Methylergonovine is an oral and parenteral semisynthetic derivative of ergonovine, an ergot alkaloid. Methylergonovine and ergonovine are preferentially used over the other ergot alkaloids in contemporary obstetric practice to prevent postpartum uterine atony and hemorrhage because they are most active of the ergot alkaloids on uterine tissues. Additionally, methylergonovine and ergonovine are less likely than other ergot alkaloids to cause ergot-related toxicity with repeated oral dosing and a limited duration of normal prescription use. Methylergonovine is also occasionally used off-label following first trimester abortion curettage to reduce blood loss. Methylergonovine is considered a second-line agent for uterine atony, used when massage and therapy with oxytocin has failed. While oxytocin stimulates contractions of the upper uterine segment, methylergonovine stimulates the upper and lower segments for stronger uterine tone. Endpoints of therapeutic effect include the onset of uterine contractions and the cessation of hemorrhaging following obstetric delivery. The drug may increase blood pressure or induce vasospasm in therapeutic use. The drug rarely may cause serious cardiovascular or cerebral responses. Recommended dosages and durations of treatment should not be exceeded.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-INJECTABLE Drugs: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
-ORAL TABLETS: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Oral Administration
-Administer orally with water.
-Advise patient not to exceed the recommended dosage or duration of methylergonovine therapy.
Injectable Administration
-For intramuscular or intravenous use only. Periarterial or intraarterial injection must be strictly avoided.
-Because methylergonovine is vasoconstrictive, monitor patient's blood pressure, heart rate, and uterine response prior to and during administration.
-Do not exceed recommended dosage limits.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The injection solution should be clear and colorless; discard discolored solutions.
Intravenous Administration
-Do not routinely administer IV because of the possibility of inducing sudden hypertensive and cerebrovascular accidents. Only use IV route if essential as a life-saving measure.
-Give IV slowly over a period of no less than 60 seconds, with careful monitoring of blood pressure, heart rate, and uterine response.
Intramuscular Administration
-Inject deeply into a large muscle.
Excessive dosing or prolonged administration of methylergonovine may inhibit lactation. This effect is related to the suppression of prolactin. However, when used for <= 1 week at recommended dosages, methylergonovine is not likely to cause significant interference with breast-feeding.
While not likely to occur with methylergonovine due to its limited indications and duration of prescription, the long-term use of certain ergot alkaloids has been associated with the development of cardiac valvulopathy. Such effects have included aortic and/or mitral regurgitation, mitral stenosis, severe tricuspid regurgitation, and pulmonary regurgitation. Chronic use of ergot preparations has caused fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves. Retroperitoneal fibrosis and pulmonary fibrosis have occurred in rare instances.
The most common adverse reaction of methylergonovine is hypertension associated in several cases with seizures and/or headache. Hypotension has also been reported. Abdominal pain (caused by uterine contractility), nausea and vomiting have occurred occasionally. Rarely observed reactions have included: hematuria, water intoxication, hallucinations, leg muscle cramps, dizziness, tinnitus, nasal congestion, diarrhea, rash, and foul taste (dysgeusia). Thrombo-phlebitis has occurred with injectable use. There have been rare isolated reports of anaphylactoid reactions or anaphylaxis with methylergonovine, without a proven causal relationship to the medication.
Although specific effects of methylergonovine are not attributable to teratogenesis, it is known that ergot alkaloids may induce fetal harm (e.g., spontaneous fetal abortion or fetal death) if used during pregnancy. Methylergonovine stimulates uterine contractions and is a potent vasoconstrictor of the placental vascular bed. Depending on the stage of labor in which methylergonovine is administered, use may cause sustained, tetanic uterine contractions or uterine rupture; the uterotonic effect of methylergonovine is utilized after delivery to assist involution and decrease hemorrhage, shortening the third stage of labor. Use caution in the sequential administration of methylergonovine following the use of other oxytocic drugs.
