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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Methylergonovine (methylergometrine): Drug information

Methylergonovine (methylergometrine): Drug information
(For additional information see "Methylergonovine (methylergometrine): Patient drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
Brand Names: US
  • Methergine
Pharmacologic Category
  • Ergot Derivative
Dosing: Adult

Prevention of hemorrhage:

Oral: 0.2 mg 3 to 4 times daily in the puerperium for up to 7 days (maximum duration: 1 week)

IM, IV: 0.2 mg after delivery of anterior shoulder, after delivery of placenta, or during puerperium; may be repeated every 2 to 4 hours as needed. Note: IV administration should only be considered during life-threatening situations.

Dosing: Renal Impairment: Adult

No dosage adjustment provided in manufacturer's labeling; use with caution.

Dosing: Hepatic Impairment: Adult

No dosage adjustment provided in manufacturer's labeling; use with caution.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as maleate:

Generic: 0.2 mg/mL (1 mL)

Solution, Injection, as maleate [preservative free]:

Generic: 0.2 mg/mL (1 mL)

Tablet, Oral, as maleate:

Methergine: 0.2 mg [contains methylparaben, propylparaben]

Generic: 0.2 mg

Generic Equivalent Available: US

Yes

Administration: Adult

IV: Administer slowly over a period of no less than 60 seconds with careful monitoring of blood pressure. Should not be routinely administered IV because of possibility of inducing sudden hypertension and cerebrovascular accident. IV administration should only be considered during life-threatening situations.

IM: May be administered intramuscularly.

Oral: Available in tablets for oral administration.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 3]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules. For injection preparation, NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs). Double gloving, a gown, and (if dosage form allows) CSTDs are required during injection administration (NIOSH 2016).

Use: Labeled Indications

Management of uterine atony, hemorrhage and subinvolution of the uterus following delivery of the placenta; control of uterine hemorrhage following delivery of the anterior shoulder in the second stage of labor

Medication Safety Issues
Sound-alike/look-alike issues:

Methergine may be confused with Brethine

Methylergonovine and terbutaline parenteral dosage forms look similar. Due to their contrasting indications, use care when administering these agents.

Administration issues:

Inadvertent administration of methylergonovine to newborns has been reported in place of routine medications (eg, vitamin K or hepatitis B vaccine); store methylergonovine injection separately from medications used for neonates.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.

Cardiovascular: Angina pectoris, atrioventricular block, bradycardia, cerebrovascular accident, chest pain, coronary artery vasospasm, hypertension, hypotension, local thrombophlebitis, myocardial infarction, palpitations, paresthesia, tachycardia, vasospasm, ventricular fibrillation

Central nervous system: Dizziness, hallucination, headache, seizure

Dermatologic: Diaphoresis, skin rash

Endocrine & metabolic: Water intoxication

Gastrointestinal: Abdominal pain, diarrhea, nausea, unpleasant taste, vomiting

Genitourinary: Hematuria

Hypersensitivity: Anaphylaxis

Neuromuscular & skeletal: Leg cramps

Otic: Tinnitus

Respiratory: Dyspnea, nasal congestion

Contraindications

Hypersensitivity to methylergonovine or any component of the formulation; hypertension; preeclampsia; pregnancy

Warnings/Precautions

Concerns related to adverse effects:

• 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.

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Alpha-/Beta-Agonists: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Risk X: Avoid combination

Alpha1-Agonists: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may enhance the vasoconstricting effect of Alpha1-Agonists. Risk X: Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Beta-Blockers: May enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

Bromocriptine: Ergot Derivatives may enhance the adverse/toxic effect of Bromocriptine. Risk X: Avoid combination

Chloroprocaine: May enhance the hypertensive effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Methylergonovine. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Delavirdine: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Erythromycin (Systemic): May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fosamprenavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Letermovir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Lisuride: May enhance the adverse/toxic effect of Ergot Derivatives. Risk X: Avoid combination

Lorcaserin (Withdrawn From US Market): May enhance the adverse/toxic effect of Ergot Derivatives. Specifically, use of these drugs together may increase the risk of developing valvular heart disease. Lorcaserin (Withdrawn From US Market) may enhance the serotonergic effect of Ergot Derivatives. This could result in serotonin syndrome. Risk X: Avoid combination

Nefazodone: May enhance the serotonergic effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Nitroglycerin: Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates) may diminish the vasodilatory effect of Nitroglycerin. Nitroglycerin may increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Management: Avoid the use of ergot derivatives in patients receiving nitroglycerin for angina (or in any angina patient) if possible. If combined, monitor for decreased effects of nitroglycerin and increased adverse effects of the ergot derivative (eg, ergotism). Risk D: Consider therapy modification

Pergolide: May enhance the adverse/toxic effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

Reboxetine: May enhance the hypertensive effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

Roxithromycin: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Serotonergic Agents (High Risk): Ergot Derivatives may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Tipranavir: May increase the serum concentration of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk X: Avoid combination

Pregnancy Risk Factor

C (show table)

Pregnancy Considerations

Methylergonovine is intended for use after delivery of the anterior shoulder, after delivery of the placenta, or during the puerperium; use is contraindicated during pregnancy.

Methylergonovine is recommended when a supplemental uterotonic agent is needed; due to maternal side effects it is not preferred for initial use (ACOG 183 2017).

Breast-Feeding Considerations

Methylergonovine is present in breast milk.

The relative infant dose (RID) of methylergonovine is 3.9% when calculated using the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 0.375 mg/day.

