PLAKVENIL

Active material: Gidroksixloroxin
When ATH: P01BA02
CCF: The 4-aminoquinoline. Antimalarial drug and amebitsidny. Immunosuppressant
ICD-10 codes (testimony): B50, B51, B52, L56.2, L93.0, M05, M08, M32
When CSF: 05.02.03
Manufacturer: Sanofi-Synthelabo Ltd. (Great Britain)

Pharmaceutical form, composition and packaging

Pills, coated white, lenticular, labeled “HCQ” on one side and “200” – another; of presentations – white.

Excipients: lactose monohydrate, povidone K25, corn starch, magnesium stearate, Purified water.

The composition of the shell: Opadry OY-L-28900 (gipromelloza, Titanium dioxide, macrogol 4000, lactose monohydrate, Purified water)

10 PC. – blisters (6) – packs cardboard.

Pharmacological action

The antimalarial. Hydroxychloroquine have several different pharmacological properties, which may be responsible for its therapeutic effect: reacting with sulfhydryl groups, changes in the activity of enzymes (incl. phospholipase, Sodium adenosine diphosphate-N-cytochrome (OVER-N-cytochrome) C reductase, cholinesterase, hydrolases and proteases); DNA binding; stabilization of lysosomal membranes; Inhibition of prostaglandin synthesis, chemotaxis and phagocytosis of polymorphonuclear cells; decrease the synthesis of interleukin-1 by monocytes and neutrophils release suleroksidaniona. The intracellular concentration and increasing pH in lysosomes explains how Antiprotozoal, and antirheumatic activity of hydroxychloroquine.

Preparation, actively inhibits asexual erythrocytic forms, а также гаметы Plasmodium vivax и Plasmodium malariae, which disappear from the blood almost simultaneously with asexual. In Plasmodium falciparum gametes Plaquenil is not valid. The drug has also immunosuppressive and anti-inflammatory effect.

Pharmacokinetics

Absorption

After oral hydroxychloroquine quickly and almost completely absorbed from the gastrointestinal tract. T_max is 2-4.5 no, C_max after oral dose 155 mg – 948 ng / ml, after oral dose 310 mg – 1895 ng / ml.

Distribution

Plasma protein binding – 45%. V_d is 5-10 l / kg. It is well distributed in the body, accumulating in blood cells, liver, light, kidney, in the retina. It accumulates in tissues with a high level exchange – liver, kidney, light, spleen, in these organs in a plasma concentration of greater than 200-700 time; CNS, erythrocytes, leukocytes and tissues, rich melanin. It penetrates through the placental barrier. In small amounts determined in breast milk.

Metabolism and excretion

In the liver, hydroxychloroquine partially converted to active metabolites and leaded displayed in the kidneys, and – the bile.

Excretion of the drug is slow. T_1/2 is about 50 days (whole blood) and 32 day (plasma).

Testimony

- Rheumatoid arthritis;

- Juvenile chronic arthritis;

- Lupus erythematosus (systemic and discoid);

- Photodermatitis.

Malaria (except for chloroquine-resistant cases):

- For the treatment of acute attacks and for suppression of malaria, caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, as well as sensitive shtammamiPlasmodium falciparum;

- For the radical treatment of malaria, caused by susceptible strains of Plasmodium falciparum.

Dosage regimen

Plaquenil is intended for oral use. The drug is taken with food or a glass of milk.

All doses given per hydroxychloroquine sulfate and equivalent doses base.

At rheumatic diseases therapeutic activity is observed in drug accumulation. For the development of a therapeutic drug to take effect within a few weeks, whereas the side effects may occur relatively early. Adequate therapeutic effect develops after a few months of taking the drug. If objective improvement in the patient's condition is not observed for 6 months of treatment, the drug should be discontinued.

At revmatoidnom ARTHRO to Adult starting dose is 400-600 mg / day, maintenance dose – 200-400 mg / day.

At juvenile chronic arthritis dose should not exceed 6.5 mg / kg body weight or 400 mg / day (should choose the lowest effective dose).

At systemic and discoid lupus erythematosus to Adult starting dose is 400-800 mg / day, maintenance dose – 200-400 mg / day.

At fotodermatite treatment should be limited to a period of maximum light exposure. To Adult It may be sufficient 400 mg / day.

To prevention of malaria adult the drug is prescribed in a dose 400 mg in the same day of the week. To children weekly dose is overwhelming 6.5 mg / kg body weight (to calculate the ideal body weight is taken), but, irrespective of body weight, should not exceed the adult dose.

