Atosiban SUN

1 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

 

1. NAME OF THE MEDICINAL PRODUCT 
 
Atosiban SUN 6.75 mg/0.9 ml solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial of 0.9 ml solution contains 6.75 mg atosiban (as acetate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection). 
Clear, colourless solution without particles. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Atosiban is indicated to delay imminent pre-term birth in pregnant adult women with: 
- regular uterine contractions of at least 30 seconds duration at a rate of ≥ 4 per 30 minutes 
- a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50% 
- a gestational age from 24 until 33 completed weeks 
- a normal foetal heart rate 
 
4.2 Posology and method of administration 
 
Posology 
 
Treatment with atosiban should be initiated and maintained by a physician experienced in the 
treatment of pre-term labour. 
 
Atosiban is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), 
performed with atosiban 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous 
high dose infusion (loading infusion 300 micrograms/min) of atosiban 37.5 mg/5 ml concentrate for 
solution for infusion during three hours, followed by a lower dose of atosiban 37.5 mg/5 ml 
concentrate for solution for infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The 
duration of the treatment should not exceed 48 hours. The total dose given during a full course of 
atosiban therapy should preferably not exceed 330.75 mg of atosiban. 
 
Intravenous therapy using the initial bolus injection should be started as soon as possible after 
diagnosis of pre-term labour. Once the bolus has been injected, proceed with the infusion (See 
Summary of Product Characteristics of Atosiban SUN 37.5 mg/5 ml, concentrate for solution for 
infusion). In the case of persistence of uterine contractions during treatment with atosiban, alternative 
therapy should be considered. 
 
The following table shows the full posology of the bolus injection followed by the infusion: 
 
 
 
 
 



3 

 

Step Regimen Infusion rate Atosiban dose 
1 0.9 ml intravenous bolus Not applicable 6.75 mg 

 injection given over 1 minute   
2 3 hours intravenous loading 24 ml/hour (300 μg/min) 54 mg 

 infusion   
3 Up to 45 hours subsequent 8 ml/hour (100 μg/min) Up to 270 mg 

 intravenous infusion   
 
Re-treatment 
 
In case a re-treatment with atosiban is needed, it should also commence with a bolus injection of 
atosiban 6.75 mg/0.9 ml, solution for injection followed by infusion with atosiban 37.5 mg/5 ml, 
concentrate for solution for infusion. 
 
Special population 
 
Patients with renal or hepatic impairment 
There is no experience with atosiban treatment in patients with impaired function of the liver or 
kidneys. Renal impairment is not likely to warrant a dose adjustment, since only a small extent of 
atosiban is excreted in the urine. In patients with impaired hepatic function, atosiban should be used 
with caution. 
 
Paediatric population 
The safety and efficacy of atosiban in pregnant women aged less than 18 years have not been 
established. No data are available. 
 
Method of administration 
 
Intravenous use 
For instructions on preparation of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Atosiban must not be used in the following conditions: 
 
- Gestational age below 24 or over 33 completed weeks 
- Premature rupture of the membranes >30 weeks of gestation 
- Abnormal foetal heart rate 
- Antepartum uterine haemorrhage requiring immediate delivery 
- Eclampsia and severe pre-eclampsia requiring delivery 
- Intrauterine foetal death 
- Suspected intrauterine infection 
- Placenta praevia 
- Abruptio placenta 
- Any other conditions of the mother or foetus, in which continuation of pregnancy is hazardous 
- Hypersensitivity to the active substance or any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
When atosiban is used in patients in whom premature rupture of membranes cannot be excluded, the 
benefits of delaying delivery should be balanced against the potential risk of chorioamnionitis. 
 
There is no experience with atosiban treatment in patients with impaired function of the liver or 
kidneys. Renal impairment is not likely to warrant a dose adjustment, since only a small extent of 



4 

 

atosiban is excreted in the urine. In patients with impaired hepatic function, atosiban should be used 
with caution (see sections 4.2 and 5.2). 
 
There is only limited clinical experience in the use of atosiban in multiple pregnancies or the 
gestational age group between 24 and 27 weeks, because of the small number of patients treated. The 
benefit of atosiban in these subgroups is therefore uncertain. 
 
Re-treatment with atosiban is possible, but there is only limited clinical experience available with 
multiple re-treatments, up to 3 re-treatments (see section 4.2). 
In case of intrauterine growth retardation, the decision to continue or reinitiate the administration of 
atosiban depends on the assessment of fetal maturity. 
 
Monitoring of uterine contractions and fetal heart rate during administration of atosiban and in case of 
persistent uterine contractions should be considered. 
As an antagonist of oxytocin, atosiban may theoretically facilitate uterine relaxation and postpartum 
bleeding therefore blood loss after delivery should be monitored. However, inadequate uterus 
contraction postpartum was not observed during the clinical trials. 
 
Multiple pregnancy and medicinal products with tocolytic activity like calcium channel blockers and 
beta-mimetics are known to be associated with increased risk of pulmonary oedema. Therefore, 
atosiban should be used with caution in case of multiple pregnancy and/or concomitant administration 
of other medicinal products with tocolytic activity (see section 4.8). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
It is unlikely that atosiban is involved in cytochrome P450 mediated drug-drug interactions as in vitro 
investigations have shown that atosiban is not a substrate for the cytochrome P450 system, and does 
not inhibit the medicinal product metabolising cytochrome P450 enzymes. 
 
Interaction studies have been performed with labetalol and betamethasone in healthy, female 
volunteers. No clinically relevant interaction was found between atosiban and bethamethasone or 
labetalol. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
Atosiban should only be used when pre-term labour has been diagnosed between 24 and 33 completed 
weeks of gestation.  
 
Breast-feeding 
 
If during pregnancy the woman is already breast-feeding an earlier child, then breast-feeding should 
be discontinued during treatment with atosiban, since the release of oxytocin during breast-feeding 
may augment uterine contractility, and may counteract the effect of tocolytic therapy. 
 
In atosiban clinical trials no effects were observed on breast-feeding. Small amounts of atosiban have 
been shown to pass from plasma into the breast milk of breast-feeding women. 
 
Fertility 
 
Embryo-fetal toxicity studies have not shown toxic effects of atosiban. No studies were performed that 
covered fertility and early embryonic development (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 



5 

 

 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Possible adverse reactions of atosiban were described for the mother during the use of atosiban in 
clinical trials. In total 48% of the patients treated with atosiban experienced adverse reactions during 
the clinical trials. The observed adverse reactions were generally of a mild severity. The most 
commonly reported adverse reaction in the mother is nausea (14 %). 
 
For the newborn, the clinical trials did not reveal any specific adverse reactions of atosiban. The infant 
adverse reactions were in the range of normal variation and were comparable with both placebo and 
beta-mimetic group incidences. 
 
Tabulated list of adverse reactions 
 
The frequency of adverse reactions listed below is defined using the following convention: very 
common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to 
<1/1,000). Within each frequency grouping, adverse reactions are presented in order of decreasing 
seriousness. 
 
