Dapsone

 Risk Factor: CM
 Class: ANTI-INFECTIVES / Leprostatics

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Dapsone (DDS), a sulfone antibacterial agent, is used in the treatment of leprosy and dermatitis herpetiformis, and for various other unlabeled indications, including antimalarial prophylaxis, the treatment of Pneumocystis carinii pneumonia, inflammatory bowel disease, rheumatic and connective tissue disorders, and relapsing polychondritis. Because the drug is known to cause blood dyscrasias in adults, some of which have been fatal, close patient monitoring is required during use.

Although reproduction studies in animals have not been conducted (1), a 1980 Reference described a study investigating carcinogenicity that was conducted in pregnant and lactating mice and rats (2). A maximum maternally tolerated dose, 100 mg/kg (usual human dose 50300 mg/day), was administered twice in late gestation and 5 times a week during lactation and then was continued in the offspring after weaning. A small but significant increase in tumors was noted.

A number of studies have described the use of dapsone during all stages of human pregnancy. A few fetal or newborn adverse effects directly attributable to dapsone have been reported, but no congenital anomalies thought to be due to the drug have been observed. The indications for use of dapsone during pregnancy have included dermatologic conditions, leprosy, malaria, and P. carinii.

A brief 1968 Reference described Heinz-body hemolytic anemia in a mother and her newborn during therapy with dapsone (3). The mother had been diagnosed with herpes gestationis at 22 weeks' gestation, for which she was treated with sulfapyridine for 1 week. At 26 weeks, treatment with dapsone was begun at 400 mg/day for 1 week, 300 mg/day during weeks 2 and 3, 200 mg/day in week 4, 100 mg/day in week 5, then 200 mg/day until delivery of a male infant at 36 weeks' gestation. She developed well-compensated Heinz-body hemolytic anemia 6 days after starting dapsone. The anemia in the infant, who had a normal glucose-6-phosphate dehydrogenase (G6PD) level, completely resolved within 10 days, and he has remained hematologically normal.

In three cases, dapsone was used for the treatment of dermatitis herpetiformis or its variant, herpes gestationis (4,5). In two other reports of herpes gestationis (also referred to as pemphigoid gestationis) occurring during pregnancy, dapsone was not started until after delivery (6,7). A 26-year-old pregnant woman with recurrent herpes gestationis was treated with dapsone and other nonspecific therapy from the 24th week of gestation until delivery of a normal male infant at 38 weeks (4). A 25-year-old woman with dermatitis herpetiformis was treated with dapsone, 100150 mg/day, during the first 3 months of pregnancy (5). The drug was discontinued briefly during the 4th month of pregnancy because of concerns of teratogenicity, then resumed at 50 mg/day because of worsening of her disease. She eventually gave birth to a full-term, normal infant who developed dapsone-induced hemolytic anemia while breast feeding (see Breast Feeding Summary below). A 33-year-old woman, treated with dapsone, 2550 mg/day, throughout pregnancy for dermatitis herpetiformis delivered a healthy full-term infant (8).

A 1978 paper described the clinical courses of 62 pregnancies in 26 women treated for leprosy (Hansen's disease) (9). All of the patients received therapy, with sulfone drugs (specific drugs not mentioned) being used in 58 (94%) of the pregnancies. Two (3.6%) infants (about the expected rate) among the 56 pregnancies with infants who reached an age of viability had congenital anomalies. One infant had a cleft palate, and another had a congenital hip dislocation. A review, published in 1993, discussed the adverse association of leprosy and pregnancy (10). Although dapsone was not thought to cause adverse toxic effects or teratogenicity in the fetus, resistance to dapsone monotherapy has become a problem, and combination therapy, such as dapsone, clofazimine, and rifampin, is recommended for all forms of leprosy (10). Normal pregnancy outcomes of 15 women treated for leprosy were noted in a 1996 letter (N=13) (11) and in a 1997 report (N=2) (12). The patients had been treated throughout gestation with dapsone, 100 mg/day, plus rifampin, 600 mg once monthly (11), or with dapsone alone (12). In addition, two had also received clofazimine, and two had taken intermittent prednisolone (11).

Neonatal hyperbilirubinemia, suspected of being due to displacement of bilirubin from albumin binding sites, has been attributed to the use of dapsone during gestation (13). A 25-year-old woman with leprosy was treated with dapsone, 300 mg/week, until 3 months before delivery. At that time, her dose was decreased to 50 mg/week and then was discontinued 1 week prior to a normal spontaneous vaginal delivery of a 3740-g male infant. The infant, who was not breast-fed and had no evidence of ABO incompatibility, developed hyperbilirubinemia that was attributed to dapsone. In a subsequent pregnancy, dapsone therapy was stopped 1 month prior to delivery of a healthy 4070-g male infant who did not develop hyperbilirubinemia.

