Sulfone

Dapsone

Approved 8 May 2024TopicalGel

The FDA lists this product in 33 strengths and forms.

Indications

Dapsone gel, 7.5%, is indicated for the topical treatment of acne vulgaris in patients 9 years of age and older. Dapsone gel, 7.5%, is a sulfone indicated for the topical treatment of acne vulgaris in patients 9 years of age and older ( 1 ).

Contraindications

None. None ( 4 )

Warnings and precautions

Methemoglobinemia: Cases of methemoglobinemia have been reported. Discontinue dapsone gel if signs of methemoglobinemia occur ( 5.1 ). Hemolysis: Some patients with Glucose-6-phosphate Dehydrogenase (G6PD) deficiency using topical dapsone developed laboratory changes suggestive of hemolysis ( 5.1 ) ( 8.6 ).

5.1Hematological Effects Methemoglobinemia Cases

of methemoglobinemia, with resultant hospitalization, have been reported postmarketing in association with twice daily dapsone gel, 5%, treatment. Patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methemoglobinemia are more susceptible to drug-induced methemoglobinemia. Avoid use of dapsone gel, 7.5% in those patients with congenital or idiopathic methemoglobinemia. Signs and symptoms of methemoglobinemia may be delayed some hours after exposure.

Initial signs and symptoms of methemoglobinemia are characterized by a slate grey cyanosis seen in e.g., buccal mucous membranes, lips, and nail beds. Advise patients to discontinue dapsone gel, 7.5% and seek immediate medical attention in the event of cyanosis. Dapsone can cause elevated methemoglobin levels particularly in conjunction with methemoglobin-inducing agents [see Drug Interactions ( 7.4 )] . He molysis 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. In clinical trials, there was no evidence of clinically relevant hemolysis or hemolytic anemia in subjects treated with topical dapsone. Some subjects with G6PD deficiency using dapsone gel, 5%, twice daily developed laboratory changes suggestive of hemolysis [see Use in Specific Populations ( 8.6 )].

Discontinue dapsone gel, 7.5%, if signs and symptoms suggestive of hemolytic anemia occur. Avoid use of dapsone gel, 7.5% in patients who are taking oral dapsone or antimalarial medications because of the potential for hemolytic reactions. Combination of dapsone gel, 7.5%, with trimethoprim/sulfamethoxazole (TMP/SMX) may increase the likelihood of hemolysis in patients with G6PD deficiency [see Drug Interactions ( 7.1 )] .

At a glance

Brand name: Dapsone
Pharmacologic class: Sulfone
Route: Topical
Dosage form: Gel
Applicant: Zydus Lifesciences
Status: Prescription
FDA approval: 8 May 2024
Application: ANDA214019-001

Warnings and precautions

5.1Hematological Effects Methemoglobinemia Cases

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are no available data on dapsone gel, 7.5%, use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. The systemic absorption of dapsone in humans following topical application is low relative to oral dapsone administration [see Clinical Pharmacology ( 12.3 )] . In animal reproduction studies, oral doses of dapsone administered to pregnant rats and rabbits during organogenesis that resulted in systemic exposures more than 400 times the systemic exposure at the maximum recommended human dose (MRHD) of dapsone gel, 7.5%, resulted in embryocidal effects.

When orally administered to rats from the onset of organogenesis through the end of lactation at systemic exposures approximately 500 times the exposure at the MRHD, dapsone resulted in increased stillbirths and decreased pup weight [see Data] . The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Da ta A nimal Data Dapsone has been shown to have an embryocidal effect in rats and rabbits when administered orally daily to females during organogenesis at dosages of 75 mg/kg/day and 150 mg/kg/day, respectively. These dosages resulted in systemic exposures that represented approximately 1,407 times [rats] and 425 times [rabbits] the systemic exposure observed in human females as a result of use of the MRHD of dapsone gel, 7.5%, based on AUC comparisons.

These effects were probably secondary to maternal toxicity. Dapsone was assessed for effects on perinatal/postnatal pup development and postnatal maternal behavior and function in a study in which dapsone was orally administered to female rats daily beginning on the seventh day of gestation and continuing until the twenty-seventh day postpartum. Maternal toxicity (decreased body weight and food consumption) and developmental effects (increase in stillborn pups and decreased pup weight) were seen at a dapsone dose of 30 mg/kg/day (approximately 563 times the systemic exposure that is associated with the MRHD of dapsone gel, 7.5%, based on AUC comparisons).

No effects were observed on the viability, physical development, behavior, learning ability, or reproductive function of surviving pups.

Adverse reactions

Most common (incidence ≥ 0.9%) adverse reactions are application site dryness and pruritus ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Viona Pharmaceuticals Inc. at 1-888-304-5011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 2,161 subjects were treated with dapsone gel, 7.5%, for 12 weeks in 2 controlled clinical trials. The population ranged in age from 12 years to 63 years, was 56% female, and 58% Caucasian.

Adverse drug reactions that were reported in at least 0.9% of subjects treated with dapsone gel, 7.5% appear in Table 1 below. Table 1 Adverse Reactions Occurring in at Least 0.9% of Subjects with Acne Vulgaris in 12-week Controlled Clinical Trials Dapsone Gel, 7.5% (N =2,161) Vehicle (N =2,175) Application Site Dryness 24 (1.1%) 21 (1%) Application Site Pruritus 20 (0.9%) 11 (0.5%)

6.2Experience with Oral Use of Dapsone Although

not observed in the clinical trials with topical dapsone, serious adverse reactions have been reported with oral use of dapsone, including agranulocytosis, hemolytic anemia, peripheral neuropathy (motor loss and muscle weakness), and skin reactions (toxic epidermal necrolysis, erythema multiforme, morbilliform and scarlatiniform reactions, bullous and exfoliative dermatitis, erythema nodosum, and urticaria).

6.3Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reactions have been identified during post-approval use of topical dapsone: methemoglobinemia, rash (including erythematous rash, application site rash) and swelling of face (including lip swelling, eye swelling).

Dapsone

Indications

Contraindications

Warnings and precautions

5.1Hematological Effects Methemoglobinemia Cases

At a glance

Two medicines in one question?

Dapsone

Indications

Contraindications

Warnings and precautions

5.1Hematological Effects Methemoglobinemia Cases

At a glance

Two medicines in one question?

5.2Peripheral Neuropathy

5.3Skin Reactions

Interactions

7.1Trimethoprim-Sulfamethoxazole

7.2Topical Benzoyl Peroxide

7.3Drug Interactions with Oral Dapsone

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Studies Experience

6.2Experience with Oral Use of Dapsone Although

6.3Postmarketing Experience

Composition

Strengths and forms

Official product information