MedDRA system organ class 
(SOC) 

Very 
common 

Common Uncommon Rare 

Immune system disorders    Allergic reaction 
Metabolism and nutrition 
disorders 

 Hyperglycaemia   

Psychiatric disorder   Insomnia  
Nervous system disorders  Headache, 

Dizziness 
  

Cardiac disorders  Tachycardia   
Vascular disorders  Hypotension, Hot 

flush 
  

Gastrointestinal disorders Nausea Vomiting   
Skin and subcutaneous tissue 
disorders 

  Pruritis, Rash  

Reproductive system and 
breast disorder 

   Uterine haemorrhage, 
uterine atony 

General disorders and 
administration site conditions 

 Injection site 
reaction 

Pyrexia  

 
Post-marketing experience 
 
Respiratory events like dyspnoea and pulmonary oedema, particularly in association with concomitant 
administration of other medicinal products with tocolytic activity, like calcium antagonists and beta-
mimetics, and/or in women with multiple pregnancy, have been reported post-marketing. 
 
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 national reporting system 
listed in Appendix V. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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4.9 Overdose 
 
Few cases of atosiban overdosing were reported, they occurred without any specific signs or 
symptoms. There is no known specific treatment in case of an overdose. 
 
 
5. PHARMACOLOGICAL PROPERTIES  
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other gynecologicals, ATC code: G02CX01 
 
Atosiban SUN contains atosiban (INN), a synthetic peptide ([Mpa1, D-Tyr(Et)2, Thr4,Orn8]-oxytocin) 
which is a competitive antagonist of human oxytocin at receptor level. In rats and guinea pigs, 
atosiban was shown to bind to oxytocin receptors, to decrease the frequency of contractions and the 
tone of the uterine musculature, resulting in a suppression of uterine contractions. Atosiban was also 
shown to bind to the vasopressin receptor, thus inhibiting the effect of vasopressin. In animals atosiban 
did not exhibit cardiovascular effects. 
 
In human pre-term labour, atosiban at the recommended dose antagonises uterine contractions and 
induces uterine quiescence. The onset of uterus relaxation following atosiban is rapid, uterine 
contractions being significantly reduced within 10 minutes to achieve stable uterine quiescence 
(≤ 4 contractions/hour) for 12 hours. 
 
Phase III clinical trials (CAP-001 studies) include data from 742 women who were diagnosed with 
pre-term labour at 23-33 weeks of gestation and were randomised to receive either atosiban (according 
to this labelling) or β-agonist (dose-titrated). 
 
Primary endpoint: the primary efficacy outcome was the proportion of women remaining undelivered 
and not requiring alternative tocolysis within 7 days of treatment initiation. The data show that 59.6% 
(n=201) and 47.7% (n=163) of atosiban- and β-agonist-treated women (p=0.0004), respectively, were 
undelivered and did not require alternative tocolysis within 7 days of starting treatment. Most of the 
treatment failures in CAP-001 were caused by poor tolerability. Treatment failures caused by 
insufficient efficacy were significantly (p=0.0003) more frequent in atosiban (n=48, 14.2%) than in the 
β-agonist-treated women (n=20, 5.8%). 
In the CAP-001 studies the probability of remaining undelivered and not requiring alternative 
tocolytics within 7 days of treatment initiation was similar for atosiban and beta-mimetics treated 
women at gestational age of 24-28 weeks. However, this finding is based on a very small sample 
(n=129 patients). 
 
Secondary endpoints: secondary efficacy parameters included the proportion of women remaining 
undelivered within 48 h of treatment initiation. There was no difference between the atosiban and 
beta-mimetic groups with regard to this parameter. 
 
Mean (SD) gestational age at delivery was the same in the two groups: 35.6 (3.9) and 35.3 (4.2) weeks 
for the atosiban and β-agonist groups, respectively (p=0.37). Admission to a neonatal intensive care 
unit (NICU) was similar for both treatment groups (approximately 30%), as was length of stay and 
ventilation therapy. Mean (SD) birth weight was 2491 (813) grams in the atosiban group and 2461 
(831) grams in the β-agonist group (p=0.58).  
 
Fetal and maternal outcome did apparently not differ between the atosiban and the β-agonist group, 
but the clinical trials were not powered enough to rule out a possible difference. 
 
Of the 361 women who received atosiban treatment in the phase III studies, 73 received at least one 
re-treatment, 8 received at least 2 re-treatments and 2 received 3 re-treatments (see section 4.4). 



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As the safety and efficacy of atosiban in women with a gestational age of less than 24 completed 
weeks has not been established in controlled randomised studies, the treatment of this patient group 
with atosiban is not recommended (see section 4.3). 
 
In a placebo-controlled study, fetal/infant deaths were 5/295 (1.7%) in the placebo group and 15/288 
(5.2%) in the atosiban group, of which two occurred at five and eight months of age. Eleven out of the 
15 deaths in the atosiban group occurred in pregnancies with a gestational age of 20 to 24 weeks, 
although in this subgroup patient distribution was unequal (19 women on atosiban, 4 on placebo). For 
women with a gestational age greater than 24 weeks there was no difference in mortality rate (1.7% in 
the placebo group and 1.5% in the atosiban group). 
 
5.2 Pharmacokinetic properties 
 
In healthy non-pregnant subjects receiving atosiban infusions (10 to 300 micrograms/min over 
12 hours), the steady state plasma concentrations increased proportionally to the dose. 
 
The clearance, volume of distribution and half-life were found to be independent of the dose. 
 
Absorption 
 
In women in pre-term labour receiving atosiban by infusion (300 micrograms/min for 6 to 12 hours), 
steady state plasma concentrations were reached within one hour following the start of the infusion 
(mean 442 ± 73 ng/ml, range 298 to 533 ng/ml). 
 
Following completion of the infusion, plasma concentration rapidly declined with an initial (tα) and 
terminal (tβ) half-life of 0.21 ± 0.01 and 1.7 ± 0.3 hours, respectively. Mean value for clearance was 
41.8 ± 8.2 litres/h.  
 
Distribution 
 
Mean value of volume of distribution was 18.3 ± 6.8 litres. 
 
Plasma protein binding of atosiban is 46 to 48% in pregnant women. It is not known whether the free 
fraction in the maternal and fetal compartments differs substantially. Atosiban does not partition into 
red blood cells. 
 
Atosiban passes the placenta. Following an infusion of 300 micrograms/min in healthy pregnant 
women at term, the fetal/maternal atosiban concentration ratio was 0.12.  
 
Biotransformation 
 
Two metabolites were identified in the plasma and urine from human subjects. The ratios of the main 
metabolite M1 (des-(Orn8, Gly-NH2 9) -29)-[Mpa1, D-Tyr(Et)2, Thr4]-oxytocin) to atosiban 
concentrations in plasma were 1.4 and 2.8 at the second hour and at the end of the infusion 
respectively. It is not known whether M1 accumulates in tissues.  
 
Elimination 
 
Atosiban is found in only small quantities in urine, its urinary concentration is about 50 times lower 
than that of M1. The proportion of atosiban eliminated in faeces is not known. The main metabolite 
M1 is approximately 10 times less potent than atosiban in inhibiting oxytocin-induced uterine 
contractions in vitro. Metabolite M1 is excreted in milk (see section 4.6). 
 



