ACZONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACZONE (ACZONE).
Dapsone (active ingredient) is a sulfone antibiotic that inhibits bacterial synthesis of dihydropteroic acid through competitive antagonism of p-aminobenzoic acid (PABA), thereby blocking folate synthesis. It also has anti-inflammatory and immunomodulatory effects, including inhibition of neutrophil chemotaxis and myeloperoxidase activity.
| Metabolism | Primarily hepatic via N-acetylation (NAT2) and N-hydroxylation (CYP2E1, CYP3A4). Also undergoes glucuronidation. Metabolites include N-acetyl-dapsone and dapsone hydroxylamine. |
| Excretion | Renal excretion accounts for approximately 70-80% of an administered dose, primarily as unchanged drug via glomerular filtration and tubular secretion. Fecal elimination contributes less than 20%, with biliary excretion playing a minor role. |
| Half-life | The terminal elimination half-life is approximately 23 hours (range 20-26 hours) in adults with normal renal function, supporting once-daily dosing. Renal impairment prolongs the half-life, requiring dose adjustment. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin. The high protein binding limits distribution and affects drug interactions due to displacement. |
| Volume of Distribution | Volume of distribution is approximately 1.5 L/kg, indicating extensive tissue penetration (e.g., skin, sebaceous glands). Distribution is consistent with the drug's lipophilic properties. |
| Bioavailability | Oral bioavailability is approximately 90% (range 84-96%) after administration with food, which enhances absorption compared to fasting. Food increases Cmax and AUC without affecting Tmax. |
| Onset of Action | Oral administration: Clinical improvement in acne lesions typically begins within 2-4 weeks of initiating therapy. Peak effect is observed by 8-12 weeks. |
| Duration of Action | Therapeutic duration persists for the dosing interval (24 hours) with steady-state achieved within 4-5 days. Clinical improvement continues with sustained use; rebound effect may occur after discontinuation. |
100 mg orally once daily with a high-fat meal. Do not crush or chew capsules.
| Dosage form | GEL |
| Renal impairment | Contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²). For moderate impairment (eGFR 30-59 mL/min/1.73 m²), no dose adjustment; use with caution. For mild impairment (eGFR ≥60 mL/min/1.73 m²), no adjustment. |
| Liver impairment | Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). No dose adjustment for mild to moderate impairment (Child-Pugh class A or B) but use with caution. |
| Pediatric use | Not approved for pediatric patients; safety and effectiveness not established. |
| Geriatric use | No specific dose adjustment; elderly patients may have increased risk of adverse effects; use with caution considering renal and hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACZONE (ACZONE).
| Breastfeeding | No M/P ratio available. Dapsone and its metabolite are excreted into human milk. Nursing infants may be at risk of hemolytic anemia (especially if G6PD deficient) and methemoglobinemia. The manufacturer recommends caution; consider temporary discontinuation during breastfeeding or use alternative therapy. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies at doses up to 12 times the MRHD. However, sulfonamides may cause kernicterus in the newborn due to bilirubin displacement. Avoid use near term (third trimester) as sulfonamides compete for bilirubin binding sites on albumin, increasing risk of neonatal hyperbilirubinemia and kernicterus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to dapsone or sulfonamides","Severe anemia (including G6PD deficiency significantly increasing hemolytic risk)","Severe hepatic impairment"]
| Precautions | ["Methemoglobinemia: Risk increased with high doses, renal impairment, or concomitant methemoglobin-inducing agents.","Hemolytic anemia: Especially in G6PD deficiency.","Hypersensitivity reactions: Including agranulocytosis, aplastic anemia, and severe cutaneous adverse reactions (e.g., DRESS syndrome).","Peripheral neuropathy: Long-term use.","Hepatic toxicity: Monitor liver function.","Sulfone syndrome: Fever, malaise, jaundice, exfoliative dermatitis."] |
| Food/Dietary | No known food interactions with topical dapsone. However, oral dapsone may interact with foods rich in fava beans or other oxidizing agents; but for ACZONE gel, no dietary restrictions are required. |
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| Fetal Monitoring | Monitor maternal complete blood count (CBC) and methemoglobin levels due to risk of hemolysis and methemoglobinemia. In neonates, monitor bilirubin and signs of hemolysis or methemoglobinemia. Assess G6PD status before therapy. |
| Fertility Effects | No adverse effects on fertility reported in animal studies. Human data limited. No known impact on spermatogenesis or oogenesis at therapeutic doses. |
| Clinical Pearls | ACZONE (dapsone) gel 5% is a topical sulfone used for acne vulgaris. It has anti-inflammatory and antimicrobial properties, and may cause localized dryness. Contraindicated in G6PD deficiency due to risk of hemolysis. Avoid concomitant use with benzoyl peroxide as it may cause temporary yellow-orange skin discoloration. Monitor for methemoglobinemia if used with other oxidizing agents. |
| Patient Advice | Apply a pea-sized amount to affected areas once daily. · Wash hands before and after application. · Avoid contact with eyes, lips, and mucous membranes. · May cause skin redness, dryness, or stinging; use moisturizer if needed. · Do not use with benzoyl peroxide products as they may cause orange-brown staining of skin and hair. · Inform your doctor if you have G6PD deficiency or a history of anemia. · Seek medical attention if you experience shortness of breath, fatigue, or pale skin (signs of hemolysis). |