Ergometrine Maleate

(BANM, rINNM)
Ergometrine Maleate Chemical formula
Synonyms: Ergobasine Maleate; Ergometriinimaleaatti; Ergométrine, maléate d’; Ergometrinhydrogenmaleat; Ergometrini maleas; Ergometrinmaleat; Ergometrin-maleát; Ergometrin-maleinát; Ergometrino maleatas; Ergonovine Bimaleate; Ergonovine Maleate; Ergostetrine Maleate; Ergotocine Maleate; Maleato de ergobasina; Maleato de ergometrina; Maleato de Ergonovina. N-[(S)-2-Hydroxy-1-methylethyl]dehydroN-[(S)-2-hydroxy-1-methylethyl]-6-methylergoline-8 carboxamide hydrogen maleate.
Cyrillic synonym: Эргометрина Малеат.

💊 Chemical information

Chemical formula: C19H23N3O2,C4H4O4 = 441.5.
CAS — 60-79-7 (ergometrine); 129-51-1 (ergometrine maleate).
ATC — G02AB03.
ATC Vet — QG02AB03.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, and US.

Ph. Eur. 6.2

(Ergometrine Maleate). A white or almost white or slightly coloured, crystalline powder. Sparingly soluble in water; slightly soluble in alcohol. A 1% solution in water has a pH of 3.6 to 4.4. Store in airtight glass containers at a temperature of 2° to 8°. Protect from light.

USP 31

(Ergonovine Maleate). A white to greyish-white or faintly yellow, odourless, microcrystalline powder. It darkens with age and on exposure to light. Sparingly soluble in water; slightly soluble in alcohol; insoluble in chloroform and in ether. Store in airtight containers at a temperature not exceeding 8°. Protect from light.

Stability.

Deterioration and degradation of ergometrine-containing injections has been seen when exposed to high temperatures in the tropics. 1-4 The mean loss in one study 3 of ergometrine injection under shipment to the tropics was 5.8%, but in some individual samples the loss was more marked: 18 of 80 test samples contained less than 80% of the stated content, and in 3 cases the content was less than 60%. A similar but much less significant pattern was seen with methylergometrine: the content varied from 98.6 to 99.5% of the labelled amount. Tablets of ergometrine and methylergometrine were also shown to be unstable under simulated tropical conditions, with humidity as the main adverse factor. 5 1. Walker GJA, et al. Potency of ergometrine in tropical countries. Lancet 1988; ii: 393. 2. Abu-Reid IO, et al. Stability of drugs in the tropics. Int Pharm J 1990; 4: 6–10. 3. Hogerzeil HV, et al. Stability of essential drugs during shipment to the tropics. BMJ 1992; 304: 210–12. 4. Hogerzeil HV, Walker GJ. Instability of (methyl)ergometrine in tropical climates: an overview. Eur J Obstet Gynecol Reprod Biol 1996; 69: 25–9. 5. de Groot ANJA, et al. Ergometrine and methylergometrine tablets are not stable under simulated tropical conditions. J Clin Pharm Ther 1995; 20: 109–13.

💊 Adverse Effects and Treatment

Nausea and vomiting, abdominal pain, diarrhoea, headache, dizziness, tinnitus, chest pain, palpitations, bradycardia and other cardiac arrhythmias, coronary artery vasospasm, myocardial infarction, dyspnoea, and pulmonary oedema have been reported after use of ergometrine. Hypertension may occur, particularly after rapid intravenous dosage; hypotension has also been reported. Hypersensitivity reactions, including shock, have occurred. Ergometrine shows less tendency to produce gangrene than ergotamine, but ergotism has been reported and symptoms of acute poisoning are similar. Adverse effects should be treated as for ergotamine.

Effects on the respiratory system.

Bronchospasm has been reported after use of ergometrine.1 Although studies in vitro on canine bronchi have suggested a direct action on smooth muscle, this could not be confirmed in studies using human bronchi.
1. Hill H, et al. Ergometrine and bronchospasm. Anaesthesia 1987; 42: 1115–16.

Overdosage.

Ergometrine maleate has been given accidentally in adult doses to neonates,1-5 sometimes instead of vitamin K. Symptoms have included peripheral vasoconstriction, encephalopathy, convulsions, respiratory failure, acute renal failure, and temporary lactose intolerance. When given with oxytocin, water intoxication has also been reported.1 In all of these cases, recovery occurred after intensive symptomatic treatment including assisted ventilation and anticonvulsants. However, deaths have also been recorded.5 The long-term outcome of ergometrine overdosage has been reported for 6 infants.5 Their ages at followup ranged from 18 months to 5 years; all had normal physical and behavioural development and neurological outcomes.
1. Whitfield MF, Salfield SAW. Accidental administration of Syntometrine in adult dosage to the newborn. Arch Dis Child 1980; 55: 68–70
2. Pandey SK, Haines CI. Accidental administration of ergometrine to newborn infant. BMJ 1982; 285: 693
3. Mitchell AA, et al. Accidental administration of ergonovine to a newborn. JAMA 1983; 250: 730–1
4. Donatini B, et al. Inadvertent administration of uterotonics to neonates. Lancet 1993; 341: 839–40
5. Dargaville PA, Campbell NT. Overdose of ergometrine in the newborn infant: acute symptomatology and long-term outcome. J Paediatr Child Health 1998; 34: 83–9.

💊 Precautions

As for Ergotamine Tartrate. Ergometrine should also be used with caution in patients with veno-atrial shunts or mitral valve stenosis. Ergometrine is contraindicated for the induction of labour or for use during the first stage of labour. If used at the end of the second stage of labour, before delivery of the placenta, there must be expert obstetric supervision. Its use should be avoided in patients with pre-eclampsia, eclampsia, or threatened spontaneous abortion.

Porphyria.

Ergometrine maleate has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

💊 Interactions

As for Ergotamine Tartrate. Halothane has been considered to diminish the effects of ergometrine on the uterus.

Sympathomimetics.

Use of dopamine in a patient treated with ergometrine was associated with subsequent development of gangrene in both hands and feet.1 In another case,2 the use of ergometrine with noradrenaline resulted in cyanosis of the hands and necrosis in some of the fingers.
1. Buchanan N, et al. Symmetrical gangrene of the extremities associated with the use of dopamine subsequent to ergometrine administration. Intensive Care Med 1977; 3: 55–6
2. Chuang S-S. Finger ischemia secondary to the synergistic agonist effect of norepinephrine and ergonovine and in a burn patient. Burns 2003; 29: 92–4.

💊 Pharmacokinetics

Ergometrine is reported to be rapidly absorbed after doses by mouth and by intramuscular injection, with onset of uterine contractions in about 5 to 15 minutes and 2 to 7 minutes, respectively. Elimination appears to be principally by hepatic metabolism.

💊 Uses and Administration

Ergometrine has a much more powerful action on the uterus than most other ergot alkaloids, especially on the puerperal uterus. Its main action is the production of intense contractions, which at higher doses are sustained, in contrast to the more physiological rhythmic uterine contractions induced by oxytocin; its action is more prolonged than that of oxytocin. Ergometrine maleate is used in the active management of the third stage of labour, and to prevent or treat postpartum or postabortal haemorrhage caused by uterine atony; by maintaining uterine contraction and tone, blood vessels in the uterine wall are compressed, and blood flow reduced. In the active management of the third stage of labour, ergometrine maleate and oxytocin are given together under full obstetric supervision. A dose of ergometrine maleate 500 micrograms and oxytocin 5 units is injected intramuscularly after delivery of the anterior shoulder, or, at the latest, immediately after de livery of the infant; contractions are reported to occur within 2 to 7 minutes. Delivery of the placenta is actively assisted while the uterus is firmly contracted. In the prevention or treatment of postpartum haemorrhage, a similar dose of ergometrine maleate with oxytocin is given intramuscularly following delivery of the placenta or when bleeding occurs. A combined intravenous preparation of ergometrine maleate with oxytocin has been used but is no longer recommended. Ergometrine maleate alone is used for prevention or treatment of postpartum or postabortal haemorrhage in a usual intramuscular dose of 200 micrograms. The dose may be repeated in severe bleeding, but is rarely needed more often than once in 2 to 4 hours. In emergencies such as excessive uterine bleeding, ergometrine maleate has been given intravenously in a dose of 200 micrograms; single doses of 250 to 500 micrograms have also been used. Intravenous doses should be given over at least 1 minute to reduce the risk of adverse effects, particularly hypertension. Parenteral treatment of haemorrhage may be followed by ergometrine maleate 200 to 400 micrograms orally 2 to 4 times daily until the danger of atony and haemorrhage has passed, which is usually 48 hours. Tablets have also been given sublingually. In the treatment of mild secondary postpartum haemorrhage, ergometrine maleate has been given orally. Ergometrine tartrate was formerly used.

Diagnosis and testing.

Ergometrine maleate1-8 or methylergometrine maleate9,10 have been used in a provocation test for the diagnosis of Prinzmetal’s angina (variant angina).
1. Waters DD, et al. Ergonovine testing in a coronary care unit. Am J Cardiol 1980; 46: 922–30
2. Health and Public Policy Committee, American College of Physicians. Performance of ergonovine provocative testing for coronary artery spasm. Ann Intern Med 1984; 100: 151–2
3. Song J-K, et al. Safety and clinical impact of ergonovine stress echocardiography for diagnosis of coronary vasospasm. J Am Coll Cardiol 2000; 35: 1850–6
4. Kashima K, et al. Long-term outcome of patients with ergonovine induced coronary constriction not associated with ischemic electrocardiographic changes. J Cardiol 2001; 37: 301–8
5. Palinkas A, et al. Safety of ergot stress echocardiography for non-invasive detection of coronary vasospasm. Coron Artery Dis 2001; 12: 649–54
6. Song JK, et al. Prognostic implication of ergonovine echocardiography in patients with near normal coronary angiogram or negative stress test for significant fixed stenosis. J Am Soc Echocardiogr 2002; 15: 1346–52
7. Sueda S, et al. Clinical impact of selective spasm provocation tests: comparisons between acetylcholine and ergonovine in 1508 examinations. Coron Artery Dis 2004; 15: 491–7
8. Coma-Canella I, et al. Ergonovine test in angina with normal coronary arteries: is it worth doing it? Int J Cardiol 2006; 107: 200–6
9. Bertrand ME, et al. Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation 1982; 65: 1299–1306
10. Lablanche JM, et al. Réflexions d’un comité d’experts de la Société française de cardiologie concernant l’usage du maléate de méthylergométrine (Methergin) dans la détection d’une vasomotricité coronaire anormale. Arch Mal Coeur Vaiss 1995; 88: 247–53.

💊 Preparations

BP 2008: Ergometrine and Oxytocin Injection; Ergometrine Injection; Ergometrine Tablets; USP 31: Ergonovine Maleate Injection; Ergonovine Maleate Tablets.

Proprietary Preparations

Arg.: Evina; Metrergina; Braz.: Ergotrate†; Gr.: Mitrotan; Mex.: Ergotrate; Thai.: Gynaemine; USA: Ergotrate. Multi-ingredient: Austral.: Syntometrine; Hong Kong: Syntometrine†; Irl.: Syntometrine; Malaysia: Syntometrine; NZ: Syntometrine; S.Afr.: Syntometrine; UK: Syntometrine.
Published October 26, 2018.