Composition, form of production and packaging
Tablets of white color, round, biconcave, with a risk for a fault on one side.
1 tab.
dapsone 50 mg
Excipients: calcium hydrophosphate dihydrate - 10 mg, microcrystalline cellulose - 11 mg, lactose monohydrate - 21 mg, copovidone - 3 mg, crospovidone - 3 mg, silicon colloidal dioxide - 1 mg, magnesium stearate (vegetable) - 1 mg.
25 pcs. - blisters (2) - packs of cardboard.
25 pcs. - blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
A protivopleznoe means of the group of sulfones. Has a bacteriostatic effect. It is active against a wide spectrum of microorganisms, it is especially effective against Mycobacterium leprae (the minimum effective concentration is within the nanograms, so the therapeutic effect with leper can be achieved with a dose of 25 mg per day), Plasmodium, Pneumocystis carinii. The mechanism of action presumably has at least 2 points of application: on the one hand, an analogue of dihydropteric acid is formed (dapsone is absorbed in place of p-aminobenzoic acid), and on the other hand, the enzyme dihydropteroate synthetase is inhibited. As a result of these processes, functions of other systems, for example, dihydrofolate reductase, whose function is to convert unused microorganisms dihydrofolic acid to tetrahydrofolic acid, may occur. Presumably, in addition to the antibacterial effect, the effect of dapsone is determined by other factors. In particular, dapsone is able to inhibit the production of cytotoxic radicals in the myeloperoxidase chain - hydrogen peroxide - halogenated compounds. Other effects of the dapsone were also described: the inhibition of the Artus reaction, the complement system when it was activated by the alternative pathway, the inhibition of some lysosomal enzyme systems, the reaction of erythrocytes to phytohemagglutinin, and finally the suppression of binding of leukotriene B 4 to its specific receptors. The effect on the immune system is obviously also an important property of the dapsone, along with its analgesic and anti-inflammatory effects, revealed in the experiment.
PHARMACOKINETICS
Dapsone is almost completely absorbed (70-80%) after oral administration. C max of the drug in plasma is achieved after 2-6 hours. At a dose of 100 mg per day, the concentration of dapsone in the blood plasma reaches 1.7 mg / l at a single dose, 3.3 mg / l in a state of equilibrium and drops to 0.7 mg / l after 24 hours. 70-90% of dapsone binds to plasma proteins. It penetrates well into various tissues and organs, and the values ​​obtained correspond approximately to the concentrations in the plasma. Dapsone also can penetrate into the intracellular space of phagocytes.
T 1/2 dapsone is relatively long, averaging about 30 hours. About 90% of the 100 mg dose orally administered is completely excreted after about 9 days, but with prolonged treatment with dapsone, the active ingredient is detected in the body for up to 35 days after the last dose. However, the relative cumulation of the drug in the body does not occur.
Dapsone is acetylated in the liver. Another important way of dapsone metabolism is its hydroxylation. It is assumed that the monohydroxylamine of dapsone is responsible for the side effects of the dapsone on the part of the blood. The drug is characterized by hepatoenteric circulation. Dapsone is excreted by about 90% by the kidneys, largely in the form of metabolites, and by 10% with feces.
INDICATIONS
For the treatment of leprosy - in combination with other drugs effective against leprosy.
Herpetiform dermatitis (DГјhringa), bullous pemphigoid (in combination with corticosteroids and immunosuppressors or monotherapy with light flow).
In some cases - treatment of vasculitis (in complex therapy).
DOSING MODE
Inside.
It is best to take after eating, washing down with plenty of water. It is used, as a rule, in complex therapy. One day a week the drug is not taken (for example, on Sundays).
Doses and duration of application
Dosing regimen is individual. The average dose of the drug is 50-100 mg of dapsone, i.e. 1-2 tablets a day, 6 days a week.
If not specified otherwise, the following dosage instructions apply:
Leprosy: The average daily dose is 50-100 mg (1-2 tablets) per day. Taking the drug for a long time for a number of years.
Herpetiform dermatitis (DГјhring): treatment should begin with 2 tablets per day (100 mg dapsone) for 1 week. The dose can then be increased to 4 tablets (200 mg dapsone) until the effect is achieved. However, in each specific case it is necessary to strive for the lowest dose - 50 mg. In some cases, 300 mg of dapsone (6 tablets) per day can be taken for a short period of time, although it is necessary to strive for a maintenance dose of 50 mg of dapsone per day, which can be achieved by combining the drug with corticosteroids.
In the event that the clinical picture of the disease is accompanied by symptoms from the gastrointestinal tract, the appointment of an agglutinous diet can help reduce the dose of the drug.
