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OXYTOCIN 10 IU/ML SOLUTION FOR INFUSION

Active substance(s): OXYTOCIN / OXYTOCIN

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Oxytocin 10 IU/ml Solution for infusion

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of solution contains 10 IU (16.7 micrograms) oxytocin.
Each 1 ml ampoule also contains 2.99 mg (0.13 mmol) sodium.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Solution for infusion.
Colourless, clear liquid with characteristic odour.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Antepartum
– Induction of labour for medical reasons, e.g. in cases of post-term gestation,
premature rupture of membranes, pregnancy-induced hypertension (pre-eclampsia).
– Stimulation of labour in hypotonic uterine inertia.
– Early stages of pregnancy as adjunctive therapy for the management of incomplete,
inevitable, or missed abortion.
Postpartum
– During caesarean section, following delivery of the child.
– Prevention and treatment of postpartum uterine atony and haemorrhage.

4.2

Posology and method of administration

Posology
Induction or enhancement of labour: Oxytocin should not be started for 6 hours
following administration of vaginal prostaglandins.
Oxytocin should be administered as an intravenous (i.v.) drip infusion or, preferably,
by means of a variable-speed infusion pump.
For drip infusion it is recommended that 5 IU (8.3 micrograms) of Oxytocin be added
to 500 ml of a physiological electrolyte solution (such as sodium chloride 0.9 %). For
patients in whom infusion of sodium chloride must be avoided, 5 % dextrose solution
may be used as the diluent (see section 4.4). To ensure even mixing, the bottle or bag
must be turned upside down several times before use.
The initial infusion rate should be set at 2 to 8 drops/minute (1 to 4 milliunits/minute).
It may be gradually increased at intervals not shorter than 20 minutes and increments
of not more than 1 to 2 milliunits/minute, until a contraction pattern similar to that of
normal labour is established. In pregnancy near term this can often be achieved with
an infusion of less than 20 drops/minute (10 milliunits/minute), and the recommended
maximum rate is 40 drops/minute (20 milliunits/minute). In the unusual event that
higher rates are required, as may occur in the management of foetal death in utero or
for induction of labour at an earlier stage of pregnancy, when the uterus is less
sensitive to oxytocin, it is advisable to use a more concentrated oxytocin solution,
e.g., 10 IU (16.7 micrograms) in 500 ml. When using a motor-driven infusion pump
which delivers smaller volumes than those given by drip infusion, the concentration
suitable for infusion within the recommended dosage range must be calculated
according to the specifications of the pump.
The frequency, strength, and duration of contractions as well as the foetal heart rate
must be carefully monitored throughout the infusion. Once an adequate level of
uterine activity is attained, aiming for 3 to 4 contractions every 10 minutes, the
infusion rate can often be reduced. In the event of uterine hyperactivity and/or foetal
distress, the infusion must be discontinued immediately.
If, in women who are at term or near term, regular contractions are not established
after the infusion of a total amount of 5 IU (8.3 micrograms), it is recommended that
the attempt to induce labour be ceased; it may be repeated on the following day,
starting again from a rate of 2 to 8 drops/minute (1 to 4 milliunits/minute) (see section
4.3).
Incomplete, inevitable, or missed abortion: 5 IU (8.3 micrograms) by i.v. infusion (5
IU diluted in physiological electrolyte solution and administered as an i.v. drip
infusion or, preferably, by means of a variable-speed infusion pump over 5 minutes),
if necessary followed by i.v. infusion at a rate of 20 to 40 milliunits/minute.
Caesarean section: 5 IU (8.3 micrograms) by i.v. infusion (5 IU diluted in
physiological electrolyte solution and administered as an i.v. drip infusion or,
preferably, by means of a variable-speed infusion pump over 5 minutes) immediately
after delivery.
Prevention of postpartum uterine haemorrhage: The usual dose is 5 IU (8.3
micrograms) by i.v. infusion (5 IU diluted in physiological electrolyte solution and
administered as an i.v. drip infusion or, preferably, by means of a variable-speed
infusion pump over 5 minutes) after delivery of the placenta. In women given
oxytocin for induction or enhancement of labour, the infusion should be continued at
an increased rate during the third stage of labour and for the next few hours thereafter.
Treatment of postpartum uterine haemorrhage: 5 IU (8.3 micrograms) by i.v.
infusion (5 IU diluted in physiological electrolyte solution and administered as an i.v.