If conditions allow, the preventive therapy should start 2 Week entry into endemic zone. If this is not possible, then adult You can assign an initial double dose 800 mg, children – 12.9 mg / kg (but not more 800 mg), dividing by 2 receiving at intervals 6 no.

Preventive therapy should be continued for 8 weeks after leaving the endemic area.

To treatment of acute attacks of malaria drug prescribed adult at an initial dose 800 mg, then 400 mg after 6 or 8 no, further – by 400 mg for 2 next days; total dose – 2 g. A single administration of a dose of 800 mg was also found to be effective.

The dose for adults as well, as for children, It can be calculated based on body weight.

Babies drug administered in a total dose 32 mg / kg (but not more 2 g) during 3 days as follows:

the first dose - 12.9 mg / kg (no more than a single dose of 800 mg);

a second dose - 6.5 mg / kg (no more 400 mg) through 6 hours after the first dose;

third dose - 6.5 mg / kg (no more 400 mg) through 18 hours after the second dose;

fourth dose - 6.5 mg / kg (not exceeding 400 mg) through 24 hours after the third dose.

For maintenance therapy to use the minimum effective dose, not exceeding 6.5 mg / kg / day (values ​​are taken for calculation of ideal body weight).

Side effect

On the part of the organ of vision: rarely – Retinopathy with changes in pigmentation and visual field defects. The early form of retinopathy is reversible when you stop treatment with hydroxychloroquine. If retinopathy is saved, there may be a risk of irreversible destruction of the retina even after discontinuation of treatment. Retinal changes may be asymptomatic, or manifest scotoma.

Described corneal changes, including swelling and blurred. They may be asymptomatic or cause such violations, as the appearance of “Shroud” before the eyes or photophobia. These changes can be reversed by cessation of treatment.

Perhaps decreased vision due to violations of the accommodation, is dose-dependent and reversible.

Dermatological reactions: possible skin rashes, itch, changes in pigmentation of the skin and mucous membranes, obestsvechivanie Volos and alopecia. These reactions usually pass quickly when you stop treatment. Possible exacerbation of psoriasis; rarely – photosensitivity; very rare cases of pemphigus (to be distinguished from psoriasis), sometimes accompanied by fever and hyperleukocytosis. After discontinuation of the drug side effects are usually reversible.

Allergic reactions: possible bullous rash, including very rare cases of erythema multiforme and Stevens-Johnson syndrome.

From the digestive system: nausea, diarrhea, anorexia, abdominal pain and, rarely, vomiting. These reactions usually take place immediately after dose reduction or discontinuation of treatment. With prolonged use and high doses can hepatotoxicity; there are reports of isolated cases of liver dysfunction; isolated cases suddenly developed liver failure. In some cases, – abnormal liver function; in a few cases – suddenly developed liver failure.

From the central and peripheral nervous system: rarely – dizziness, noise in ears, hearing loss, headache, irritability, emotional instability, psychoses, convulsions, muscular weakness, ataxia; in some cases – myopathy of skeletal muscle or neyromiopatiya, leading to progressive weakness and atrophy of proximal muscle groups. Myopathy may be reversible after drug withdrawal, but full recovery may take several months. Possible weak sensory changes, suppression of tendon reflexes and decreased nerve conduction.

Cardio-vascular system: rarely – cardiomyopathy, reduction of conductivity and contractility; long-term use in high doses – miokardiodistrofija.

In case of detection of myocardial hypertrophy and ventricular conduction disturbances (AV блокада) it should be borne in mind the possibility of chronic intoxication (these situations require removal of the drug).

From the hematopoietic system: rarely – suppression of bone marrow hematopoiesis. Hydroxychloroquine may worsen porphyria.

Contraindications

- Maculopathy history;

- Children's age, if necessary, long-term therapy;

- Children up to age 6 years (tablets 200 mg is not intended for children weighing less than 35 kg);

- Hypersensitivity to the 4-aminoquinoline.

FROM caution should take the drug if retinopathy (maculopathy when the drug is contraindicated), violation of bone marrow hematopoiesis, psychosis (incl. history), porfirii, psoriaze, definition, glucose-6-fosfatdegidrogenazы, with hepatic and / or renal insufficiency, gepatite.

Pregnancy and lactation

Data on the use of the drug during pregnancy is limited. Hydroxychloroquine crosses the placental barrier. It should be noted, that the 4-aminoquinolines, in therapeutic doses may cause damage to the CNS, incl. ototoxicity (auditory and vestibular toxicity, congenital deafness), retinal hemorrhage and abnormal retinal pigmentation. Considering this, Avoid the use of hydroxychloroquine during pregnancy except in cases, when the potential benefits of treatment to the mother outweighs the potential risk to the fetus.

