Fansidar

General characteristics. Structure:

Active agents: sulphadoxine of 500 mg; Pyrimethaminum of 25 mg

Excipients: starch corn, lactose, gelatin, talc, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Fansidar affects sexless intraerythrocyte forms of malarial plasmodiums. Thanks to a synergism of action of two components of drug – sulphadoxine and Pyrimethaminum – activity of two enzymes participating in biosynthesis of folinovy acid in parasites is suppressed.
Fansidar is active against the strains steady against chloroquine. However in Southeast Asia and South America strains of P. falciparum at which resistance to Fansidar developed often meet; such strains also meet in East and Central Africa therefore in these regions Fansidar has to be applied with care.
Fansidar is effective at the infections caused by Toxoplasma gondii and Pneumocystis carinii.

Pharmacokinetics. Absorption. After reception of one tablet the maximum plasma concentration of Pyrimethaminum (about 0.2 mg/l) and sulphadoxine (about 60 mg/l) are reached approximately in 4 hours.

Distribution. The volume of distribution of sulphadoxine and Pyrimethaminum makes, respectively, 0.14 and 2.3 l/kg. At reception of 1 tablet in a week (the recommended dose for prevention of malaria at adults) it is possible to expect that average equilibrium plasma concentration of Pyrimethaminum will make 0.15 mg/l (approximately in 4 weeks), and sulphadoxine - 98.4 mg/l (approximately in 7 weeks). Linkng with proteins equals about 90% both for Pyrimethaminum, and for sulphadoxine. Pyrimethaminum and sulphadoxine get through a placental barrier and are excreted with breast milk.

Metabolism. About 5% of sulphadoxine are in blood in the form of an acetylized metabolite, about 2-3% - in the form of a glucuronide. Pyrimethaminum is exposed to biotransformation with formation of several metabolites.

Removal. Rather big elimination half-life is characteristic of both components. Its average value for Pyrimethaminum makes about 100 hours, and for sulphadoxine – about 200 hours. Both Pyrimethaminum, and sulphadoxine are removed, generally through kidneys.

Pharmacokinetics in special groups of patients. At patients with malaria pharmacokinetic parameters after one-time reception can differ from those at healthy faces, depending on population.
At patients with a renal failure it is possible to expect the slowed-down removal of components of Fansidar.

Indications to use:

The malaria which is especially caused by P. falciparum, steady against other antimalarial drugs.
Fansidar is not recommended for routine prevention of malaria.

Prevention of malaria by Fansidar is carried out only in regions, endemic on
P. falciparum which are sensitive to Fansidar and also in case of contraindications or lack of other antimalarial drugs (watch the section "Contraindications").
Parasitic infections: treatment of a toxoplasmosis and prevention of a pneumocystic infection.

Route of administration and doses:

Pill should be taken after food, without chewing and washing down with a large amount of water.
Treatment and prevention of malaria

Treatment of uncomplicated malaria single dose of drug

Children
> 5 and ≤ 10 kg (approximately ≤ 2 years)	0.5 tablets
> 10 - 20 kg (about 2 - 5 years)	1 tablet
> 20 - 30 kg (about 5 - 10 years)	1.5 tablets
> 30 - 45 kg (about 10 - 14 years)	2 tablets
Adults
≤45 kg	2 tablets
> 45 kg	3 tablets

Treatment of the complicated malaria

The standard scheme of therapy of heavy or cerebral malaria consists in reception of quinine within 7-10 days. Reception of quinine can be reduced to 2-3 days if after therapy by quinine to add a single dose of Fansidar. Consecutive therapy by quinine and Fansidar effectively prevents the recurrence which is often celebrated at monotherapy by quinine.

Prevention of malaria
The risk of a disease of malaria should be compared with risk of serious undesirable reactions to drug carefully.
If Fansidar is appointed for prevention, the doctor is obliged to obtain information on intolerance of streptocides, to point out to the patient the increased risk and need of immediate drug withdrawal at emergence of skin reactions.

For prevention the following doses are recommended:

Children
> 5 and ≤ 10 kg (approximately? 2 years)	0.5 tablets each 2 weeks
> 10 - 30 kg (about 2 - 10 years)	1 tablet each 2 weeks
> 30 - 45 kg (about 10 - 14 years)	1.5 tablets each 2 weeks
Adults
≤ 45 kg	1.5 tablets each 2 weeks
> 45 kg	1 tablet weekly

For prevention of malaria the first dose of Fansidar needs to be accepted one week prior to arrival in the endemic region; then continue administration of drug in the above-stated doses during all term of stay and in the first 4-6 weeks after departure from this region.

Duration of prevention makes no more than 2 years as experience of more prolonged use of drug is absent.

Emergency independent treatment of malaria
Fansidar can be used as means for rendering independent acute management when medical care is unavailable. Independent therapy consists in a single dose of Fansidar according to the scheme provided in the section "Treatment of Uncomplicated Malaria Single Dose of Drug".
The patient needs to see a doctor as soon as possible even if he feels completely recovered, for confirmation of the diagnosis, and also, if necessary, additional treatment.

Treatment of a toxoplasmosis
Adults: on 2 tablets once a week within 6 weeks (at defeat of TsNS - in a combination to Spheromycinum in a dose of 3 g a day for 3-4 weeks).

Prevention of the pneumonia caused by Pneumocystis carinii
Adults: on 1-2 tablets a week.

