SYNTOMETRINE Solution for injection Ref.[28070] Active ingredients: Ergometrine Oxytocin

Active management of the third stage of labour requires expert obstetric supervision.

In breech presentations and other abnormal presentations, Syntometrine should not be given until after delivery of the child, and in multiple births not until the last child has been delivered (see section 4.6 Fertility, pregnancy and lactation).

Ergometrine derivatives are excreted in breast milk but in unknown amounts. It can also suppress lactation, so repeated use should be avoided (see section 4.6 Fertility, pregnancy and lactation).

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.

Ergometrine can cause vasoconstriction and should therefore be used with caution in patients with Raynaud’s phenomenon.

Caution is required in patients with mild or moderate hypertension, cardiac disorder, or hepatic or renal impairment. Severe forms are contraindications (see section 4.3 Contraindications).

Patients with coronary artery disease may be more susceptible to angina or myocardial ischaemia and infarction caused by ergometrine-induced vasospasm.

Oxytocin should be considered as potentially arrhythmogenic. Caution is required when using Syntometrine in patients with other risk factors for torsades de pointes such as drugs which prolong the QT interval or in patients with a history of long QT syndrome (see section 4.5 Interaction with other medicinal products and other forms of interaction).

In postpartum haemorrhage, if bleeding is not arrested by the injection of Syntometrine, the possibility of retained placental fragments, of soft tissue injury (cervical or vaginal laceration), or of a clotting defect, should be excluded before a further injection is given.

Ergot alkaloids are substrates of CYP3A4.The concomitant use of Syntometrine with strong CYP3A4 inhibitors such as macrolide antibiotics (e.g. troleandomycin, erythromycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g. ritonavir, indinavir, nelfinavir, delavirdine), or azole antifungals (e.g. ketoconazole, itraconazole, voriconazole) should be avoided, since this can result in an elevated exposure to methylergometrine and ergot toxicity (vasospasm and ischaemia of the extremities and other tissues). Caution should be exercised when Syntometrine is used concurrently with other vasoconstrictors or other ergot alkaloids. Concurrent use of vasoconstrictors and Syntometrine after delivery during anaesthesia may lead to severe postpartum hypertension. Methylergometrine may enhance the vasoconstrictor/vasopressor effects of other drugs such as triptans (5HT1B/1D receptor agonists), sympathomimetics (including those in local anaesthetics), beta-blockers or other ergot alkaloids (see section 4.5 Interaction with other medicinal products and other forms of interaction).

Caution is required when using Syntometrine alone or in combination with prostaglandins and their analogues in the treatment of postpartum atonic uterine haemorrhage (see section 4.5 Interaction with other medicinal products and other forms of interaction).

Syntometrine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.

Interactions related to both oxytocin and ergometrine administration

Interactions resulting in concomitant use not recommended (see section 4.4 Special warnings and precautions for use)

Vasoconstrictors/Sympathomimetics

Syntometrine may enhance the vasopressor effects of vasoconstrictors and sympathomimetics, even those contained in local anaesthetics.

Prostaglandins and their analogues

Prostaglandins and their analogues facilitate contraction of the myometrium hence Syntometrine can potentiate the uterine action of prostaglandins and analogues and vice versa.

Interactions to be considered

Inhalation anaesthetics

Inhalation anaesthetics (e.g. halothane, cyclopropane, sevoflurane, desflurane, isoflurane) have a relaxing effect on uterus and produce a notable inhibition of uterine tone and thereby, may diminish the uterotonic effect of Syntometrine.

Interactions related to oxytocin administration

Interactions resulting in concomitant use not recommended (see section 4.4 Special warnings and precautions for use)

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.

Interactions related to ergometrine administration

Interactions resulting in concomitant use not recommended (see section 4.4 Special warnings and precautions for use)

CYP3A4 inhibitors

Strong CYP3A4 inhibitors such as protease inhibitors, macrolide antibiotics (e.g. troleandomycin, erythromycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g. ritonavir, indinavir, nelfinavir, delavirdine), azole antifungals (e.g. ketoconazole, itraconazole, voriconazole), quinolones might raise the levels of ergot derivatives, which may lead to ergotism. Combined use with Syntometrine should be avoided. Other weaker CYP3A4 inhibitors (e.g cimetidine, delavirdine, grapefruit juice, quinupristin, dalfopristin) might interact similarly, although possibly to a lesser extent.

Ergot alkaloids/ergot derivatives

Concurrent use of other ergot alkaloids (e.g methysergide) and other ergot derivatives can increase the risk of severe and persistent spasm of major arteries in some patients.

Triptans

Additive vasoconstriction may occur when ergometrine is concomitantly given with triptans (e.g. sumatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan).

Beta-blockers

Concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids.

Glyceryl trinitrate and other antianginal drugs

Ergometrine produces vasoconstriction and can be expected to reduce the effect of glyceryl trinitrate and other antianginal drugs.

Interactions to be considered

CYP3A4 inducers

CYP3A4 inducers (e.g nevirapine, rifampicin) may reduce the clinical effect of ergometrine.

Pregnancy

Ergometrine has potent uterotonic activity. Therefore Syntometrine is contraindicated during pregnancy and during induction of labour; first stage labour and second stage labour prior to the delivery of the anterior shoulder (see section 4.3 Contraindications).

In breech presentation and other abnormal presentations, Syntometrine should not be given before delivery of the child is completed, and in multiple births not before the last child has been delivered (see section 4.4 Special warnings and precautions for use).

Breast-feeding

Ergometrine derivatives are excreted in breast milk but in unknown amounts. There is no specific data available for elimination of ergometrine partitioned in breast-milk. Ergometrine can inhibit prolactin secretion and in turn can suppress lactation, so its repeated use should be avoided.

Taking Syntometrine can start labour. Women with contractions should not drive or use machines.

Patients should be warned of the possibility of dizziness and hypotension (see section 4.8 Undesirable effects).

The following adverse drug reactions have been reported during post-approval use of Syntometrine via spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a population of uncertain size and subject to confounding factors, it is not possible to reliably estimate their frequency which is therefore quoted as not known. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system class organ class, ADRs are presented in order of decreasing seriousness.

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow card in the Google Play or Apple App Store.

None.