Ergo-M

Ergo-M Injection is used in the active management of the third stage of labour and in the treatment of post-partum haemorrhage. Ergo-M Injection may be given by intramuscular or intravenous injection.

Ergo-M Injection should be used under medical supervision only

Adults:

Active Management of the Third Stage of Labour

Ergo-M 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 Ergo-M are given intramuscularly, following expulsion of the placenta or when bleeding occurs. In emergencies, Ergo-M 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 Ergo-M 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.

-

- ).

- 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

Paediatric population

No data are available.

Elderly

Not applicable.

Method of administration

Intramuscular injection is the recommended route.

Intravenous administration of Ergo-M 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.

-

- ).

- 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

Ergo-M may give rise to widespread vasoconstriction and rarely acute pulmonary oedema.

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

Ergo-M 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 Ergo-M-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 Ergo-M Injection can start labour. Women with contractions should not drive or use machines. Patients should be warned of the possibility of dizziness and hypotension.

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.

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 Ergo-M-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.

Pharmacotherapeutic group: Ergot alkaloids

ATC code: G02AB03

Ergo-M 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 Ergo-M has an effect on the non-pregnant uterus. Ergo-M 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 Ergo-M are effective in controlling uterine haemorrhage.

Ergo-M has weak antagonist actions at dopaminergic receptors in certain blood vessels. Compared with other ergot alkaloids, effects of Ergo-M 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 Ergo-M 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.

-

- ).

- 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

Ergo-M may give rise to widespread vasoconstriction and rarely acute pulmonary oedema.

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

Ergo-M 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 Ergo-M-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.).

Concomitant use of Ergo-M Injection with the following medicinal products is not recommended:

Vasoconstrictors/Sympathomimetics

Ergo-M 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 Ergo-M 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 Ergo-M 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 Ergo-M 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

Ergo-M 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 Ergo-M 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 Ergo-M.

CYP3A4 inducers

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

Pregnancy

Ergo-M has potent uterotonic activity. Therefore, Ergo-M 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

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

Receiving Ergo-M Injection can start labour. Women with contractions should not drive or use machines. Patients should be warned of the possibility of dizziness and hypotension.

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.

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 Ergo-M-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.

Pharmacotherapeutic group: Ergot alkaloids

ATC code: G02AB03

Ergo-M 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 Ergo-M has an effect on the non-pregnant uterus. Ergo-M 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 Ergo-M are effective in controlling uterine haemorrhage.

Ergo-M has weak antagonist actions at dopaminergic receptors in certain blood vessels. Compared with other ergot alkaloids, effects of Ergo-M 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.

Absorption

Ergo-M 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 Ergo-M in healthy man is reported to be 1.04 L/kg. The plasma protein binding of Ergo-M is unknown. Ergo-M is known to cross the placenta and its clearance from the foetus is slow. Concentrations of Ergo-M achieved in foetus are not known. Ergo-M is also expected to be excreted in the breast milk and to reduce milk secretion.

Metabolism/Biotransformation

Ergo-M 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 Ergo-M 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-hydroxyErgo-M glucuronide. It is eliminated unchanged in the urine and can be detected up to 8 h after injection.

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.

Ergo-M 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. Ergo-M may, however, be diluted to a volume of 5mls with 0.9% Sodium Chloride Injection prior to IV administration.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.