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Patients with renal or liver impairment 
 
There is no experience with atosiban treatment in patients with impaired function of the liver or 
kidneys. Renal impairment is not likely to warrant a dose adjustment, since only a small extent of 
atosiban is excreted in the urine. In patients with impaired hepatic function, atosiban should be used 
with caution (see sections 4.2 and 4.4). 
 
It is unlikely that atosiban inhibits hepatic cytochrome P450 isoforms in humans (see section 4.5). 
 
5.3 Preclinical safety data 
 
No systemic toxic effects were observed during the two-week intravenous toxicity studies (in rats and 
dogs) at doses which are approximately 10 times higher than the human therapeutic dose, and during 
the three-months toxicity studies in rats and dogs (up to 20 mg/kg/day s.c.). The highest atosiban 
subcutaneous dose not producing any adverse effects was approximately two times the therapeutic 
human dose. 
 
No studies were performed that covered fertility and early embryonic development. Reproduction 
toxicity studies, with dosing from implantation up to late stage pregnancy, showed no effects on 
mothers and fetuses. The exposure of the rat fetus was approximately four times that received by the 
human fetus during intravenous infusions in women. Animal studies have shown inhibition of 
lactation as expected from the inhibition of action of oxytocin. 
 
Atosiban was neither oncogenic nor mutagenic in in vitro and in vivo tests. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Hydrochloric acid 1M 
Water for injections 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years. 
 
Once the vial has been opened, the medicinal product must be used immediately. 
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2°C - 8°C). 
 
Store in the original package in order to protect from light. 
 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 



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One vial of solution for injection contains 0.9 ml solution, corresponding to 6.75 mg atosiban. 
Colourless tubular glass vial (type I) with bromobutyl flange grey rubber stopper and sealed with flip 
off violet colour aluminium seal. 
 
6.6 Special precautions for disposal and other handling 
 
The vials should be inspected visually for particulate matter and discoloration prior to administration. 
 
Preparation of the initial intravenous injection: 
Withdraw 0.9 ml of a 0.9 ml labelled vial of atosiban 6.75 mg/0.9 ml, solution for injection and 
administer slowly as an intravenous bolus dose over one minute, under adequate medical supervision 
in an obstetric unit. The atosiban 6.75 mg/0.9 ml solution for injection should be used immediately. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/852/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 31 July 2013  
Date of latest renewal: 28 May 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



10 

 

1. NAME OF THE MEDICINAL PRODUCT 
 
Atosiban SUN 37.5 mg/5 ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial of 5 ml solution contains 37.5 mg atosiban (as acetate). 
Each ml of solution contains 7.5 mg atosiban. 
 
After dilution, the concentration of atosiban is 0.75 mg/ml. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion (sterile concentrate). 
Clear, colourless solution without particles. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Atosiban is indicated to delay imminent pre-term birth in pregnant adult women with: 
- regular uterine contractions of at least 30 seconds duration at a rate of ≥ 4 per 30 minutes 
- a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50% 
- a gestational age from 24 until 33 completed weeks 
- a normal foetal heart rate 
 
4.2 Posology and method of administration 
 
Posology 
 
Treatment with atosiban should be initiated and maintained by a physician experienced in the 
treatment of pre-term labour. 
 
Atosiban is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), 
performed with atosiban 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous 
high dose infusion (loading infusion 300 micrograms/min) of atosiban 37.5 mg/5 ml concentrate for 
solution for infusion during three hours, followed by a lower dose of atosiban 37.5 mg/5 ml 
concentrate for solution for infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The 
duration of the treatment should not exceed 48 hours. The total dose given during a full course of 
atosiban therapy should preferably not exceed 330.75 mg of atosiban. 
 
Intravenous therapy using the initial bolus injection of atosiban 6.75 mg/0.9 ml, solution for injection 
(see Summary of Product Characteristics of this medicinal product) should be started as soon as 
possible after diagnosis of pre-term labour. Once the bolus has been injected, proceed with the 
infusion. In the case of persistence of uterine contractions during treatment with atosiban, alternative 
therapy should be considered. 
 
 
 
 



11 

 

The following table shows the full posology of the bolus injection followed by the infusion: 
 

Step Regimen Infusion rate Atosiban dose 
1 0.9 ml intravenous bolus Not applicable 6.75 mg 

 injection given over 1 minute   
2 3 hours intravenous loading 24 ml/hour (300 μg/min) 54 mg 

 infusion   
3 Up to 45 hours subsequent 8 ml/hour (100 μg/min) Up to 270 mg 

 intravenous infusion   
 
Re-treatment 
 
In case a re-treatment with atosiban is needed, it should also commence with a bolus injection of 
atosiban 6.75 mg/0.9 ml, solution for injection followed by infusion with atosiban 37.5 mg/5 ml, 
concentrate for solution for infusion. 
 
Special population 
 
Patients with renal or hepatic impairment 
There is no experience with atosiban treatment in patients with impaired function of the liver or 
kidneys. Renal impairment is not likely to warrant a dose adjustment, since only a small extent of 
atosiban is excreted in the urine. In patients with impaired hepatic function, atosiban should be used 
with caution. 
 
Paediatric population 
The safety and efficacy of atosiban in pregnant women aged less than 18 years have not been 
established. No data are available. 
 
Method of administration 
 
Intravenous use 
For instructions on preparation of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Atosiban must not be used in the following conditions: 
- Gestational age below 24 or over 33 completed weeks 
- Premature rupture of the membranes >30 weeks of gestation 
- Abnormal foetal heart rate 
- Antepartum uterine haemorrhage requiring immediate delivery 
- Eclampsia and severe pre-eclampsia requiring delivery 
- Intrauterine foetal death 
- Suspected intrauterine infection 
- Placenta praevia 
- Abruptio placenta 
- Any other conditions of the mother or foetus, in which continuation of pregnancy is hazardous 
- Hypersensitivity to the active substance or any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
When atosiban is used in patients in whom premature rupture of membranes cannot be excluded, the 
benefits of delaying delivery should be balanced against the potential risk of chorioamnionitis. 
 
There is no experience with atosiban treatment in patients with impaired function of the liver or 
kidneys. Renal impairment is not likely to warrant a dose adjustment, since only a small extent of 



12 

 

atosiban is excreted in the urine. In patients with impaired hepatic function, atosiban should be used 
with caution (see sections 4.2 and 5.2). 
 
There is only limited clinical experience in the use of atosiban in multiple pregnancies or the 
gestational age group between 24 and 27 weeks, because of the small number of patients treated. The 
benefit of atosiban in these subgroups is therefore uncertain. 
 
Re-treatment with atosiban is possible, but there is only limited clinical experience available with 
multiple re-treatments, up to 3 re-treatments (see section 4.2). 
In case of intrauterine growth retardation, the decision to continue or reinitiate the administration of 
atosiban depends on the assessment of fetal maturity. 
 
Monitoring of uterine contractions and fetal heart rate during administration of atosiban and in case of 
persistent uterine contractions should be considered. 
As an antagonist of oxytocin, atosiban may theoretically facilitate uterine relaxation and postpartum 
bleeding therefore blood loss after delivery should be monitored. However, inadequate uterus 
contraction postpartum was not observed during the clinical trials. 
 
