Symptoms of acute poisoning include nausea, vomiting, diarrhoea, extreme thirst, coldness, tingling and itching of the skin, tachycardia, vasospastic reactions, respiratory depression, confusion, convulsions and coma. Angina, hypertension or hypotension may also occur.
In cases of oral ingestion, although the benefit of gastric decontamination is uncertain, activated charcoal may be given to patients who present within 1 hour of ingesting a toxic dose (more than 125 micrograms/kg in adults) or any amount in a child or in adults with peripheral vascular disease, ischaemic heart disease, severe infection, or hepatic or renal impairment. Alternatively, gastric lavage may be considered in adults within 1 hour of ingesting a potentially life-threatening overdose.
In both acute and chronic poisoning by all routes, attempts must be made to maintain an adequate circulation to the affected parts of the body in order to prevent the onset of gangrene. In severe arterial vasospasm, vasodilators such as sodium nitroprusside by intravenous infusion have been given; heparin and dextran 40 have also been advocated to minimise the risk of thrombosis. Analgesics may be required for severe ischaemic pain.
Accidental administration of Ergometrin Lek-containing medicinal products to the newborn infant has been reported and has proved fatal. In these accidental neonatal overdosage cases, symptoms such as respiratory depression, convulsions, cyanosis, oliguria, hypertonia and heart arrhythmia have been reported. Treatment has been symptomatic in most cases; respiratory and cardiovascular support have been required.
-
- ).
- Primary or secondary uterine inertia.
- Severe hypertension, pre-eclampsia, eclampsia.
- Severe cardiac disorders.
- Severe hepatic or renal impairment.
- Occlusive vascular disease e.g. Raynaud's disease / phenomenon
- Sepsis
Ergometrin Lek Injection is incompatible with various drugs according to resulting Ph, temperature and concentration of drugs. Mixing with other drugs in the same syringe should therefore be avoided. Ergometrin Lek may, however, be diluted to a volume of 5mls with 0.9% Sodium Chloride Injection prior to IV administration.
Immune system disorders
Anaphylactic/Anaphylactoid reactions with associated symptoms of dyspnoea, hypotension, collapse or shock
Nervous system disorders
Headache, dizziness
Ear & labyrinth disorders
Tinnitus
Cardiac disorders
)Vascular disorders
Hypertension, vasoconstriction
Respiratory disorders
Dyspnoea, pulmonary oedema
Gastrointestinal disorders
Nausea, vomiting, abdominal pain
Skin & subcutaneous tissue disorders
Skin rashes
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 Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections of the Summary of Product Characteristics.
Ergometrin Lek Injection is used in the active management of the third stage of labour and in the treatment of post-partum haemorrhage. Ergometrin Lek Injection may be given by intramuscular or intravenous injection.
Pharmacotherapeutic group: Ergot alkaloids
ATC code: G02AB03
Ergometrin Lek produces sustained tonic uterine contraction via agonist or partial agonist effects at myometrial 5-HT2 receptors and alpha-adrenergic receptors. Both upper and lower uterine segments are stimulated to contract in a tetanic manner. Unlike oxytocin Ergometrin Lek has an effect on the non-pregnant uterus. Ergometrin Lek inhibits prolactin secretion and in turn can reduce lactation. Uterine stimulation occurs within 7 minutes of intramuscular injection and almost immediately following intravenous injection. The sustained uterine contractions produced by Ergometrin Lek are effective in controlling uterine haemorrhage.
Ergometrin Lek has weak antagonist actions at dopaminergic receptors in certain blood vessels. Compared with other ergot alkaloids, effects of Ergometrin Lek on cardiovascular and central nervous system are less pronounced. It has a partial agonist action in blood vessels (less than ergotamine) and has little or no antagonist action at α adrenergic receptors.
Paediatric population
No data are available.
Elderly
Not applicable.
Method of administration
Intramuscular injection is the recommended route.
Intravenous administration of Ergometrin Lek Injection at a dose of 250 micrograms to 500 micrograms (by slow injection) is possible, but should be limited to use only in cases of severe haemorrhage due to uterine atony.
4.3 Contraindications-
- ).
- Primary or secondary uterine inertia.
- Severe hypertension, pre-eclampsia, eclampsia.
- Severe cardiac disorders.
- Severe hepatic or renal impairment.
- Occlusive vascular disease e.g. Raynaud's disease / phenomenon
- Sepsis
4.4 Special warnings and precautions for useErgometrin Lek may give rise to widespread vasoconstriction and rarely acute pulmonary oedema.
Active management of the third stage of labour requires expert obstetric supervision.
Ergometrin Lek derivatives are excreted in breast milk but in unknown amounts.).