drip infusion or, preferably, by means of a variable-speed infusion pump over 5
minutes), followed in severe cases by i.v. infusion of a solution containing 5 to 20 IU
(8.3 to 33.4 micrograms) of oxytocin in 500 ml of an electrolyte-containing diluent,
run at the rate necessary to control uterine atony.
Special populations
Renal impairment
No studies have been performed in renally impaired patients.
Hepatic impairment
No studies have been performed in hepatically impaired patients.
Paediatric population
There are no indications for use of Oxytocin in children or adolescents.
Older people (65 years and over)
There are no indications for use of Oxytocin in elderly.
Method of administration
Intravenous infusion.

4.3

Contraindications
– Hypersensitivity to the active substance or to any of the excipients listed in
section 6.1.
– Hypertonic uterine contractions, mechanical obstruction to delivery, foetal distress.
Any condition in which, for foetal or maternal reasons, spontaneous labour is
inadvisable and/or vaginal delivery is contraindicated: e.g.:
– Significant cephalopelvic disproportion
– Foetal malpresentation
– Placenta praevia and vasa praevia
– Placental abruption
– Cord presentation or prolapse
– Overdistension or impaired resistance of the uterus to rupture as in multiple
pregnancy
– Polyhydramnios
– Grand multiparity
– In the presence of a uterine scar resulting from major surgery including classical
caesarean section.
Oxytocin should not be used for prolonged periods in patients with oxytocin-resistant
uterine inertia, severe pre-eclamptic toxaemia or severe cardiovascular disorders.
Oxytocin must not be administered within 6 hours after vaginal prostaglandins have
been given (see section 4.5).

4.4

Special warnings and precautions for use
Oxytocin must only be administered as an i.v. infusion and never by i.v. bolus
injection as it may cause an acute short-lasting hypotension accompanied with
flushing and reflex tachycardia.
Induction of labour
The induction of labour by means of oxytocin should be attempted only when strictly
indicated for medical reasons. Administration should only be under hospital
conditions and qualified medical supervision.
Cardiovascular disorders
Oxytocin should be used with caution in patients who have a pre-disposition to
myocardial ischaemia due to pre-existing cardiovascular disease (such as
hypertrophic cardiomyopathy, valvular heart disease and/or ischaemic heart disease
including coronary artery vasospasm), to avoid significant changes in blood pressure
and heart rate in these patients.
QT Syndrome
Oxytocin should be given with caution to patients with known ‘long QT syndrome’ or
related symptoms and to patients taking drugs that are known to prolong the QTc
interval (see section 4.5).
When Oxytocin is given for induction and enhancement of labour:
– Foetal distress and foetal death: Administration of oxytocin at excessive doses
results in uterine overstimulation which may cause foetal distress, asphyxia and
death, or may lead to hypertonicity, tetanic contractions or rupture of the uterus.
Careful monitoring of foetal heart rate and uterine motility (frequency, strength, and
duration of contractions) is essential, so that the dosage may be adjusted to individual
response.
– Particular caution is required in the presence of borderline cephalopelvic
disproportion, secondary uterine inertia, mild or moderate degrees of pregnancyinduced hypertension or cardiac disease, and in patients above 35 years of age or with
a history of lower-uterine-segment caesarean section.
– Disseminated intravascular coagulation: In rare circumstances, the pharmacological
induction of labour using uterotonic agents, including oxytocin increases the risk of
postpartum disseminated intravascular coagulation (DIC). The pharmacological
induction itself and not a particular agent is linked to such risk. This risk is increased
in particular if the woman has additional risk factors for DIC such as being 35 years
of age or over, complications during pregnancy and gestational age more than 40
weeks. In these women, oxytocin or any other alternative drug should be used with
care, and the practitioner should be alerted by signs of DIC.
Intrauterine death
In the case of foetal death in utero, and/or in the presence of meconium-stained
amniotic fluid, tumultuous labour must be avoided, as it may cause amniotic fluid
embolism.
Water intoxication

