INDICES> INDICES clofazimine, dapsone, rifampicin in pregnancy? (7)

[Kirsten Myhr <myhr@online.no>]

INDICES> clofazimine, dapsone, rifampicin in pregnancy? (7)
--------------------------------------------------------

Steve,

> Is neonatal jaundice not a concern with Dapsone?

Yes I agree it is. It seems that because of limited experience, little
focus has been put on this as well. In fact the only reference mentioned in
Reprotox database was number 6 from 1989

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

[Copied from Reprotox]
Dapsone (diaminodiphenylsulfone) is used chiefly in the
treatment of leprosy and dermatitis herpetiformis (1) and
occasionally in the treatment of malaria (see also,
Pyrimethamine, #1483).
A rare hypersensitivity reaction to this and related drugs, the
"sulfone syndrome", has been reported.  This potentially fatal
syndrome consists of fever, malaise, hepatitis with hepatic
necrosis, exfoliative dermatitis, lymphadenopathy,
methemoglobinemia, and hemolytic anemia (2).  Prompt
discontinuance of dapsone treatment and early institution of
prednisone therapy can reverse this condition (1).  The
manufacturer of dapsone (Jacobus Pharmaceuticals) reports that,
even in the absence of the sulfone syndrome, dose-related
hemolytic anemia is an important side effect of dapsone therapy
in adults and children.
We did not locate any reproduction studies in animals, but one
study that reported administration of dapsone to mice and rats
beginning in late gestation and continuing through lactation and
after weaning found a small but significant increase in tumor
formation among exposed animals (12).
Pregnant women have been treated with dapsone without adverse
effect (3-5,10,14,15); however, the number of exposed
pregnancies is relatively small.  Some cases of hemolytic anemia
have occurred in mothers and their offspring after exposure to
dapsone, both during gestation and during lactation (8,13).  In
these cases, the anemias resolved once dapsone exposure was
discontinued and no long term effects were observed.

Dapsone is structurally related to the sulfonamides, and may
compete with bilirubin to increase the possibility of
kernicteris from hyperbilirubinemia in neonates exposed to
dapsone while in utero (6).  Some clinicians have recommended
the discontinuation of dapsone therapy one month before the
expected date of delivery to minimize the development of
neonatal kernicteris (6).

Dapsone and its primary metabolite, monoacetyldapsone, are
excreted in breast milk (7,8,16).  Milk:plasma ratios ranging
between 0.22 and 0.45 have been reported (7).  The maximum
percentage of the maternal dapsone dose that a suckling neonate
would ingest was estimated as 14.3% (7).  One case report
described an infant who developed hemolytic anemia while exposed
to dapsone in breast milk (8).  The infant's serum contained
significant amounts of dapsone and its major acetylated
metabolite (8).  Because toxic doses of this drug may be
ingested by an exposed suckling, the WHO Working Group on Drugs
and Human Lactation concluded that the use of dapsone during
breastfeeding is not safe (9).

Selected References
1.  Johnson DA et al:  Liver involvement in the sulfone
syndrome.  Arch Intern Med 146:875-877, 1986.
2.  Millikan LE and Harrell ER:  Drug reactions to the sulfones.
Arch Dermatol 102:220-224, 1970.
3.  Tuffanelli DL:  Successful pregnancy in a patient with
dermatitis herpetiformis treated with low-dose dapsone.  Arch
Dermatol 118:876, 1982.
4.  Kahn G:  Dapsone is safe during pregnancy.  J Am Acad
Dermatol 13:838-9, 1985.
5.  Maurus JN:  Hansen's disease in pregnancy.  Obstet Gynecol
52:22-25, 1978.
6.  Thornton YS, Bowe ET:  Neonatal hyperbilirubinemia after
treatment of maternal leprosy.  S Med J 82:668, 1989.
7.  Edstein MD et al:  Excretion of chloroquine, dapsone and
pyrimethamine in human milk.  Br J Clin Pharmacol 22:733-5,
1986.
8.  Sanders SW, Zone JJ, Flotz RL, Tolman KG, Rollins DE:
Haemolytic anaemia induced by dapsone transmitted through breast
milk.  Ann Intern Med 90:465066, 1982.
9.  The WHO Working Group, Bennet PN (ed).:  Drugs and Human
Lactation.  Elsevier, Amsterdam, New York, Oxford, 1988.  pp.
275-6.
10.  Collier PM, Kelly SE, Wojnarowska F:  Linear IgA disease
and pregnancy.  J Am Acad Dermatol 30:407-411, 1994.
12.  Griciute L, Tomatis L:  Carcinogenicity of dapsone in mice
and rats.  Int J Cancer 1980;25:123-9.  1980.
13.  Hocking DR:  Neonatal hemolytic disease due to dapsone.
Med J Aust 1968;1:1130-1.
14.  Diamond WJ:  Herpes gestationis.  S Afr Med J
1976;50:739-40.
15.  Bhargava P, Kuldeep CM, Mathur NK:  Antileprosy drugs,
pregnancy and fetal outcome.  Int J Lepr Other Mycobact Dis
1996;64:457.
16.  Dreisbach JA:  Sulphone levels in breast milk of mothers on
sulphone therapy.  Lepr Rev 1952;23:101-6.

[thanks, Kirsten! WB]


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