Although serious cardiac and cerebrovascular events are rare, such events have been reported following postpartum administration of methylergonovine, particularly with intravenous administration. Intravenous administration should be avoided unless medically necessary due to the risk for hypertensive episodes and cerebrovascular accidents. Rarely observed reactions to methylergonovine have included: acute myocardial infarction, transient chest pain (unspecified), peripheral vasoconstriction, coronary vasospasm, coronary arterial spasm, bradycardia, sinus tachycardia, dyspnea, diaphoresis, and palpitations. During postmarketing use, cerebrovascular accident (stroke), paresthesias, and cardiac disorders such as ventricular fibrillation, ventricular tachycardia, angina pectoris, and atrioventricular block (AV block) have been reported. Symptoms of ergotism are rare with the appropriate dosing and limited duration of use of methylergonovine; symptoms of acute overdose may include nausea, vomiting, oliguria, abdominal pain, numbness and tingling of the extremities (paresthesias), rise in blood pressure and in severe, rare cases these may be followed by hypotension, respiratory depression, hypothermia, convulsions, and coma.
Inadvertent administration of methylergonovine injection to newborn infants has been reported. In these cases of inadvertent neonatal exposure, symptoms such as neonatal respiratory depression, convulsions, cyanosis and oliguria have been reported. Usual treatment is symptomatic. However, in severe cases, respiratory and cardiovascular support is required.
Methylergonovine is contraindicated in those with known ergot alkaloid hypersensitivity.
Methylergonovine use is contraindicated in patients with hypertension. Intravenous administration of methylergonovine should not be used routinely because of the possibility of inducing sudden hypertensive crisis and cerebrovascular accidents (stroke). If IV administration is considered essential as a lifesaving measure, methylergonovine maleate injection should be given slowly over a period of no less than 60 seconds with careful monitoring of blood pressure. Intraarterial administration or periarterial injection should be strictly avoided.
Patients with angina, coronary artery disease, or risk factors for coronary artery disease (e.g., tobacco smoking, obesity, diabetes mellitus, hypercholesterolemia) may be more susceptible to developing myocardial ischemia and myocardial infarction associated with methylergonovine-induced vasospasm. Caution should be exercised when using methylergonovine in the presence of sepsis or obliterative vascular disease (e.g., peripheral vascular disease, Raynaud's phenomenon, or arteriosclerosis).
Methylergonovine, like other ergot alkaloids, is extensively metabolized by the liver and partially excreted in the bile. Caution should be exercised in the presence of impaired hepatic function (hepatic disease).
Caution should be exercised with use of methylergonovine in the presence of renal impairment.
Use of methylergonovine is contraindicated during pregnancy because of the potent oxytocic and uterotonic effects. It is also not known whether methylergonovine can cause fetal harm or can affect reproductive capacity. The drug is most commonly utilized after obstetric delivery to assist involution and decrease hemorrhage, shortening the third stage of labor. Methylergonovine is also used for control of uterine bleeding in the second stage of labor following delivery of the anterior shoulder, but caution during the second stage of labor is needed. The necessity for manual removal of a retained placenta should occur only rarely with proper technique and adequate allowance of time for its spontaneous separation. Methylergonovine is contraindicated in patients with eclampsia or preeclampsia (toxemia of pregnancy); these conditions may be exacerbated by ergot alkaloids and these patients may be more likely to experience methylergonovine-related side effects, such as sudden hypertensive or cerebrovascular accidents. The drug should not be used in the elective induction of labor. The accidental administration of methylergonovine during labor may produce fetal distress (fetal bradycardia, etc.) secondary to uterine tetany.
Methylergonovine may be administered orally for a maximum of 1 week postpartum to control uterine bleeding. Methylergonovine may produce adverse effects in the breast-feeding infant and may also reduce the yield of breast milk. Mothers should avoid breast-feeding during treatment with methylergonovine and for at least 12 hours after administration of the last dose. Milk secreted during this period should be discarded.
