dapsone (systemic)

PO:

Leprosy (in combination with other agents)
Dermatitis herpetiformis.

REMS

Unlabeled Use:

PO: Prevention (as monotherapy) or treatment of Pneumocystis jirovecii pneumonia (in combination with trimethoprim or other agents).

Action ⬆ ⬇

Interferes with folate synthesis in susceptible organisms.

Therapeutic effects:

Bacteriostatic action.

Spectrum:

Active against:
- Mycobacterium leprae,
- Pneumocystis jirovecii.

Pharmacokinetics ⬆ ⬇

Absorption: Slowly absorbed (70–80%) following oral administration; acidic environment promotes absorption.

Distribution: Widely distributed to tissues.

Protein Binding: Dapsone: 70–90%; Monoacetyl dapsone (MADDS): 99%.

Metabolism/Excretion: Mostly metabolized by the liver to MADDS, its major metabolite, which is then metabolized back to dapsone.

Half-Life: 10–50 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	unknown	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity (cross-sensitivity with sulfonamides may occur);
Congenital or idiopathic methemoglobinemia;
Lactation: Lactation (can cause hemolytic reactions in infants).

Use Cautiously in:

Severe anemia;
Glucose-6–phosphate dehydrogenase (G6PD) deficiency (↑ risk of severe hemolysis or methemoglobinemia);
Hepatic impairment;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: exfoliative dermatitis, hypersensitivity reactions (including erythema nodosum leprosum), photosensitivity, STEVENS-JOHNSON SYNDROME, systemic lupus erythematosus

EENT: blurred vision, tinnitus

GI: abdominal pain, HEPATOTOXICITY, nausea, PANCREATITIS, vomiting

Hemat: hemolytic anemia, AGRANULOCYTOSIS, METHEMOGLOBINEMIA, reticulocytosis

Neuro: headache, insomnia, mood changes, peripheral neuropathy, vertigo

Interactions ⬆ ⬇

Drug-drug:

Antacids may ↓ absorption and effectiveness (separate administration by 2 hr).
Amiodarone,fluconazole,ketoconazole,itraconazole,clarithromycin,erythromycin,quinidine,verapamil, and diltiazem may ↑ levels and risk of toxicity.
Rifampin,phenytoin, phenobarbital, and carbamazepine may ↓ levels and effectiveness.
Trimethoprim/sulfamethoxazole↑ levels and risks of toxicity of both agents.
Rifampin, anticonvulsants, or pyrimethamine may ↑ risk of hemolysis.
Acetaminophen, chloroquine, isosorbide dinitrate, isosorbide mononitrate, nitrofurantoin, nitroglycerin, nitroprusside, phenobarbital, phenytoin, primaquine, quinine, and sulfonamides may ↑ risk of methemoglobinemia

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness.

Route/Dosage ⬆ ⬇

Leprosy

PO (Adults ): 50–100 mg/day for 3–10 yr.
PO (Children ): 1–2 mg/kg/day, up to 100 mg/day.

Dermatitis Herpetiformis

PO (Adults ): Initiate therapy with 50 mg/day, up to 300 mg/day may be required.

Pneumocystis jiroveciiPneumonia

PO (Adults ): Prophylaxis: 100 mg/day;Treatment: 100 mg/day (in combination with trimethoprim) for 21 days.
PO (Children >1 mo): Prophylaxis: 2 mg/kg/day (up to 100 mg/day) once daily, or 4 mg/kg once weekly (up to 200 mg/dose).

Availability ⬆ ⬇

(Generic available)

Tablets: 25 mg; 100 mg

Assessment ⬆ ⬇

Leprosy: Assess skin lesions prior to and periodically throughout therapy.
Assess skin for new or toxic dermatologic reactions during therapy. Unless dermatologic reaction is leprosy reactional state, dapsone should be discontinued promptly. Large doses of corticosteroids should be given if severe reactions or neuritis occurs.
Pneumocystis jirovecii pneumonia: Assess for infection (vital signs, sputum, WBC) and monitor respiratory status (rate, character, lung sounds, dyspnea, sputum) at beginning of and throughout therapy.
Obtain specimens for culture and sensitivity prior to initiating therapy. 1^st dose may be given before receiving results.

Lab Test Considerations:

Monitor AST and ALT before and periodically during therapy. Discontinue dapsone if there is evidence of progressive hepatic damage.
- Monitor patients for hemolysis. Screen patients at higher risk for G6PD deficiency (patients of African American or Mediterranean ancestry) before PO therapy. If hemolysis occurs, discontinue and do not restart dapsone.
- Monitor CBC and reticulocyte counts before treatment, then weekly for 1st mo, then monthly for 6 mo, and then semiannually thereafter. In patients with HIV, monitor counts every 2–3 days for the 1st 2–3 wk of therapy. If significant ↓ in leukocytes, platelets, or hematocrit occurs or if there is an ↑ in reticulocyte count, discontinue dapsone and monitor patient closely.
- Obtain serum methemoglobin in patients with slate-grey cyanosis in buccal mucous membranes, lips and nail beds, lightheadedness, fatigue, headache, or shortness of breath. Patients with G6PD deficiency are at ↑ risk. If signs/symptoms of methemoglobinemia occur, discontinue dapsone.

Implementation ⬆ ⬇

PO: Administer with food if GI upset occurs.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed, at the same time each day, for full course of therapy, even if feeling well. Take missed doses as soon as possible if not time for next dose; do not double doses.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Advise patients to stop dapsone and notify health care professional if signs/symptoms of methemoglobinemia occur. May occur hours after exposure.
Advise patient to notify health care professional immediately if rash, sore throat, fever, chills, persistent fatigue, yellow eyes/skin, bruising, or bleeding occur.
Emphasize the importance of regular follow-up and blood work to check progress. Advise patient to notify health care professional if no improvement is seen in 2–3 mo in patients with leprosy, 1 wk in patients with Pneumocystis jirovecii pneumonia, or within a few days in patients with dermatitis herpetiformis.
Rep: Advise women of reproductive potential to notify health care professional is pregnancy is planned or suspected. Avoid breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