Leitlinien & Arzneimittelsicherheit

HOS-096072 · has-adverse-reaction-information · PDF-Seite 13

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 Very Common Uncommon Rare (SOC) common Immune system disorders Allergic reaction Metabolism and nutrition Hyperglycaemia disorders Psychiatric disorder Insomnia Nervous system disorders Headache, Dizziness Cardiac disorders Tachycardia Vascular disorders Hypotension, Hot flush Gastrointestinal disorders Nausea Vomiting Skin and subcutaneous tissue Pruritis, Rash disorders Reproductive system and Uterine haemorrhage, breast disorder uterine atony General disorders and Injection site Pyrexia administration site conditions reaction 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 sus

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HOS-096066 · has-adverse-reaction-information · PDF-Seite 5

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 Very Common Uncommon Rare (SOC) common Immune system disorders Allergic reaction Metabolism and nutrition Hyperglycaemia disorders Psychiatric disorder Insomnia Nervous system disorders Headache, Dizziness Cardiac disorders Tachycardia Vascular disorders Hypotension, Hot flush Gastrointestinal disorders Nausea Vomiting Skin and subcutaneous tissue Pruritis, Rash disorders Reproductive system and Uterine haemorrhage, breast disorder uterine atony General disorders and Injection site Pyrexia administration site conditions reaction 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

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HOS-096062 · has-contraindication-information · PDF-Seite 3

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.

HOS-096068 · has-contraindication-information · PDF-Seite 11

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.

HOS-096067 · has-indication-information · PDF-Seite 10

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

HOS-096061 · has-indication-information · PDF-Seite 2

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

HOS-096064 · has-interaction-information · PDF-Seite 4

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.

HOS-096070 · has-interaction-information · PDF-Seite 12

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.

HOS-096065 · has-pregnancy-information · PDF-Seite 4

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).

HOS-096071 · has-pregnancy-information · PDF-Seite 12

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). 12

HOS-096069 · has-warning-information · PDF-Seite 11

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 11 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).

HOS-096063 · has-warning-information · PDF-Seite 3

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 3 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).