During use, take precautions to avoid accidental exposure of the neonate to methylergonovine. Inadvertent administration of methylergonovine maleate injection to neonates has been reported. In these cases of inadvertent neonatal exposure, symptoms such as respiratory depression, convulsions, cyanosis and oliguria have been reported. Usual treatment is symptomatic. However, in severe cases, respiratory and cardiovascular support is required. Methylergonovine injection has been administered instead of vitamin K and hepatitis B vaccine, medications which are routinely administered to the newborn. Due to the potential for accidental neonatal exposure, this drug should be stored separately from medications intended for neonatal administration.
Methylergonovine has not been studied in geriatric patients 65 years of age or older. Reported clinical experience has not identified differences in response between geriatric and younger adult patients. In general, the older adult may be more susceptible to vasoconstrictive effects of ergot alkaloids. Use with caution in the older adult to account for differences in renal, hepatic, or cardiac systems as well as concomitant disease states and medications.
For the management of uterine atony, subinvolution of the uterus, and postpartum bleeding after delivery of the placenta or uterine hemorrhage in the second stage of labor after delivery of the anterior shoulder:
Oral dosage:
Adults: 0.2 mg PO 3 to 4 times daily for up to 7 days.
Intramuscular dosage:
Adults: 0.2 mg IM as a single dose, initially, after delivery of the anterior shoulder or placenta, or during the puerperium, initially; may repeat dose every 2 to 4 hours as needed. However, it is unlikely that additional doses will be of benefit if there is no response after first dose.
Intravenous dosage:
Adults: 0.2 mg IV as a single dose, initially, after delivery of the anterior shoulder or placenta, or during the puerperium; may repeat dose every 2 to 4 hours as needed. Guidelines do not recommend intravenous administration.
Maximum Dosage Limits:
-Adults
0.8 mg/day PO for up to 7 days.
-Geriatric
0.8 mg/day PO for up to 7 days.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Not indicated.
Patients with Hepatic Impairment Dosing
Specific data are not available; use caution in patients with hepatic impairment as ergot alkaloids are primarily metabolized and excreted via the liver.
Patients with Renal Impairment Dosing
Specific data are not available; use caution in patients with renal impairment.
*non-FDA-approved indication
Acebutolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Acetaminophen; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Acetaminophen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Acrivastine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Adagrasib: (Major) Avoid concomitant use of methylergonovine with adagrasib. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
Almotriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Amiodarone: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and amiodarone. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and amiodarone is a moderate CYP3A inhibitor.
Amobarbital: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of methylergonovine with clarithromycin. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Amphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Amphetamine; Dextroamphetamine Salts: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Amphetamine; Dextroamphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Angiotensin II: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Apalutamide: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and apalutamide. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and apalutamide is a strong CYP3A inducer.
Aprepitant, Fosaprepitant: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and aprepitant/fosaprepitant. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and aprepitant/fosaprepitant is a moderate CYP3A inhibitor.
Articaine; Epinephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Atazanavir: (Major) Avoid concomitant use of methylergonovine with atazanavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of methylergonovine with atazanavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. (Major) Avoid concomitant use of methylergonovine with cobicistat. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Atenolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Atenolol; Chlorthalidone: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Barbiturates: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Benzphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Berotralstat: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and berotralstat. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor.
Beta-blockers: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Betaxolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Bisoprolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Brimonidine; Timolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Bromocriptine: (Contraindicated) The concomitant use of bromocriptine, an ergot derivative, with ergot alkaloids may potentially lead to ergot toxicity; therefore the combination should be avoided. Symptoms of ergotism include angina, asthenia, chest pain (unspecified), coronary vasospasm, muscle cramps (claudication), myalgia, paresthesias, and palpitations or changes in heart rate (e.g., sinus bradycardia or sinus tachycardia). Peripheral vasoconstriction of the arteries may result in hypothermia or tissue necrosis, which may lead to gangrene. Other serious complications include hypertension (portal), mesenteric artery thrombosis, myocardial infarction, and renal tubular necrosis. Symptoms such as confusion, depression, drowsiness, and seizures rarely occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Brompheniramine; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Brompheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Bupivacaine; Epinephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Butalbital; Acetaminophen: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Carbamazepine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and carbamazepine. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and carbamazepine is a strong CYP3A inducer.
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.
Carteolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Carvedilol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Ceritinib: (Major) Avoid concomitant use of methylergonovine with ceritinib. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Cetirizine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chloramphenicol: (Major) Avoid concomitant use of methylergonovine with chloramphenicol. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Chlorpheniramine; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Chlorpheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Ciprofloxacin: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and ciprofloxacin. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor.
Clarithromycin: (Major) Avoid concomitant use of methylergonovine with clarithromycin. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Cobicistat: (Major) Avoid concomitant use of methylergonovine with cobicistat. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Cocaine: (Contraindicated) Ergot alkaloids should not be administered with vasoconstrictors such as cocaine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Ergoloid mesylates preparations are not expected to interact with sympathomimetics because this compound does not possess the vasoconstrictor properties of other ergot alkaoloids.
Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Conivaptan: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and conivaptan. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and crizotinib. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor.
Cyclosporine: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and cyclosporine. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and cyclosporine is a moderate CYP3A inhibitor.
Danazol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and danazol. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Darunavir: (Major) Avoid concomitant use of methylergonovine with darunavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat: (Major) Avoid concomitant use of methylergonovine with cobicistat. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Major) Avoid concomitant use of methylergonovine with darunavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of methylergonovine with cobicistat. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. (Major) Avoid concomitant use of methylergonovine with darunavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and darunavir is a strong CYP3A inhibitor.
Delavirdine: (Major) Avoid concomitant use of methylergonovine with delavirdine. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor.
Desloratadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Dexbrompheniramine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Dextroamphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Diltiazem: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and diltiazem. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and diltiazem is a moderate CYP3A inhibitor.
Dinoprostone, Prostaglandin E2: (Contraindicated) Concomitant use of dinoprostone with other oxytocics can result in uterine hypertonus with subsequent uterine rupture, particularly in the absence of adequate cervical dilation. The concurrent use of dinoprostone and other oxytocic drugs is considered contraindicated; 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 and the patient should be monitored closely for adverse effects.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Dobutamine: (Major) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension.
Dopamine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Dorzolamide; Timolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Dronedarone: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and dronedarone. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor.
Droxidopa: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Duvelisib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and duvelisib. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Eletriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of methylergonovine with cobicistat. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of methylergonovine with cobicistat. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor.
Encorafenib: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and encorafenib. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and encorafenib is a strong CYP3A inducer.
Enzalutamide: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and enzalutamide. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and enzalutamide is a strong CYP3A inducer.
Ephedrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Ephedrine; Guaifenesin: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Epinephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Erythromycin: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and erythromycin. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor.
Esmolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Fedratinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and fedratinib. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and fedratinib is a moderate CYP3A inhibitor.
Fexofenadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Fluconazole: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and fluconazole. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
Fluvoxamine: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and fluvoxamine. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and fluvoxamine is a moderate CYP3A inhibitor.
Fosamprenavir: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and fosamprenavir. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and phenytoin/fosphenytoin. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer.
Frovatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Grapefruit juice: (Major) Methylergonovine should not interact with most food. However, the risk of ergot toxicity (e.g., vasospasm leading to cerebral ischemia, peripheral ischemia and/or other serious effects) is potentially increased by the use of CYP3A4 inhibitors. Grapefruit juice inhibits the cytochrome P-450 3A4 isozyme in the gut wall. Grapefruit juice contains furanocoumarins that are metabolized by CYP3A4 to reactive intermediates. These intermediates form a covalent bond to the active site of the CYP3A4 enzyme, causing irreversible inactivation (mechanism-based inhibition). Consequently, CYP3A4 activity in the gut wall is inhibited until de novo synthesis returns the enzyme to its previous level. Therefore, grapefruit juice may decrease ergot alkaloid metabolism via CYP3A4.According to the manufacturer of methylergonovine, caution should be used when coadministering with grapefruit juice. Elderly patients have the greatest possibility of ingesting grapefruit and interacting medications and are the most vulnerable to the adverse clinical consequences.
Guaifenesin; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Guaifenesin; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor for a decrease in nitrate efficacy if concomitant use with methylergonovine is necessary. Methylergonovine produces vasoconstriction and may interfere with antianginal medications.