The combination of dapsone and pyrimethamine (Maloprim) has been frequently used during pregnancy for the chemoprophylaxis of malaria (14,15,16,17,18,19,20 and 21). Most consider the benefits of this combination in the prevention of maternal malaria to outweigh the risks to the fetus (16,17,18,19,20 and 21), but two authors classified the combination as contraindicated in pregnancy (14,15). The adverse effects of the combination were reviewed in a 1993 Reference (22). Because of the potential for significant dose-related toxicity, the authors considered the drug combination to be a second-line choice for use in areas where the risk of malaria was high. Folic acid supplements should be given when pyrimethamine is used (21) (see also Pyrimethamine).

A study published in 1990 compared chlorproguanil plus dapsone (N=44), chloroquine alone (N=58), and pyrimethamine plus sulfadoxine (N=54) in a group of pregnant women with falciparum malaria parasitemia (23). A single dose of chlorproguanil plus dapsone during the 3rd trimester cleared the parasitemia in all women within 1 week, compared with 84% and 94%, respectively, in the other two groups. Six weeks after treatment, the proportion of those with parasitemia in each group was 81%, 84%, and 23%, respectively. No adverse effects of the therapy in the fetuses or newborns were mentioned.

An adverse pregnancy outcome in a mother who received malarial chemoprophylaxis with three drugs was the subject of a brief 1983 communication (24). During the 1st month of pregnancy the 31-year-old woman had taken chloroquine (100 mg/day) and Maloprim (dapsone 100 mg plus pyrimethamine 12.5 mg) on days 10, 20, and 30 after conception. The stillborn male infant was delivered at 26 weeks' gestation with a defect of the abdominal and thoracic wall with exteriorization of most of the abdominal viscera, the heart, and the lungs (a variant of ectopia cordis?) and a missing left arm. The authors concluded that the defects were due to pyrimethamine, but others have questioned this conclusion (see Pyrimethamine).

Dapsone, either alone or in combination with pyrimethamine or trimethoprim, has been suggested as having utility in the prophylaxis of P. carinii during pregnancy (25,26). Although the efficacy of these therapeutic options has not been confirmed, the risks of the disease to the mother far outweigh the risks to the fetus (26).

A 1992 report described an attempted suicide with dapsone and alcohol in a 29-year-old pregnant woman (length of gestation not specified) under treatment for dermatitis herpetiformis (27). The woman had ingested 50 tablets (100 mg each) of dapsone plus six alcoholic drinks. She developed severe methemoglobinemia and hemolytic anemia, treated successfully with methylene blue (total dose about 7 mg/kg) and other therapy, and splenomegaly that resolved spontaneously. No mention was made of the pregnancy outcome.

In summary, the use of dapsone during pregnancy does not appear to present a major risk to the fetus or the newborn. The agent has been used extensively for malarial treatment or chemoprophylaxis and for the treatment of leprosy and certain other dermatologic conditions without producing major fetotoxicity or causing birth defects. If used in combination with pyrimethamine (a folic acid antagonist) for malaria prophylaxis, folic acid supplements (5 mg/day) or folinic acid (leucovorin, 5 mg/week) should be given (21,28).

Breast Feeding Summary

Dapsone and its primary metabolite, monoacetyldapsone, are excreted into human milk (5,29,30). A 25-year-old woman with dermatitis herpetiformis was treated with dapsone throughout most of her pregnancy and continued this therapy while breast feeding her infant (5). During the latter two-thirds of her pregnancy and during lactation she took dapsone, 50 mg/day. Approximately 6 weeks after delivery, mild hemolytic anemia was diagnosed in the mother and her infant. Measurements of dapsone and the metabolite were conducted on the mother's serum and milk and on the infant's serum. Dapsone concentrations were 1622, 1092, and 439 ng/mL, respectively, whereas those of the metabolite were 744 ng/mL, none detected, and 204 ng/mL, respectively. The milk:plasma ratio of dapsone was 0.67. The investigators noted that the weak base properties of dapsone, its high lipid solubility, and its long serum half-life (about 20 hours) all favored excretion and entrapment of the drug in milk (5). Moreover, both the mother and her infant appeared to be rapid acetylator phenotypes because of the relatively high ratios of metabolite to parent drug in both (0.459 in the mother, 0.465 in the infant) (5). Neither patient was tested for G6PD deficiency, although persons with this genetic defect are especially susceptible to dapsone-induced hemolytic anemia. Dose-related hemolytic anemia is the most common toxicity reported with dapsone and occurs in patients with or without G6PD deficiency (1).

A 1952 Reference studied the excretion into breast milk of dapsone (diaminodiphenylsulfone) and another sulfone antibacterial agent in one and five women, respectively, with leprosy (29). Although stating that dapsone was excreted in the mother's milk and absorbed and excreted in the infant's urine, the investigator did not quantify the amount in the milk.

