a novel study on transdermal clonidine treatment of hyperemesis gravidarum
Post on 30-Mar-2017
212 Views
Preview:
TRANSCRIPT
A novel study on transdermal clonidine treatment of hyperemesisgravidarum
O Stephanssona,b
aClinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, SwedenbDepartment 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 grav-
idarum (HG) is defined as severe
nausea and persistent vomiting, weight
loss, ketonuria, electrolyte abnor-
malities 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, antihis-
tamines, 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, dou-
ble-blind, placebo-controlled cross-
over design (RCT) study (Maina et al.,
BJOG 2014; DOI: 10.1111/1471-0528.
12757). The study found that transder-
mal clonidine treatment leads to
improvement in symptoms, with less
nausea and vomiting and reduced
morning ketonuria as well as a reduc-
tion of other antiemetic drug doses
and a smaller requirement of intrave-
nous rehydration. The study reports a
novel treatment opportunity for
women with severe nausea and vomit-
ing during pregnancy. The transder-
mal route of drug administration is an
advantage especially in patients treated
in antenatal outpatient clinics without
the need for intravenous administra-
tion. The main concern about the
study is regarding the safety in off-la-
bel use of clonidine for treatment of
HG. It is obvious that a study on only
12 patients cannot rule out risk of con-
genital malformation or other adverse
pregnancy outcomes. Clonidine has
been used for treatment of hyperten-
sive 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-
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 organogen-
esis. Furthermore, because the low-
ered blood pressure with clonidine it
is not known how this will affect nor-
motensive 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 interestsNone declared.&
1563ª 2014 Royal College of Obstetricians and Gynaecologists
Transdermal clonidine in severe hyperemesis gravidarum
top related