Ibuprofen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Idelalisib: (Major) Avoid concomitant use of methylergonovine with idelalisib. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Imatinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and imatinib. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor.
Indinavir: (Major) Avoid concomitant use of methylergonovine with indinavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and indinavir is a strong CYP3A inhibitor.
Isavuconazonium: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and isavuconazonium. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and rifampin. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Isoniazid, INH; Rifampin: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and rifampin. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Isoproterenol: (Contraindicated) The concomitant administration of ergot alkaloids and sympathomimetics has resulted in dangerous hypertension. Ergot alkaloids exacerbate the effect of isoproterenol on increased cardiac output while producing peripheral vasoconstriction, resulting in increased blood pressure.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor for a decrease in nitrate efficacy if concomitant use with methylergonovine is necessary. Methylergonovine produces vasoconstriction and may interfere with antianginal medications.
Isosorbide Mononitrate: (Moderate) Monitor for a decrease in nitrate efficacy if concomitant use with methylergonovine is necessary. Methylergonovine produces vasoconstriction and may interfere with antianginal medications.
Itraconazole: (Major) Avoid concomitant use of methylergonovine with itraconazole. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor.
Ketoconazole: (Major) Avoid concomitant use of methylergonovine with ketoconazole. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Labetalol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of methylergonovine with clarithromycin. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Lefamulin: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and oral lefamulin. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and oral lefamulin is a moderate CYP3A inhibitor.
Lenacapavir: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and lenacapavir. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and letermovir. Avoid concomitant use of methylergonovine with combination letermovir plus cyclosporine. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and letermovir is a moderate CYP3A inhibitor; letermovir plus cyclosporine acts as a strong CYP3A inhibitor.
Levobunolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Levoketoconazole: (Major) Avoid concomitant use of methylergonovine with ketoconazole. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
Lidocaine; Epinephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Lisdexamfetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Lonafarnib: (Major) Avoid concomitant use of methylergonovine with lonafarnib. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of methylergonovine with ritonavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Loratadine; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Lumacaftor; Ivacaftor: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and lumacaftor; ivacaftor. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer.
Lumacaftor; Ivacaftor: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and lumacaftor; ivacaftor. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer.
Mepivacaine: (Major) If epinephrine is added to mepivacaine, do not use the mixture in a patient taking ergot alkaloids. Severe hypertension that may be persistent or a cerebrovascular accident can result from concomitant use of a vasopressor and an ergot type oxytocic drug.
Methamphetamine: (Major) Amphetamines, which increase catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with amphetamines may be advisable.
Methohexital: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Metoprolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Midodrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Mifepristone: (Major) Avoid concomitant use of methylergonovine with mifepristone. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Mitotane: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and mitotane. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and mitotane is a strong CYP3A inducer.
Nadolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Naproxen; Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Naratriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Nebivolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Nebivolol; Valsartan: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Nefazodone: (Major) Avoid concomitant use of methylergonovine with nefazodone. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor.
Nelfinavir: (Major) Avoid concomitant use of methylergonovine with nelfinavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and netupitant. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor.
Nicotine: (Major) Advise patients to avoid nicotine while taking ergot alkaloids. Concurrent use of vasoconstrictors, such as nicotine, with ergot alkaloids may result in enhanced vasoconstriction.
Nilotinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and nilotinib. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of ritonavir-boosted nirmatrelvir and ergot alkaloids is contraindicated; consider an alternative COVID-19 therapy. Coadministration may increase ergot alkaloids' exposure resulting in increased toxicity. Ergot alkaloids are CYP3A substrates and nirmatrelvir is a CYP3A inhibitor. (Major) Avoid concomitant use of methylergonovine with ritonavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Nirogacestat: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and nirogacestat. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and nirogacestat is a moderate CYP3A inhibitor.
Nitrates: (Moderate) Monitor for a decrease in nitrate efficacy if concomitant use with methylergonovine is necessary. Methylergonovine produces vasoconstriction and may interfere with antianginal medications.
