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Medication Safety Issues
Sound-alike/look-alike issues:
Dapsone may be confused with Diprosone®
Pronunciation
(DAP sone)
U.S. Brand Names
Index Terms
Generic Available
Yes: Tablet
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of leprosy and dermatitis herpetiformis (infections caused by Mycobacterium leprae); topical treatment of acne vulgaris
Use: Dental
Used in lupus and in selected ulcerative conditions in consult with patient's physician
Use: Unlabeled/Investigational
Prophylaxis of toxoplasmosis in severely-immunocompromised patients; alternative agent for Pneumocystis jiroveci pneumonia (PCP) prophylaxis (monotherapy) and treatment (in combination with trimethoprim)
Pregnancy Risk Factor
C
Pregnancy Considerations
Due to a lack of controlled studies in animals or humans, dapsone is classified as pregnancy category C. Per the manufacturer, dapsone has not shown an increased risk of congenital anomalies when given during all trimesters of pregnancy. Several reports have described adverse effects in the newborn after in utero exposure to dapsone, including neonatal hemolytic disease, methemoglobinemia, and hyperbilirubinemia. Dapsone is an alternative for prophylaxis and treatment of Pneumocystis jiroveci pneumonia (PCP) in pregnant, HIV-infected patients. Dapsone is also recommended for pregnant women requiring maintenance therapy of either leprosy or dermatitis herpetiformis.
Lactation
Enters breast milk/not recommended (AAP rates “compatible”)
Breast-Feeding Considerations
Dapsone is excreted in breast milk. Although the AAP considers dapsone to be "usually compatible with breast-feeding," breast-feeding is not recommended by the manufacturer due to the potential for carcinogenicity observed in animal studies and the potential for hemolysis in the neonate, especially if there is a family history of G6PD deficiency. The relative infant dose is higher than that of most medications. Hemolytic anemia has been reported in a breast-fed infant.
Contraindications
Hypersensitivity to dapsone or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Blood dyscrasias: Aplastic anemia, agranulocytosis and other severe blood dyscrasias have resulted in death; monitor carefully.
• Dermatologic reactions: Serious dermatologic reactions (including toxic epidermal necrolysis) are rare but potential occurrences.
• Peripheral neuropathy: Motor loss and muscle weakness have been reported with use.
• Sulfonamide allergy: Use with caution in patients with hypersensitivity to other sulfonamides; sulfone reactions may also occur as potentially fatal hypersensitivity reactions, these, but not leprosy reactional states, require drug discontinuation.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea and pseudomembranous colitis.
Disease-related concerns:
• Anemia: Use with caution in patients with severe anemia; treat prior to therapy.
Special populations:
• G6PD deficiency: Use with caution in patients with G6PD deficiency.
• Hemoglobin M deficiency: Use with caution in patients with hemoglobin M deficiency.
• Methemoglobin reductase deficiency: Use with caution in patients with methemoglobin reductase deficiency.
• Pediatrics: Safety and efficacy of topical dapsone have not been established in children <12 years of age.
Adverse Reactions
Adverse reactions reported for oral formulation unless otherwise noted.
>10%: Hematologic: Hemolysis (dose related; seen in patients with and without G6PD deficiency), hemoglobin decrease (1-2 g/dL; almost all patients), reticulocyte increase (2% to 12%), methemoglobinemia, red cell life span shortened
Frequency not always defined.