You should carefully consider the need to use during lactation (breast-feeding), tk. shows, that hydroxychloroquine in small amounts excreted in breast milk, as well known, that infants are particularly sensitive to the toxic effects of 4-aminoquinolines.

Cautions

The frequency of retinopathy, if you do not exceed the recommended daily dose, slight. Exceeding the recommended daily dose increases the risk of retinal damage and speeds up the process.

Before the course of treatment should be to conduct a thorough examination of both eyes. The survey should include a definition of visual acuity, color vision and visual fields of study. During therapy, the survey should be carried out not less 1 times a 6 months.

More frequent inspection should be carried out in the following cases:

- The daily dose, exceeding 6.5 mg / kg of ideal (not increased) body weight (in calculating the dose, taking into account the absolute body weight in obese possible overdose patients);

- Renal failure;

- Cumulative dose more 200 g;

- Elderly patients;

- Reduced visual acuity.

If there are negative changes in vision (incl. reduced visual acuity, changes in color vision), immediately remove the drug. Patients require prolonged observation, tk. possible progression of these disorders. Retinal changes may progress even after discontinuation of the drug.

The caution is recommended to use the drug in patients with liver and kidneys. Because the drug affects the liver and kidneys, may require dose reduction.

C caution should primenenyat on patients, suffering from gastrointestinal, neurological or hematological diseases, hypersensitivity to quinine.

When long-term therapy should be periodically complete blood count, when a violation of hydroxychloroquine should be abolished.

It should not be prescribed to patients with congenital galactose intolerance, lapp lactase deficiency or malabsorption syndrome glucose / galactose.

Children are especially vulnerable to the toxic effects of 4-aminoquinolines, therefore patients should be especially careful to watch the, to remove from places hydroxychloroquine, Available for kids.

All patients, receiving long-term medication, We must be periodically examined by a neurologist in relation to skeletal muscle function and severity of tendon reflexes. If there is a weakness, the drug should be discontinued.

Gidroksihlorohin neéffektiven in otnoshenii chloroquine-rezistentnyh strains of Plasmodium faiciparum, as well as activity against Plasmodium vivax form vneeritrotsitnyh, Plasmodium ovale and Plasmodium malariae and therefore can not prevent infection by these microorganisms in appointing him as a preventive measure, and can not prevent recurrence of the disease, caused by them.

Effects on ability to drive vehicles and management mechanisms

Patients should exercise caution when driving or performing transport works, requiring attention, tk. hydroxychloroquine may violate accommodation and cause blurred vision. If this condition persists itself, the dose can be temporarily reduced.

Overdose

Overdose 4-aminoquinolines is especially dangerous in children, even when use of the drug in a dose 1-2 g possible death.

Symptoms: headache, visual impairment, collapse, convulsions, kaliopenia, rhythm and conduction, followed by cardiac arrest and respiratory system. Unnecessarily. These effects may occur immediately after taking an overdose of the drug, require emergency treatment. Should take immediate steps to remove the drug from the stomach, designate activated carbon in a dose, at least 5 times greater than that adopted by the dose of the drug, that may suspend further removals (with the introduction of coal into the stomach through the probe for 30 minutes after taking the drug). To the appointment of diazepam parenteral (Describes reducing cardiotoxicity of chloroquine on his background).

Treatment: Optionally should be IVL and protivosokovu therapy. Needs constant medical supervision for at least 6 hours after cupping overdose symptoms.

Drug Interactions

While applying gidroksihlorohina and digoxin may increase the concentration of Digoxin in serum (When this combination should carefully monitor the concentration of Digoxin in serum).

Because hydroxychloroquine may exacerbate the effects of hypoglycemic drugs, You may need to reduce the dose of insulin or gipoglikemicakih drugs.

Interactions are also possible gidroksihlorohina sulfate with antibiotics group aminoglikozidov (inhibition of neuromuscular transmission); with cimetidine (inhibition of metabolism of gidroksihlorohina sulfate, that can lead to increase its concentration in the blood plasma); antagonism action against neostigmina and piridostigmina; reduction in antibody production in response to a primary intradermal immunization of human diploid cell rabies vaccine.

With simultaneous use of antacids the interval between doses should be at least 4 no, tk. may reduce the absorption of the drug.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or below 25 ° C. Shelf life – 3 year.