Because oxytocin possesses slight antidiuretic activity, its prolonged i.v.
administration at high doses in conjunction with large volumes of fluid, as may be the
case in the treatment of inevitable or missed abortion or in the management of
postpartum haemorrhage, may cause water intoxication associated with
hyponatraemia. The combined antidiuretic effect of oxytocin and the i.v. fluid
administration may cause fluid overload leading to a haemodynamic form of acute
pulmonary oedema without hyponatraemia. To avoid these rare complications, the
following precautions must be observed whenever high doses of oxytocin are
administered over a long time: an electrolyte-containing diluent must be used (not
dextrose); the volume of infused fluid should be kept low (by infusing oxytocin at a
higher concentration than recommended for the induction or enhancement of labour
at term); fluid intake by mouth must be restricted; a fluid balance chart should be
kept, and serum electrolytes should be measured when electrolyte imbalance is
suspected.
Caution should be exercised in patients with severe renal impairment because of
possible water retention and possible accumulation of oxytocin (see section 5.2).

4.5

Interaction with other medicinal products and other forms of interaction
Interactions resulting in a concomitant use not recommended
Prostaglandins and their analogues
Prostaglandins and their analogues facilitate contraction of the myometrium hence
oxytocin can potentiate the uterine action of prostaglandins and analogues and vice
versa (see section 4.3).
Drugs prolonging the QT interval
Oxytocin should be considered as potentially arrhythmogenic, particularly in patients
with other risk factors for Torsades de Pointes such as drugs which prolong the QT
interval or in patients with history of long QT syndrome (see section 4.4).
Interactions to be considered
Inhalation anaesthetics
Inhalation anaesthetics (e.g. cyclopropane, halothane, sevoflurane, desflurane) have a
relaxing effect on the uterus and produce a notable inhibition of uterine tone and
thereby, may diminish the uterotonic effect of oxytocin. Their concurrent use with
oxytocin has also been reported to cause cardiac rhythm disturbances.
Vasoconstrictors/Sympathomimetics
Oxytocin may enhance the vasopressor effects of vasoconstrictors and
sympathomimetics, even those contained in local anaesthetics.
Caudal anaesthetics
When given during or after caudal block anaesthesia, oxytocin may potentiate the
pressor effect of sympathomimetic vasoconstrictor agents.

4.6

Fertility, pregnancy and lactation
Pregnancy

The induction of labour by means of oxytocin should be attempted only when strictly
indicated for medical reasons.
Animal reproduction studies have not been conducted with oxytocin. Based on the
wide experience with this drug and its chemical structure and pharmacological
properties, it is not expected to present a risk of foetal abnormalities when used as
indicated.
Breastfeeding
Oxytocin may be found in small quantities in mother's breast milk. However,
oxytocin is not expected to cause harmful effects in the newborn because it passes
into the alimentary tract where it undergoes rapid inactivation.
Fertility
Animal reproduction studies have not been conducted with oxytocin. The effects of
oxytocin on fertility are unknown.

4.7

Effects on ability to drive and use machines
Oxytocin can induce labour, therefore caution should be exercised when driving or
operating machines. Women with uterine contractions should not drive or use
machines.

4.8

Undesirable effects
As there is a wide variation in uterine sensitivity, uterine spasm may be caused in
some instances by what are normally considered to be low doses. When oxytocin is
used by i.v. infusion for the induction or enhancement of labour, administration at too
high doses results in uterine overstimulation which may cause foetal distress,
asphyxia, and death, or may lead to hypertonicity, tetanic contractions, soft tissue
damage or rupture of the uterus.
Rapid i.v. bolus injection of oxytocin at doses amounting to several IU may result in
acute short-lasting hypotension accompanied with flushing and reflex tachycardia
(see section 4.4). These rapid haemodynamic changes may result in myocardial
ischaemia, particularly in patients with pre-existing cardiovascular disease. Rapid i.v.
bolus injection of oxytocin at doses amounting to several IU may also lead to QTc
prolongation.
In rare circumstances the pharmacological induction of labour using uterotonic
agents, including oxytocin, increases the risk of postpartum disseminated
intravascular coagulation (see section 4.4).
Water intoxication
Water intoxication associated with maternal and neonatal hyponatraemia has been
reported in cases where high doses of oxytocin together with large amounts of
electrolyte-free fluid have been administered over a prolonged period of time (see
section 4.4).
The combined antidiuretic effect of oxytocin and the i.v. fluid administration may
cause fluid overload leading to a haemodynamic form of acute pulmonary oedema
without hyponatraemia (see section 4.4).
Symptoms of water intoxication include:
1. Headache, anorexia, nausea, vomiting and abdominal pain.

