with methylergonovine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension; hypotension; acute MI; transient chest pains; palpitation.

CNS

Headache; seizure; hallucinations; dizziness.

Dermatologic

Diaphoresis.

EENT

Tinnitus; nasal congestion.

GI

Nausea; vomiting; diarrhea; foul taste.

Genitourinary

Hematuria.

Hypersensitivity

Anaphylaxis.

Metabolic

Water intoxication.

Musculoskeletal

Leg cramps.

Respiratory

Dyspnea.

Miscellaneous

Thrombophlebitis.

Precautions

Pregnancy

Category C .

Lactation

Small quantity excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Special Risk Patients

Use with caution in patients with sepsis, obliterative vascular disease, hepatic or renal involvement, or in second stage of labor.

Retained placenta

Manual removal of retained placenta should occur only rarely with proper technique and adequate allowance of time for spontaneous separation.

IV use

Because of possibility of inducing sudden hypertensive and cerebrovascular accidents, do not use IV administration for routine use. Consider administration as a lifesaving measure and give slowly over a period of no less than 60 sec with careful monitoring of BP.

Overdosage

Symptoms

Nausea, vomiting, abdominal pain, numbness, tingling of extremities, rise in BP, hypotension, respiratory depression, hypothermia, convulsions, coma.

Patient Information

• Advise patient that injection will be prepared and administered by a health care provider in a medical setting.
• Advise patient taking tablets to take each dose without regard to meals but to take with food if stomach upset occurs.
• Advise patient to stop taking the medication and notify health care provider if any of the following occur: numbness, tingling, coldness, or paleness in the fingers or toes; muscle pain in arms or legs; weakness in the legs; chest pain, tightness, or pressure; changes in heart rate.