Active ingredients: Oxytocin
Syntocinon 5 IU / ml solution for injection
Why is Syntocinon used? What is it for?
Syntocinon contains the active ingredient synthetic oxytocin, obtained by chemical synthesis. Syntocinon is indicated for:
- induce labor of childbirth, in case of
- pregnancy beyond term
- premature rupture of membranes
- pre-eclampsia, a condition characterized by high blood pressure, the presence of protein in the urine and edema (swelling) from the 20th week of pregnancy
- selected cases of primary or secondary uterine inertia, a condition in which the musculature of the uterus is unable to contract adequately to carry out the delivery
- treat postpartum (postpartum) bleeding (haemorrhages).
Contraindications When Syntocinon should not be used
Do not use Syntocinon
- if you are allergic to oxytocin or any of the other ingredients of this medicine (listed in section 6)
- if you have severe contractions of the uterus
- if there is suffering of the fetus when the birth is not imminent
- if spontaneous labor is not recognizable and / or natural birth is contraindicated for example if:
- the fetal head is too large to cross the pelvis (major pelvic cephalus disproportion)
- the fetus is in an abnormal position
- have placenta previa and vasa previ, a condition in which the placenta and vessels are positioned above or near the neck of the uterus and which can cause severe bleeding
- have a rupture of the placenta
- have an umbilical cord presentation or prolapse
- has an "excessive distension or compromised resistance of the uterus to rupture as in multiple pregnancy, in polyhydramnios (a condition associated with an excessive and pathological production of amniotic fluid)
- is elderly and has had many pregnancies (multiple parities), has had twin births or many pregnancies (multiparity), has a uterine scar from major surgery, including caesarean delivery
- if you have severe toxemia, a condition characterized by an accumulation of substances in the blood at toxic concentrations
- if there is a predisposition to amniotic fluid embolism (intrauterine fetal death, placental abruption)
- for prolonged use over time in case of uterine inertia in the 6 hours following the "use of prostaglandins by the vaginal route (see section" Other medicines and Syntocinon ").
Talk to your doctor if you think one or more of the conditions listed above apply to you.
Precautions for use What you need to know before taking Syntocinon
Talk to your doctor before taking Syntocinon.
Syntocinon will be administered to you to induce childbirth only when strictly necessary for medical reasons and in an equipped hospital environment where it can be kept under the constant observation of specialized medical personnel.
Tell your doctor before you are given Syntocinon:
- if you have had a caesarean section in the lower part of the uterus
- if you have oxytocin-resistant uterine inertia, secondary uterine inertia, severe pre-eclamptic toxaemia (see section "You must not be given Syntocinon")
- if you have medium or moderate high blood pressure (hypertension during pregnancy)
- if the fetus's head is at the limit of size to cross its pelvis (borderline pelvic cephalic disproportion)
- if you have severe heart and blood vessel problems e.g. hypertrophic cardiomyopathy, valvular and / or ischemic heart disease including coronary vasospasm
- if you have changes in your heart rhythm such as the so-called long QT syndrome, a prominent sign on the electrocardiogram, or related symptoms
- if you are using medicines that lengthen the QTc interval (see section "Other medicines and Syntocinon")
- if you have severe kidney problems.
Important information
- When oxytocin is used by intravenous infusion to induce or facilitate labor, the administration of excessive doses causes hyperstimulation of the uterus which can cause problems for the fetus and mother (suffering, suffocation and death of the fetus or excessive tonicity of the fetus). "uterus, tetanic contractions or rupture of the uterus in the mother). While you are being treated with Syntocinon, your doctor will closely observe you and your child in order to give the correct dose and to avoid side effects for you or your child.
- In rare circumstances, induction of labor with utero tonic substances, such as oxytocin, increases the risk of blood clots disseminated in the blood vessels (disseminated intravascular coagulation - DIC) after delivery. The risk of this occurring is particularly increased if you have risk factors for DIC such as: o age 35 or older o complications during pregnancy o gestational age over 40 weeks
- Prolonged intravenous administration of high doses of oxytocin together with a large amount of fluids can cause water intoxication associated with low sodium levels in the mother and newborn caused by fluid overload leading to a pulmonary complication (edema of the lungs ).
Interactions Which drugs or foods can modify the effect of Syntocinon
Tell your doctor if you are using, have recently used or might use any other medicines.
