DAPSONE Drug Interactions: What You Need to Know

INTERACTIONS Trimethoprim/sulfamethoxazole (TMP/SMX) increases the level of dapsone and its metabolites ( 7.1 ). Topical benzoyl peroxide used at the same time as dapsone may result in temporary local yellow or orange skin discoloration ( 7.2 ).

7.1 Trimethoprim-Sulf a methoxazole A drug-drug interaction study evaluated the effect of the use of dapsone gel, 5%, in combination with double strength (160 mg/800 mg) trimethoprim-sulfamethoxazole (TMP/SMX). During co-administration, systemic levels of TMP and SMX were essentially unchanged. However, levels of dapsone and its metabolites increased in the presence of TMP/SMX. Systemic exposure (AUC 0-12 ) of dapsone and N-acetyl-dapsone (NAD) were increased by about 40% and 20% respectively in the presence of TMP/SMX. Notably, systemic exposure (AUC 0-12 ) of dapsone hydroxylamine (DHA) was more than doubled in the presence of TMP/SMX. Exposure from the proposed topical dose is about 1% of that from the 100 mg oral dose, even when co-administered with TMP/SMX.

7.2 Topical Benzoyl Peroxide Topical application of dapsone gel followed by benzoyl peroxide in subjects with acne vulgaris resulted in a temporary local yellow or orange discoloration of the skin and facial hair (reported by 7 out of 95 subjects in a clinical study) with resolution in 4 to 57 days.

7.3 Drug Interactions with Oral Dapsone Certain concomitant medications (such as rifampin, anticonvulsants, St. John’s wort) may increase the formation of dapsone hydroxylamine, a metabolite of dapsone associated with hemolysis. With oral dapsone treatment, folic acid antagonists such as pyrimethamine have been noted to possibly increase the likelihood of hematologic reactions.

7.4 Concomitant Use with Drugs that Induce Methemoglobinemia Concomitant use of dapsone gel with drugs that induce methemoglobinemia such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para‐aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine may increase the risk for developing methemoglobinemia [ see Warnings and Precautions ( 5.1 )] .

7.3 Drug Interactions with Oral Dapsone Certain concomitant medications (such as rifampin, anticonvulsants, St. John’s wort) may increase the formation of dapsone hydroxylamine, a metabolite of dapsone associated with hemolysis. With oral dapsone treatment, folic acid antagonists such as pyrimethamine have been noted to possibly increase the likelihood of hematologic reactions.

CONTRAINDICATIONS Hypersensitivity to Dapsone and/or its derivatives.

AND PRECAUTIONS

• Methemoglobinemia: Cases of methemoglobinemia have been reported. Discontinue dapsone g el 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 ).

5.1 Hematological 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 <span class="opacity-50 text-xs">[see Drug Interactions (7.4) ]</span> .

Hemolysis

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) ] .

5.2 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 dapsone treatment.

5.3 Skin Reactions 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 dapsone treatment.