Multiple pregnancy and medicinal products with tocolytic activity like calcium channel blockers and 
beta-mimetics are known to be associated with increased risk of pulmonary oedema. Therefore, 
atosiban should be used with caution in case of multiple pregnancy and/or concomitant administration 
of other medicinal products with tocolytic activity (see section 4.8). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
It is unlikely that atosiban is involved in cytochrome P450 mediated drug-drug interactions as in vitro 
investigations have shown that atosiban is not a substrate for the cytochrome P450 system, and does 
not inhibit the medicinal product metabolising cytochrome P450 enzymes. 
 
Interaction studies have been performed with labetalol and betamethasone in healthy, female 
volunteers. No clinically relevant interaction was found between atosiban and bethamethasone or 
labetalol. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
Atosiban should only be used when pre-term labour has been diagnosed between 24 and 33 completed 
weeks of gestation.  
 
Breast-feeding 
 
If during pregnancy the woman is already breast-feeding an earlier child, then breast-feeding should 
be discontinued during treatment with atosiban, since the release of oxytocin during breast-feeding 
may augment uterine contractility, and may counteract the effect of tocolytic therapy. 
 
In atosiban clinical trials no effects were observed on breast-feeding. Small amounts of atosiban have 
been shown to pass from plasma into the breast milk of breast-feeding women. 
 
Fertility 
 
Embryo-fetal toxicity studies have not shown toxic effects of atosiban. No studies were performed that 
covered fertility and early embryonic development (see section 5.3). 
 



13 

 

4.7 Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
Possible adverse reactions of atosiban were described for the mother during the use of atosiban in 
clinical trials. In total 48% of the patients treated with atosiban experienced adverse reactions during 
the clinical trials. The observed adverse reactions were generally of a mild severity. The most 
commonly reported adverse reaction in the mother is nausea (14 %). 
 
For the newborn, the clinical trials did not reveal any specific adverse reactions of atosiban. The infant 
adverse reactions were in the range of normal variation and were comparable with both placebo and 
beta-mimetic group incidences. 
 
Tabulated list of adverse reactions 
 
The frequency of adverse reactions listed below is defined using the following convention: very 
common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to 
<1/1,000). Within each frequency grouping, adverse reactions are presented in order of decreasing 
seriousness. 
 
MedDRA system organ class 
(SOC) 

Very 
common 

Common Uncommon Rare 

Immune system disorders    Allergic reaction 
Metabolism and nutrition 
disorders 

 Hyperglycaemia   

Psychiatric disorder   Insomnia  
Nervous system disorders  Headache, 

Dizziness 
  

Cardiac disorders  Tachycardia   
Vascular disorders  Hypotension, Hot 

flush 
  

Gastrointestinal disorders Nausea Vomiting   
Skin and subcutaneous tissue 
disorders 

  Pruritis, Rash  

Reproductive system and 
breast disorder 

   Uterine haemorrhage, 
uterine atony 

General disorders and 
administration site conditions 

 Injection site 
reaction 

Pyrexia  

 
Post-marketing experience 
 
Respiratory events like dyspnoea and pulmonary oedema, particularly in association with concomitant 
administration of other medicinal products with tocolytic activity, like calcium antagonists and beta-
mimetics, and/or in women with multiple pregnancy, have been reported post-marketing. 
 
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 national reporting system 
listed in Appendix V. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


14 

 

 
4.9 Overdose 
 
Few cases of atosiban overdosing were reported, they occurred without any specific signs or 
symptoms. There is no known specific treatment in case of an overdose. 
 
 
5. PHARMACOLOGICAL PROPERTIES  
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other gynecologicals, ATC code: G02CX01 
 
Atosiban SUN contains atosiban (INN), a synthetic peptide ([Mpa1, D-Tyr(Et)2, Thr4,Orn8]-oxytocin) 
which is a competitive antagonist of human oxytocin at receptor level. In rats and guinea pigs, 
atosiban was shown to bind to oxytocin receptors, to decrease the frequency of contractions and the 
tone of the uterine musculature, resulting in a suppression of uterine contractions. Atosiban was also 
shown to bind to the vasopressin receptor, thus inhibiting the effect of vasopressin. In animals atosiban 
did not exhibit cardiovascular effects. 
 
In human pre-term labour, atosiban at the recommended dose antagonises uterine contractions and 
induces uterine quiescence. The onset of uterus relaxation following atosiban is rapid, uterine 
contractions being significantly reduced within 10 minutes to achieve stable uterine quiescence 
(≤ 4 contractions/hour) for 12 hours. 
 
Phase III clinical trials (CAP-001 studies) include data from 742 women who were diagnosed with 
pre-term labour at 23-33 weeks of gestation and were randomised to receive either atosiban (according 
to this labelling) or β-agonist (dose-titrated). 
 
Primary endpoint: the primary efficacy outcome was the proportion of women remaining undelivered 
and not requiring alternative tocolysis within 7 days of treatment initiation. The data show that 59.6% 
(n=201) and 47.7% (n=163) of atosiban- and β-agonist-treated women (p=0.0004), respectively, were 
undelivered and did not require alternative tocolysis within 7 days of starting treatment. Most of the 
treatment failures in CAP-001 were caused by poor tolerability. Treatment failures caused by 
insufficient efficacy were significantly (p=0.0003) more frequent in atosiban (n=48, 14.2%) than in the 
β-agonist-treated women (n=20, 5.8%). 
In the CAP-001 studies the probability of remaining undelivered and not requiring alternative 
tocolytics within 7 days of treatment initiation was similar for atosiban and beta-mimetics treated 
women at gestational age of 24-28 weeks. However, this finding is based on a very small sample 
(n=129 patients). 
 
Secondary endpoints: secondary efficacy parameters included the proportion of women remaining 
undelivered within 48 h of treatment initiation. There was no difference between the atosiban and 
beta-mimetic groups with regard to this parameter. 
 
Mean (SD) gestational age at delivery was the same in the two groups: 35.6 (3.9) and 35.3 (4.2) weeks 
for the atosiban and β-agonist groups, respectively (p=0.37). Admission to a neonatal intensive care 
unit (NICU) was similar for both treatment groups (approximately 30%), as was length of stay and 
ventilation therapy. Mean (SD) birth weight was 2491 (813) grams in the atosiban group and 2461 
(831) grams in the β-agonist group (p=0.58).  
 
Fetal and maternal outcome did apparently not differ between the atosiban and the β-agonist group, 
but the clinical trials were not powered enough to rule out a possible difference. 
 



15 

 

Of the 361 women who received atosiban treatment in the phase III studies, 73 received at least one 
re-treatment, 8 received at least 2 re-treatments and 2 received 3 re-treatments (see section 4.4). 
 
As the safety and efficacy of atosiban in women with a gestational age of less than 24 completed 
weeks has not been established in controlled randomised studies, the treatment of this patient group 
with atosiban is not recommended (see section 4.3). 
 
