Methylergometrine
JFDA label: METHYLERGOMETRINE MALEATE
Mechanism of Action
Increases the tone, rate and amplitude of contractions on the smooth muscles of the uterus, producing sustained contractions which shortens the third stage of labor and reduces blood loss.
Contraindications
Source: Lexicomp
- Hypersensitivity to methylergonovine or any component of the formulation Absolute
- hypertension Absolute
Adverse Reactions
Cardiac disorders (15)
Not Known Angina pectoris · atrioventricular block · bradycardia · cerebrovascular accident · chest pain · coronary artery vasospasm · hypertension · hypotension · local thrombophlebitis · myocardial infarction · palpitations · paresthesia · tachycardia · vasospasm · ventricular fibrillation
Nervous system disorders (4)
Not Known Dizziness · hallucination · headache · seizure
Renal and urinary disorders (1)
Not Known Hematuria
Immune system disorders (1)
Not Known Anaphylaxis
Metabolism and nutrition disorders (1)
Not Known Water intoxication
Gastrointestinal disorders (5)
Not Known Abdominal pain · diarrhea · nausea · unpleasant taste · vomiting
Skin and subcutaneous tissue disorders (2)
Not Known Diaphoresis · skin rash
Musculoskeletal and connective tissue disorders (1)
Not Known Leg cramps
Ear and labyrinth disorders (1)
Not Known Tinnitus
Respiratory, thoracic and mediastinal disorders (2)
Not Known Dyspnea · nasal congestion
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Coronary artery disease
Patients with coronary artery disease (CAD) or risk factors for CAD may be more likely to develop myocardial ischemia and infarction following methylergonovine-induced vasospasm.
Ergotism
Ergot alkaloid use may result in ergotism (intense vasoconstriction) resulting in peripheral vascular ischemia and possible gangrene. Ergotism is usually associated with overdosage or prolonged chronic use; do not exceed dosing guidelines and avoid prolonged administration.
Pleural/retroperitoneal fibrosis
Rare cases of pleural and/or retroperitoneal fibrosis have been reported with prolonged daily use of other ergot alkaloids. Disease-related concerns:
Hepatic impairment
Use with caution in patients with hepatic impairment.
Labor
Use with caution in the second stage of labor.
Renal impairment
Use with caution in patients with renal impairment.
Sepsis
Use with caution in patients with sepsis.
Vascular disease
Use with caution in patients with obliterative vascular disease. Concurrent drug therapy issues:
CYP3A4 inhibitors
Concomitant use with potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics) and ergot alkaloids has been associated with acute ergot toxicity (ergotism); concurrent use of certain ergot alkaloids (eg, ergotamine and dihydroergotamine) are not recommended by the manufacturer. Other warnings/precautions:
IV administration
Not for routine IV administration due to risk of inducing sudden hypertensive and cerebrovascular accidents. IV administration should only be considered during life-threatening situations.
Medication errors
Inadvertent administration to newborns has been reported.
Pregnancy & Lactation
Pregnancy
Animal reproduction studies have not been conducted. Methylergonovine is intended for use after delivery of the infant; use is contraindicated during pregnancy.
Lactation
At normal doses used to control postpartum uterine bleeding, small amounts are excreted in breast milk. In one study, ten women were given a single dose of methylergonovine 0.5 mg once lactation was established. Simultaneous maternal milk and plasma samples were taken 1 and 2 hours later. Maximum milk concentrations were 410-830 pg/mL, 2-3 hours after the dose and declined to 0.2 pg/mL (median) at 5 hours. The mean M/P ratios were 0.18 (at 1 hour) and 0.17 (at 2 hours) (Vogel, 2004). Methylergon
Monitoring
| Clinical pearl | Blood pressure |
|---|
Chemistry & Properties
| Formula | C20H25N3O2 |
|---|---|
| Molecular weight | 339.44 g/mol |
| IUPAC name | (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide |
| CAS | 113-42-8 |
| PubChem CID | 8226 |
| InChIKey | UNBRKDKAWYKMIV-QWQRMKEZSA-N |
| logP | 1.92 (XLogP 2.3) |
| Polar surface area | 68.36 Ų |
| H-bond acceptors / donors | 3 / 3 |
| Drug-likeness (QED) | 0.80 |
| Lipinski violations | 0 |
SMILES
CC[C@@H](CO)NC(=O)[C@@H]1C=C2c3cccc4[nH]cc(c34)C[C@H]2N(C)C1Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | No |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Substrate | — |
| CYP2C19 | Substrate | — |
| CYP2C9 | Substrate | — |
| CYP2D6 | Inhibitor | IC₅₀ 0.20000000000000004 µM |
| CYP2D6 | Substrate | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 4)
| Target | Action | Affinity |
|---|---|---|
| 5-HT2A receptor (HTR2A) | Agonist | pKi 9.4 |
| 5-HT2B receptor (HTR2B) | Agonist | pKi 9.3 |
| 5-HT2C receptor (HTR2C) | Agonist | pKi 8.3 |
| 5-HT1F receptor (HTR1F) | Antagonist | pKi 7.5 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Drug–drug interactions (90, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Ceritinib | major | |
| Clarithromycin | major | |
| Cobicistat | major | |
| Ephedrine | major | |
| Ephedrine (nasal) | major | |
| Epinephrine | major | |
| Epinephrine (ophthalmic) | major | |
| Epinephrine (topical) | major | |
| Erythromycin | major | |
| Idelalisib | major | |
| Isometheptene | major | |
| Ketoconazole | major | |
| Lorcaserin | major | |
| Naphazoline (nasal) | major | |
| Naphazoline (ophthalmic) | major | |
| Oxymetazoline (nasal) | major | |
| Oxymetazoline (ophthalmic) | major | |
| Oxymetazoline (topical) | major | |
| Phenylephrine | major | |
| Phenylephrine (nasal) | major | |
| Phenylephrine (ophthalmic) | major | |
| Phenylephrine (topical) | major | |
| Phenylpropanolamine | major | |
| Pseudoephedrine | major | |
| Tetryzoline (nasal) | major | |
| Tetryzoline (ophthalmic) | major | |
| Xylometazoline (nasal) | major | |
| Abiraterone | moderate | |
| Aminoglutethimide | moderate | |
| Amyl Nitrite | moderate | |
| Apalutamide | moderate | |
| Aprepitant | moderate | |
| Bexarotene | moderate | |
| Bicalutamide | moderate | |
| Brigatinib | moderate | |
| Chloramphenicol | moderate | |
| Cimetidine | moderate | |
| Clotrimazole | moderate | |
| Crizotinib | moderate | |
| Cyclosporine | moderate |
Showing 40 of 90.
Registered Products (6)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Sunnymetrine | Ampoule 0.2 mg/ml | 5 amp | Sahar Drug Store | 1.100 |
| Demergin Amp | Ampoule 0.2 mg/ml | 5 amp pack varies | Al Hilal Drug Store | 1.140 |
| METHERGIN Amp | Ampoule 0.2 mg/ml | 5 amp | The Jordan Drugstore Co | 2.020 |
| Demergin Amp | Ampoule 0.2 mg/ml | 10 amp pack varies | Al Hilal Drug Store | 2.160 |
| METHYLERGOMETRINE MALEATE | Ampoule 0.2 mg/ml | 10 amp | Reda Jardaneh Drug Store | 2.600 |
| Demergin Amp | Ampoule 0.2 mg/ml | 50 amp pack varies | Al Hilal Drug Store | 10.230 |