The duration of treatment with DГјhring's dermatitis is long, for many years. The duration of the break between courses increases with the use of corticosteroids. The possibility and duration of breaks are determined on a case by case basis.
Bullous pemphigoid - 100-150 mg / day.
Vasculitis - 50-150 mg / day.
SIDE EFFECT
From the side of the circulatory system: hemolytic anemia, methemoglobinemia, eosinophilia, agranulocytosis.
Hypersensitivity reactions: in the form of the so-called dapsone syndrome: fever, poor health, skin rashes, jaundice, swelling of the lymph nodes, mononucleosis, methemoglobinemia and anemia, in severe cases, erythema multiforme or exfoliative deramatitis.
From the nervous system: peripheral neuropathies, dizziness, visual impairment, psychosis, insomnia.
Other: at the beginning of treatment, headaches, abdominal pain and nausea, vomiting, pancreatitis, fever, phototoxicity, tachycardia, albuminuria, hypoalbuminuria without proteinuria, nephrotic syndrome, papillary necrosis, male infectility, systemic lupus erythematosus, syndrome similar to infectious mononucleosis , usually taking place with further administration of the drug.
In very rare cases, agranulocytosis, peripheral motor neuropathy and hypoalbuminemia are possible.
CONTRAINDICATIONS
- hypersensitivity to dapsone or other components of the drug, to sulfonamides and sulfones;
- severe anemia (hemoglobin content less than 10g%). In an emergency situation (for example, with DГјhring-Brokk syndrome), it may be necessary to perform dapsone treatment with strict control, first of all, the red blood formula;
- severe liver disease;
- Children under 18 years.
PREGNANCY AND LACTATION
If it is necessary to use dapsone in pregnancy, the expected benefit for the mother and the possible risk to the fetus should be correlated. In the first 4 months of pregnancy and during lactation, the drug should be prescribed only in case of emergency, with the utmost care. Since dapsone is secreted into breast milk, women taking the drug should refrain from breastfeeding.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe liver disease.
APPLICATION FOR CHILDREN
Contraindicated in childhood to 18 years.
SPECIAL INSTRUCTIONS
If there is a skin rash when taking the drug, take the drug immediately and immediately consult a doctor. With caution apply dapsone in patients with insufficiency of glucose-6-phosphate dehydrogenase (G6PDG), since in this case the risk of side effects increases substantially. In an emergency, you should try to limit yourself to half the usual recommended dose.
Regular monitoring of the blood condition is necessary (blood tests at the beginning of therapy weekly, and several months later). In the event of a significant decrease in the level of white blood cells, platelets or hemopoiesis, treatment with dapsone should be discontinued. It should be borne in mind that side effects from the blood are usually more pronounced in elderly patients.
Impact on the ability to drive vehicles and manage mechanisms. The effect of the drug on the ability to drive a car and drive mechanisms is unlikely.
OVERDOSE
Symptoms of intoxication: dyspnea, nausea and vomiting, headaches, cyanosis, tachycardia, methemoglobinemia, hemolysis, hematuria, renal failure, neurological and psychiatric disorders, vision loss and coma.
There are no exact data on the lethal doses. In one case, taking 1.4 g led to a fatal outcome, and in another, the patient survived after taking 15 g of dapsone.
Therapy for overdose.
It is necessary to do a gastric lavage (always hold). After that, it is necessary to take activated charcoal and possibly laxative for several days (40 ml of 20-40% solution of sorbitol).
To increase the excretion of the sulfone and prevent renal failure, infusion therapy is performed (introduction of sufficient quantities of liquid with diuretics and sodium bicarbonate to alkalinize urine).
Treatment of methemoglobinemia is performed by administration of methylene blue 1% 0.2 ml / kg iv and / or vitamin C (2 g / d).
In the case of a severe overdose, early hemodialysis, an infusion of erythrocyte mass or blood transfusion is indicated. Oxygen therapy or artificial respiration when controlling pO 2 . Symptomatic therapy.
DRUG INTERACTION
Dapsone increases the effectiveness of isoniazid, protionamide and rifampicin, which allows to reduce their doses, especially protionamide. Rifampicin increases the plasma clearance of the dapsone and lowers the dapsone level by 7-10 times.
With simultaneous use with probenecid, there is a decrease in the excretion of dapsone and an increase in its concentration in the blood.
Pyrimethamine may alter certain pharmacokinetic parameters of dapsone (V d , C max of the drug in plasma and saliva).
The intake of cimetidine and moderate consumption of alcohol do not affect the absorption of dapsone.
Trimetaprim affects the level of dapsone and vice versa.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in a dry, dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children
Shelf life - 3 years. The drug should not be used after the expiry date indicated on the package.