2. Lethargy, drowsiness, unconsciousness and grand-mal type seizures.
3. Low blood electrolyte concentration.
Undesirable effects (Tables 1 and 2) are ranked under heading of frequency, the most
frequent first, using the following convention: very common (≥1/10); common
(≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000);
very rare (<1/10,000), including isolated reports; not known (cannot be estimated
from the available data). The adverse reactions (ADRs) tabulated below are based on
clinical trial results as well as post-marketing reports.
The adverse drug reactions derived from post-marketing experience with oxytocin are
via spontaneous case reports and literature cases. Because these reactions are reported
voluntarily from a population of uncertain size, it is not possible to reliably estimate
their frequency which is therefore categorised as not known. Adverse drug reactions
are listed according to system organ classes in MedDRA. Within each system organ
class, ADRs are presented in order of decreasing seriousness.
Table 1 Adverse drug reactions in mother

System organ class

Adverse drug reaction

Immune system disorders

Rare: Anaphylactoid reaction associated
with dyspnoea, hypotension or shock

Nervous system disorders

Common: Headache

Cardiac disorders

Common: Tachycardia, bradycardia
Uncommon: Arrhythmia
Not known: Myocardial ischaemia,
QTc prolongation

Vascular disorders

Not known: Hypotension, haemorrhage

Gastrointestinal disorders

Common: Nausea, vomiting

Skin and subcutaneous tissue disorders

Rare: Rash

Pregnancy, puerperium and perinatal

Not known: Uterine hypertonicity,
tetanic contractions, rupture of the
uterus

conditions
Metabolism and nutrition disorders

Not known: Water intoxication,
maternal
hyponatraemia

Respiratory, thoracic and mediastinal

Not known: Acute pulmonary oedema

disorders
General disorders and administration site

Not known: Flushing

conditions
Blood and lymphatic system disorders

Not known: Disseminated intravascular

coagulation

Table 2 Adverse drug reactions in foetus/neonate

System organ class

Adverse drug reaction

Pregnancy, puerperium and perinatal
conditions

Not known: Foetal distress, asphyxia and
death

Metabolism and nutrition disorders

Not known: Neonatal hyponatraemia

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via:
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard

4.9

Overdose
The fatal dose of oxytocin has not been established. Oxytocin is subject to
inactivation by proteolytic enzymes of the alimentary tract. Hence it is not absorbed
from the intestine and is not likely to have toxic effects when ingested.
The symptoms and consequences of overdosage are those mentioned under section
4.8. In addition, as a result of uterine overstimulation, placental abruption and/or
amniotic fluid embolism have been reported.
Treatment: When signs or symptoms of overdosage occur during continuous i.v.
administration of oxytocin, the infusion must be discontinued at once and oxygen
should be given to the mother. In cases of water intoxication it is essential to restrict
fluid intake, promote diuresis, correct electrolyte imbalance, and control convulsions
that may eventually occur, by judicious use of diazepam. In the case of coma, a free
airway should be maintained with routine measures normally employed in the nursing
of the unconscious patient.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Systemic hormonal preparations, excl. sex hormones and
insulins, oxytocin and analogues, ATC code: H01BB02
Mechanism of action
Oxytocin is a cyclic nonapeptide that is obtained by chemical synthesis. This
synthetic form is identical to the natural hormone that is stored in the posterior
pituitary and released into the systemic circulation in response to suckling and labour.