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

The RID of methylergonovine was calculated using a milk concentration of 1.3 ng/mL, providing an estimated daily infant dose via breast milk of 195 ng/kg/day. This milk concentration was obtained following maternal administration methylergonovine 0.125 mg three times daily for 5 days to eight women treated for incomplete postpartum involution. Milk concentrations were evaluated 1 and 8 hours after the morning dose on day 5. The highest milk concentrations were observed 1 hour after the dose and ranged from <0.5 ng/mL (lower limit of detection) to 1.3 ng/mL (Erkkola 1978). Higher doses are recommended in current product labeling.

Adverse events may be observed in breastfed infants and may include agitation, diarrhea, increased blood pressure, bradycardia, seizures, tachycardia, or vomiting (Methylergometrine 2014). Prolactin concentrations (and possibly milk supply) may be changed following methylergonovine administration; this may be dependent upon dose and route of administration (Del Pozo 1975; Weiss 1975).

Some manufacturers do not recommend breastfeeding during therapy or for 12 hours after the last dose due to adverse reactions reported in breastfeeding infants. However, other sources note use may be acceptable if breastfeeding (Ito 2000).

Monitoring Parameters

Blood pressure

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.

Pharmacodynamics and Pharmacokinetics

Onset of action: Oxytocic: Oral: 5-10 minutes; IM: 2-5 minutes; IV: Immediately

Duration: Oral: ~3 hours; IM: ~3 hours; IV: 45 minutes

Absorption: Rapid

Distribution: Vd: 39-73 L

Metabolism: Hepatic

Bioavailability: Oral: 60%; IM: 78%

Half-life elimination: ~3 hours (range: 1.5-12.7 hours)

Time to peak, serum: Oral: 0.3-2 hours; IM: 0.2-0.6 hours

Excretion: Urine and feces

Pricing: US

Solution (Methylergonovine Maleate Injection)

0.2 mg/mL (per mL): $8.80 - $32.54

Tablets (Methergine Oral)

0.2 mg (per each): $74.70

Tablets (Methylergonovine Maleate Oral)

0.2 mg (per each): $67.23 - $70.97

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Basofortina (AR, PY);
  • Bledstop (ID);
  • Demergin (GR);
  • Ergogin (IN);
  • Ergojen (PH);
  • Ergomet (PH);
  • Ergomin (IN);
  • ERruvin (KR);
  • Expogin (TH);
  • Femitranol (PY);
  • Ingagen-M (IN);
  • Mem (PH);
  • Mergot (PH);
  • Mergotrex (PH);
  • Methergin (AE, BD, BE, BF, BG, BH, BJ, BR, CH, CI, CL, CO, CZ, DE, DK, EE, ES, ET, FI, FR, GB, GH, GM, GN, HK, HN, ID, IE, IL, IS, IT, JO, JP, KE, KR, KW, LR, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NL, PE, PH, PK, PT, QA, RU, SC, SD, SE, SG, SI, SK, SL, SN, TN, TW, TZ, UG, UY, VE, VN, ZA, ZM, ZW);
  • Methergine (CY, SA, TR);
  • Metiagin (ID);
  • Metrine (TH);
  • Metvell (ID);
  • Mitrotan (BG);
  • Morgin (ID);
  • Myotonic (ID);
  • Neo-Ergo (TW);
  • Pospargin (VN);
  • Uterine (PH)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins - Obstetrics. Practice bulletin no. 183: postpartum hemorrhage. Obstet Gynecol. 2017;130(4):e168-e186. [PubMed 28937571]
  2. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. [PubMed 27060684]
  3. Cohen V, Jellinek SP, Teperikidis L, et al, “Room-Temperature Storage of Medications Labeled for Refrigeration,” Am J Health-Syst Pharm, 2007, 64(16):1711-15. [PubMed 17687059]
  4. de Groot AN, van Dongen PW, Vree TB, et al, “Ergot Alkaloids. Current Status and Review of Clinical Pharmacology and Therapeutic Use Compared With Other Oxytocics in Obstetrics and Gynaecology,” Drugs, 1998, 56(4):523-35. [PubMed 9806101]
  5. Del Pozo E, Brun Del Re R, Hinselmann M. Lack of effect of methyl-ergonovine on postpartum lactation. Am J Obstet Gynecol. 1975;123(8):845-846. [PubMed 1200082]
  6. Erkkola R, Kanto J, Allonen H, Kleimola T, Mäntylä R. Excretion of methylergometrine (methylergonovine) into the human breast milk. Int J Clin Pharmacol Biopharm. 1978;16(12):579-580. [PubMed 730424]
  7. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  8. Methergine (methylergonovine maleate) [prescribing information]. Baltimore, MD: Lupin Pharma; January 2016.
  9. Methylergometrine: adverse effects in breastfed infants. Prescrire Int. 2014;23(148):102. [PubMed 24860899]
  10. Methylergonovine maleate [prescribing information]. Berlin, CT: Breckenridge Pharmaceutical, Inc; October 2019.
  11. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.
  12. Vogel D, Burkhardt T, Rentsch K, et al, "Misoprostol versus Methylergometrine: Pharmacokinetics in Human Milk," Am J Obstet Gynecol, 2004, 191(6):2168-73. [PubMed 15592308]
  13. Weiss G, Klein S, Shenkman L, Kataoka K, Hollander CS. Effect of methylergonovine on puerperal prolactin secretion. Obstet Gynecol. 1975;46(2):209-210. [PubMed 1080266]
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