INDICES> clofazimine, dapsone, rifampicin in pregnancy? (5)

[Kirsten Myhr <myhr@online.no>]

INDICES>clofazimine, dapsone, rifampicin in pregnancy? (5)
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Dear Julia,

Having finally better access to electronic sources and reference books, I
am catching up on old INDICES messages and here is my response to your
question:

Rifampicin

The last issue of Drug Safety (www.adis.com <http://www.adis.com>) has an
article on treatment of tuberculosis in pregnancy (Bothamley G. Drug
treatment for tuberculosis during pregnancy. Drug Safety 2001; 24(7):
553-65. It says about rifampicin:
[..] A review of 442 women taking rifampicin during 446 pregnancies,
including 109 exposed during the first trimester, did not show an excess of
birth defects. One of these studies reported a malformation rate of 4.4 %
in 204 pregnancies, including hydrocephalus (1), anencephaly (1) and limb
defects (4), at rates significantly higher than the general rate of 1.8 %,
but was counterbalanced by the other studies in which malformations were
rarer than expected. No excess of birth defects has been noted in the
babies of more than 2000 pregnant mothers taking rifampicin.
An association between rifampicin and haemorrhagic disease of the newborn
has been suggested and prophylactic vitamin K is especially recommended in
the infants of mothers treated for tuberculosis.
And it concludes:
First line treatment of TB with isoniazid, rifampicin and ethambutol is
widely recognised to be safe in pregnancy [?..]

Clofazimine

AHFS Drug Information 2001 says:
[..] Clofazimine did not appear to be teratogenic in rabbits or rats when
given at dosages 8 or 25 times the usual human dosage, respectively.
However, in reproduction studies in mice using clofazimine dosages 12-25
times the usual human dosage, the drug caused retardation of fetal skull
ossification, an increased incidence of abortions and stillbirths, and
impaired neonatal survival. There are no adequate and controlled studies to
date using clofazimine in pregnant women, and the drug should be used
during pregnancy only when the potential benefits justify the possible
risks to the fetus. Clofazimine has been used during (including throughout)
pregnancy in a limited number of women without evidence of teratogenicity.
However, clofazimine does cross the placenta, and the skin of some neonates
born to women who received the drug during pregnancy was discoloured at
birth; the discoloration gradually faded over the first year. Several
neonates born to women receiving the drug during pregnancy have died, but a
causal relationship to clofazimine has not been established [. ??]

Dapsone

[..] Animal reproduction studies have not been performed with dapsone.
Although dapsone has been used in pregnant women without evidence of fetal
abnormalities, the drug should be used during pregnancy only when clearly
needed. In patients with leprosy, some clinicians consider that the
benefits of maintaining dapsone therapy during pregnancy outweighs the
potential risk to the fetus. [..] Because it is distributed into milk and
because of the tumorigenic potential demonstrated in animal studies,
dapsone should not be used in nursing women. A decision should be made
whether to discontinue nursing or the drug.

Meyler's side effects of drugs 14th ed. says:

[..] Dapsone passes into the breast-milk, but usually no adverse effects
are noted in the newborn (I should add that they also say that
tumor-inducing effects have not been reported, which contradicts the info
quoted above), but mild haemolytic anemia occurred in one breast-fed infant
and his mother. The use of antileprosy drugs during pregnancy depends upon
the severity of the disease and the relative need for treatment. Even
though untoward effects on the fetus have not been reported, treatment of
leprosy during pregnancy probably predisposes to erythema nodosum leprosum.
If this occurs during pregnancy, clofazimine is considered the best drug
available. [..]

Regards

Kirsten

Kirsten Myhr
Head of Eastern Region Drug Information Centre

RELIS Ost
Ulleval University Hospital
0407 Oslo, Norway
Tel.: +47 23 01 64 11(o)   Fax: +47 23 01 64 10
+47 22 56 05 85 (h)   mobile: +47 416 38 747
myhr@online.no
www.relis.no


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