Adverse reactions : תופעות לוואי

4.8. Undesirable effects
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 IV. 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).
Water intoxication
Water intoxication associated with maternal and neonatal hyponatraemia has been reported in cases where high doses of oxytocin together with large amounts of electrolyte-free fluid have been administered over a prolonged period of time (see section 4.4 Special warnings and precautions for use). The combined antidiuretic effect of oxytocin and the I.V. fluid administration may cause fluid overload leading to a haemodynamic form of acute pulmonary oedema without hyponatraemia (see section 4.4. 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 post marketing reports.
The adverse drug reactions derived from post marketing experience with Oxytocin -Grindeks 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 categorized 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
Not known: Uterine hypertonus, tetanic
Pregnancy, puerperium and perinatal conditions        contractions of uterus, rupture of the uterus Not known: Water intoxication,
Metabolism and nutrition disorders                    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            Not known: Foetal distress perinatal conditions                 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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il