Nitroglycerin: (Moderate) Monitor for a decrease in nitrate efficacy if concomitant use with methylergonovine is necessary. Methylergonovine produces vasoconstriction and may interfere with antianginal medications.
Norepinephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Oxytocin: (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.
Pentobarbital: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenobarbital: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Phentermine: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable.
Phentermine; Topiramate: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable.
Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Phenytoin: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and phenytoin/fosphenytoin. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer.
Pindolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Posaconazole: (Major) Avoid concomitant use of methylergonovine with posaconazole. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor.
Prilocaine; Epinephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Primidone: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Promethazine; Phenylephrine: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Propranolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Pseudoephedrine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Pseudoephedrine; Triprolidine: (Contraindicated) Ergot alkaloids should not be administered with pseudoephedrine since combining these agents may produce a synergistic increase in blood pressure. There is also an additive risk of peripheral ischemia or gangrene. Of note, at therapeutic doses, ergoloid mesylates lack the vasoconstrictor properties of the natural ergot alkaloids; therefore, ergoloid mesylates are not expected to interact with sympathomimetics.
Ranolazine: (Major) In vitro studies indicate that ranolazine and its metabolite are inhibitors of CYP3A isoenzymes. The impact of coadministering ranolazine with other CYP3A4 substrates has not been studied. Ranolazine may theoretically increase plasma concentrations of CYP3A4 substrates, such as ergot alkaloids, potentially leading to adverse reactions.
Ribociclib: (Major) Avoid concomitant use of methylergonovine with ribociclib. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Ribociclib; Letrozole: (Major) Avoid concomitant use of methylergonovine with ribociclib. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor.
Rifampin: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and rifampin. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and rifampin is a strong CYP3A inducer.
Rifapentine: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and rifapentine. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Ritlecitinib: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and ritlecitinib. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Avoid concomitant use of methylergonovine with ritonavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor.
Rizatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Saquinavir: (Major) Avoid concomitant use of methylergonovine with saquinavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor.
Secobarbital: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and barbiturates. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and barbiturates are strong CYP3A inducers.
Serotonin-Receptor Agonists: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Sotalol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor for a decrease in methylergonovine efficacy during concomitant use of methylergonovine and St. John's wort. Concomitant use may decrease methylergonovine exposure. Methylergonovine is a CYP3A substrate and St. John's wort is a strong CYP3A inducer.
Sumatriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Sumatriptan; Naproxen: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Timolol: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and beta-blockers. Beta-blockers may potentiate the vasoconstrictive actions of methylergonovine.
Tipranavir: (Major) Avoid concomitant use of methylergonovine with tipranavir. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking ergot alkaloids. Concurrent use of vasoconstrictors, such as nicotine, with ergot alkaloids may result in enhanced vasoconstriction. Nicotine acts indirectly as a sympathomimetic agent by releasing catecholamines, potentially resulting in effects such as hypertension, coronary spasm, coronary ischemia, or cardiac arrhythmias, which may be additive with ergot alkaloids.
Trandolapril; Verapamil: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and verapamil. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Tucatinib: (Major) Avoid concomitant use of methylergonovine with tucatinib. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor.
Vasopressin, ADH: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Vasopressors: (Moderate) Monitor for adverse effects if concomitant use of methylergonovine and vasoconstrictors, such as vasopressors, is necessary. Concomitant use may produce a synergistic increase in blood pressure and may also increase the risk for vasospasm which may lead to cerebral or peripheral ischemia.
Verapamil: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and verapamil. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of methylergonovine with clarithromycin. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor.
Voriconazole: (Major) Avoid concomitant use of methylergonovine with voriconazole. Concomitant use may increase methylergonovine exposure and the risk for vasospasm which may lead to cerebral or peripheral ischemia. Methylergonovine is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor.
Voxelotor: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and voxelotor. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zolmitriptan: (Contraindicated) Serotonin-receptor agonists (triptans) are contraindicated for use within 24 hours of treatment with ergot alkaloids (e.g., dihydroergotamine, methysergide) or ergot-type medications to avoid the potential for serious coronary ischemia. Ergot alkaloids have been reported to cause prolonged vasospastic reactions which may be additive with the effects of triptans. Additionally, ergot alkaloids are serotonergic agents whose effects on serotonin may be additive to those of the serotonin-receptor agonists.
