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Maternal–Foetal Medicine
Atosiban Clinical Experience – Efficacy and Safety
Ruta Deshpande
1
and Jim G Thornton
2
1. Specialty Registrar in Obstetrics and Gynaecology; 2. Professor of Obstetrics and Gynaecology, City Hospital, Nottingham
Abstract
Atosiban is an oxytocin receptor antagonist that is licensed in Europe as a tocolytic for the treatment of pre-term labour. Randomised
trials show that it is of similar effectiveness as a tocolytic to beta sympathomimetics, which are effective in prolonging gestation. It has
fewer side effects than alternative treatments. However, similar to all other tocolytics, it has never been evaluated in large enough
placebo-controlled trials to conclusively demonstrate that it reduces important adverse peri-natal outcomes. This has led to controversy.
It remains unlicensed in the US, and even in Europe the ‘off-label’ use of unlicensed alternatives such as nifedipine is widespread. In this
article, we summarise the trials, systematic reviews and clinical guidelines and suggest that, despite the controversy, atosiban remains
the drug of choice for tocolysis.
Keywords
Pre-term labour, tocolysis, atosiban, nifedipine, beta-mimetics
Disclosure: Ruta Deshpande has no conflicts of interest to declare. Jim G Thornton has acted as an advisor to Ferring and received honoraria to chair conferences and give
lectures. While he was Editor of the British Journal of Obstetrics and Gynaecology, the journal received sponsorship from Ferring to publish supplements.
Received: 2 March 2009 Accepted: 13 April 2009
Correspondence: Jim G Thornton, Division of Obstetrics and Gynaecology, Maternity Department, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK.
E: jim.thornton@nottingham.ac.uk
Systematic Reviews mimetics and appears to be equally effective. Calcium channel
Most of the trial evidence for the relative effectiveness and safety of blockers have never been studied in a placebo-controlled trial, but
tocolytics is contained in a series of Cochrane reviews. Three drug have been compared with other tocolytics (mainly beta-mimetics)
classes can be dismissed fairly easily. Neither magnesium sulphate in a number of small trials. They appear to be more effective,
nor nitric oxide donors are effective in preventing pre-term delivery,
1,2
reduce some measures of foetal morbidity and have fewer
and although cyclo-oxygenase (COX) inhibitors probably do delay maternal side effects than beta-mimetics. The Cochrane authors
6
pre-term delivery with relatively few maternal side effects,
3
there are recommend their use above other tocolytics. A Cochrane review
many foetal safety worries. They may impair foetal renal function, about maintenance tocolysis with oxytocin antagonists
7
included
cause premature closure of the ductus arteriosus and increase the only one placebo-controlled trial of atosiban and concluded that
risk of intraventricular haemorrhage and necrotising enterocolitis, so the active drug did not prolong gestation or reduce any substantive
are rarely used outside of controlled trials. This leaves three drug adverse foetal outcomes.
classes for consideration: beta-mimetics, oxytocin antagonists and
calcium channel blockers. The trials of beta-mimetics have been Clinical Guidelines
large, of good quality and placebo-controlled.
4
They are effective in The National Institute for Clinical Excellence (NICE) has not yet
reducing pre-term delivery, but there is no evidence that they reduce produced a guideline for pre-term labour, but the UK Royal College
peri-natal mortality or other important foetal morbidity, and they of Obstetricians and Gynaecologists (RCOG) guidelines,
8
which are
carry significant maternal risks. The Cochrane reviewers advise that due to be updated, state that “It is reasonable not to use tocolytic
they may be used with caution for a short period to gain the drugs, as there is no clear evidence that they improve outcome.
maximum benefit from steroid administration. However, tocolysis should be considered if the few days gained
would be put to good use, such as completing a course of
The oxytocin antagonist atosiban has been evaluated in two corticosteroids, or in utero transfer.” The guidelines also state that
placebo-controlled trials and a larger number of trials against other “If a tocolytic drug is used, ritodrine no longer seems the best
tocolytics, mainly beta-mimetics.
5
The placebo-controlled trials all choice. Atosiban or nifedipine appear preferable as they have fewer
involved the early use of rescue tocolysis and showed no difference adverse effects and seem to have similar effectiveness. Atosiban is
in gestation at delivery. A non-significant excess of foetal deaths in licensed for this usage in the UK but nifedipine is not.”
one of the trials was probably explained by a chance imbalance
in the number of extremely pre-term pregnancies recruited to the In the remainder of this article we will consider whether the
atosiban arm. Atosiban has fewer maternal side effects than beta- evidence really is neutral between oxytocin antagonists and calcium
46 © TOUCH BRIEFINGS 2009
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