Caution is required in patients with mild or moderate hypertension, or with mild or moderate degrees of cardiac, liver or kidney disease. Severe forms are contraindications.
Patients with coronary artery disease may be more susceptible to angina or myocardial ischaemia and infarction caused by Ergometrin Lek-induced vasospasm.
If in the treatment of postpartum haemorrhage, bleeding is not arrested by the injection, the possibility of a retained placental fragment, or soft tissue injury (cervical or vaginal laceration), or of a clotting defect should be considered and appropriate measures taken before a further injection is given.
Ergot alkaloids are substrates of CYP3A4.).
4.5 Interaction with other medicinal products and other forms of interactionConcomitant use of Ergometrin Lek Injection with the following medicinal products is not recommended:
Vasoconstrictors/Sympathomimetics
Ergometrin Lek Injection 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 Ergometrin Lek Injection can potentiate the uterine action of prostaglandins and analogues and vice versa.
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 Ergometrin Lek 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 Ergometrin Lek 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
Ergometrin Lek produces vasoconstriction and can be expected to reduce the effect of glyceryl trinitrate and other antianginal drugs.
Consideration should be given to the concomitant use of Ergometrin Lek Injection with the following medicinal products:
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 Ergometrin Lek.
CYP3A4 inducers
CYP3A4 inducers (e.g nevirapine, rifampicin) may reduce the clinical effect of Ergometrin Lek.
4.6 Fertility, pregnancy and lactationPregnancy
Ergometrin Lek has potent uterotonic activity. Therefore, Ergometrin Lek Injection is contraindicated during pregnancy, during induction of labour, and during first and second stage labour prior to the delivery of the anterior shoulder.
Breast-feeding
Ergometrin Lek derivatives are excreted in breast milk but in unknown amounts. There is no specific data available for elimination of Ergometrin Lek partitioned in breast-milk. Ergometrin Lek can inhibit prolactin secretion and in turn can suppress lactation, so its repeated use should be avoided.
4.7 Effects on ability to drive and use machinesReceiving Ergometrin Lek Injection can start labour. Women with contractions should not drive or use machines. Patients should be warned of the possibility of dizziness and hypotension.
4.8 Undesirable effectsImmune system disorders
Anaphylactic/Anaphylactoid reactions with associated symptoms of dyspnoea, hypotension, collapse or shock
Nervous system disorders
Headache, dizziness
Ear & labyrinth disorders
Tinnitus
Cardiac disorders
)Vascular disorders
Hypertension, vasoconstriction
Respiratory disorders
Dyspnoea, pulmonary oedema
Gastrointestinal disorders
Nausea, vomiting, abdominal pain
Skin & subcutaneous tissue disorders
Skin rashes
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 Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 OverdoseSymptoms of acute poisoning include nausea, vomiting, diarrhoea, extreme thirst, coldness, tingling and itching of the skin, tachycardia, vasospastic reactions, respiratory depression, confusion, convulsions and coma. Angina, hypertension or hypotension may also occur.
In cases of oral ingestion, although the benefit of gastric decontamination is uncertain, activated charcoal may be given to patients who present within 1 hour of ingesting a toxic dose (more than 125 micrograms/kg in adults) or any amount in a child or in adults with peripheral vascular disease, ischaemic heart disease, severe infection, or hepatic or renal impairment. Alternatively, gastric lavage may be considered in adults within 1 hour of ingesting a potentially life-threatening overdose.
In both acute and chronic poisoning by all routes, attempts must be made to maintain an adequate circulation to the affected parts of the body in order to prevent the onset of gangrene. In severe arterial vasospasm, vasodilators such as sodium nitroprusside by intravenous infusion have been given; heparin and dextran 40 have also been advocated to minimise the risk of thrombosis. Analgesics may be required for severe ischaemic pain.
Accidental administration of Ergometrin Lek-containing medicinal products to the newborn infant has been reported and has proved fatal. In these accidental neonatal overdosage cases, symptoms such as respiratory depression, convulsions, cyanosis, oliguria, hypertonia and heart arrhythmia have been reported. Treatment has been symptomatic in most cases; respiratory and cardiovascular support have been required.
5. Pharmacological properties 5.1 Pharmacodynamic propertiesPharmacotherapeutic group: Ergot alkaloids
ATC code: G02AB03
Ergometrin Lek produces sustained tonic uterine contraction via agonist or partial agonist effects at myometrial 5-HT2 receptors and alpha-adrenergic receptors. Both upper and lower uterine segments are stimulated to contract in a tetanic manner. Unlike oxytocin Ergometrin Lek has an effect on the non-pregnant uterus. Ergometrin Lek inhibits prolactin secretion and in turn can reduce lactation. Uterine stimulation occurs within 7 minutes of intramuscular injection and almost immediately following intravenous injection. The sustained uterine contractions produced by Ergometrin Lek are effective in controlling uterine haemorrhage.