Clinically, methylergonovine increases the strength, duration, and frequency of uterine contractions and decreases uterine bleeding. The drug acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss. The onset of action after intravenous administration is immediate; after intramuscular administration, 2 to 5 minutes, and after oral administration, 5 to 10 minutes.
The pharmacologic properties of the ergot alkaloids are complex. Methylergonovine is a selective and potent antagonist of serotonin receptors in various smooth muscles, a partial agonist of serotonin receptors in human umbilical and placental blood vessels, and a partial agonist and antagonist in some areas of the CNS. Although all ergot alkaloids exhibit the ability to produce uterine contractions, methylergonovine and its parent compound, ergonovine, are the most active of the ergot alkaloids on uterine smooth muscle. Methylergonovine and ergonovine are additionally partial agonists of alpha-adrenergic receptors in blood vessels, but are less potent agonists than ergotamine. The normal response of the coronary arteries in response to the ergot alkaloids is coronary vasospasm and a resultant decrease in luminal diameter. The vasoconstrictive response is most evident after parenteral administration of methylergonovine but rarely occurs with appropriate oral prescription use. Methylergonovine is a weak antagonist of dopamine in certain blood vessels, and a partial agonist and antagonist of dopamine receptors in the CNS. Methylergonovine is less potent than bromocriptine in its ability to produce emesis or inhibit the secretion of prolactin.
Methylergonovine is administered orally, or parenterally by intramuscular or intravenous injection. Bioavailability is highly dependent on the storage conditions of the pharmaceutical preparations. All formulations are highly unstable if exposed to tropical conditions of heat, light, and moisture prior to use. Although methylergonovine exhibits good penetration into the breast milk in canines, average human maternal breast-milk concentrations are clinically nonsignificant. It has a short elimination half-life (normal 0.5-3.5 hours), low volume of distribution and the high total plasma clearance in healthy adults, factors that indicate rapid elimination of the drug. It is metabolized extensively by the liver; biliary excretion and limited enterohepatic recirculation may also occur.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
The risk of ergot toxicity (e.g., severe peripheral vasospasm with possible ischemia, potentially leading to gangrene, cyanosis, stroke, numbness of the extremities and/or other serious effects) is potentially increased by the use of CYP3A4 inhibitors.
-Route-Specific Pharmacokinetics
Oral Route
The bioavailability of methylergonovine after oral administration is roughly 60%. The rate of oral absorption is slower in females during puerperium (Tmax 3 h) in comparison with healthy adult males (Tmax 0.5 h). The duration of action following oral dosing is roughly 3 hours.
Less than 5% of an oral dose is excreted into the urine. No accumulation of methylergonovine occurs after repeated oral administration.
Intravenous Route
Usually a single parenteral dose of methylergonovine is needed to initiate therapy in a timely manner. When given intravenously, a distribution half-life of only a few minutes results in an immediate, strong oxytocic and cardio- and cerebrovascular response. The duration of action following parenteral dosing is roughly 3 hours.
Intramuscular Route
Usually a single parenteral dose of methylergonovine is needed to initiate therapy in a timely manner. Intramuscular administration causes uterine contractions within 2-5 minutes and is the preferred parenteral route due to a lower incidence of side effects. The duration of action following parenteral dosing is roughly 3 hours.
-Special Populations
Hepatic Impairment
Patients with hepatic disease may require reduced dosages of methylergonovine, but pharmacokinetic data are not available.
Renal Impairment
Data for severe renal impairment are unavailable; cautious use of methylergonovine is advised.
Pediatrics
Inadvertent administration of methylergonovine to the neonate may result in a prolonged duration of action due to immature organ functions.
Gender Differences
The rate of oral absorption of methylergonovine is slower in females during puerperium (Tmax 3 h) in comparison with healthy adult males (Tmax 0.5 h).