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DRUG INTERACTIONS
Rifampin lowers Dapsone levels 7 to 10-fold by accelerating plasma clearance;
in leprosy this reduction has not required a change in dosage. Folic acid
antagonists such as pyrimethamine may increase the likelihood of hematologic
reactions.
A modest interaction has been reported for patients receiving 100 mg Dapsone
daily in combination with trimethoprim 5 mg/kg q6h. On Day 7, the serum Dapsone
levels averaged 2.1 ± 1.0 μg/mL in comparison to 1.5 ± 0.5 μg/mL for Dapsone
alone. On Day 7, trimethoprim levels averaged 18.4 ± 5.2 μg/mL in comparison to
12.4 ± 4.5 μg/mL for patients not receiving Dapsone. Thus, there is a mutual
interaction between Dapsone and trimethoprim in which each raises the level of
the other about 1.5 times.
A crossover study1 designed to assess the potential of
a drug interaction between Dapsone, 100 mg/day and trimethoprim, 200 mg every 12
hours, in eight asymptomatic HIV positive volunteers (average CD4 count 524
cells/mm3) demonstrated that there was not a significant
drug intreraction between Dapsone and trimethoprim. However, an earlier
report2 also by Lee et al, in 78 HIV infected patients
with acute Pneumocystis carinii pneumonia, receiving
Dapsone, 100 mg/day and higher trimethoprim dose, 20 mg/kg/day, demonstrated
that the serum levels of Dapsone were increased by 40% and trimethoprim levels
were increased by 48% when the drugs were administered concurrently.
Carcinogenesis, mutagenesis: Dapsone has
been found carcinogenic (sarcomagenic) for male rats and female mice causing
mesenchymal tumors in the spleen and peritoneum, and thyroid carcinoma in female
rats. Dapsone is not mutagenic with or without microsomal activation in S. typhimurium tester strains 1535, 1537, 1538, 98, or 100.
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OVERDOSAGE
Nausea, vomiting, hyperexcitability can appear a few minutes up to 24 hours
after ingestion of an overdosage. Methemoglobin induced depression, convulsions
or severe cyanosis requires prompt treatment. In normal and methemoglobin
reductase deficient patients, methylene blue, 1-2 mg/kg of body weight, given
slowly intravenously, is the treatment of choice. The effect is complete in 30
minutes, but may have to be repeated if methemoglobin reaccumulates. For
non-emergencies, if treatment is needed, methylene blue may be given orally in
doses of 3-5 mg/kg every 4-6 hours. Methylene blue reduction depends on G6PD and
should not be given to fully expressed G6PD deficient patients.
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CONTRAINDICATIONS
Hypersensitivity to Dapsone and/or its derivatives.
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REFERENCES
- Lee, B., et al., Zidovudine, Trimethoprim, and Dapsone Pharmacokinetic
Interactions in Patients with HIV Infection. Antimicrobial
Agents and Chemotherapy, May 1996; 1231-1236.
- Lee, B., et al., Dapsone, Trimethoprim, and Sulfamethoxazole Plasma Levels
During Treatment of Pneumocystis Carinii Pneumonia in Patients with AIDS, Annals of Internal Medicine, 1989; 110:606-611.
Store at 20°- 25° C (68°- 77°F). [see USP Controlled Room
Temperature]. Protect from light.
Rx only. Keep this and all medication out of the reach of
children.
JACOBUS PHARMACEUTICAL CO., INC.
P.O. Box 5290
Princeton, NJ 08540
Revised August 2009
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