Three women, 25 days postpartum, who were not breast-feeding were given a single dose of dapsone (100 mg plus pyrimethamine 12.5 mg) (Maloprim) and a single dose of chloroquine (300 mg base) (30). Milk and serum samples for dapsone analysis were collected at intervals up to 52, 102, and 124 hours, yielding milk: plasma ratios, based on area under the concentration-time curve, of 0.38, 0.45, and 0.22, respectively. The authors calculated that the amounts of dapsone excreted into milk, based on 1000 mL/day, were 0.31, 0.85, and 0.59 mg, respectively, which are too small to afford malarial chemoprophylaxis to a nursing infant (30).

Although not citing the case of dapsone-induced hemolytic anemia in a nursing infant described above, the American Academy of Pediatrics considers dapsone to be compatible with breast feeding (31).

References

1. Product information. Dapsone. Jacobus Pharmaceutical, 1997.
2. Griciute L, Tomatis L. Carcinogenicity of dapsone in mice and rats. Int J Cancer 1980;25:1239.
3. Hocking DR. Neonatal haemolytic disease due to dapsone. Med J Aust 1968;1:11301.
4. Diamond WJ. Herpes gestationis. S Afr Med J 1976;50:73940.
5. Sanders SW, Zone JJ, Foltz RL, Tolman KG, Rollins DE. Hemolytic anemia induced by dapsone transmitted through breast milk. Ann Intern Med 1982;96:4656.
6. Sills ES, Mabie WC. A refractory case of herpes gestationis. J Tenn Med Assoc 1992;85:55960.
7. Kirtschig G, Collier PM, Emmerson RW, Wojnarowska F. Severe case of pemphigoid gestationis with unusual target antigen. Br J Dermatol 1994;131:10811.
8. Tuffanelli DL. Successful pregnancy in a patient with dermatitis herpetiformis treated with low-dose dapsone. Arch Dermatol 1982;118:876.
9. Maurus JN. Hansen's disease in pregnancy. Obstet Gynecol 1978;52:225.
10. Duncan ME. An historical and clinical review of the interaction of leprosy and pregnancy: a cycle to be broken. Soc Sci Med 1993;37:45772.
11. Bhargava P, Kuldeep CM, Mathur NK. Antileprosy drugs, pregnancy and fetal outcome. Int J Lepr Other Mycobact Dis 1996;64:457.
12. Lyde CB. Pregnancy in patients with Hansen disease. Arch Dermatol 1997;133:6237.
13. Thornton YS, Bowe ET. Neonatal hyperbilirubinemia after treatment of maternal leprosy. South Med J 1989;82:668.
14. Sturchler D. Malaria prophylaxis in travellers: the current position. Experientia 1984;40:135762.
15. Brown GV. Chemoprophylaxis of malaria. Med J Aust 1986;144:696702.
16. Anonymous. Prevention of malaria in pregnancy and early childhood. Br Med J 1984;289:12967.
17. Greenwood AM, Armstrong JRM, Byass P, Snow RW, Greenwood BM. Malaria chemoprophylaxis, birth weight and child survival. Trans R Soc Trop Med Hyg 1992;86:4835.
18. Greenwood AM, Menendez C, Todd J, Greenwood BM. The distribution of birth weights in Gambian women who received malaria chemoprophylaxis during their first pregnancy and in control women. Trans R Soc Trop Med Hyg 1994;88:3112.
19. Menendez C, Todd J, Alonso PL, Lulat S, Francis N, Greenwood BM. Malaria chemoprophylaxis, infection of the placenta and birth weight in Gambian primigravidae. J Trop Med Hyg 1994;97:2448.
20. Kahn G. Dapsone is safe during pregnancy. J Am Acad Dermatol 1985;13:8389.
21. Spracklen FHN, Monteagudo FSE. Malaria prophylaxis. S Afr Med J 1986;70:316.
22. Luzzi GA, Peto TEA. Adverse effects of antimalarials. An update. Drug Saf 1993;8:295311.
23. Keuter M, van Eijk A, Hoogstrate M, Raasveld M, van de Ree M, Ngwawe WA, Watkins WM, Were JBO, Brandling-Bennett AD. Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and nonpregnant women, Kakamega district, Kenya. Br Med J 1990;301:46670.
24. Harpey J-P, Darbois Y, Lefebvre G. Teratogenicity of pyrimethamine. Lancet 1983;2:399.
25. Connelly RT, Lourwood DL. Pneumocystis carinii pneumonia prophylaxis during pregnancy. Pharmacotherapy 1994;14:4249.
26. American College of Obstetricians and Gynecologists. Human immunodeficiency virus infections in pregnancy. Educational Bulletin. No. 232, January 1997.
27. Erstad BL. Dapsone-induced methemoglobinemia and hemolytic anemia. Clin Pharm 1992;11:8005.
28. Spracklen FHN. Malaria 1984. Part I. Malaria prophylaxis. S Afr Med J 1984;65:103741.
29. Dreisbach JA. Sulphone levels in breast milk of mothers on sulphone therapy. Lepr Rev 1952;23:1016.
30. Edstein MD, Veenendaal JR, Newman K, Hyslop R. Excretion of chloroquine, dapsone and pyrimethamine in human milk. Br J Clin Pharmacol 1986;22:7335.
31. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
    
    

Questions and Answers

How to stop taking Dapsone? Any suggestions?, Hi I am Allergic to Gluten and I am taking Dapsone as a medication.I have observed that i am loosing weight due to the medication.I dont want to take it any more.Can somebody suggest what are the precautions that should be taken before stopping the medication?
Thanks in advance.

If you are taking this medication for skin problems, it would be a good idea to check with the doctor that prescribed this treatment as I am sure that it is not a drug you can just stop using cold-turkey. Rather, it may have to be on a gradual basis, and since I'm not absolutely certain what the reason is that he prescribed this for you, I cannot with any amount of certainty advise you to stop.

Your allergy to gluten, I am assuming appears in the form of a skin problem? rash? hives? or worst?

No one here is qualified to give you an answer since we are not doctors or medical personnel. My advice is speak with your doctor.

Has anyone had to take the drug dapsone?, Were there any side effects? experiences?

I haven't.

But in the "studies" of many people taking dapsone, the "common reactions" were:

Fever
Muscle aches
Headaches
Chills
Fatigue
Malaise
Dizziness
Nausea
Joint pain
Pancreatitis
Sensitivity to light
Rash
Vomiting
Abdominal pain
Loss of appetite
Blurred vision
Ringing in ears


=

Of course, even for aspirin via studies, "common reactions" are:
Stomach discomfort
Nausea
Vomiting
Loss of appetite
Rash
Bleeding
Ringing in ears
Dizziness

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I hope this helped some.

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What are the treatments for leukocytoclastic vasculitis?, I am taking a medication called Dapsone, but it doesn't seem to be working any longer.

You could try FLP Aloe Vera Drinking Gel and FLP topical Aloe Vera Gelly

What is the drug Dapsone used for, and has anybody heard of it being used for CD (Celiacs Disease)?,

Dapsone is an pharmacological medication most commonly used for the treatment of Mycobacterium leprae infections (leprosy).

after using dapsone what we should do.?,

take vitamin pills and sleep off.

Should i give up the dermatologist cleanser and go back to proactiv?, i had been using proactiv for a while but there's still some acne on my chin that don't seem to clear up, i went to a dermatologist and he gave me a set of cleanser, toning pad and lotion and moisturizer. i've been using them but been seeing one or two pimple breakout everyday.

since i already got the prescription he got me, aczone(dapsone 5%) cream, should i just go back to using proactiv and use the cream for spot treatment?

don't use either one
if there are still problems when you use the proactiv or the stuff from the dermatologist then...start using something different
[Pro-Sarcasmâ„¢]

anyone tried aczone gel (dapsone) for acne?, The doctor prescribed me this aczone gel and says my acne should all clear up in 6 weeks. have anyone tried it?

i had the worst case of acne, i have ever seen. don't use the aczone, , the side effects can cause blindness. you can get rid of the acnr by yourself, but you need patience. my cousin has a son whos face broke out.brians dad is a dr and told his kid to use it. well now he is living with the side effects that will never go away. if you keep your face as clean and use witch hazel on it, the soars will start to dry up. for gods sake don't pick at them, you will scar your face. your face broke out because you have a horemone imbalance. if you are patien t your face will heal up and and you will not have any scaring. clean and clear that you can get at the drug store with witch hazel on a cotton pad, will work wonders. for gods sake don't introduce any germs into the infections by picking. hang in there you will se how good looking you are as they start to heal. i'd get myself a new dermatologest.

do antibiotics have any anxiolytic potential?, iv read about dapsone having an anti anxiety effect. do any other antibiotics have an anti anxiety effect?

No. Most antibiotics actually increase anxiety slightly in typical individuals,
and
in people with chronic anxiety, they usually have to increase their dose of anti-anxiety medication when they are on an antibiotic.

advancement in treatment of phemphigous follicious ?, can dapsone 100 mg., nicotinamide 1.5 gm,cyclophosphomide 50 mg.prednisolone 80 mg daily can be used along with potent topical steroids.in 50 years old patiant showing remission.SGPT,SGOT, S.creatine and blood counts are with in normal limit .
Any dermatologist pl. No need to explain DCP theory, any experionce?

Very difficult to accept that asker couldn't spell it correctly. Dear Asker no collusion next time please. OK.........
Yes all can be used to gather.
what you have mentioned about the tt. is latest.
DCP pulse show very good result .