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Aczone (Dapsone Topical) - Warnings and Precautions

 
 



WARNINGS AND PRECAUTIONS

Hematological Effects

Oral dapsone treatment has produced dose-related hemolysis and hemolytic anemia. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are more prone to hemolysis with the use of certain drugs. G6PD deficiency is most prevalent in populations of African, South Asian, Middle Eastern, and Mediterranean ancestry.

There was no evidence of clinically relevant hemolysis or anemia in patients treated with ACZONE ® Gel, 5%, including patients who were G6PD deficient. Some subjects with G6PD deficiency using ACZONE ® Gel developed laboratory changes suggestive of mild hemolysis.

If signs and symptoms suggestive of hemolytic anemia occur, ACZONE ® Gel, 5% should be discontinued. ACZONE ® Gel, 5% should not be used in patients who are taking oral dapsone or antimalarial medications because of the potential for hemolytic reactions. Combination of ACZONE ® Gel, 5%, with trimethoprim/sulfamethoxazole (TMP/SMX) may increase the likelihood of hemolysis in patients with G6PD deficiency.

Peripheral Neuropathy

Peripheral neuropathy (motor loss and muscle weakness) has been reported with oral dapsone treatment. No events of peripheral neuropathy were observed in clinical trials with topical ACZONE ® Gel, 5% treatment.

Skin

Skin reactions (toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria) have been reported with oral dapsone treatment. These types of skin reactions were not observed in clinical trials with topical ACZONE ® Gel, 5% treatment.

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects: Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. Dapsone has been shown to have an embryocidal effect in rats and rabbits when administered orally in doses of 75 mg/kg/day and 150 mg/kg/day (approximately 800 and 500 times the systemic exposure observed in human females as a result of use of the maximum recommended topical dose, based on AUC comparisons), respectively. These effects were probably secondary to maternal toxicity. ACZONE ® Gel, 5%, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Although systemic absorption of dapsone following topical application of ACZONE ® Gel, 5%, is minimal relative to oral dapsone administration, it is known that dapsone is excreted in human milk. Because of the potential for oral dapsone to cause adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue ACZONE ® Gel, 5%, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and efficacy was evaluated in 1169 children aged 12-17 years old treated with ACZONE ® Gel, 5%, in the clinical studies. The adverse event rate for ACZONE ® Gel, 5%, was similar to the vehicle control group. Safety and efficacy was not studied in pediatric patients less than 12 years of age, therefore ACZONE ® Gel, 5%, is not recommended for use in this age group.

Geriatric Use

Clinical studies of ACZONE ® Gel, 5%, did not include sufficient number of patients aged 65 and over to determine whether they respond differently from younger patients.

G6PD Deficiency

ACZONE ® Gel, 5% and vehicle were evaluated in a randomized, double-blind, cross-over design clinical study of 64 patients with G6PD deficiency and acne vulgaris. Subjects were Black (88%), Asian (6%), Hispanic (2%) or of other racial origin (5%). Blood samples were taken at Baseline, Week 2, and Week 12 during both vehicle and ACZONE ® Gel, 5% treatment periods. There were 56 out of 64 subjects who had a Week 2 blood draw and applied at least 50% of treatment applications. Table 3 contains results from testing of relevant hematology parameters for these two treatment periods. ACZONE ® Gel was associated with a 0.32 g/dL drop in hemoglobin after two weeks of treatment, but hemoglobin levels generally returned to baseline levels at Week 12.

Table 3 – Mean Hemoglobin, Bilirubin, and Reticulocyte Levels in Acne Subjects with G6PD Deficiency in ACZONE®/Vehicle Cross-Over Study
ACZONE ® Vehicle
N Mean N Mean
Hemoglobin (g/dL) Pre-treatment 53 13.44 56 13.36
2 weeks 53 13.12 55 13.34
12 weeks 50 13.42 50 13.37
Bilirubin (mg/dL) Pre-treatment 54 0.58 56 0.55
2 weeks 53 0.65 55 0.56
12 weeks 50 0.61 50 0.62
Reticulocytes (%) Pre-treatment 53 1.30 55 1.34
2 weeks 53 1.51 55 1.34
12 weeks 50 1.48 50 1.41

There were no changes from baseline in haptoglobin or lactate dehydrogenase during ACZONE ® or vehicle treatment at either the 2-week or 12-week time point.

The proportion of subjects who experienced decreases in hemoglobin ≥1 g/dL was similar between ACZONE ® Gel, 5% and vehicle treatment (8 of 58 subjects had such decreases during ACZONE ® treatment compared to 7 of 56 subjects during vehicle treatment among subjects with at least one on-treatment hemoglobin assessment). Subgroups based on gender, race, or G6PD enzyme activity did not display any differences in laboratory results from the overall study group. There was no evidence of clinically significant hemolytic anemia in this study. Some of these subjects developed laboratory changes suggestive of mild hemolysis.

Page last updated: 2013-03-28

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