In a placebo-controlled study, fetal/infant deaths were 5/295 (1.7%) in the placebo group and 15/288 
(5.2%) in the atosiban group, of which two occurred at five and eight months of age. Eleven out of the 
15 deaths in the atosiban group occurred in pregnancies with a gestational age of 20 to 24 weeks, 
although in this subgroup patient distribution was unequal (19 women on atosiban, 4 on placebo). For 
women with a gestational age greater than 24 weeks there was no difference in mortality rate (1.7% in 
the placebo group and 1.5% in the atosiban group). 
 
5.2 Pharmacokinetic properties 
 
In healthy non-pregnant subjects receiving atosiban infusions (10 to 300 micrograms/min over 
12 hours), the steady state plasma concentrations increased proportionally to the dose. 
 
The clearance, volume of distribution and half-life were found to be independent of the dose. 
 
Absorption 
 
In women in pre-term labour receiving atosiban by infusion (300 micrograms/min for 6 to 12 hours), 
steady state plasma concentrations were reached within one hour following the start of the infusion 
(mean 442 ± 73 ng/ml, range 298 to 533 ng/ml). 
 
Following completion of the infusion, plasma concentration rapidly declined with an initial (tα) and 
terminal (tβ) half-life of 0.21 ± 0.01 and 1.7 ± 0.3 hours, respectively. Mean value for clearance was 
41.8 ± 8.2 litres/h.  
 
Distribution 
 
Mean value of volume of distribution was 18.3 ± 6.8 litres. 
 
Plasma protein binding of atosiban is 46 to 48% in pregnant women. It is not known whether the free 
fraction in the maternal and fetal compartments differs substantially. Atosiban does not partition into 
red blood cells. 
 
Atosiban passes the placenta. Following an infusion of 300 micrograms/min in healthy pregnant 
women at term, the fetal/maternal atosiban concentration ratio was 0.12.  
 
Biotransformation 
 
Two metabolites were identified in the plasma and urine from human subjects. The ratios of the main 
metabolite M1 (des-(Orn8, Gly-NH2 9) -29)-[Mpa1, D-Tyr(Et)2, Thr4]-oxytocin) to atosiban 
concentrations in plasma were 1.4 and 2.8 at the second hour and at the end of the infusion 
respectively. It is not known whether M1 accumulates in tissues.  
 
Elimination 
 
Atosiban is found in only small quantities in urine, its urinary concentration is about 50 times lower 
than that of M1. The proportion of atosiban eliminated in faeces is not known. The main metabolite 
M1 is approximately 10 times less potent than atosiban in inhibiting oxytocin-induced uterine 
contractions in vitro. Metabolite M1 is excreted in milk (see section 4.6). 



16 

 

 
Patients with renal or liver impairment 
 
There is no experience with atosiban treatment in patients with impaired function of the liver or 
kidneys. Renal impairment is not likely to warrant a dose adjustment, since only a small extent of 
atosiban is excreted in the urine. In patients with impaired hepatic function, atosiban should be used 
with caution (see sections 4.2 and 4.4). 
 
It is unlikely that atosiban inhibits hepatic cytochrome P450 isoforms in humans (see section 4.5). 
 
5.3 Preclinical safety data 
 
No systemic toxic effects were observed during the two-week intravenous toxicity studies (in rats and 
dogs) at doses which are approximately 10 times higher than the human therapeutic dose, and during 
the three-months toxicity studies in rats and dogs (up to 20 mg/kg/day s.c.). The highest atosiban 
subcutaneous dose not producing any adverse effects was approximately two times the therapeutic 
human dose. 
 
No studies were performed that covered fertility and early embryonic development. Reproduction 
toxicity studies, with dosing from implantation up to late stage pregnancy, showed no effects on 
mothers and fetuses. The exposure of the rat fetus was approximately four times that received by the 
human fetus during intravenous infusions in women. Animal studies have shown inhibition of 
lactation as expected from the inhibition of action of oxytocin. 
 
Atosiban was neither oncogenic nor mutagenic in in vitro and in vivo tests. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Hydrochloric acid 1M 
Water for injections 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products except those mentioned in section 6.6. 
 
6.3 Shelf life 
 
2 years. 
 
Once the vial has been opened, the dilution must be performed immediately. 
Diluted solution for intravenous administration should be used within 24 hours after preparation. 
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2°C - 8°C). 
 
Store in the original package in order to protect from light. 
 
For storage conditions after first opening and dilution of the medicinal product, see section 6.3. 
 



17 

 

6.5 Nature and contents of container  
 
One vial of concentrate for solution for infusion contains 5 ml solution, corresponding to 37.5 mg 
atosiban. 
Colourless tubular glass vial (type I) with bromobutyl flange grey rubber stopper and sealed with 
violet flip top aluminium seal. 
 
6.6 Special precautions for disposal and other handling 
 
The vials should be inspected visually for particulate matter and discoloration prior to administration. 
 
Preparation of the intravenous infusion solution: 
 
For intravenous infusion, following the bolus dose, atosiban 37.5 mg/5 ml concentrate for solution for 
infusion should be diluted in one of the following solutions: 
- sodium chloride 9 mg/ml (0.9%) solution for injection 
- Ringer's lactate solution 
- 5% w/v glucose solution. 
 
Withdraw 10 ml solution from a 100 ml infusion bag and discard. Replace it by 10 ml atosiban 
37.5 mg/5 ml concentrate for solution for infusion from two 5 ml vials to obtain a concentration of 
75 mg atosiban in 100 ml. 
 
The reconstituted medicinal product is a clear, colourless solution without particles. 
 
The loading infusion is given by infusing 24 ml/hour (i.e. 18 mg/h) of the above prepared solution 
over the 3 hour period under adequate medical supervision in an obstetric unit. After three hours the 
infusion rate is reduced to 8 ml/hour. 
 
Prepare new 100 ml bags in the same way as described to allow the infusion to be continued. 
 
If an infusion bag with a different volume is used, a proportional calculation should be made for the 
preparation. 
 
To achieve accurate dosing, a controlled infusion device is recommended to adjust the rate of flow in 
drops/min. An intravenous microdrip chamber can provide a convenient range of infusion rates within 
the recommended dose levels for atosiban. 
 
If other medicinal products need to be given intravenously at the same time, the intravenous cannula 
can be shared or another site of intravenous administration can be used. This permits the continued 
independent control of the rate of infusion. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/852/002 
 



18 

 

 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 31 July 2013 
Date of latest renewal: 28 May 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



19 

 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



20 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
NETHERLANDS 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal products subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
• Periodic safety update reports  
 

The requirements for submission of periodic safety update reports for this medicinal product 
are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) 
of Directive 2001/83/EC and any subsequent updates published on the European medicines 
web-portal. 

 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile or 
as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached.  

 
 



21 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



22 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



23 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Atosiban SUN 6.75 mg/0.9 ml solution for injection 
atosiban 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial of 0.9 ml solution contains 6.75 mg of atosiban (as acetate). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, hydrochloric acid 1M, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
1 vial (6.75 mg/0.9 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Do not use if shrink wrap is tampered. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



24 

 

Store in a refrigerator. 
Store in the original package in order to protect from light. 
Once the vial has been opened, the solution must be used immediately. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V.  
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/852/001 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



25 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Atosiban SUN 6.75 mg/0.9 ml injection  
atosiban 
IV 
 
 
2. METHOD OF ADMINISTRATION 
 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.9 ml (6.75 mg/0.9 ml) 
 
 
6. OTHER 
 
EU/1/13/852/001 



26 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Atosiban SUN 37.5 mg/5 ml concentrate for solution for infusion 
atosiban 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial of 5 ml solution contains 37.5 mg of atosiban (as acetate). 
Each ml of solution contains 7.5 mg atosiban. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: mannitol, hydrochloric acid 1M, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
1 vial (7.5 mg/ml) 
 
Provides 0.75 mg/ml when diluted as recommended. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For intravenous use after dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Do not use if shrink wrap is tampered. 
 
