Dapsone
When ATH:
J04BA02
Characteristic.
White or creamy-white crystalline powder, without smell. Practically insoluble in water, sparingly soluble in ethanol. Molecular weight 248,3.
Pharmacological action.
Antibacterial, protivoleproznoe.
Application.
Leprosy (Hansen's disease), dermatitis herpetiformis Duhring, tuberculosis.
Contraindications.
Hypersensitivity, incl. to sulfamilamidam, abnormal liver function, severe anemia, deficiency of glucose-6-fosfatdegidrogenazы or metgemoglobinreduktazы (may develop hemolytic anemia).
Pregnancy and breast-feeding.
Probably only for maintenance therapy in patients with leprosy and dermatitis herpetiformis pregnant women (adequate and well-controlled studies in humans and animals have not been conducted).
Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)
At the time of treatment should stop breastfeeding (concentration in serum reaches the infant 27% that of the mother, Besides, dapsone can cause hemolytic anemia in newborns with deficiency of glucose-6-phosphate dehydrogenase).
Side effects.
Cardio-vascular system and blood (hematopoiesis, hemostasis): dose-dependent hemolysis with decreasing hemoglobin levels and increased number of reticulocytes (all patients), gemoliticheskaya anemia (backache, legs, stomach, loss of appetite, pale skin, unusual tiredness or weakness, fever), metgemoglobinemiâ (cyanosis of the fingernails, lips or skin, shortness of breath, and others.), blood dyscrasias (fever, sore throat, unusual bleeding and hemorrhage, and others.), incl. agranulocytosis and aplastic anemia fatal, heartbeat, kardialgija.
For the skin: exfoliative dermatitis (itch, dryness, redness or scaling of the skin, hair loss), Toxic erythema, erythema multiforme, toxic epidermal necrolysis, erythema nodosum, crust- and scarlatiniform reaction.
From the nervous system and sensory organs: mental disorders, incl. mood changes, peripheral neuritis (benumbed sensation, tingling, burning, pain or weakness in the arms and legs), neurotoxicity (headache, insomnia, nervousness).
Allergic reactions: skin rash, "Sulfone syndrome" (fever, malaise, exfoliative dermatitis, jaundice, lymphadenopathy, metgemoglobinemiâ, anemia), usually develops after 6-8 weeks of therapy.
From the digestive tract: liver (yellow skin or sclera), anorexia, nausea, vomiting.
Cooperation.
Incompatible with barbiturates and aminophenazone. Rifampicin reduces dapsone 7-10 times, by stimulating the activity of liver microsomal enzymes (while the application for the treatment of leprosy dapsone dose adjustment is not required, t. to. its concentration remains above the MIC). Reduces the absorption of didanosine, tk. assigned to the buffer, neutralizing gastric acidity. Preparations, causing hemolysis (folic acid antagonists, in t. no. pirimetamin), increase the risk of toxic side effects. Trimethoprim increases concentration (mutually). Preparations, causing pathological changes in the blood picture, enhance the myelotoxic effects. Aminoʙenzoatы (PABA) reduce bacteriostatic effect against Mycobacterium leprae.
Overdose.
Symptoms: nausea, vomiting, hypererethism, depression, convulsions, metgemoglobinemiâ, strong cyanosis.
Treatment: gastric lavage, appointment of activated carbon (30 g) in conjunction with laxative every 6 h for at least 48-72 hours (Carbon repeated doses reduce T1/2 dapsone and monoatsetildapsona about 50% to 12,7 no). In cases of emergency is slow in/with the introduction of methylene blue (0,05% solution 0,9% solution of sodium chloride with initial velocity 0,1 mg / kg / hr) at a dose of 1-2 mg/kg (should not be administered to patients with severe deficiency of glucose-6-phosphate dehydrogenase); re-introduction of the methylene blue is possible at reakkumulyatsii methemoglobin; in non-emergency situations, if necessary, methylene blue, appointed interior, the dose of 3-5 mg/kg every 4-6 h.
Dosing and Administration.
Inside. When leprosy (in combination with one or more other protivoleproznymi means to reduce secondary resistance to dapsone) appoint cycles of 4-5 weeks for a one-day break every 6 days. During the first cycle 2 weeks — on 50 mg 2 once a day, in the following 3 weeks — on 100 mg 2 once a day. Then you should break 2 Sun, then a second cycle under the same scheme. A course of treatment - 4 cycle. After the fourth cycle-1 break-1, 5 months. Treatment of long-, during 6 Mon − 3 years or longer if undifferentiated and tuberkuloidnoj leprosy, 2-10 years with border (dimorfnoj) leprosy, from 2 years before the end of his life, in the case of lepromatoznoj leprosy.
Children - 1,4 mg / kg 1 once a day.
When gerpetiformnom dermatitis Duringa — on 50-100 mg 2 times a day in cycles of 5-6 days with a break 1 day, the course is 3-5 cycles and more. The maximum daily dose is up to 300 mg. After the disappearance of clinical manifestations of the disease — in supporting the dose- 50 mg a day or 1-2 times a week. Children — dose 2 mg / kg / day, if necessary, increase the dose, then as soon as possible to reduce the lowest effective maintenance dose.
Precautions.
Treatment is carried out under constant monitoring of patients, which comprises: definition of ALT and AST in the blood (before and periodically during treatment, If signs of progressive liver disease treatment should be stopped), determine the level of urea nitrogen and creatinine in the blood (periodically during treatment in patients with impaired renal function, may reduce the dose or cancel the drug in development anurii); conduct of a clinical blood test, including determination of the number of platelets, and reticulocytes (before treatment, monthly for 1-3 months and then every six months; with a significant decrease in the number of white blood cells, Platelet, hematocrit, or increasing the number of reticulocytes required removal of the drug and close monitoring of patients); definition activities glucose-6-fosfatdegidrogenazы (to treat patients with high-risk) and methemoglobin (necessary in patients with cyanosis, dizziness, fatigue, headache or shortness of breath).
In patients with HIV infection in the first 2-3 weeks of therapy clinical blood tests should be performed every 2-3 days.
In patients with deficiency of glucose-6-phosphate dehydrogenase need special care, in connection with the chance of increasing the hemolytic effects (dose adjustments may be necessary). With an increase in the level of methemoglobin 20% drug overturned, on 30% (in combination with the presence of clinical symptoms) -examine the feasibility of methylene blue.
Leprosy patients must comply with the regimen and the use of the entire course of treatment (take medication at the same time). Omitting receive another dose as soon as possible to take the drug, but do not take, If almost time for your next dose or double the dose.
Dieting, not containing gluten, during 6 months in the treatment of dermatitis herpetiformis may allow a reduction in dose of approximately 50% or cancel product.
In the application for the treatment of leprosy dapsone monotherapy may develop bacterial resistance, it is recommended that co-administration of rifampicin and ethionamide. In the event of heavy "return" reactions (type 1) neuritis or during treatment of leprosy prescribed corticosteroids (large doses). With the development of new or toxic skin reactions drug overturned. Reactive states, associated with the leprosy, do not require discontinuation of therapy. If within 2-3 months (leprosy) or more days (dermatitis herpetiformis) treatment does not improve, Talk to your doctor. In the treatment of dermatitis herpetiformis aminobenzoates not affect the action of dapsone.
