Dapsone (dapsone)

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Dapsone is administered orally.

For administration to children, commercially available tablets of dapsone have been crushed and dissolved in strawberry syrup; however, studies evaluating bioavailability of the drug following administration of this preparation have not been published to date.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Dapsone/Didanosine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Unknown. Suspected to be due to decreased dissolution of dapsone in the gastrointestinal tract, reducing the bioavailability of dapsone.

CLINICAL EFFECTS: Decreased pharmacological effect of dapsone.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Separate the administration times of didanosine packets and dapsone by at least two hours. Didanosine chewable tablets did not significantly affect dapsone plasma concentrations.

DISCUSSION: Eleven of 28 patients receiving dapsone for the prophylaxis of pneumocystis carinii pneumonia (PCP) developed PCP when didanosine packets (contains sodium citrate buffer) was administered concurrently.(1) In an earlier unpublished study, 2 of 162 patients treated with dapsone and zidovudine developed PCP.(2) The difference in the treatment groups was attributed to poor dissolution of dapsone resulting from the effects of the citrate-phosphate buffer contained in the packets of didanosine. In two separate studies, didanosine chewable tablets that do not contain sodium citrate buffer did not significantly affect the plasma concentration of dapsone. Two separate randomized, two-period, two treatment, crossover studies with a 21 day washout between treatment groups showed that didanosine, antacids, and other excipients used in didanosine chewable tablets did not significantly affect dapsone plasma concentrations.(3)

Dapsone/Rifamycins

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown but likely involves induction of hepatic enzymes resulting in increased clearance of dapsone.(1-3)

CLINICAL EFFECTS: Concurrent use may lead to decreased levels and clinical effects of dapsone when it is used for treatment or prophylaxis of Pneumocystis jiroveci pneumonia (PCP).(1-5) Since dapsone is extremely potent for treatment of leprosy, this interaction is not clinically relevant in the setting of leprosy.(5)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US Department of Health and Human Service guidelines for prevention and treatment of opportunistic infections in patients with HIV recommend avoiding concomitant administration of dapsone with rifamycins if possible and considering use of alternatives to dapsone.(4) Since dapsone is extremely potent for treatment of leprosy, this interaction is not clinically relevant in the setting of leprosy.(5)

DISCUSSION: When given with rifampin, dapsone levels have been found to decrease by 7- to 10-fold.(3,4) In a trial of 16 HIV-positive patients, rifabutin (300 mg daily) lowered the area-under-curve (AUC) of dapsone (50 mg daily) by 27% to 40%.(2,4) Although dapsone dose adjustment is not necessary when it is used for leprosy, the implications of this interaction when dapsone is used for PCP is unknown. Mycobacterium leprae is very sensitive to dapsone, with a minimum inhibitory concentration (MIC) of 2.5 to 10 mcg/L. In contrast, the MIC of dapsone against P. jiroveci is 100 to 10,000 mcg/L. Dapsone concentrations reached with typical PCP therapy is in the range of 100 to 7,000 mcg/L. Thus, a 10-fold reduction in dapsone levels could result in dapsone levels below the MIC for PCP.(5)

Dapsone/Saquinavir

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Saquinavir, a strong CYP3A4 inhibitor, may inhibit the metabolism of dapsone at CYP3A4.(1)

CLINICAL EFFECTS: Concurrent administration may result in increased levels and adverse effects of dapsone. Higher dapsone levels may increase risk for agranulocytosis, aplastic anemia, and other blood dyscrasias; dose-related hemolysis; toxic hepatitis and cholestatic jaundice; cutaneous reactions including exfoliative dermatitis; and peripheral neuropathy.(2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of saquinavir states concurrent administration of saquinavir/ritonavir with drugs that are CYP3A4 substrates including dapsone is not recommended.(1) Patient monitoring should include frequent complete blood counts and liver function tests. Dapsone should be discontinued if a significant reduction in leukocytes, platelets or hemopoiesis occurs.(2)

DISCUSSION: In a study of 16 healthy subjects, saquinavir/ritonavir (1000/100 mg BID) increased the area-under-curve (AUC) and maximum concentration (Cmax) of midazolam (7.5 mg single dose) 1144% and 327%, respectively.(1) Midazolam is a sensitive CYP3A4 substrate.(3)

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

• Glucose-6-phosphate dehydrogenase (g6Pd) deficiency
• Hemoglobin H disease
• Hemolytic anemia from pyruvate kinase and g6PD deficiencies

• Anemia
• NADH methemoglobin reductase deficiency

• Disease of liver

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More Frequent

• Allergic dermatitis
• Hemolytic anemia
• Methemoglobinemia
• Skin rash
• Urticaria

Rare or Very Rare

• Agranulocytosis
• Altered mental status
• Anemia
• Blood dyscrasias
• Exfoliative dermatitis
• Fever
• Glucose-6-phosphate dehydrogenase (g6Pd) deficiency anemia
• Hepatocellular damage
• Jaundice
• Lymphadenopathy
• Malaise
• Mood changes
• Peripheral neuropathy
• Pruritus of skin

Rare or Very Rare

• Anorexia
• Gastrointestinal irritation
• Headache disorder
• Insomnia
• Nausea
• Nervousness
• Vomiting

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Animal reproduction studies have not been performed with dapsone. Although dapsone has been used in pregnant women without evidence of fetal abnormalities, the drug should be used during pregnancy only when clearly needed.

In patients with leprosy, some clinicians recommend maintaining dapsone treatment during pregnancy. In addition, dapsone has been important for the management of dermatitis herpetiformis in some pregnant women.

Because dapsone is distributed into milk and because of the tumorigenic potential demonstrated in animal studies, a decision should be made to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

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