Cardiovascular: Facial edema (topical), tachycardia
Central nervous system: Depression (topical), fever, headache, insomnia, psychosis (oral/topical), suicide attempt (topical), tonic clonic movement (topical), vertigo
Dermatologic: Bullous and exfoliative dermatitis, erythema nodosum, exfoliative dermatitis, morbilliform and scarlatiniform reactions, phototoxicity, Stevens-Johnson syndrome, toxic epidural necrolysis, urticaria
Endocrine & metabolic: Hypoalbuminemia (without proteinuria), male infertility
Gastrointestinal: Abdominal pain (oral/topical), nausea, pancreatitis (oral/topical), vomiting (oral/topical)
Hematologic: Agranulocytosis, anemia, leukopenia, pure red cell aplasia (case report)
Hepatic: Cholestatic jaundice, hepatitis
Neuromuscular & skeletal: Drug-induced lupus erythematosus, lower motor neuron toxicity (prolonged therapy), peripheral neuropathy (rare, nonleprosy patients)
Ocular: Blurred vision
Otic: Tinnitus
Renal: Albuminuria, nephrotic syndrome, renal papillary necrosis
Respiratory: Interstitial pneumonitis, pulmonary eosinophilia, sinusitis (topical 2%)
Miscellaneous: Infectious mononucleosis-like syndrome (rash, fever, lymphadenopathy, hepatic dysfunction)
Metabolism/Transport Effects
Substrate of CYP2C8 (minor), 2C9 (major), 2C19 (minor), 2E1 (minor), 3A4 (major)
Drug Interactions
CYP2C9 Inducers (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Didanosine: May decrease the absorption of Dapsone. Didanosine enteric coated capsules should not affect dapsone. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
Rifamycin Derivatives: May increase the metabolism of Dapsone. Risk D: Consider therapy modification
Trimethoprim: May increase the serum concentration of Dapsone. Dapsone may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification
Uricosuric Agents: May decrease the excretion of Dapsone. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: St John's wort may decrease dapsone levels.
Storage
Store at 20°C to 25°C (68°F to 76°F). Protect tablets from light. Do not freeze gel.
Mechanism of Action
Competitive antagonist of para-aminobenzoic acid (PABA) and prevents normal bacterial utilization of PABA for the synthesis of folic acid
Pharmacodynamics/Kinetics
Absorption:
Oral: Well absorbed
Topical: ~1% of the absorption of 100 mg tablet
Protein binding: Dapsone: 70% to 90%; Metabolite: ~99%
Distribution: Vd: 1.5 L/kg; throughout total body water and present in all tissues, especially liver and kidney
Metabolism: Hepatic (acetylation and hydroxylation); forms multiple metabolites
Half-life elimination: 30 hours (range: 10-50 hours)
Excretion: Urine (~85%)
Dosage
Oral:
Leprosy:
Children: 1-2 mg/kg/24 hours, up to a maximum of 100 mg/day
Adults: 50-100 mg/day for 3-10 years
Dermatitis herpetiformis: Adults: Start at 50 mg/day, increase to 300 mg/day, or higher to achieve full control, reduce dosage to minimum level as soon as possible
Pneumocystis carinii pneumonia (unlabeled use):
Prophylaxis:
Children >1 month: 2 mg/kg/day once daily (maximum dose: 100 mg/day) or 4 mg/kg/dose once weekly (maximum dose: 200 mg)
Adults: 100 mg/day
Treatment: Adults: 100 mg/day in combination with trimethoprim (15-20 mg/kg/day) for 21 days
Topical: Acne: Children ?12 years and Adults: Apply pea-sized amount (approximately) in a thin layer to affected areas twice daily; reevaluate patient if no improvement after 12 weeks of therapy
Dosing adjustment in renal impairment: No specific guidelines are available
Administration: Oral
May administer with meals if GI upset occurs.
Administration: Topical
Topical: Skin should be clean and dry before applying. Rub in gently and completely. Wash hands after applying. Gel may be gritty. For external use only; avoid applying to inside nose, mouth, eyes, and mucous membranes.
Monitoring Parameters
Oral: Check G6PD levels prior to initiation. Monitor patients for signs of jaundice and hemolysis; CBC weekly for first month, monthly for 6 months and semiannually thereafter.
Topical: For patients at risk of anemia, monitor with CBC, reticulocyte counts at baseline and routinely thereafter.
Dietary Considerations
Oral: Do not give with antacids, alkaline foods, or drugs.
