OFOST Solution for injection/infusion Ref.[50401] Active ingredients: Oxytocin

Precaution should be observed in patients with a history of ceasarean section or other surgical uterus interventions.

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.

When given for induction and enhancement of labour, oxytocin must only be administered as an intravenous drip infusion.

Ofost should not be used for prolonged periods in patients with oxytocin‑resistant uterine inertia, severe pre-eclamptic toxaemia or severe cardiovascular disorders.

Ofost should never be administered by intravenous bolus injection as it may cause a short-lasting hypotension accompanied with flushing and reflex tachycardia.

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 QT interval.

When Ofost is given for induction and enhancement of labour:

• Administration of oxytocin at excessive doses can be hazardous to both mother and foetus, resulting in uterine overstimulation which may cause foetal distress (foetal bradycardia, meconium-stained amniotic fluid, foetal asphyxia and death) and hypertonicity, tetanic contractions or rupture of the uterus. Careful monitoring of foetal heart rate (if possible cardiotocography (CTG)) and uterine motility is essential, so that the dosage may be adjusted to individual response. For patients with cardiovascular disease, the volume of infused fluid should be kept low by infusing oxytocin at a higher concentration.
• Particular caution is required in the presence of borderline cephalopelvic disproportion, secondary uterine inertia, mild or moderate degrees of pregnancy-induced hypertension or cardiac disease, and in patients above 35 years of age or with a history of lower-uterine-segment caesarean section.
• In rare circumstances, the pharmacological induction of labour using uterotonic agents increases the risk of postpartum disseminated intravascular coagulation (DIC). The pharmacological induction itself and not a particular agent 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 (such as gestational diabetes, hypertension, hypothyroidism) during pregnancy and gestational age more than 40 weeks. In these women, oxytocin or any other alternative medicine should be used with caution, and the practitioner should be alerted by signs of DIC. Women with the above mentioned risk factors should be examined concerning fibrinolysis immediately after labour.

Water intoxication

Since 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 and the intravenous 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.

Parenteral oxytocin must not be given simultaneously with oxytocin‑containing nasal spray.

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.

Anaphylaxis in women with latex allergy

There have been reports of anaphylaxis following administration of oxytocin in women with a known latex allergy. Due to the existing structural homology between oxytocin and latex, latex allergy/intolerance may be an important predisposing risk factor for anaphylaxis following oxytocin administration.

Other medicinal products contraindicated

Prostaglandins and their analogues

Prostaglandins and its analogues facilitate contraction of the myometrium, hence oxytocin can potentiate the uterine action of prostaglandins and analogues and vice versa (see section 4.3).

Concomitant use not recommended

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.

Pregnancy

Animal reproduction studies have not been conducted with oxytocin. Based on the wide experience with this medicine and its chemical structure and pharmacological properties, it is not expected to present a risk of foetal abnormalities when used as indicated. Oxytocin is contraindicated in pregnancy with exception of use for strictly medical reasons such as induction or enhancement of labour or at spontaneous or induced abortion.

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.

No studies on the effects on the ability to drive and use machines have been performed. Women with uterine contractions should not drive or use machines.

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 Special warnings and precautions for use). 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 Special warnings and precautions for use).

Adverse reactions are presented according to the MedDRA system organ classes and MedDRA frequency 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), not known (cannot be estimated from the available data).

Adverse drug reactions in mother

Blood and lymphatic system disorders

Not known: disseminated intravascular coagulation

Immune system disorders

Rare: Anaphylactoid reactions associated with dyspnoea, hypotension or shock

Metabolism and nutrition disorders

Not known: Water intoxication, maternal hyponatraemia

Nervous system disorders

Common: Headache

Cardiac disorders

Common: Tachycardia, bradycardia

Uncommon: Arrhythmia

Not known: Myocardial ischaemia, electrocardiogram QTc prolongation, reflex tachycardia.

Vascular disorders

Not known: Hypotension, haemorrhage

Respiratory, thoracic and mediastinal disorders

Not known: Acute pulmonary oedema

General disorders and administration site conditions

Not known: Flushing

Gastrointestinal disorders

Common: Nausea, vomiting

Skin and subcutaneous tissue disorders

Rare: Rash, urticaria

Not known: Angioedema

Pregnancy, puerperium and perinatal conditions

Not known: Uterine hypertonus, tetanic contractions of uterus, rupture of the Uterus.

Adverse drug reactions in foetus/neonate

Pregnancy, puerperium and perinatal conditions

Not known: foetal distress syndrome, 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 the HPRA Pharmacovigilance Website: www.hpra.ie.

Oxytocin should not be infused via the same apparatus as blood or plasma, because oxytocin can be inactivated.

Oxytocin is incompatible with solutions containing sodium metabisulphite as stabiliser.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.