Pyrimethamine + Sulfadoxine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Other synthetic antibacterial agents

Included in the formulation

Fancidar®

pills inwards

Hoffmann-La Roche Ltd. Switzerland

АТХ:

P.01.B.D.51 Pyrimethamine in combination with other drugs

Pharmacodynamics:

The pharmacological action is antiprotozoal, antimalarial.

It acts on asexual intra-erythrocytic forms of malarial plasmodia. Due to the synergistic effect of the two components of the drug - sulfadoxine and pyrimethamine - the activity of two enzymes involved in the biosynthesis of folinic acid in parasites is suppressed.

The drug is active against strains resistant to chloroquine. However, in South-East Asia and South America strains P. falciparum, which developed resistance to the drug; such strains are also found in East and Central Africa, so in these regions Pyrimethamine + Sulfadoxine should be used with caution.

Effective for infections caused by Toxoplasma gondii and Pneumocystis carinii.

Pharmacokinetics:

Suction. After taking one tablet, the maximum plasma concentrations of pyrimethamine (about 0.2 mg / l) and sulfadoxine (about 60 mg / l) are reached after about 4 hours.

Distribution. The volume of distribution of sulfadoxine and pyrimethamine is 0.14 and 2.3 l / kg, respectively.If you take 1 tablet a week (the recommended dose for the prevention of malaria in adults), you can expect that the average equilibrium plasma concentrations of pyrimethamine will be 0.15 mg / l (after about 4 weeks), and sulfadoxine - 98.4 mg / l (about 7 weeks). Binding to proteins is approximately 90% for both pyrimethamine and sulfadoxine. Pyrimethamine and sulfadoxine penetrate the placental barrier and are excreted in breast milk.

Metabolism. About 5% of sulfadoxine is in the blood in the form of acetylated metabolite, about 2-3% - in the form of glucuronide. Pyrimethamine undergoes biotransformation with the formation of several metabolites.

Excretion. Both components have a relatively long half-life. Its average value for pyrimethamine is about 100 hours, and for sulfadoxine it is about 200 hours. how pyrimethamine, and sulfadoxine are excreted mainly through the kidneys.

Pharmacokinetics in special groups of patients. In patients with malaria, pharmacokinetic parameters after a single admission may differ from those in healthy individuals, depending on the population.

In patients with renal insufficiency, slow release of the drug components can be expected.

Indications:

Malaria, especially caused by P. falciparum, resistant to other antimalarial drugs. The prevention of malaria with the drug is carried out only in regions endemic to P. falciparum, which are sensitive to the combination of sulfadoxine and pyrimethamine, as well as in the case of contraindications or the absence of other antimalarial drugs.

Parasitic infections: treatment of toxoplasmosis and prevention of pneumocystis infection.

ICD-10

I.B50-B64.B54 Malaria, unspecified

I.B50-B64.B52 Malaria caused by Plasmodium malariae

I.B50-B64.B51 Malaria caused by Plasmodium vivax

I.B50-B64.B50 Malaria caused by Plasmodium falciparum

I.B50-B64.B58 Toxoplasmosis

I.B50-B64.B59 Pneumocystis

Contraindications:Hypersensitivity; pregnancy (I trimester); the possibility of conception during the period of treatment; lactation period; early infancy (up to 2 months); hepatic and / or renal insufficiency; oppression of bone marrow hematopoiesis.

Carefully:Pregnancy. If it is necessary to prescribe the drug to children over the age of 2 months, you should carefully study the instructions for using the drug.

Pregnancy and lactation:

Contraindications: pregnancy (I trimester); the possibility of conception during the period of treatment; lactation period.

Recommendations FDA category C. The limited experience of using the drug for treatment or prevention in pregnant women does not indicate a harmful effect of the drug on the fetus, which could be feared on the basis of the results of animal experiments. Nevertheless, the drug can be prescribed during pregnancy only if there are absolute indications, carefully weighing the expected benefit to the mother and the possible risk to the fetus.

Women of childbearing age should use contraceptive methods during the prophylactic use of the drug and within 3 months after the last intake.

Nursing mothers should not take the medication, otherwise a translation for artificial feeding is necessary for the duration of treatment.

Dosing and Administration:

Inside after eating, without chewing and washing with a lot of water. For treatment of malaria appoint single doses: adults - 7.5 ml solution in ampoules or 3 tablets (pyrimethamine 25 mg + sulfadoxine 500 mg), children 10-14 years - 5 ml or 2 tablets, children 7-9 years - 3.5 ml or 1.5 tablets, children 4-6 years - 2.5 ml or 1 tablet, Children under 4 years of age - 1-1.5 ml or 1/2 tablet.

The solution in the ampoules is administered intramuscularly deep.To achieve a rapid therapeutic effect and prevent relapse, it is recommended to additionally prescribe quinine within 3-7 days.