Ergometrin Lek has weak antagonist actions at dopaminergic receptors in certain blood vessels. Compared with other ergot alkaloids, effects of Ergometrin Lek on cardiovascular and central nervous system are less pronounced. It has a partial agonist action in blood vessels (less than ergotamine) and has little or no antagonist action at α adrenergic receptors.
5.2 Pharmacokinetic propertiesAbsorption
Ergometrin Lek is rapidly absorbed after administration by mouth or by intramuscular injection. Uterotonic effect can be observed within 10 minutes following oral administration and within 7 minutes of intramuscular injection.
Distribution
The average steady state volume of distribution of Ergometrin Lek in healthy man is reported to be 1.04 L/kg. The plasma protein binding of Ergometrin Lek is unknown. Ergometrin Lek is known to cross the placenta and its clearance from the foetus is slow. Concentrations of Ergometrin Lek achieved in foetus are not known. Ergometrin Lek is also expected to be excreted in the breast milk and to reduce milk secretion.
Metabolism/Biotransformation
Ergometrin Lek is mainly metabolised in the liver by hydroxylation and glucuronic acid conjugation and possibly N-demethylation. Like other ergot alkaloids it is a substrate for CYP3A4 enzymes.
Elimination
The plasma half life of Ergometrin Lek is reported to be in the range of 30-120 min. When administered orally, the drug is mainly eliminated with the bile into the faeces as 12-hydroxyErgometrin Lek glucuronide. It is eliminated unchanged in the urine and can be detected up to 8 h after injection.
Paediatric population
No data are available.
Elderly
Not applicable.
Method of administration
Intramuscular injection is the recommended route.
Intravenous administration of Ergometrin Lek Injection at a dose of 250 micrograms to 500 micrograms (by slow injection) is possible, but should be limited to use only in cases of severe haemorrhage due to uterine atony.
4.3 Contraindications-
- ).
- Primary or secondary uterine inertia.
- Severe hypertension, pre-eclampsia, eclampsia.
- Severe cardiac disorders.
- Severe hepatic or renal impairment.
- Occlusive vascular disease e.g. Raynaud's disease / phenomenon
- Sepsis
4.4 Special warnings and precautions for useErgometrin Lek may give rise to widespread vasoconstriction and rarely acute pulmonary oedema.
Active management of the third stage of labour requires expert obstetric supervision.
Ergometrin Lek derivatives are excreted in breast milk but in unknown amounts.).
Caution is required in patients with mild or moderate hypertension, or with mild or moderate degrees of cardiac, liver or kidney disease. Severe forms are contraindications.
Patients with coronary artery disease may be more susceptible to angina or myocardial ischaemia and infarction caused by Ergometrin Lek-induced vasospasm.
If in the treatment of postpartum haemorrhage, bleeding is not arrested by the injection, the possibility of a retained placental fragment, or soft tissue injury (cervical or vaginal laceration), or of a clotting defect should be considered and appropriate measures taken before a further injection is given.
Ergot alkaloids are substrates of CYP3A4.).
Receiving Ergometrin Lek Injection can start labour. Women with contractions should not drive or use machines. Patients should be warned of the possibility of dizziness and hypotension.
Ergometrin Lek Injection should be used under medical supervision only
Adults:
Active Management of the Third Stage of Labour
Ergometrin Lek Injection is administered (often in combination with synthetic oxytocin 5 units) intramuscularly as a dose of 500 micrograms following the delivery of the anterior shoulder of the infant or at the latest immediately after delivery of the baby.
Prevention and Treatment of Postpartum Haemorrhage
Doses of 200 micrograms to 500 micrograms of Ergometrin Lek are given intramuscularly, following expulsion of the placenta or when bleeding occurs. In emergencies, Ergometrin Lek Injection may be given intravenously at a dose of 250 micrograms to 500 micrograms.
Use in special populations
Patients with renal impairment or hepatic impairment
No studies have been performed in patients with renal or hepatic impairment.4 Special warnings and precautions for use and 5.2 Pharmacokinetic properties).
Paediatric population
No data are available.
Elderly
Not applicable.
Method of administration
Intramuscular injection is the recommended route.
Intravenous administration of Ergometrin Lek Injection at a dose of 250 micrograms to 500 micrograms (by slow injection) is possible, but should be limited to use only in cases of severe haemorrhage due to uterine atony.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