Patient Education
Do not take any new prescription or OTC medications or herbal products during therapy without consulting prescriber. Use exactly as directed; do not increase or discontinue without consulting prescriber. Oral: Do not take with antacids, alkaline foods, or other medications. Topical: Gently wash skin and pat dry. Apply a small amount (pea size) and rub in gently and completely as frequently as directed (may appear gritty with visible particles). Wash hands after applying. May reduce fertility (discuss with prescriber). Frequent blood tests may be required. Report persistent sore throat, fever, or chills; CNS changes (constant fatigue, depression, insomnia, spastic movements, headache); yellowing of skin or eyes; unusual bruising or bleeding; gastrointestinal upset (nausea, vomiting, abdominal pain); blurred vision; new skin rash, eruption, tenderness, or peeling; worsening of condition; or other adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Evaluate patient history for sulfonamide hypersensitivity and all applicable use cautions (eg, anemia, G6PD deficiency, other blood dyscrasias). Assess potential for interactions or toxicity with other pharmacological agents or herbal products patient may be taking. Evaluate results of laboratory tests, therapeutic effectiveness (according to purpose for use), and adverse response on a regular basis during therapy. Teach patient appropriate use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, topical:
Aczone®: 5% (30 g, 60 g)
Tablet: 25 mg, 100 mg
Pricing: U.S. (www.drugstore.com)
Gel (Aczone)
5% (30): $139.99
Extemporaneously Prepared
One report indicated that dapsone may not be well absorbed when administered to children as suspensions made from pulverized tablets
Mirochnick M, Clarke D, Brenn A, et al, “Low Serum Dapsone Concentrations in Children Receiving an Extemporaneously Prepared Oral Formulation,” [Abstract Th B 365], APS-SPR, Baltimore, MD: 1992.
Jacobus Pharmaceutical Company (609) 921-7447 makes a 2 mg/mL proprietary liquid formulation available under an IND for the prophylaxis of Pneumocystis carinii pneumonia
References
“1997 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected With Human Immunodeficiency Virus. USPHS/IDSA Prevention of Opportunistic Infections Working Group,” MMWR Recomm Rep, 1997, 46(RR-12):1-46.
Barnett ED, Pelton SI, Mirochnick M, et al, “Dapsone for Prevention of Pneumocystis Pneumonia in Children With Acquired Immunodeficiency Syndrome,” Pediatr Infect Dis J, 1994, 13(1):72-4.
Borras-Blasco J, Conesa-Garcia V, Navarro-Ruiz A, et al, "Pure Red Cell Aplasia Associated With Dapsone Therapy," Ann Pharmacother, 2005, 39(6):1137-8.
El-Sadr WM, Murphy RL, Yurik TM, et al, “Atovaquone Compared With Dapsone for the Prevention of Pneumocystis carinii in Patients With HIV Infection Who Cannot Tolerate Trimethoprim, Sulfonamides, or Both,” N Engl J Med, 1998, 339(26):1889-95.
Hansen DG, Challoner KR, and Smith DE, “Dapsone Intoxication: Two Case Reports,” J Emerg Med, 1994, 12(3):347-51.
Holtzer CD, Flaherty Jr JF, and Coleman RL, “Cross Reactivity in HIV-Infected Patients Switched From Trimethoprim-Sulfamethoxzole to Dapsone,” Pharmacotherapy, 1998, 18(4):831-5.
Letko E, Zafirakis P, Baltatzis S, et al, “Relapsing Polychondritis: A Clinical Review,” Semin Arthritis Rheum, 2002, 31(6):384-95.
McGoldrick MD and Bailie GR, “Severe Accidental Dapsone Overdose,” Am J Emerg Med, 1995, 13(4):414-5.
Medina I, Mills J, Leoung G, et al, “Oral Therapy for Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome. A Controlled Trial of Trimethoprim-Sulfamethoxazole Versus Trimethoprim-Dapsone,” N Engl J Med, 1990, 323(12):776-82.
Meier K, “Dapsone,” Poisoning and Drug Overdose, 2nd ed, Olson KR, ed, East Norwalk, CT: Appleton and Lange, 1994, 150-2.
Mirochnick M, Michaels M, Clarke D, et al, “Pharmacokinetics of Dapsone in Children,” J Pediatr, 1993, 122(5 Pt 1):806-9.
Stavola JJ and Noel GJ, “Efficacy and Safety of Dapsone Prophylaxis Against Pneumocystis carinii Pneumonia in Human Immunodeficiency Virus-Infected Children,” Pediatr Infect Dis J, 1993, 12(8):644-7.
Tracqui A, Gutbub AM, Kintz P, et al, “A Case of Acute Dapsone Poisoning: Toxicological Data and Review of the Literature,” J Anal Toxicol, 1995, 19(4):229-35.
Wynn RF, Laing RB, and Leen CL, “Case Report of Dapsone-Related Thrombocytosis in an AIDS Patient,” Am J Med, 1995, 98(6):602.
Zuidema J, Hilbers-Modderman ES, and Merkus FW, “Clinical Pharmacokinetics of Dapsone,” Clin Pharmacokinet, 1986, 11(4):299-315.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2009
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