For the prevention of malaria, patients with partial immunity are given a single dose of 2-3 tablets once every 4 weeks; patients who lack immunity are prescribed 1 tablet once a week. Children, depending on age, are prescribed 1 / 2-2 tablets once in 4 weeks (with partial immunity) or 1 / 2-1,5 tablets once every 2 weeks (without immunity).

The first dose of the drug is taken 1 week before the departure to the endemic area, the reception continues for the entire period of stay in the area, as well as 6 more weeks after the return.

When toxoplasmosis adults - 2 tablets once a week for 6-8 weeks (with CNS - in combination with spiramycin at a dose of 3 g per day for 3-4 weeks).

For the prevention of pneumonia, infants and young children are prescribed 40 mg / kg (calculated according to the content of sulfadoxine) 1 every 2 weeks; adults - 1-2 tablets a week.

Side effects:

The recommended doses are usually well tolerated. Like other drugs containing sulfonamides and pyrimethamine, can cause the following side effects or hypersensitivity reactions.

From the side skin and its appendages: rashes, itching, hives, photosensitization reactions and slight hair loss. Usually, these phenomena are poorly expressed and disappear on their own after the drug is discontinued. In rare cases, in particular, in patients with hypersensitivity, such severe (possibly life-threatening) skin reactions as erythema multiforme, Stevens-Johnson syndrome and Lyell's syndrome, exfoliative dermatitis, toxic epidermal necrolysis may develop. If skin reactions occur, stop taking the medication immediately and consult a doctor.

From the side hematopoiesis system: rarely - leukopenia, thrombocytopenia and megaloblastic anemia, usually asymptomatic, aplastic anemia, hemolytic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia. It is extremely rare - agranulocytosis or purpura, as a rule, these changes are reversible after discontinuation of the drug.

From the side gastrointestinal tract: sensation of overflow, nausea; rarely - vomiting, diarrhea, stomatitis, glossitis, abdominal pain, hepatitis, pancreatitis, hepatocellular necrosis.Some cases of transient increase in hepatic enzyme activity, as well as hepatitis, coincide with the appointment of the drug.

From the side nervous system: depression, convulsions, ataxia, hallucinations, ringing in the ears, insomnia, nervousness, peripheral neuritis.

From the side urinary tract: renal failure, interstitial nephritis, increased urea nitrogen and plasma creatinine, toxic nephrosis with oliguria and anuria, crystalluria.

Other: sometimes - general weakness, apathy, fatigue, muscle weakness, headaches, dizziness, chills, injection of conjunctiva and sclera, drug fever and polyneuritis, anaphylactoid reactions, periorbital edema, arthralgia, nodular periarteritis, lupus-like syndrome; rarely - pulmonary infiltrates, similar to those with eosinophilic or allergic alveolitis. If during treatment such symptoms as cough or shortness of breath appear, the drug should be discarded. Separate cases of serum sickness and allergic pericarditis, myocarditis are also described.

Sulfonamides are similar in chemical structure to some goitrogens, diuretics (acetazolamide and thiazides) and oral hypoglycemic agents. Due to the presence of cross-sensitivity between the listed drugs, polyuria and hypoglycemia rarely occur in patients taking sulfonamides.

Overdose:

Symptoms: loss of appetite, headache, nausea, vomiting, signs of arousal, sometimes convulsions and hematologic changes (megaloblastic anemia, leukopenia, thrombocytopenia), glossitis, crystalluria.

Treatment: when acute poisoning - gastric lavage or vomiting, replenishment of fluid; with convulsions - parenteral administration of diazepam or barbiturates. Control the function of the kidneys, liver and repeated determination of the formed elements of the blood within 4 weeks after an overdose. When a decrease in the level of platelets and leukocytes in the blood is indicated, intramuscular administration of calcium folinate (Leucovorin) in a dose of 5-15 mg per day for 3 or more days.

Interaction:

Incompatible with trimethoprim or combinations of trimethoprim and sulfonamides (possibly increased folate deficiency with appropriate hematological changes).

When combined with chloroquine, side effects can be observed more often and in a more severe form.

Special instructions:

Therapy with the drug for more than 3 months is carried out under regular control of the blood picture. With prolonged use, simultaneous administration of folic acid is recommended.

Patients should be informed that sore throat, fever, cough, shortness of breath or purpura may be the first signs of serious side effects. In particular, the drug should be immediately discontinued at the first signs of skin rash, a significant reduction in the number of blood cells, bacterial or fungal superinfection, when there is a cough or dyspnea on the background of treatment.

Not recommended for routine malaria prevention.

Excessively long exposure to the sun should be strictly avoided.

Instructions

Pyrimethamine + Sulfadoxine (Pyrimethaminum + Sulfadoxinum)