Syntocinon should not be given together with:
- other medicines similar to oxytocin (oxytocytes) even when administered by the oral or nasal route.
Syntocinon should be administered with caution together with:
- prostaglandins and their analogs, used to increase uterine motility; inhalation anesthetics, eg cyclopropane, halothane, sevoflurane and desflurane;
- QTc interval prolongation medications vasoconstrictor and sympathomimetic agents, used to induce anesthesia, including those contained in local anesthetics;
- caudal anesthetics (used to induce local anesthesia in the sacrum area).
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
Based on the extensive experience with this medicine, no risk of abnormalities for the fetus is expected.
Feeding time
Oxytocin can be found in breast milk in small amounts and no side effects are expected for the newborn.
Driving and using machines
Syntocinon can induce labor, so be especially careful when driving vehicles or using machines. Women with uterus contractions should not drive or operate machinery.
Syntocinon contains sodium and ethanol
Syntocinon contains sodium This medicinal product contains less than 1 mmol (23 mg) sodium per dose, ie it is essentially "sodium-free".
Syntocinon contains ethyl alcohol
This medicine contains small amounts of ethanol (alcohol) less than 100 mg per dose.
For those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positivity to doping tests in relation to the alcohol concentration limits indicated by some sports federations.
Dosage and method of use How to use Syntocinon: Dosage
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Induction or facilitation of labor
Syntocinon will be given to you by intravenous infusion drop by drop or through a variable speed infusion pump. The recommended dose is 5 IU.
Treatment of postpartum hemorrhages
Syntocinon will be given to you either intramuscularly or slowly into a vein (slow intravenous route). The recommended dose is 5-10 IU intramuscularly or 5 IU slowly intravenously (drip or with an infusion pump). In severe cases, 5 to 20 IU intravenously at the rate necessary to control uterine atony.
How to open the vials
To open the vials correctly, follow the instructions below:
- The opening line is below the colored dot.
- To open the vials, place your thumb on the colored dot and push back.
Overdose What to do if you have taken too much Syntocinon
In case of accidental ingestion or administration of an excessive dose of Syntocinon, notify your doctor or nurse immediately.
The symptoms and consequences of overdose of Syntocinon are those listed in the sections "Warnings and precautions" and "Undesirable effects". In addition, rupture of the placenta and / or amniotic embolism (formation of an embolus caused by amniotic fluid entering the mother's bloodstream) have been reported.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Syntocinon
Like all medicines, this medicine can cause side effects, although not everybody gets them.
UNDESIRABLE EFFECTS IN THE MOTHER
Common (may affect up to 1 in 10 people)
- headache (headache)
- increased heart rate (tachycardia)
- decreased heart rate (bradycardia)
- nausea
- He retched
Uncommon (may affect up to 1 in 100 people)
- changes in the rhythm of the heart (arrhythmia)
Rare (may affect up to 1 in 1,000 people)
- severe allergic reactions (anaphylactoid reaction associated with difficulty in breathing (dyspnoea), low blood pressure (hypotension), anaphylactoid shock
- skin rash (rash)
Not known (frequency cannot be estimated from the available data)
- heart problems (myocardial ischaemia, QTc lengthening)
- low blood pressure (hypotension)
- excessive tone of the uterus muscles (uterine hypertonicity), tetanic contractions of the uterus, rupture of the uterus
- water poisoning, low levels of sodium in the blood (hyponatremia)
- acute pulmonary edema (accumulation of fluid in the lungs)
- sudden redness (flushing)
- disseminated intravascular coagulation (DIC)
- postpartum bleeding (postpartum haemorrhages) pelvic hematoma
UNDESIRABLE EFFECTS IN THE FETUS / NEWBORN
Not known (frequency cannot be estimated from the available data)
- fetal distress (fetal distress), suffocation (asphyxia), death
- low levels of sodium in the blood (neonatal hyponatremia)
OTHER UNDESIRABLE EFFECTS
- When oxytocin is used by intravenous infusion to induce or facilitate labor, the administration of excessive doses causes hyperstimulation of the uterus which can cause problems for the fetus and mother (suffering, suffocation and death of the fetus or excessive tonicity of the fetus). "uterus, tetanic contractions or rupture of the uterus in the mother). See section "Warnings and precautions".
- Rapid administration by bolus injection into a vein of many IU doses of oxytocin can cause:
- a severe short-term decrease in blood pressure, accompanied by redness and rapid heartbeat (reflex tachycardia). These effects can cause ischaemia of the heart, especially in patients who have or have had problems with the heart and blood vessels (see section "Warnings and precautions").
- a lengthening of the QTc interval (see section "Warnings and precautions").
- In rare circumstances, induction of labor with utero tonic substances, such as oxytocin, increases the risk of blood clots disseminated in the blood vessels (disseminated intravascular coagulation - DIC) after delivery, see section "Warnings and precautions" .
- Prolonged intravenous administration of high doses of oxytocin together with large amounts of fluids may cause water intoxication associated with low sodium levels in the mother and newborn (see section "Warnings and precautions").
- The antidiuretic effect due to the administration of oxytocin and intravenous fluids can cause fluid overload that a complication in the lungs (acute pulmonary edema) without reducing sodium levels (hyponatremia) and, in addition, can cause excessive and transient water retention associated with headache (headache), decreased or loss of appetite (anorexia), vomiting and abdominal pain, drowsiness, unconsciousness, seizure status, low blood salt levels (see section "Warnings and precautions").
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2 ° C - 8 ° C). Store in the original package to protect the medicine from light.
Do not use this medicine after the expiry date which is stated on the package after EXP. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What Syntocinon contains
- The active ingredient is synthetic oxytocin. Each vial contains 25 mg of concentrated oxytocin solution (equivalent to 5 IU of synthetic oxytocin).
- The other ingredients are sodium acetate trihydrate, chlorobutanol, glacial acetic acid, 94% ethanol, sodium chloride, water for injections.
What Syntocinon looks like and contents of the pack
Each pack contains 6 1 ml glass ampoules containing solution for injection for intramuscular, intravenous and intravenous infusion use.
The following information is intended for healthcare professionals only
DOSAGE AND METHOD OF ADMINISTRATION
Induction or facilitation of labor Syntocinon should be administered by intravenous drip infusion or, preferably, with a variable rate infusion pump. Using drip infusion, it is recommended to add Syntocinon 5 IU to 500 mL of electrolyte saline (for example 9% sodium chloride). For patients in whom sodium chloride solution is to be avoided, it is recommended to you can use a 5% dextrose solution as diluent (see Special warnings and precautions for use). To ensure uniform mixing of the solution, it is recommended that the bottle or drip bag be turned over several times before use.
The initial infusion rate should be 1-4 milliunits / minute (2 to 8 drops / minute). It can be gradually increased, at intervals of at least 20 minutes, and no more than 1-2 milliunits / minute until regular contractions, similar to normal labor, are achieved. In near term pregnancies, regular contractions are achieved if less than 10 milliunits / minute (20 drops / minute) are administered and the recommended maximum rate is 20 milliunits / minute (40 drops / minute).
When using a motorized pump, which infuses volumes lower than those infused drop by drop, the adequate infusion flow should be calculated based on the technical specifications of the pump, keeping the dosage within the recommended limits for the drop-to-drop infusion. drop.
The frequency, strength and duration of contractions, as well as the fetal heartbeat, must be kept under constant observation throughout the infusion. Once regular uterine activity is achieved, the rate of infusion can be reduced. In the case of uterine hyperactivity and / or fetal distress, the infusion should be stopped immediately.
If regular contractions have not been obtained in full-term or near-term women after infusion of the total 5 IU, it is recommended to abandon any attempt to induce labor; in general, it can be repeated the following day, restarting at a speed of 1-4 milliunits / minute.
Note
An occasional involuntary paravenous infusion of oxytocin is not harmful.
Treatment of postpartum uterine hemorrhage
5 I.U. by infusion (5 IU diluted in 500 mL of electrolyte saline and administered as an intravenous drop-by-drop infusion or, preferably, with an infusion pump; the initial infusion rate should be set from 1 to 4 milliunits / minute (2 to 8 drops / minute) or from 5 to 10 intramuscular IU In severe cases, infusion of a solution containing 5 to 20 IU of oxytocin in 500 mL of a physiological electrolyte solution, at the rate necessary to control uterine atony.
OVERDOSE
Symptoms and consequences of overdose are those reported in sections 4.4 and 4.8. Furthermore, as a result of uterine overstimulation, rupture of the placenta and / or amniotic embolism have been reported.
Treatment: If signs and symptoms of overdose occur during continuous i.v. of Syntocinon, the infusion must be stopped immediately and oxygen given to the mother. In case of water intoxication, it is essential to limit fluid intake, promote diuresis, correct electrolyte imbalance and control possible seizures through use appropriate of diazepam.
INCOMPATIBILITY
In the absence of compatibility studies, Syntocinon must not be mixed with other medicinal products.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SYNTOCINON 5 I.U./ML INJECTABLE SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 vial contains:
Active principle:
Oxytocin solution concentrated 25 mg (equal to synthetic Oxytocin 5 I.U.)
Excipients with known effects:
ethanol 94%
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Injectable solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
• Medical induction of labor (in cases of over-term pregnancy, premature rupture of membranes, pre-eclampsia). Selected cases of primary or secondary uterine inertia.
• Post-partum haemorrhages (in these indications Methergin is preferred, which has a longer duration of action).
04.2 Posology and method of administration
- Induction or facilitation of labor
Syntocinon should be administered by intravenous infusion drop by drop or, preferably, with a variable speed infusion pump. Using drip infusion, it is recommended to add Syntocinon 5 IU to 500 mL of electrolyte saline (for example 9% sodium chloride). For patients in whom sodium chloride solution is to be avoided, it is recommended to you can use a 5% dextrose solution as diluent (see Special warnings and precautions for use). To ensure uniform mixing of the solution, it is recommended to turn the bottle or drip bag several times before use.
The initial infusion rate should be 1-4 milliunits / minute (2 to 8 drops / minute). It can be gradually increased, at intervals of at least 20 minutes, and no more than 1-2 milliunits / minute until regular contractions, similar to normal labor, are achieved. In near term pregnancies, regular contractions are achieved if less than 10 milliunits / minute (20 drops / minute) are administered and the recommended maximum rate is 20 milliunits / minute (40 drops / minute).
When using a motorized pump, which infuses volumes lower than those infused drop by drop, the adequate infusion flow should be calculated based on the technical specifications of the pump, keeping the dosage within the recommended limits for the drop-to-drop infusion. drop.
The frequency, strength and duration of contractions, as well as the fetal heartbeat, must be kept under constant observation throughout the infusion. Once regular uterine activity is achieved, the rate of infusion can be reduced. In the case of uterine hyperactivity and / or fetal distress, the infusion should be stopped immediately.
If regular contractions have not been obtained in full-term or near-term women after infusion of the total 5 IU, it is recommended to abandon any attempt to induce labor; generally, it can be repeated the following day, restarting at a speed of 1-4 milliunits / minute.
Note
An occasional involuntary paravenous infusion of oxytocin is not harmful.
• Postpartum hemorrhages: 5-10 I.U. i.m. o 5 I.U. slow intravenous.
To open the vials correctly, follow the instructions on the leaflet included in the package.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypertonic uterine contractions, fetal distress when delivery is not imminent.
Any condition in which, due to problems of the mother or the fetus, spontaneous labor is not recognizable and or natural birth is contraindicated: eg: significant cephalo-pelvic disproportion, abnormal presentations of the fetus; placenta previa and vasa previ, placental rupture, cord presentation or prolapse; overstretching or impaired resistance of the uterus to rupture as in multiple pregnancy, polyhydramnios, in elderly pluriparous, large multiparities and in the presence of uterine scar for major surgery, including the classic caesarean section.
Severe toxemia, predisposition to amniotic fluid embolism (intrauterine fetal death, abrupto placentae).
Prolonged use in uterine inertia is contraindicated.
Syntocinon should not be administered within 6 hours after vaginal use of prostaglandins (see section 4.5).
04.4 Special warnings and appropriate precautions for use
The induction of delivery with oxytocin must be carried out only when it is strictly indicated for medical reasons rather than for convenience and in suitably equipped hospital environments where patients can be kept under constant observation by specialized medical personnel.
Syntocinon should not be used for prolonged periods in patients with oxytocin-resistant uterine inertia, severe pre-eclamptic toxaemia or severe cardiovascular disease.
Syntocinon should not be administered by intravenous bolus as this may cause acute short-term hypotension accompanied by flushing and reflex tachycardia.
Syntocinon should be administered with caution in patients with predisposition to myocardial ischaemia due to pre-existing cardiovascular disease (such as hypertrophic cardiomyopathy, valvular and / or ischemic heart disease including coronary vasospasm), to avoid significant changes in blood pressure and heart rate in these patients.
