Treatment: When signs or symptoms of overdosage occur during continuous i.v. administration of Syntocinon, 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. In the case of coma, a free airway should be maintained with routine measures normally employed in the nursing of the unconscious patient.
Five years
Syntocinon should not be infused via the same apparatus as blood or plasma, because the peptide linkages are rapidly inactivated by oxytocin-inactivating enzymes. Syntocinon is incompatible with solutions containing sodium metabisulphite as a stabiliser.
Sodium acetate tri-hydrate, acetic acid, chlorobutanol, ethanol and water for injections.
Water intoxication
“Special warnings and precautions for useâ€). Special warnings and precautions for use).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, < 1/10); uncommon (> 1/1,000, < 1/100); rare (> 1/10,000, < 1/1,000); very rare (< 1/10,000), including isolated reports; not known (cannot be estimated from the available data).The ADRs tabulated below are based on clinical trial results as well as postmarketing reports.
The adverse drug reactions derived from post-marketing experience with Syntocinon 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: Anaphylactic/Anaphylactoid reaction associated with dyspnoea, hypotension or Anaphylactic/Anaphylactoid shock |
| Nervous system disorders | Common: Headache |
| Cardiac disorders | Common Tachycardia, bradycardia Uncommon: Arrhythmia Not known: Myocardial ischaemia, Electrocardiogram QTc prolongation |
| Vascular disorders | Not known: Hypotension, haemorrhage |
| Gastrointestinal disorders | Common: Nausea, vomiting |
| Skin and subcutaneous tissue disorders | Rare: Rash |
| Pregnancy, puerperium and perinatal conditions | Not known: Uterine hypertonus, tetanic contractions of uterus, rupture of the uterus |
| Metabolism and nutrition disorders | Not known: Water intoxication, maternal hyponatraemia |
| Respiratory, thoracic and mediastinal disorders | Not known: acute pulmonary oedema |
| General disorders and administration site conditions | Not known: Flushing |
| Blood and lymphatic system disorders | Not known: disseminated intravascular coagulation |
| Skin and subcutaneous tissue disorders | Not Known: Angioedema |
Table 2 Adverse drug reactions in foetus/neonate
| System organ class | Adverse drug reaction |
| 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 Yellow Card Scheme (www.mhra.gov.uk/yellowcard) or search for MHRA Yellow Card in the Google Play or Apple App Store.
Pre-clinical data for oxytocin reveal no special hazard for humans based on conventional studies of single dose acute toxicity, genotoxicity, and mutagenicity.
Pharmacotherapeutic group: Posterior pituitary lobe hormones
ATC code: H01B B02
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 Syntocinon 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 oxytocin-binding sites, destabilisation of oxytocin receptors mRNA and internalisation of oxytocin receptors.
Plasma levels and onset/duration of effect
Intravenous infusion. When Syntocinon 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.
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 min. 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.
02 May 2018
Novartis Pharmaceuticals UK Ltd
Frimley Business Park
Frimley
Camberley
Surrey
UK
GU16 7SR
Store between 2°C and 8°C. May be stored up to 30°C for 3 months, but must then be discarded.
Clear glass 1ml ampoules. Boxes of 5 ampoules.
PL 00101/0960
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.
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.
Syntocinon can induce labour, therefore caution should be exercised when driving or operating machines. Women with uterine contractions should not drive or use machines.
Snap ampoules: no file required.
Syntocinon is compatible with the following infusion fluids, but due attention should be paid to the advisability of using electrolyte fluids in individual patients: sodium/potassium chloride (103mmol Na+ and 51mmol K+), sodium bicarbonate 1.39%, sodium chloride 0.9%, sodium lactate 1.72%, dextrose 5%, laevulose 20%, macrodex 6%, rheomacrodex 10%, Ringer's solution.
|
Date of First Authorisation: Date of Last Renewal: |
03 October 1977 22 March 2005 |
Interaction resulting in a concomitant use not recommended
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.
Drugs prolonging the QT interval
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.