Features of use:

It is necessary to avoid strictly excessively long stay in the sun.
Patients need to be informed that pharyngalgias, fever, cough, short wind or a purpura can be the first signs of serious side effects. In particular, Fansidar's reception should be stopped at once at the first symptoms of skin rash, essential decrease in number of uniform elements of blood, bacterial or fungal superinfection.
If administration of drug continues more than 3 months, it is regularly recommended to control hematologic indicators, "hepatic" enzymes and a crystalluria.
At long reception of high doses of drug, for example, at treatment of a toxoplasmosis for the prevention of deficit of folic acid appoint folic acid or фолинат calcium.

Side effects:

The recommended Fansidar's doses usually well are transferred. As well as other drugs containing streptocides and Pyrimethaminum, Fansidar can cause the following by-effects or hypersensitivity reactions.

Co of the side of skin and its appendages: rash, itch, urticaria, reactions of a photosensitization and insignificant hair loss. Usually these phenomena are expressed poorly and independently disappear after drug withdrawal. In rare instances, in particular, at patients with hypersensitivity, skin reactions as a multiformny erythema, Stephens-Johnson's syndrome and a Lyell's disease, exfoliative dermatitis, a toxic epidermal necrolysis can develop such heavy (perhaps, life-threatening).

At emergence of skin reactions it is necessary to stop immediately administration of drug and to consult with the doctor.

From system of a hemopoiesis: seldom - a leukopenia, thrombocytopenia and megaloblastny anemia, usually asymptomatic, aplastic anemia, hemolitic anemia, a prothrombinopenia, a methemoglobinemia, an eosinophilia. Extremely seldom - an agranulocytosis or a purpura, as a rule, these changes are reversible after drug withdrawal.

From digestive tract: feeling of overflow, nausea; seldom - vomiting, diarrhea, stomatitis, a glossitis, abdominal pains, hepatitis, pancreatitis, a hepatocellular necrosis. The separate cases of tranzitorny increase in activity of liver enzymes, and also hepatitis on time matching Fansidar's appointment are described.

From a nervous system: a depression, spasms, an ataxy, hallucinations, a ring in ears, sleeplessness, nervousness, peripheral neuritis.

From urinary tract: a renal failure, intersticial nephrite, increase in an urea nitrogen and creatinine of plasma, a toxic nephrosis with an oliguria and an anury, a crystalluria.

Others: sometimes - the general weakness, apathy, fatigue, muscular weakness, headaches, dizziness, a fever, an injection of a conjunctiva and a sclera, medicinal fever and polyneurites, anaphylactoid reactions, periorbital hypostasis, arthralgias, a nodular periarteritis, a volchanochnopodobny syndrome; seldom - the pulmonary infiltrates similar to those at an eosinophilic or allergic alveolitis. If during treatment by Fansidar there are such symptoms as cough or short wind, drug should be cancelled. Also separate cases of a serum disease and an allergic pericardis, myocarditis are described.

Sulfonamides are similar on chemical structure to some goytrogena, diuretics (acetazoleamide and tiazida) and peroral glucose-lowering drugs. Due to the existence of cross sensitivity between the listed drugs the patients accepting sulfonamides seldom have a polyuria and a hypoglycemia.

Interaction with other medicines:

It is not necessary to appoint Fansidar along with Trimethoprimum or a combination of Trimethoprimum with streptocide as it can strengthen disturbance of exchange of folic acid with the subsequent development of hematologic side reactions.

There are messages on possible increase of frequency and strengthening of weight of side reactions at co-administration of Fansidar with chloroquine, in comparison with monotherapy by Fansidar.

Contraindications:

Hypersensitivity to streptocides or any other components of drug.
Documentary confirmed megaloblastny anemia as a result of deficit of folic acid.
Children's age up to 2 months.

For preventive (long) use: heavy renal or liver failure, blood dyscrasias, pregnancy and period of feeding by a breast.

With care
Pregnancy.
Pregnancy and period of feeding by a breast

Category C drug.
Limited experience of use of Fansidar for treatment or prevention at pregnant women does not demonstrate harmful effects of drug on a fruit of which it would be possible to be afraid on the basis of results of experiments on animals. Nevertheless, Fansidar it is possible to appoint at pregnancy only in the presence of absolute indications, having carefully weighed the expected advantage for mother and possible risk for a fruit.

Women of childbearing age have to use contraception methods during preventive use of Fansidar and within 3 months after the last reception.

Nursing mothers should not accept Fansidar, otherwise for the period of treatment transfer into artificial feeding is necessary.

Overdose:

Symptoms: appetite loss, headache, nausea, vomiting, excitement signs, sometimes spasms and hematologic changes (megaloblastny anemia, leukopenia, thrombocytopenia), glossitis, crystalluria.

Treatment: at acute poisonings - a gastric lavage or calling of vomiting, liquid completion; at spasms - parenteral administration of diazepam or barbiturates. Control of function of kidneys, a liver and repeated definitions of uniform elements of blood within 4 weeks after overdose. At identification of decrease in level of thrombocytes and leukocytes in blood appoint intramuscular administration of calcium of a folinat (Leykovorin) in a dose of 5-15 mg/days within 3 and more days.

Storage conditions:

To store at a temperature not above 35 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 500 mg/25 mg
On 3 tablets in strips from aluminum foil.
1 or 4 strips together with the application instruction place in a cardboard pack.