Oxytocin stimulates the smooth muscle of the uterus, more powerfully towards the
end of pregnancy, during labour, and immediately postpartum. At these times, the
oxytocin receptors in the myometrium are increased.
The oxytocin receptors are G-proteins coupled receptors. Activation of receptor by
oxytocin triggers release of calcium from intracellular stores and thus leads to
myometrial contraction.
Oxytocin elicits rhythmic contractions in upper segment of uterus, similar in
frequency, force and duration to those observed during labour.
Being synthetic, oxytocin in this product does not contain vasopressin, but even in its
pure form oxytocin possesses some weak intrinsic vasopressin-like antidiuretic
activity.
Based on in vitro studies, prolonged exposure of oxytocin had been reported to cause
desensitisation of oxytocin receptors probably due to down-regulation of oxytocinbinding sites, destabilisation of oxytocin receptors mRNA and internalisation of
oxytocin receptors.
Plasma levels and onset/duration of effect
Intravenous infusion. When oxytocin is given by continuous i.v. infusion at doses
appropriate for induction or enhancement of labour, the uterine response sets in
gradually and usually reaches a steady state within 20 to 40 minutes. The
corresponding plasma levels of oxytocin are comparable to those measured during
spontaneous first-stage labour.
For example, oxytocin plasma levels in 10 pregnant women at term receiving a 4
milliunits per minute intravenous infusion were 2 to 5 microunits/mL. Upon
discontinuation of the infusion, or following a substantial reduction in the infusion
rate, e.g. in the event of overstimulation, uterine activity declines rapidly but may
continue at an adequate lower level.

5.2

Pharmacokinetic properties
Absorption
Plasma levels of oxytocin following intravenous infusion at 4 milliunits per minute in
pregnant women at term were 2 to 5 microunits/mL.
Distribution
The steady-state volume of distribution determined in 6 healthy men after i.v.
injection is 12.2 L or 0.17 L/kg. Plasma protein binding is negligible for oxytocin. It
crosses the placenta in both directions. Oxytocin may be found in small quantities in
mother’s breast milk.
Biotransformation/Metabolism
Oxytocinase is a glycoprotein aminopeptidase that is produced during pregnancy and
appears in the plasma. It is capable of degrading oxytocin. It is produced from both
the mother and the foetus. Liver and kidney plays a major role in metabolising and
clearing oxytocin from the plasma. Thus, liver, kidney and systemic circulation
contribute to the biotransformation of oxytocin.
Elimination
Plasma half-life of oxytocin ranges from 3 to 20 minutes. The metabolites are
excreted in urine whereas less than 1 % of the oxytocin is excreted unchanged in
urine. The metabolic clearance rate amounts to 20 mL/kg/min in the pregnant woman.

Renal impairment
No studies have been performed in renally impaired patients. However, considering
the excretion of oxytocin and its reduced urinary excretion because of anti-diuretic
properties, the possible accumulation of oxytocin can result in prolonged action.
Hepatic impairment
No studies have been performed in hepatically impaired patients. Pharmacokinetic
alteration in patients with impaired hepatic function is unlikely since metabolising
enzyme, oxytocinase, is not confined to liver alone and the oxytocinase levels in
placenta during the term has significantly increased. Therefore, biotransformation of
oxytocin in impaired hepatic function may not result in substantial changes in
metabolic clearance of oxytocin.

5.3

Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to
those already included in other sections of the Summary of Product Characteristics.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Acetic acid, glacial
Sodium acetate trihydrate
Sodium chloride
Sodium hydroxide
Water for injections

6.2

Incompatibilities
Oxytocin should not be infused via the same apparatus as blood or plasma, because
the peptide linkages are rapidly inactivated by oxytocin-inactivating enzymes.
Oxytocin is incompatible with solutions containing sodium metabisulphite as a
stabiliser.

6.3

Shelf life

4 years.

Chemical and physical in-use stability has been demonstrated for 48 hours at 25 °C
when diluted with the solutions stated in section 6.6. From a microbiological point of
view, the product should be used immediately. If not used immediately, in-use storage
times and conditions prior to use are the responsibility of the user and would normally
not be longer than 24 hours at 2 to 8 °C, unless dilution has taken place in controlled
and validated aseptic conditions.

6.4

Special precautions for storage
Store in a refrigerator (2 °C – 8 °C). May be stored up to 30°C for 3 months, but must
then be discarded.
See section 6.3 for storage of diluted product.
Keep the ampoules in the outer carton in order to protect from light.

6.5

Nature and contents of container
Transparent 1 ml PhEur type 1 glass ampoules.
Pack sizes:
5 ampoules
10 ampoules
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
Oxytocin is compatible with the following infusion fluids: sodium chloride 0.9 %,
dextrose 5 %, Ringer's solution, acetated Ringer's solution.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
Peckforton Pharmaceuticals Limited,
Crewe Hall, Crewe, Cheshire,
CW1 6UL
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 15760/0036

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23/04/2014

10

DATE OF REVISION OF THE TEXT
29/04/2015

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Source: Medicines and Healthcare Products Regulatory Agency

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