Transdermal clonidine in severe hyperemesis gravidarum
A novel study on transdermal clonidine treatment of hyperemesis gravidarum O Stephanssona,b a Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden b Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden Linked article: This article is a mini commentary on Maina A et al., pp. 1556–62 in this issue. To view this article visit http://dx.doi.org/10.1111/1471-0528.12757. Nausea and vomiting are common during pregnancy, affecting more than 50% of pregnant women. Among these, 10–15% receive drug treatment (Pasternak et al., N Engl J Med 2013;368:814–23). Hyperemesis gravidarum (HG) is defined as severe nausea and persistent vomiting, weight loss, ketonuria, electrolyte abnormalities and dehydration, and affect approximately 1% of pregnancies. Women with HG should be referred to a hospital and require intravenous hydration with multivitamins including thiamine. Pharmacologic treatment for HG includes: Vitamin B6, antihistamines, phenothiazines, dopamine agonists, 5-hydroxytryptamine3-receptor antagonists, glucocorticoids or a combination of these agents. The clinical challenge is that these drugs may have a limited effect on HG, and there is a need for new treatment strategies. In this issue of BJOG, Maina et al. report the findings on a pilot trial using transdermal clonidine in the treatment for HG. Twelve patients with HG were randomly treated with and without clonidine for two consecutive periods of 5 days in a randomised, double-blind, placebo-controlled cross-
over design (RCT) study (Maina et al., BJOG 2014; DOI: 10.1111/1471-0528. 12757). The study found that transdermal clonidine treatment leads to improvement in symptoms, with less nausea and vomiting and reduced morning ketonuria as well as a reduction of other antiemetic drug doses and a smaller requirement of intravenous rehydration. The study reports a novel treatment opportunity for women with severe nausea and vomiting during pregnancy. The transdermal route of drug administration is an advantage especially in patients treated in antenatal outpatient clinics without the need for intravenous administration. The main concern about the study is regarding the safety in off-label use of clonidine for treatment of HG. It is obvious that a study on only 12 patients cannot rule out risk of congenital malformation or other adverse pregnancy outcomes. Clonidine has been used for treatment of hypertensive disease during pregnancy and is categorized as category C by the FDA (should be used during pregnancy only if clearly needed). It crosses the placenta but no established teratogenic effect has so far been reported. How-
ª 2014 Royal College of Obstetricians and Gynaecologists
ever, safety data on use of clonidine are limited for the first trimester of pregnancy, which is a concern as we therefore lack data on the most important period for fetal organogenesis. Furthermore, because the lowered blood pressure with clonidine it is not known how this will affect normotensive pregnant women and their fetuses. A much larger RCT will have to be carried out to address the safety concerns with a novel treatment for HG. Still, it can be difficult to extrapolate safety data from trials designed to study efficacy because of power limitations. Furthermore, some adverse outcomes such as preterm delivery and growth retardation may be related to HG itself and not drug use, whereas this would not apply for congenital malformation (Boelig et al., Cochrane Database Syst Rev 2013;6:CD010607). In conclusion, treatment with transdermal clonidine may be an opportunity for women with HG but more data on safety are required.
Disclosure of interests None declared. &
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A novel study on transdermal clonidine treatment of hyperemesis gravidarum O Stephanssona,b a Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden b Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden Linked article: This article is a mini commentary on Maina A et al., pp. 1556–62 in this issue. To view this article visit http://dx.doi.org/10.1111/1471-0528.12757. Nausea and vomiting are common during pregnancy, affecting more than 50% of pregnant women. Among these, 10–15% receive drug treatment (Pasternak et al., N Engl J Med 2013;368:814–23). Hyperemesis gravidarum (HG) is defined as severe nausea and persistent vomiting, weight loss, ketonuria, electrolyte abnormalities and dehydration, and affect approximately 1% of pregnancies. Women with HG should be referred to a hospital and require intravenous hydration with multivitamins including thiamine. Pharmacologic treatment for HG includes: Vitamin B6, antihistamines, phenothiazines, dopamine agonists, 5-hydroxytryptamine3-receptor antagonists, glucocorticoids or a combination of these agents. The clinical challenge is that these drugs may have a limited effect on HG, and there is a need for new treatment strategies. In this issue of BJOG, Maina et al. report the findings on a pilot trial using transdermal clonidine in the treatment for HG. Twelve patients with HG were randomly treated with and without clonidine for two consecutive periods of 5 days in a randomised, double-blind, placebo-controlled cross-
over design (RCT) study (Maina et al., BJOG 2014; DOI: 10.1111/1471-0528. 12757). The study found that transdermal clonidine treatment leads to improvement in symptoms, with less nausea and vomiting and reduced morning ketonuria as well as a reduction of other antiemetic drug doses and a smaller requirement of intravenous rehydration. The study reports a novel treatment opportunity for women with severe nausea and vomiting during pregnancy. The transdermal route of drug administration is an advantage especially in patients treated in antenatal outpatient clinics without the need for intravenous administration. The main concern about the study is regarding the safety in off-label use of clonidine for treatment of HG. It is obvious that a study on only 12 patients cannot rule out risk of congenital malformation or other adverse pregnancy outcomes. Clonidine has been used for treatment of hypertensive disease during pregnancy and is categorized as category C by the FDA (should be used during pregnancy only if clearly needed). It crosses the placenta but no established teratogenic effect has so far been reported. How-
ª 2014 Royal College of Obstetricians and Gynaecologists
ever, safety data on use of clonidine are limited for the first trimester of pregnancy, which is a concern as we therefore lack data on the most important period for fetal organogenesis. Furthermore, because the lowered blood pressure with clonidine it is not known how this will affect normotensive pregnant women and their fetuses. A much larger RCT will have to be carried out to address the safety concerns with a novel treatment for HG. Still, it can be difficult to extrapolate safety data from trials designed to study efficacy because of power limitations. Furthermore, some adverse outcomes such as preterm delivery and growth retardation may be related to HG itself and not drug use, whereas this would not apply for congenital malformation (Boelig et al., Cochrane Database Syst Rev 2013;6:CD010607). In conclusion, treatment with transdermal clonidine may be an opportunity for women with HG but more data on safety are required.
Disclosure of interests None declared. &
1563
