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RESEARCH: Roel de Heus, Ben Willem Mol, Jan-Jaap H M Erwich, Herman P van Geijn, Wilfried J Gyselaers, Myriam Hanssens, Linda Härmark, Caroline D van Holsbeke, Johannes J Duvekot, Fred F A M Schobben, Hans Wolf, and Gerard H A Visser Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study BMJ 2009; 338: b744 [Abstract] [Full text]

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Adverse drug reaction of Tocolytics in India

Vikas Dhikav, Richa Gupta, Gynecologist, Gaziabad (UP)   (11 March 2009)

No indication for tocolysis by beta adrenoreceptor agonists

Souhail Alouini   (29 March 2009)

Direct comparison between nifedipine and atosiban

Yves Jacquemyn   (29 March 2009)

Adverse drug reaction of Tocolytics in India 11 March 2009
Vikas Dhikav, Senior Research Officer All India Institute of Medical Sciences, New Delhi-110029, INDIA, Richa Gupta, Gynecologist, Gaziabad (UP) Send response to journal: Re: Adverse drug reaction of Tocolytics in India	We read the article by de Heus1 with interest. They have studied prospectively, 1920 women in 28 hospitals and have come up with interesting conclusions. We feel that in India ritodrine, terbutaline and isoxsuprine remains to be the major tocolytics. Hundreds of thousands of women in preterm labour are given these drugs on daily basis. Though, obstetricians using these drugs say that "theoretically, there are many side effects; but practically we do not see many side effects". The side effects which many obstetricians feel are palpitations, restlessness but are not of ‘serious’ nature etc. Routine monitoring of potassium levels is not done. Hypotension, arrhythmias and worsening of ischemic heart disease are rarely seen. Indeed, few studies have reported no significant adverse effects of ritodrine, a beta-2 agonist used for premature labour2. This makes a fit case to initiate the intensive monitoring of side effects of tocolytics in India. We feel that we need to look at the side effect profile of tocolytics in india more closely. References 1. de Heus R, Mol BW, Erwich JJ, van Geijn HP, Gyselaers WJ, Hanssens M, Härmark L, van Holsbeke CD, Duvekot JJ, Schobben FF, Wolf H, Visser GH. 2. Sharma A, Suri V, Gupta I. Tocolytic therapy in conservative management of symptomatic placenta previa. Int J Gynaecol Obstet. 2004;84(2):109-13. Competing interests: None declared
No indication for tocolysis by beta adrenoreceptor agonists 29 March 2009
Souhail Alouini, Obstetrician and Gynaecologist surgeon, M.D., Ph.D. Centre Hospitalier Regional d'Orléans, 45000, France Send response to journal: Re: No indication for tocolysis by beta adrenoreceptor agonists	Roel de Heus et al. (1) report that the tocolysis by beta-adrenergic agonists is associated with high incidence of serious adverse drug reactions contrary to the atosiban and the indometacin. Nevertheless, it is surprising that beta adrenoreceptor agonists were still used for tocolysis in this recent study (2006-2007) given their potentially serious side effects for the maternal cardiovascular functions previously known. Indeed, the calcium channel blockers and the atosiban are at least as effective as the beta-adrenergic agonists with fewer severe side effects (2). In addition, antenatal indometacin described in the study as having no severe maternal side effects may be associated with severe neonatal outcomes such as periventricular leukomalacia and necrotising enterocolitis that limit its indications (3). References 1. De Heus R, Mol BW, Erwich JJ, van Geijn HP, Gyselaers WJ, Hanssens M, Härmark L, van Holsbeke CD, Duvekot JJ, Schobben FF, Wolf H, Visser GH. Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study. BMJ. 2009;338:b744. 2. The Worldwide Atosiban versus Beta-agonists Study Group. Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. BJOG. 2001;108:133-42. 3. Amin SB, Sinkin RA, Glantz JC. Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes. Am J Obstet Gynecol. 2007;197:486.e1-10. Competing interests: None declared
Direct comparison between nifedipine and atosiban 29 March 2009
Yves Jacquemyn, Head of ObGyn Antwerp University Hospital Wilrijkstraat 10 2650 Edegem Belgium Send response to journal: Re: Direct comparison between nifedipine and atosiban	We read with great intrest the study by de Heus et al. (1) on adverse drug reactions to tocolytic treatment for preterm labour. In their conclusion the authors point to the need for a direct comparison between oxytocin antagonists and calcium channel blockers in terms of tocolytic efficiency and side effects. Actually 2 (small)randomized controlled trials comparing atosiban and nifedipine have been published (2,3). Pooling data from these trials for tocolysis before 35 weeks gestation results in 71 women in the atosiban and 72 in the nifedipin group. Delivery could be postponed in 57 (80.3%) with atosiban and 56 (77.7%), the difference not being significant ( p in Chi square test = 0.713, odds ratio 1.08; 95% confidence interval 0.71-1.65). Both studies also mention side effects such as arterial hypotension, 1 (1.4%) versus 25 (34.7%)in the atosiban and nifedipine group respectively ( p< 0.001, odds ratio 16.7, 95% confidence interval 2.43-115.9. 1.De Heus R, Mol BW, Erwich JJ, van Geijn HP, Gyselaers WJ, Hanssens M, Härmark L, van Holsbeke CD, Duvekot JJ, Schobben FF, Wolf H, Visser GH. Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study. BMJ. 2009: 338:b744.doi 10.1136/bmj.b744 2.Kashanian M, Aklbarian AR, Soltanzadeh M. Atosiban and nifedipine for the treatment of preterm labor. Int J Gynaecol Obstet 2005; 91: 10-14 3. Al-Omari WR, Al-Shammaa HB, Al-Tikriti EM, Ahmed KW. Atosiban and nifedipine in acute tocolysis: a comparative study. Eur J Obstet Gynecol Reprod Biol 2006; 128: 129-134 Competing interests: None declared