Syntocinon should be administered with caution to patients with "long QT syndrome" or related symptoms and to patients taking QTc interval prolongation medications.
When Syntocinon is given for induction and facilitation of labor:
• It must only be administered by intravenous drip infusion, and never by the intramuscular, subcutaneous or intravenous bolus route.
• The administration of oxytocin in excessive doses produces uterine hyperstimulation which can cause suffering, asphyxiation and death of the fetus, or can cause hypertonicity, tetanic contractions or rupture of the uterus. A careful observation of the fetal heartbeat and uterine motility (frequency, intensity and duration of contractions) is essential for the dosage to be adapted to the individual patient's response.
• It should only be administered as an intravenous drip infusion, and never by the intramuscular, subcutaneous or intravenous bolus route.
• The administration of excessive doses of oxytocin causes uterine hyperstimulation which can cause fetal distress, asphyxia and death, or can lead to hypertonicity, tetanic contractions or rupture of the uterus. Careful control of blood pressure, fetal heart rate and also uterine motility (frequency, intensity and duration of contractions) is essential in order to better adapt the dosage to individual responses.
• Particular caution is required in the presence of borderline head and pelvic disproportion, secondary uterine inertia, medium or moderate hypertension gravidarum or heart disease and in patients over the age of 35 or with a history of caesarean section in the lower uterine segment.
• In rare circumstances, drug induction of labor with utero tonic substances, including oxytocin, increases the risk of postpartum disseminated intravascular coagulation (DIC). Pharmacological induction itself is related to this risk. The risk increases particularly if the woman has additional risk factors for DIC such as age 35 and over, complications during pregnancy and gestational age over 40 weeks. . In these women, oxytocin or any other alternative drug should be used with caution and the physician should be alerted to signs of DIC.
When Syntocinon is used for the treatment of uterine haemorrhage, rapid bolus administration of high doses of oxytocin should be avoided as this may cause acute short-term hypotension accompanied by flushing and reflex tachycardia.
In the event of fetal death in the uterus and / or amniotic fluid contaminated with meconium, tumultuous labor must be avoided, as it can cause amniotic embolism.
Since oxytocin exerts a mild antidiuretic activity, its prolonged iv use at high doses in addition to large volumes of fluids, as in the case of treatment of unavoidable or missed abortion, or in the management of postpartum haemorrhage, can cause water intoxication with hyponatremia. The combined antidiuretic effect of oxytocin and intravenous fluid administration may cause fluid overload leading to a hemodynamic form of acute pulmonary edema without hyponatremia. In order to avoid these rare complications, the following precautions should be observed whenever high doses of oxytocin are administered for a long time: an electrolyte diluent (not dextrose) should be used; the volume of the infused liquid should be kept low (oxytocin infusion at concentrations higher than those recommended for induction or facilitation of full term labor); fluid intake by mouth should be reduced; fluid balance should be tracked and, if an electrolyte imbalance is suspected, serum electrolytes should be measured.
Caution should be exercised in patients with severe deterioration of renal function due to possible fluid retention and possible accumulation of oxytocin (see section 5.2).
Important information about some of the excipients
This medicinal product contains less than 1mmol (23 mg) sodium per dose, ie it is essentially "sodium-free".
This medicine contains small amounts of ethanol (alcohol) less than 100 mg per dose.
04.5 Interactions with other medicinal products and other forms of interaction
Syntocinon should not be administered concomitantly with other oxytocytes even if by oral or nasal route.
Prostaglandins can enhance the uterotonic effect of oxytocin and vice versa; careful monitoring is therefore recommended in case of simultaneous administration.
Some inhaled anesthetics, such as cyclopropane or halothane, can facilitate the hypotensive effect of oxytocin and reduce its oxytocic effect. Their recurrent use with oxytocin has also been reported to cause heart rhythm disturbances.
Oxytocin should be administered with caution in patients taking drugs for lengthening the QTc interval or in patients with a history of long QT (see section 4.4).
Oxytocin, when administered during or after caudal block anesthesia, may potentiate the pressure effect of vasoconstrictor and sympathomimetic agents.
04.6 Pregnancy and breastfeeding
This is a product to be used at the end of pregnancy and in the post-partum period.
Pregnancy
There are no standard studies of teratogenicity and the effect of oxytocin on reproduction (see section 5.3).
Based on the extensive experience with this drug and its chemical structure as well as pharmacological properties, a risk of fetal abnormalities is not to be expected if it is used as prescribed.
Feeding time
Oxytocin can be found in breast milk in small quantities. However, no dangerous effects are expected for the newborn as oxytocin passes into the alimentary tract, where it is rapidly inactivated.
04.7 Effects on ability to drive and use machines
Syntocinon can induce labor, so caution should be exercised when driving or operating machinery. Women with uterine contractions should not drive or operate machinery.
04.8 Undesirable effects
When oxytocin is used for i.v.In inducing or facilitating labor, the administration of excessive doses causes uterine hyperstimulation which can cause fetal distress, asphyxia and death, or can lead to hypertonicity, tetanic contractions or rupture of the uterus.
The rapid administration by intravenous bolus injection of doses that amount to many I.U. of oxytocin can cause acute short-term hypotension accompanied by flushing and reflex tachycardia (see section 4.4). These rapid haemodynamic changes can cause myocardial ischaemia, especially in patients with pre-existing cardiovascular disease. The rapid administration by intravenous bolus injection of doses that amount to many I.U. of oxytocin can also cause a lengthening of the QTc interval.
In rare circumstances (incidence rate
Water intoxication
In cases where high doses of oxytocin with large amounts of electrolyte-free fluids have been administered over an extended period of time, water intoxication associated with maternal and neonatal hyponatraemia has been reported (see section 4.4).
The combined antidiuretic effect of oxytocin with intravenous fluid administration can cause fluid overload leading to a hemodynamic form of acute pulmonary edema without hyponatremia; furthermore, it can cause transient excess fluid retention with headache, anorexia, vomiting and abdominal pain, somnolence, unconsciousness, seizure status epileptiform, lowering of serum electrolyte level (see section 4.4).
With any method of administration, oxytocin can cause the following side effects:
Adverse reactions are listed by frequency, most frequent first, using the following convention: very common (≥ 1/10) common (≥ 1/100,
Adverse drug reactions resulting from post-marketing experience with Syntocinon originated from spontaneous and literature reports. As these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency, which is therefore classified as not known. Adverse reactions are listed by MedDRA system organ class. Within each frequency class, adverse reactions are presented in order of decreasing severity.
ADVERSE REACTIONS IN THE MOTHER
Postpartum haemorrhages and pelvic hematoma have also been reported.
ADVERSE REACTIONS IN THE FETUS / NEWBORN
04.9 Overdose
Symptoms and consequences of overdose are those reported in sections 4.4 and 4.8. Furthermore, as a result of uterine overstimulation, rupture of the placenta and / or amniotic embolism have been reported.
Treatment: if signs and symptoms of overdose occur during continuous i.v. of Syntocinon, the infusion must be stopped immediately and oxygen given to the mother. In case of water intoxication, it is essential to limit fluid intake, promote diuresis, correct electrolyte imbalance and control possible seizures through use appropriate of diazepam.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Hormones of the posterior lobe of the pituitary (ATC code: H01B B02).
Oxytocin is a cyclic nonapeptide which is obtained by chemical synthesis. This synthetic form is identical to the natural hormone which is produced by the hypothalamus and deposited in the posterior pituitary and released into the systemic circulation in response to sucking and labor. Oxytocin stimulates the smooth muscle of the uterus, particularly towards the end of the uterus. pregnancy, during labor, and immediately after delivery. At these times, the oxytocin receptors in the myometrium are increased. The oxytocin receptors are calcium receptors from intracellular deposits and causes rhythmic contractions of the upper segment of the uterus, similar in frequency, strength and duration to those seen during labor. Syntocinon does not contain vasopressin, but even in its pure form oxytocin has a weak intrinsic antidiuretic-like activity.
In vitro studies show that prolonged exposure of the oxytocin receptor causes receptor desensitization, possibly by a down-regulation mechanism that results in destabilization of the oxytocin receptor mRNA and receptor internalization.