 
8. EXPIRY DATE 
 
EXP 
 



27 

 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Store in the original package in order to protect from light. 
The diluted solution must be used within 24 hours. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Sun Pharmaceutical Industries Europe B.V.  
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/852/002 
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



28 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  



29 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Atosiban SUN 37.5 mg/5 ml sterile concentrate  
atosiban 
IV after dilution 
 
 
2. METHOD OF ADMINISTRATION 
 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml (7.5 mg/ml) 
 
 
6. OTHER 

 
EU/1/13/852/002 



30 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET  



31 

 

Package leaflet: Information for the user 
 

Atosiban SUN 6.75 mg/0.9 ml solution for injection 
atosiban 

 
 

Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, midwife or pharmacist. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Atosiban SUN is and what it is used for 
2. What you need to know before you are given Atosiban SUN 
3. How Atosiban SUN will be given 
4. Possible side effects 
5. How to store Atosiban SUN 
6. Contents of the pack and other information 
 
 
1. What Atosiban SUN is and what it is used for 
 
Atosiban SUN contains atosiban. Atosiban SUN is used to delay the premature birth of your baby. 
Atosiban SUN is used in pregnant adult women, from week 24 to week 33 of the pregnancy. 
 
Atosiban SUN works by making the contractions in your womb (uterus) weaker. It also makes the 
contractions happen less often. It does this by blocking the effect of a natural hormone in your body 
called “oxytocin” which causes your womb (uterus) to contract. 
 
 
2. What you need to know before you are given Atosiban SUN 
 
Do not use Atosiban SUN 
- If you are allergic to atosiban or any of the other ingredients of this medicine (listed in 

section 6). 
- If you are less than 24 weeks pregnant. 
- If you are more than 33 weeks pregnant. 
- If your waters have broken (premature rupture of your membranes) and you have completed 

30 weeks of your pregnancy or more. 
- If your unborn baby (foetus) has an abnormal heart rate. 
- If you have bleeding from your vagina and your doctor wants your unborn baby to be delivered 

straight away. 
- If you have something called “severe pre-eclampsia” and your doctor wants your unborn baby 

to be delivered straight away. Severe pre-eclampsia is when you have very high blood pressure, 
fluid retention and/or protein in your urine. 

- If you have something called “eclampsia” which is similar to “severe pre-eclampsia” but you 
would also have fits (convulsions). This will mean your unborn baby needs to be delivered 
straight away. 

- If your unborn baby has died. 
- If you have or could have an infection of your womb (uterus). 
- If your placenta is covering the birth canal. 



32 

 

- If your placenta is detaching from the wall of your womb. 
- If you or your unborn baby have any other conditions where it would be dangerous to continue 

with your pregnancy. 
 
Do not use Atosiban SUN if any of the above apply to you. If you are not sure, talk to your doctor, 
midwife or pharmacist before you are given Atosiban SUN. 
 
Warnings and precautions 
Talk to your doctor, midwife or pharmacist before you are given Atosiban SUN 
- If you think your waters might have broken (premature rupture of your membranes). 
- If you have kidney or liver problems. 
- If you are between 24 and 27 weeks pregnant. 
- If you are pregnant with more than one baby. 
- If your contractions start again, treatment with Atosiban SUN can be repeated up to three more 

times. 
- If your unborn baby is small for the time of your pregnancy. 
- Your womb may be less able to contract after your baby has been born. This may cause 

bleeding. 
- If you are pregnant with more than one baby and/or are given medicines that can delay the birth 

of your baby, such as medicines used for high blood pressure. This may increase the risk of lung 
oedema (accumulation of fluid in the lungs). 

 
If any of the above apply to you (or you are not sure), talk to your doctor, midwife or pharmacist 
before you are given Atosiban SUN. 
 
Children and adolescents 
Atosiban SUN has not been studied in pregnant women less than 18 years old. 
 
Other medicines and Atosiban SUN 
Tell your doctor, midwife or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Pregnancy and breast-feeding 
If you are pregnant and breast-feeding an earlier child, you should stop breast-feeding while you are 
given Atosiban SUN. 
 
 
3. How Atosiban SUN will be given 
 
Atosiban SUN will be given to you in a hospital by a doctor, nurse or midwife. They will decide how 
much you need. They will also make sure the solution is clear and free from particles. 
 
Atosiban SUN will be given into a vein (intravenously) in three stages: 
- The first injection of 6.75 mg in 0.9 ml will be slowly injected into your vein over one minute. 
- Then a continuous infusion (drip) will be given at a dose of 18 mg per hour for 3 hours. 
- Then another continuous infusion (drip) at a dose of 6 mg per hour will be given for up to 

45 hours, or until your contractions have stopped. 
Treatment should last no longer than 48 hours in total. 
 
Further treatment with Atosiban SUN can be used if your contractions start again. Treatment with 
Atosiban SUN can be repeated up to three more times. 
 
During treatment with Atosiban SUN, your contractions and your unborn baby’s heart rate may be 
monitored. 
 



33 

 

It is recommended that no more than three re-treatments should be used during a pregnancy. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The side 
effects seen in the mother are generally mild. There are no known side effects on the unborn or new-
born baby. 
 
The following side effects may happen with this medicine: 
 
Very common (may affect more than 1 in 10 people) 
- Feeling sick (nausea). 
 
Common (may affect less than 1 in 10 people) 
- Headache. 
- Feeling dizzy. 
- Hot flushes. 
- Being sick (vomiting). 
- Fast heart beat. 
- Low blood pressure. Signs may include feeling dizzy or light-headed. 
- A reaction at the site where the injection was given. 
- High blood sugar. 
 
Uncommon (may affect less than 1 in 100 people) 
- High temperature (fever). 
- Difficulty sleeping (insomnia). 
- Itching. 
- Rash. 
 
Rare (may affect less than 1 in 1,000 people) 
- Your womb may be less able to contract after your baby has been born. This may cause 

bleeding. 
- Allergic reactions. 
 
You may experience shortness of breath or lung oedema (accumulation of fluid in the lungs), 
particularly if you are pregnant with more than one baby and/or are given medicines that can delay the 
birth of your baby, such as medicines used for high blood pressure. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, midwife 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 listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Atosiban SUN 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label after EXP {MM/YYYY}. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Once the vial has been opened, the medicinal product must be used 
straight away. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


34 

 

 
Store in the original package in order to protect from light. 
 
Do not use Atosiban SUN if you notice particulate matter and discoloration prior to administration. 
 
