Dapsone 25 mg Tablet, 100-count — NDC 64980-567-01 (Billing 64980-0567-01)

WARNINGS The patient should be warned to respond to the presence of clinical signs such as sore throat, fever, pallor, purpura or jaundice. Deaths associated with the administration of Dapsone have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias. Complete blood counts should be done frequently in patients receiving Dapsone.

The FDA Dermatology Advisory Committee recommended that, when feasible, counts should be done weekly for the first month, monthly for six months and semi-annually thereafter. If a significant reduction in leucocytes, platelets or hemopoiesis is noted, Dapsone should be discontinued and the patient followed intensively. Folic acid antagonists have similar effects and may increase the incidence of hematologic reactions; if co-administered with Dapsone the patient should be monitored more frequently.

Patients on weekly pyrimethamine and Dapsone have developed agranulocytosis during the second and third month of therapy. Severe anemia should be treated prior to initiation of therapy and hemoglobin monitored. Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.

Cutaneous reactions, especially bullous, include exfoliative dermatitis and are probably one of the most serious, though rare, complications of sulfone therapy. They are directly due to drug sensitization. Such reactions include toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria and erythema nodosum.

If new or toxic dermatologic reactions occur, sulfone therapy must be promptly discontinued and appropriate therapy instituted. Leprosy reactional states, including cutaneous, are not hypersensitivity reactions to Dapsone and do not require discontinuation. See special section.

ADVERSE REACTIONS In addition to the warnings listed above, the following syndromes and serious reactions have been reported in patients on Dapsone. Hematologic Effects: Dose-related hemolysis is the most common adverse effect and is seen in patients with or without G6PD deficiency. Almost all patients demonstrate the inter-related changes of a loss of 1-2g of hemoglobin, an increase in the reticulocytes (2-12%), a shortened red cell life span and a rise in methemoglobin.

G6PD deficient patients have greater responses. Nervous System Effects: Peripheral neuropathy is a definite but unusual complication of Dapsone therapy in non-leprosy patients. Motor loss is predominant.

If muscle weakness appears, Dapsone should be withdrawn. Recovery on withdrawal is usually substantially complete. The mechanism of recovery is reported by axonal regeneration.

Some recovered patients have tolerated retreatment at reduced dosage. In leprosy this complication may be difficult to distinguish from a leprosy reactional state. Falsely Reduced HbA1c: Falsely reduced HbA1c measurements have been reported with dapsone use.

Alternate measures of glycemic control (e.g., fructosamine and/or more frequent blood glucose monitoring) are recommended when a discordance between HbA1c and blood glucose concentrations are observed or suspected. Falsely reduced HbA1c may occur without overt evidence of hemolysis or anemia. Body As A Whole: In addition to the warnings and adverse effects reported above, additional adverse reactions include: nausea, vomiting, abdominal pains, pancreatitis, vertigo, blurred vision, tinnitus, insomnia, fever, headache, psychosis, phototoxicity, pulmonary eosinophilia, tachycardia, albuminuria, the nephrotic syndrome, hypoalbuminemia without proteinuria, renal papillary necrosis, male infertility, drug-induced Lupus erythematosus and an infectious mononucleosis-like syndrome.

In general, with the exception of the complications of severe anoxia from overdosage (retinal and optic nerve damage, etc.) these adverse reactions have regressed off drug. To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

PRECAUTIONS General: Hemolysis and Heinz body formation may be exaggerated in individuals with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, or methemoglobin reductase deficiency, or hemoglobin M. This reaction is frequently dose-related. Dapsone should be given with caution to these patients or if the patient is exposed to other agents or conditions such as infection or diabetic ketosis capable of producing hemolysis.

Drugs or chemicals which have produced significant hemolysis in G6PD or methemoglobin reductase deficient patients include Dapsone, sulfanil amide, nitrite, aniline, phenylhydrazine, napthalene, niridazole, nitro-furantoin and 8-amino-antimalarials such as primaquine. Toxic hepatitis and cholestatic jaundice have been reported early in therapy. Hyperbilirubinemia may occur more often in G6PD deficient patients.

When feasible, baseline and subsequent monitoring of liver function is recommended; if abnormal, Dapsone should be discontinued until the source of the abnormality is established. Falsely Reduced HbA1c: Falsely reduced HbA1c measurements have been reported with dapsone use. Alternate measures of glycemic control (e.g., fructosamine and/or more frequent blood glucose monitoring) are recommended when a discordance between HbA1c and blood glucose concentrations are observed or suspected.

Falsely reduced HbA1c may occur without overt evidence of hemolysis or anemia. Drug Interactions: Rifampin lowers Dapsone levels 7 to 10-fold by accelerating plasma clearance; in leprosy this reduction has not required a change in dosage. Folic acid antagonists such as pyrimethamine may increase the likelihood of hematologic reactions.

A modest interaction has been reported for patients receiving 100 mg Dapsone daily in combination with trimethoprim 5 mg/kg q6h. On Day 7, the serum Dapsone levels averaged 2.1 ± 1.0 μg/mL in comparison to 1.5 ± 0.5 μg/mL for Dapsone alone. On Day 7, trimethoprim levels averaged 18.4 ± 5.2 μg/mL in comparison to 12.4 ± 4.5 μg/mL for patients not receiving Dapsone.

Thus, there is a mutual interaction between Dapsone and trimethoprim in which each raises the level of the other about 1.5 times. A crossover study 1 designed to assess the potential of a drug interaction between Dapsone, 100 mg/day and trimethoprim, 200 mg every 12 hours, in eight asymptomatic HIV positive volunteers (average CD4 count 524 cells/mm 3 ) demonstrated that there was not a significant drug interaction between Dapsone and trimethoprim. However, an earlier report 2 also by Lee et al, in 78 HIV infected patients with acute Pneumocystis carinii pneumonia, receiving Dapsone, 100 mg/day and higher trimethoprim dose, 20 mg/kg/day, demonstrated that the serum levels of Dapsone were increased by 40% and trimethoprim levels were increased by 48% when the drugs were administered concurrently.

Carcinogenesis, mutagenesis: Dapsone has been found carcinogenic (sarcomagenic) for male rats and female mice causing mesenchymal tumors in the spleen and peritoneum, and thyroid carcinoma in female rats. Dapsone is not mutagenic with or without microsomal activation in S . typhimurium tester strains 1535, 1537, 1538, 98, or 100. Pregnancy: Teratogenic Effects: Animal reproduction studies have not been conducted with Dapsone.

Extensive, but uncontrolled experience and two published surveys on the use of Dapsone in pregnant women have not shown that Dapsone increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can affect reproduction capacity. Because of the lack of animal studies or controlled human experience, Dapsone should be given to a pregnant woman only if clearly needed. In general, for leprosy, USPHS at Carville recommends maintenance of Dapsone.

Dapsone has been important for the management of some pregnant D.H. patients. Nursing Mothers: Dapsone is excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates.

See section on hemolysis. Because of the pote… [Excerpted — this section continues on DailyMed.]