05.2 Pharmacokinetic properties
Plasma levels and onset / duration of the effect
Intravenous infusion : when Syntocinon is administered by i.v. continued at appropriate doses for induction or facilitation of labor, the uterine response occurs gradually and usually reaches steady state within 20-40 minutes. Corresponding plasma levels of oxytocin are comparable to those measured during the first stage of labor For example, plasma levels of oxytocin in 10 full-term pregnant women receiving 4 milliunits per minute as an intravenous infusion were 2 to 5 microunits / ml. Following interruption of the infusion, or a substantial reduction in the infusion rate. , for example in the case of overstimulation, uterine activity recedes rapidly but may continue at an appropriate lower level.
Intravenous and intramuscular injection: when given by i.v. injection or i.m. For the prevention or treatment of postpartum haemorrhage, Syntocinon acts rapidly with a latency period of less than 1 minute with IV injection and between 2 and 4 minutes with IM injection The oxytocic response lasts 30 to 60 minutes after administration im, possibly less after an "IV injection
Distribution
Oxytocin distributes into the extracellular fluid reaching the fetus with minimal quantities. The steady-state volume of distribution in 6 healthy volunteer men after intravenous injection was 12.2 or 0.17 l / kg. Plasma protein binding is highly low. Oxytocin can be found in small amounts in breast milk.
Biotransformation
Oxytocinase, a glycoprotein aminopeptidase, is produced during pregnancy and appears in the plasma. It is capable of degrading oxytocin. Enzyme activity gradually increases until late pregnancy, when it rises very rapidly to high levels. Then, after delivery, enzymatic activity is reduced. Enzyme activity during this period is also high in the placenta and uterine tissue. Oxytocin degradation is minimal or absent in the plasma of men, non-pregnant women, or cord blood.
Elimination
The relative ease with which the frequency and intensity of uterine contractions can be regulated by an IV infusion. of Syntocinon is due to the short half-life of oxytocin. The values reported by various investigations range from 3 to 20 minutes. The elimination of oxytocin from plasma occurs mainly in the liver and kidneys.
The metabolic clearance rate is approximately 20 ml / kg per minute in men as well as pregnant women. Less than 1% of the administered dose is excreted unchanged in the urine.
05.3 Preclinical safety data
Preclinical data based on conventional studies of acute single dose toxicity, genotoxicity and mutagenicity reveal no special hazards for humans.
Effects (fetal loss in rats) observed in a pre-clinical study resulted only from exposures considered sufficiently in excess of the maximum human exposure, indicating little relevance to clinical use.
Acute toxicity
Single dose toxicity studies with oxytocin were conducted in rats and mice with oral, intravenous and subcutaneous administrations. Acute oral (and subcutaneous) toxicity was 20.5 mg / kg in rats and over 514 mg / kg in mice. Following intravenous administration, the lethal dose of oxytocin amounted to 2.3 mg / kg in rats and 5.8 mg / kg in mice. Thus, the lethal intravenous dose of oxytocin in mice is greater than the usual intravenous dose in humans by a factor greater than a thousand.
Mutagenicity
An in vitro study of genotoxicity and mutagenicity has been reported with oxytocin. Tests were negative for chromosomal aberration and sister chromatid exchange in human peripheral lymphocyte culture. No significant change in mitotic index was noted. Oxytocin has no genotoxic properties.
Carcinogenicity, teratogenicity and reproductive toxicity
Treatment of rats with oxytocin in early pregnancy with doses thousands of times higher than the dose used to induce labor in humans caused fetal loss in one study, but its relevance is unknown.
With oxytocin, standard studies of teratogenicity, reproductive performance and carcinogenesis are not available.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sodium acetate trihydrate, chlorobutanol, glacial acetic acid, 94% ethanol, sodium chloride, water for injections.
06.2 Incompatibility
In the absence of compatibility studies, Syntocinon must not be mixed with other medicinal products.
06.3 Period of validity
36 months
06.4 Special precautions for storage
Store in the refrigerator (2-8 ° C). Store in the original packaging to protect the product from light.
06.5 Nature of the immediate packaging and contents of the package
Glass ampoules - 6 ampoules of 1ml
06.6 Instructions for use and handling
The unused product and the waste derived from this medicinal product must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.
Viale Shakespeare, 47 - 00144 Rome
Dealership for sale:
BIOFUTURA PHARMA S.p.A.
Via Pontina km 30,400 - 00040 Pomezia (Rome)
08.0 MARKETING AUTHORIZATION NUMBER
AIC. n. 014684029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
First authorization: 19.12.1958
Renewal: 1.06.2010
10.0 DATE OF REVISION OF THE TEXT
December 2015