Do not throw away any medicines in wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Atosiban SUN contains 
- The active substance is atosiban. 
- Each vial of Atosiban SUN 6.75 mg/0.9 ml solution for injection contains atosiban acetate 

equivalent to 6.75 mg of atosiban in 0.9 ml. 
- The other ingredients are mannitol, hydrochloric acid 1M and water for injections. 
 
What Atosiban SUN looks like and contents of the pack 
Atosiban SUN 6.75 mg/0.9 ml solution for injection is a clear, colourless solution without particles. 
One pack contains one vial containing 0.9 ml solution. 
 
Marketing Authorisation Holder and Manufacturer 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien/България/Česká republika/ 
Danmark/Eesti/Ελλάδα/Hrvatska/Ireland/Ísland/Κύπρος/ 
Latvija/Lietuva/Luxembourg/Luxemburg/Magyarország/ 
Malta/Nederland/Norge/Österreich/Portugal/Slovenija/ 
Slovenská republika/Suomi/Finland/Sverige 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
Nederland/Pays-Bas/Niederlande/Нидерландия/Nizozemsko/ 
Nederlandene/Ολλανδία/Nizozemska/The Netherlands/Holland/ 
Ολλανδία/Nīderlande/Nyderlandai/Pays-Bas/Niederlande/ 
Hollandia/L-Olanda/Nederland/Niederlande/Países Baixos/ 
Nizozemska/Holandsko/Alankomaat/Nederländerna 
Tel./тел./tlf./τηλ./Sími/τηλ./Tlf./Puh./ 
+31 (0)23 568 5501 
 
Deutschland 
Sun Pharmaceuticals Germany GmbH 
Hemmelrather Weg 201 
51377 Leverkusen 
Deutschland 
tel. +49 214 403 990 
 
España 
Sun Pharma Laboratorios, S.L.  



35 

 

Rambla de Catalunya 53-55 
08007 Barcelona 
España 
tel. +34 93 342 78 90 
 
France 
Sun Pharma France 
11-15, Quai de Dion Bouton 
92800 Puteaux 
France 
tel. +33 1 41 44 44 50 
 
Italia 
Ranbaxy Italia S.p.A. 
Viale Giulio Richard, 1 
20143 Milano 
Italia 
tel. +39 02 33 49 07 93 
 
Polska 
Ranbaxy (Poland) Sp. Z. o. o. 
ul. Kubickiego 11  
02-954 Warszawa  
Polska 
tel. +48 22 642 07 75 
 
România 
Terapia S.A. 
Str. Fabricii nr 124 
Cluj-Napoca, Judeţul Cluj 
România 
tel. +40 (264) 501 500 
 
United Kingdom 
Ranbaxy UK Ltd 
a Sun Pharma Company 
Millington Road 11 
Hyde Park, Hayes 3 
5th Floor 
UB3 4AZ HAYES 
United Kingdom 
tel. +44 (0) 208 848 8688 
 
This leaflet was last revised in  
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


36 

 

INSTRUCTION FOR THE HEALTHCARE PROFESSIONAL 
 
The following information is intended for healthcare professionals only: 
(See also section 3) 
 
Instructions for use 
Before using Atosiban SUN, the solution should be examined to ensure it is clear and free from 
particles. 
 
Atosiban SUN is given intravenously in three successive stages: 
- The initial intravenous injection of 6.75 mg in 0.9 ml is slowly injected into a vein over one 

minute. 
- A continuous infusion at a rate of 24 ml/hour is given for 3 hours. 
- A continuous infusion at a rate of 8 ml/hour is given for up to 45 hours, or until the contractions 

of the uterus have subsided. 
 
The total duration of the treatment should be no more than 48 hours. Further treatment cycles of 
Atosiban SUN can be used should contractions recur. It is recommended that no more than three 
retreatments should be used during a pregnancy. 
 



37 

 

Package leaflet: Information for the user 
 
 

Atosiban SUN 37.5 mg/5 ml concentrate for solution for infusion 
atosiban 

 
 

Read all of this leaflet carefully before you are given this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, midwife or pharmacist. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Atosiban SUN is and what it is used for 
2. What you need to know before you are given Atosiban SUN 
3. How Atosiban SUN will be given 
4. Possible side effects 
5. How to store Atosiban SUN 
6. Contents of the pack and other information 
 
 
1. What Atosiban SUN is and what it is used for 
 
Atosiban SUN contains atosiban. Atosiban SUN is used to delay the premature birth of your baby. 
Atosiban SUN is used in pregnant adult women, from week 24 to week 33 of the pregnancy. 
 
Atosiban SUN works by making the contractions in your womb (uterus) weaker. It also makes the 
contractions happen less often. It does this by blocking the effect of a natural hormone in your body 
called “oxytocin” which causes your womb (uterus) to contract. 
 
 
2. What you need to know before you are given Atosiban SUN  
 
Do not use Atosiban SUN 
- If you are allergic to atosiban or any of the other ingredients of this medicine (listed in 

section 6). 
- If you are less than 24 weeks pregnant. 
- If you are more than 33 weeks pregnant. 
- If your waters have broken (premature rupture of your membranes) and you have completed 

30 weeks of your pregnancy or more. 
- If your unborn baby (foetus) has an abnormal heart rate. 
- If you have bleeding from your vagina and your doctor wants your unborn baby to be delivered 

straight away. 
- If you have something called “severe pre-eclampsia” and your doctor wants your unborn baby 

to be delivered straight away. Severe pre-eclampsia is when you have very high blood pressure, 
fluid retention and/or protein in your urine. 

- If you have something called “eclampsia” which is similar to “severe pre-eclampsia” but you 
would also have fits (convulsions). This will mean your unborn baby needs to be delivered 
straight away. 

- If your unborn baby has died. 
- If you have or could have an infection of your womb (uterus). 



38 

 

- If your placenta is covering the birth canal. 
- If your placenta is detaching from the wall of your womb. 
- If you or your unborn baby have any other conditions where it would be dangerous to continue 

with your pregnancy. 
 
Do not use Atosiban SUN if any of the above apply to you. If you are not sure, talk to your doctor, 
midwife or pharmacist before you are given Atosiban SUN. 
 
Warnings and precautions  
Talk to your doctor, midwife or pharmacist before you are given Atosiban SUN 
- If you think your waters might have broken (premature rupture of your membranes). 
- If you have kidney or liver problems. 
- If you are between 24 and 27 weeks pregnant. 
- If you are pregnant with more than one baby. 
- If your contractions start again, treatment with Atosiban SUN can be repeated up to three more 

times. 
- If your unborn baby is small for the time of your pregnancy. 
- Your womb may be less able to contract after your baby has been born. This may cause 

bleeding. 
- If you are pregnant with more than one baby and/or are given medicines that can delay the birth 

of your baby, such as medicines used for high blood pressure. This may increase the risk of lung 
oedema (accumulation of fluid in the lungs). 

 
If any of the above apply to you (or you are not sure), talk to your doctor, midwife or pharmacist 
before you are given Atosiban SUN. 
 
Children and adolescents 
Atosiban SUN has not been studied in pregnant women less than 18 years old. 
 
Other medicines and Atosiban SUN 
Tell your doctor, midwife or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Pregnancy and breast-feeding 
If you are pregnant and breast-feeding an earlier child, you should stop breast-feeding while you are 
given Atosiban SUN. 
 
