Ergometrine Maleate
A white or yellowish, odourless, crystalline powder. It dark-
ens with age and on exposure to light. Sparingly soluble in
water; slightly soluble in alcohol: practically insoluble in
chloroform and ether. A 1% solution in water has a pH of 3.6
to 4.4. Store in airtight glass containers at a temperature of 2Β°
to 8Β°. Protect from light.
Stability. Reports of deterioration and degradation of er-
gometrine-containing injections when exposed to high tem-
peratures in the tropics. The mean loss in one study 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%
of the stated amount. A similar but much less significant pat-
tern was seen with methylergometrine: the content varied
from 98.6 to 99.5% of the labelled amount.
Adverse Effects and Treatment
Nausea and vomiting, abdominal pain. diarrhoea, headache,
dizziness, tinnitus, chest pain, palpitations, bradycardia. and
dyspnoea have been reported after administration of er-
gometrine. Hypertension has occurred, particularly after rap-
id intravenous administration. Hypersensitivity reactions
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 cardiovascular system. For reference to
cardiovascular effects, including arrhythmias and myocardial
infarction, associated with the administration of ergometrine
maleate, see Diagnosis and Testing under Uses, below.
Effects on the respiratory system. Bronchospasm has
been reported after administration of ergometrine. Although
studies in vitro on canine bronchi have suggested a direct ac-
tion on smooth muscle, this could not be confirmed in studies
using human bronchi.
Overdosage. There have been reports of accidental admin-
istration of adult doses of ergometrine maleate to neonates,
sometimes instead of vitamin K. Symptoms have included
peripheral vasoconstriction, convulsions, respiratory failure,
acute renal failure, and temporary lactose intolerance. After
administration of ergometrine with oxytocin. water intoxica-
tion has also been reported. In all of these cases recovery
occurred after intensive symptomatic treatment including as-
sisted ventilation and anticonvulsants.
Precautions
As for Ergotamine Tartrate. Ergometrine maleate
should not be used for the induction of labour or during the
first stage of labour. If used at the end of the second stage of
labour, prior to delivery of the placenta, there must be expert
obstetric supervision. Its use should be avoided in patients
with eclampsia.
Porphyria. Ergometrine maleate has been associated with
clinical exacerbations of porphyria and is considered unsafe
in porphyric patients.
Interactions
Halothane has been considered to diminish the effects of er-
gometrine on the uterus.
Sympathomimetics. Use of dopamine in a patient treat-
ment with ergometrine was associated with subsequent devel-
opment of gangrene in both hands and feet.
Pharmacokinetics
Ergometrine is reported to be rapidly absorbed after adminis-
tration by mouth and by intramuscular injection, with onset of
uterine contractions in about 5 to 15 minutes after an oral dose
and 2 or 3 minutes after an intramuscular dose. Elimination
appears to be principally by metabolism in the liver.
Uses and Administration
Ergometrine has a much more powerful action on the uterus
than most of the other alkaloids of ergot, 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 in-
duced by oxytocin; its action is more prolonged than that of
oxytocin.
Ergometrine maleate may be used in the prevention and treat-
ment of postpartum 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
UK it is generally given with oxytocin. Following intramus-
cular injection of ergometrine with oxytocin contractions are
reported to occur within 2 or 3 minutes. Ergometrine and ox-
ytocin are administered under full obstetric supervision in the
active management of the third stage of labour of normal con-
finements. A dose of ergometrine maleate 500 mcg and oxytoc-
in 5 units is injected intramuscularly after delivery of the
anterior shoulder of the infant Delivery of the placenta is ac-
tively assisted while the uterus is firmly contracted. Alterna-
tively, a similar dose may be given following delivery of the
placenta to prevent or treat postpartum haemorrhage. In pa-
tients considered at high risk of postpartum haemorrhage er-
gometrine maleate may be given intravenously in a dose of
125 to 250 mcg. Oxytocin may be used as an alternative but
intravenous administration of the combined preparation is no
longer recommended. In the treatment of mild secondary
postpartum haemorrhage ergometrine maleate has been given
by mouth in a dose of 500 ng three times daily for 3 days.
In the USA ergometrine maleate is usually given alone and is
not generally recommended before delivery of the placenta.
Doses have generally been lower than those used in the UK.
A typical regimen is 200 mcg intramuscularly or by slow intra-
venous injection every 2 to 4 hours as needed, for up to 5
doses. This may be followed by 200 to 400 mcg by mouth two
to four times a day for up to 7 days, until the danger of atony
and haemorrhage has passed.
Ergometrine maleate has been administered by the sublingual
and rectal routes.
Ergometrine tartrate was formerly used.
Diagnosis and testing. Ergometrine maleate or methyl-
ergometrine maleate have been used in a provocation test
for the diagnosis of variant angina (Prinzmetal's angina).
Ergometrine maleate has also been used in the diag-
nosis of oesophageal spas .
Postpartum haemorrhage. In normal labour, once the
child is born myometrial retraction and strong uterine con-
tractions cause shortening and kinking of the uterine blood
vessels and a retraction of the placenta) bed: these changes
operate to minimise blood loss. However, if the uterus fails to
contract adequately (uterine atony) or if retained placental
remnants prevent retraction of the placental bed. postpartum
haemorrhage may occur. These two causes account for about
80% of cases of postpartum haemorrhage; in the remainder it
is usually due to trauma of the genital tract.
Postpartum haemorrhage may well be fatal to the mother un-
less promptly dealt with: management generally involves re-
moval of the placenta if this has not been expelled, the use of
oxytocics to contract the uterus, and. if blood loss is severe,
transfusion. Prophylactic management is favoured in some
countries but in others may be reserved for women at greater
risk. including those who have undergone prolonged labour,
those who have an over distended uterus (for example in mul-
tiple pregnancy), or after antepartum haemorrhage, or deep
general anaesthesia.
A policy of active management of the third stage of labour
(prophylactic administration of an oxytocic, cord clamping
before placental delivery, and cord traction) is common in the
UK. The rationale for such management has been exam-
ined. A meta-analysis of all known, randomized. controlled
studies of routine prophylactic oxytocics has shown that.
when labour is actively managed, routine oxytocics (usually
with crowning of the head, delivery of the anterior shoulder.
or after delivery of the placenta) reduced the risk of postpar-
tum haemorrhage by about 40%.2 These studies were further
analyzed to compare the efficacy and safety of the different
oxytocic agents: ergot alkaloids, oxytocin, prostaglandins,
and a mixture of ergometrine and oxytocin (Syntometrine).
Comparison of oxytocin and ergot alkaloids suggested that,
although they may be of similar efficacy in decreasing post-
partum haemorrhage, oxytocin is less likely to predispose to
delayed placental delivery and also less likely to cause hyper-
tension. Syntometrine and ergot alkaloids also appeared to be
of similar efficacy, but Syntometrine may be less likely to be
associated with a prolonged third stage of labour. The availa-
ble evidence from two studies comparing Syntometrine (used
preferentially in the UK) and oxytocin (used preferentially in
North America) suggests that Syntometrine is the more effec-
tive prophylactic, but possibly at the expense of a higher risk
of hypertension. A subsequent Australian study involving
3497 women found no significant difference in efficacy be-
tween intramuscular oxytocin and Syntometrine for active
management of third stage labour,' but a higher incidence of
adverse effects (nausea, vomiting, hypertension) with the lat-
ter. This group concluded that there were no advantages to the
use of Syntometrine, but their analysis has been criticized on
the grounds that there was a lower incidence of postpartum
haemorrhage in the group given Syntometrine, which would
be clinically significant even if it failed to achieve
statistical significance.
There are numerous reports suggesting the efficacy of pros-
taglandins such as carboprost, dinoprostone, or sulprostone in
the treatment of established postpartum haemorrhage but
there is little evidence of their role in active management of
third stage labour. However, prophylactic use of misoprostol.
given orally immediately after delivery was effective in one
study, although comparative trials are needed.