 
3. How Atosiban SUN will be given 
 
Atosiban SUN will be given to you in a hospital by a doctor, nurse or midwife. They will decide how 
much you need. They will also make sure the solution is clear and free from particles. 
 
Atosiban SUN will be given into a vein (intravenously) in three stages: 
- The first injection of 6.75 mg in 0.9 ml will be slowly injected into your vein over one minute. 
- Then a continuous infusion (drip) will be given at a dose of 18 mg per hour for 3 hours. 
- Then another continuous infusion (drip) at a dose of 6 mg per hour will be given for up to 

45 hours, or until your contractions have stopped. 
Treatment should last no longer than 48 hours in total. 
 
Further treatment with Atosiban SUN can be used if your contractions start again. Treatment with 
Atosiban SUN can be repeated up to three more times. 
 
During treatment with Atosiban SUN, your contractions and your unborn baby’s heart rate may be 
monitored. 



39 

 

 
It is recommended that no more than three re-treatments should be used during a pregnancy. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The side 
effects seen in the mother are generally mild. There are no known side effects on the unborn or new-
born baby. 
 
The following side effects may happen with this medicine: 
 
Very common (may affect more than 1 in 10 people) 
- Feeling sick (nausea). 
 
Common (may affect less than 1 in 10 people) 
- Headache. 
- Feeling dizzy. 
- Hot flushes. 
- Being sick (vomiting). 
- Fast heart beat. 
- Low blood pressure. Signs may include feeling dizzy or light-headed. 
- A reaction at the site where the injection was given. 
- High blood sugar. 
 
Uncommon (may affect less than 1 in 100 people) 
- High temperature (fever). 
- Difficulty sleeping (insomnia). 
- Itching. 
- Rash. 
 
Rare (may affect less than 1 in 1,000 people) 
- Your womb may be less able to contract after your baby has been born. This may cause 

bleeding. 
- Allergic reactions. 
 
You may experience shortness of breath or lung oedema (accumulation of fluid in the lungs), 
particularly if you are pregnant with more than one baby and/or are given medicines that can delay the 
birth of your baby, such as medicines used for high blood pressure. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, midwife 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 listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Atosiban SUN 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label after EXP {MM/YYYY}. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Dilutions for intravenous administration must be used within 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


40 

 

24 hours after preparation. 
 
Store in the original package in order to protect from light. 
 
Do not use Atosiban SUN if you notice particulate matter and discoloration prior to administration. 
 
Do not throw away any medicines in wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Atosiban SUN contains 
- The active substance is atosiban. 
- Each vial of Atosiban SUN 37.5 mg/5 ml concentrate for solution for infusion contains atosiban 

acetate equivalent to 37.5 mg of atosiban in 5 ml. 
- The other ingredients are mannitol, hydrochloric acid 1M and water for injections. 
 
What Atosiban SUN looks like and contents of the pack 
Atosiban SUN 37.5 mg/5 ml concentrate for solution for infusion is a clear, colourless solution 
without particles.  
One pack contains one vial containing 5 ml solution. 
 
Marketing Authorisation Holder and Manufacturer 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
The Netherlands 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien/България/Česká republika/ 
Danmark/Eesti/Ελλάδα/Hrvatska/Ireland/Ísland/Κύπρος/ 
Latvija/Lietuva/Luxembourg/Luxemburg/Magyarország/ 
Malta/Nederland/Norge/Österreich/Portugal/Slovenija/ 
Slovenská republika/Suomi/Finland/Sverige 
Sun Pharmaceutical Industries Europe B.V. 
Polarisavenue 87 
2132 JH Hoofddorp 
Nederland/Pays-Bas/Niederlande/Нидерландия/Nizozemsko/ 
Nederlandene/Ολλανδία/Nizozemska/The Netherlands/Holland/ 
Ολλανδία/Nīderlande/Nyderlandai/Pays-Bas/Niederlande/ 
Hollandia/L-Olanda/Nederland/Niederlande/Países Baixos/ 
Nizozemska/Holandsko/Alankomaat/Nederländerna 
Tel./тел./tlf./τηλ./Sími/τηλ./Tlf./Puh./ 
+31 (0)23 568 5501 
 
Deutschland 
Sun Pharmaceuticals Germany GmbH 
Hemmelrather Weg 201 
51377 Leverkusen 
Deutschland  
tel. +49 214 403 990 
 



41 

 

España 
Sun Pharma Laboratorios, S.L.  
Rambla de Catalunya 53-55 
08007 Barcelona 
España 
tel. +34 93 342 78 90 
 
France 
Sun Pharma France 
11-15, Quai de Dion Bouton 
92800 Puteaux 
France 
tel. +33 1 41 44 44 50 
 
Italia 
Ranbaxy Italia S.p.A. 
Viale Giulio Richard, 1 
20143 Milano 
Italia 
tel. +39 02 33 49 07 93 
 
Polska 
Ranbaxy (Poland) Sp. Z. o. o. 
ul. Kubickiego 11  
02-954 Warszawa  
Polska 
tel. +48 22 642 07 75 
 
România 
Terapia S.A. 
Str. Fabricii nr 124 
Cluj-Napoca, Judeţul Cluj 
România 
tel. +40 (264) 501 500 
 
United Kingdom 
Ranbaxy UK Ltd 
a Sun Pharma Company 
Millington Road 11 
Hyde Park, Hayes 3 
5th Floor 
UB3 4AZ HAYES 
United Kingdom 
tel. +44 (0) 208 848 8688 
 
This leaflet was last revised in  
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


42 

 

INSTRUCTION FOR THE HEALTHCARE PROFESSIONAL 
 
The following information is intended for healthcare professionals only: 
(See also section 3) 
 
Instructions for use 
Before using Atosiban SUN, the solution should be examined to ensure it is clear and free from 
particles. 
 
Atosiban SUN is given intravenously in three successive stages:  
- The initial intravenous injection of 6.75 mg in 0.9 ml is slowly injected into a vein over one 

minute. 
- A continuous infusion at a rate of 24 ml/hour is given for 3 hours. 
- A continuous infusion at a rate of 8 ml/hour is given for up to 45 hours, or until the contractions 

of the uterus have subsided. 
 
The total duration of the treatment should be no more than 48 hours. Further treatment cycles of 
Atosiban SUN can be used should contractions recur. It is recommended that no more than three 
retreatments should be used during a pregnancy. 
 
Preparation of the intravenous infusion 
The intravenous infusion is prepared by diluting Atosiban SUN 37.5 mg/5 ml, concentrate for solution 
for infusion in sodium chloride 9 mg/ml (0.9%) solution for injection, Ringer's lactate solution or 5% 
w/v glucose solution. This is done by removing 10 ml of solution from a 100 ml infusion bag and 
replacing it with 10 ml Atosiban SUN 37.5 mg/5 ml concentrate for solution for infusion from two 
5 ml vials to obtain a concentration of 75 mg atosiban in 100 ml. If an infusion bag with a different 
volume is used, a proportional calculation should be made for the preparation.  
Atosiban SUN should not be mixed with other medicinal products in the infusion bag. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET