Hydroxychloroquine (Hydroxychloroquine sulfate) tablets p / o, No. 30

• Malaria - for the relief of acute attacks and the prevention of malaria caused by Plasmodium vivax, R. ovale and R. malariae, as well as sensitive strains of P. falciparum;

• for radical treatment of malaria caused by susceptible strains of P. falciparum.

• Rheumatoid arthritis, chronic juvenile chronic arthritis.

• Dermatological diseases - lupus erythematosus (systemic and discoid), dermatological diseases caused or exacerbated by exposure to sunlight (photodermatosis).

Assign inside. The tablets are taken with meals or washed down with a glass of milk. All doses are for hydroxychloroquine sulfate and are not equivalent to hydroxychloroquine base!

Suppression of malaria: For adults: 400 mg every seventh day.

For children over 6 years of age, the weekly dose is 6.5 mg / kg, but regardless of body weight, it should not exceed the adult dose.

If conditions permit, prophylactic treatment should be started 2 weeks before travel to the endemic area. If this is not possible, adults can be prescribed an initial double dose of 800 mg, children - 12.9 mg / kg (but not more than 800 mg), divided into 2 doses with an interval of 6 hours. Prophylactic treatment should be continued for 8 weeks after leaving the endemic zones.

Treatment for acute attacks of malaria : the initial dose for adults is 800 mg, then 400 mg after 6 or 8 hours and 400 mg for the next two days (only 2 g of hydroxychloroquine). As an alternative method, a single dose of 800 mg is possible. The dose for adults, as well as for children, can be calculated based on body weight (see below).

For children over the age of 6 years, the total dose of 32 mg / kg (but not exceeding 2 g) is applied for more than three days as follows: - the first dose - 12.9 mg / kg (but not more than 800 mg per dose); - the second dose - 6.5 mg / kg (but not more than 400 mg) 6 hours after the 1st dose; - the third dose - 6.5 mg / kg (but not more than 400 mg) 18 hours after the 2nd dose ; - fourth dose - 6.5 mg / kg (but not more than 400 mg) 24 hours after the third dose.

Rheumatoid diseases:

The drug has a cumulative effect, and it takes several weeks to achieve its therapeutic effect, while side effects can appear relatively early. If within 6 months the patient's condition does not improve, then the drug is canceled. The initial dose for adults is 400-600 mg / day, the maintenance dose is 200-400 mg / day.

Systemic and discoid lupus erythematosus:

Doses should not exceed 6.5 mg / kg of body weight (calculated by the 'ideal body weight) or 400 mg / day, the minimum effective dose should be prescribed or 200-400 mg / day. For light-sensitive dermatological conditions, treatment should be limited to periods of maximum light exposure. For adults, a dose of 400 mg / day may be sufficient.

1 film-coated tablet contains:

active substance : hydroxychloroquine sulfate - 200 mg;

excipients: croscarmellose sodium - 3.0 mg, magnesium stearate - 4.0 mg, colloidal silicon dioxide - 0.5 mg, microcrystalline cellulose (PH 102) - 92.5 mg;

film shell: hyprolose (hydroxypropyl cellulose), LF - 2.4 mg, hypromelose 2910 (hydroxypropyl methylcellulose) - 0.6 mg, macrogol (polyethylene glycol) 8000 - 1.8 mg, titanium dioxide (E 171) - 2.4 mg.

• Hypersensitivity to 4-aminoquinoline derivatives or any other component of the drug

• Maculopathy

• Antecedent maculopathy

• Children under 6 years of age (200 mg tablets are not adapted for use in children weighing less than 31 kg).

• Children's age, if long-term therapy is necessary (increased risk of developing toxic effects)

• Pregnancy (may be used for health reasons)

• Lactation period

• Congenital abnormalities such as galactose intolerance, lactase deficiency or glucose / galactose malabsorption syndrome.

Carefully

With retinopathy, visual disturbances (changes in visual fields, decreased visual acuity), concomitant use of medications that can cause visual disturbances, suppression of bone marrow hematopoiesis, psychosis (including in history), porphyria, psoriasis, concomitant use of medications that can cause skin reactions, deficiency of glucose-6-phosphate dehydrogenase, with renal or hepatic insufficiency (if necessary, the dose of hydroxychloroquine is selected while monitoring the plasma concentration), hepatitis, severe gastrointestinal diseases.

Composition

1 film-coated tablet contains:

active substance : hydroxychloroquine sulfate - 200 mg;

excipients: croscarmellose sodium - 3.0 mg, magnesium stearate - 4.0 mg, colloidal silicon dioxide - 0.5 mg, microcrystalline cellulose (PH 102) - 92.5 mg;

film shell: hyprolose (hydroxypropyl cellulose), LF - 2.4 mg, hypromelose 2910 (hydroxypropyl methylcellulose) - 0.6 mg, macrogol (polyethylene glycol) 8000 - 1.8 mg, titanium dioxide (E 171) - 2.4 mg.

Description

White or nearly white, capsule-shaped, biconvex, film-coated tablets with beveled edges, 'APO' engraving on one side and engraving 'HCQ 200' on the other. Fractured view: the core is white or almost white, surrounded by a shell of white or almost white.

Pharmacotherapeutic group

Antimalarial agent

Pharmacodynamics

Hydroxychloroquine in chemical structure and pharmacological action is close to chloroquine (hingamine). Hydroxychloroquine has several pharmacological effects that determine its therapeutic effect: interacts with sulfhydryl groups, changes the activity of enzymes (including phospholipase, NADH-cytochrome C-reductase, choline proteases and stabilizes lysosomal membranes, inhibits the formation of prostaglandins, inhibit chemotaxis and phagocytosis of polymorphonuclear cells. MalariaHydroxychloroquine actively suppresses the erythrocytic forms, as well as the gametes of P. vivax and P. malariae, which disappear from the blood almost simultaneously with the asexual forms, does not act on the gametes of P. falciparum. Hydroxychloroquine does not prevent recurrent attacks of malaria caused by P. vivax and P. malariae, since it is ineffective against the exoerythrocytic forms of the pathogen P. vivax, P. malariae and P. ovale, and also does not protect against infection with these microorganisms when taken prophylactically. At the same time, it reduces the severity of seizures, stops seizures and significantly lengthens the interval between the treatment course and the next seizure in a disease caused by these pathogens. In malaria caused by P. falciparum, it eliminates acute attacks and leads to a complete cure, unless we are talking about resistant variants of the parasite.The frequency of forms of P. falciparum resistant to derivatives of 4-aminoquinoline depends on the geographical location, most often observed in some regions of I, South Asia, Central and South America, East Africa, Oceania.Rheumatoid Arthritis and Lupus Erythematosus Hydroxychloroquine has an immunosuppressive and anti-inflammatory (discoid and systemic forms) and in acute and chronic rheumatoid arthritis. The exact mechanism of action in these diseases is unknown.

Pharmacokinetics

Being a weak base, hydroxychloroquine is rapidly and completely absorbed in the small intestine of the gastrointestinal tract (GIT). The rate and completeness of absorption may vary from person to person, but they are independent of food intake. In the blood, hydroxychloroquine is approximately 40 - 45% bound to plasma proteins (albumin and a 1-glycoprotein), the degree of availability is about 74% (from 70 to 80%). After a single oral ingestion of 200 mg hydroxychloroquine sulfate (1 tablet) in a healthy subject, the mean peak concentration (Cmax) is 244 ng / ml (188-427 ng / ml) 2-4.5 hours after ingestion (Tmax). The concentration of the drug in plasma is 7-8 times lower than in whole blood. The drug is easily distributed between body tissues, having a significant apparent volume of distribution (Vd) (5.50 ± 2.20 L and 44.0 ± 21.0 L at calculation for whole blood and plasma, respectively).The drug is concentrated in the brain, kidneys, liver, spleen, lungs and erythrocytes; its concentration in these organs is higher than in plasma. Both chloroquine and hydroxychloroquine show a high affinity for melanin; their highest concentrations are observed in the epidermis, retina, choroid and ciliary body of the eyeball. Small concentrations of hydroxychloroquine (about 3.2 ?g after 48 hours) were found in the breast milk of women who received 800 mg of the drug. Hydroxychloroquine is partially metabolized in the liver. In one pass, an insignificant part of the drug is metabolized (6%). In this case, a number of decomposition products are formed in the following sequence:so hydroxychloroquine show a high affinity for melanin; their highest concentrations are observed in the epidermis, retina, choroid and ciliary body of the eyeball. Small concentrations of hydroxychloroquine (about 3.2 ?g after 48 hours) were found in the breast milk of women who received 800 mg of the drug. Hydroxychloroquine is partially metabolized in the liver. In one pass, a small part of the drug is metabolized (6%). In this case, a number of decomposition products are formed in the following sequence:so hydroxychloroquine show a high affinity for melanin; their highest concentrations are observed in the epidermis, retina, choroid and ciliary body of the eyeball. Small concentrations of hydroxychloroquine (about 3.2 ?g after 48 hours) were found in the breast milk of women who received 800 mg of the drug. Hydroxychloroquine is partially metabolized in the liver. In one pass, a small part of the drug is metabolized (6%). In this case, a number of decomposition products are formed in the following sequence:In one pass, a small part of the drug is metabolized (6%). In this case, a number of decomposition products are formed in the following sequence:In one pass, an insignificant part of the drug is metabolized (6%). In this case, a number of decomposition products are formed in the following sequence:

• secondary amine, deethylhydrochloroquine or deethylchloroquine;

• primary amine, bisdeethylchloroquine;

• 4 '- aldehyde derivative, a small part is further reduced to alcohol;

• 4 '- carboxy derivative. The main decomposition product is deethylhydrochloroquine, which also has antiplasmodial activity. Hydroxychloroquine, conjugated to glucuronic acid, is found in bile.

After administering 200 mg of hydroxychloroquine sulfate orally to adult volunteers, the elimination half-life of the drug (t1 / 2) is, according to data for whole blood, 50 ± 16 days (about 32 days in plasma). Elimination of hydroxychloroquine from the body occurs in 2 stages. In the liver, about 30 - 60% of the drug that has entered the body is metabolized. A small amount is excreted by the kidneys - from 15 to 25% of the total; even a few months after the end of treatment, traces of the medication are found in the urine. After a single dose of 200 mg of hydroxychloroquine sulfate, the total urinary excretion of the unchanged substance and its metabolites after 86 days is 16% and 1.3% of the administered dose, respectively. Unabsorbed substance (up to 15-24%) is excreted through the gastrointestinal tract.An unspecified amount is deposited in epithelial cells and excreted when they are exfoliated. Some part of the dose taken is eliminated by hepatic metabolism, followed by excretion in the bile, as well as by the renewal of pigmented epithelial tissues, for example, skin. A number of works indicate that from 21 to 47% of the drug is released unchanged.

Indications

• Malaria - for the relief of acute attacks and the prevention of malaria caused by Plasmodium vivax, R. ovale and R. malariae, as well as sensitive strains of P. falciparum;

• for radical treatment of malaria caused by susceptible strains of P. falciparum.

• Rheumatoid arthritis, chronic juvenile chronic arthritis.

• Dermatological diseases - lupus erythematosus (systemic and discoid), dermatological diseases caused or exacerbated by exposure to sunlight (photodermatosis).

Contraindications

• Hypersensitivity to 4-aminoquinoline derivatives or any other component of the drug

• Maculopathy

• Antecedent maculopathy

• Children under 6 years of age (200 mg tablets are not adapted for use in children weighing less than 31 kg).

• Children's age, if long-term therapy is necessary (increased risk of developing toxic effects)

• Pregnancy (may be used for health reasons)

• Lactation period

• Congenital abnormalities such as galactose intolerance, lactase deficiency or glucose / galactose malabsorption syndrome.

Carefully

With retinopathy, visual disturbances (changes in visual fields, decreased visual acuity), concomitant use of medications that can cause visual disturbances, suppression of bone marrow hematopoiesis, psychosis (including in history), porphyria, psoriasis, concomitant use of medications that can cause skin reactions, deficiency of glucose-6-phosphate dehydrogenase, with renal or hepatic insufficiency (if necessary, the dose of hydroxychloroquine is selected while monitoring the plasma concentration), hepatitis, severe gastrointestinal diseases.

Methods of administration and dosage

Assign inside. The tablets are taken with meals or washed down with a glass of milk. All doses are for hydroxychloroquine sulfate and are not equivalent to hydroxychloroquine base!

Suppression of malaria: For adults: 400 mg every seventh day.

For children over 6 years of age, the weekly dose is 6.5 mg / kg, but regardless of body weight, it should not exceed the adult dose.

If conditions permit, prophylactic treatment should be started 2 weeks before travel to the endemic area. If this is not possible, adults can be prescribed an initial double dose of 800 mg, children - 12.9 mg / kg (but not more than 800 mg), divided into 2 doses with an interval of 6 hours. Prophylactic treatment should be continued for 8 weeks after leaving the endemic zones.

Treatment for acute attacks of malaria : the initial dose for adults is 800 mg, then 400 mg after 6 or 8 hours and 400 mg for the next two days (only 2 g of hydroxychloroquine). As an alternative method, a single dose of 800 mg is possible. The dose for adults, as well as for children, can be calculated based on body weight (see below).

For children over the age of 6 years, the total dose of 32 mg / kg (but not exceeding 2 g) is applied for more than three days as follows: - the first dose - 12.9 mg / kg (but not more than 800 mg per dose); - the second dose - 6.5 mg / kg (but not more than 400 mg) 6 hours after the 1st dose; - the third dose - 6.5 mg / kg (but not more than 400 mg) 18 hours after the 2nd dose ; - fourth dose - 6.5 mg / kg (but not more than 400 mg) 24 hours after the third dose.

Rheumatoid diseases:

The drug has a cumulative effect, and it takes several weeks to achieve its therapeutic effect, while side effects can appear relatively early. If within 6 months the patient's condition does not improve, then the drug is canceled. The initial dose for adults is 400-600 mg / day, the maintenance dose is 200-400 mg / day.

Systemic and discoid lupus erythematosus:

Doses should not exceed 6.5 mg / kg of body weight (calculated by the 'ideal body weight) or 400 mg / day, the minimum effective dose should be prescribed or 200-400 mg / day. For light-sensitive dermatological conditions, treatment should be limited to periods of maximum light exposure. For adults, a dose of 400 mg / day may be sufficient.

Side effects

On the part of the organs of vision:rarely - retinopathy with changes in pigmentation and visual field defects. At an early stage, it is reversible after discontinuation of the drug. If the drug is not discontinued in time, there is a risk of progression of retinopathy even after discontinuation of the drug. Retinal changes may be asymptomatic at first, or may present with paracentral, pericentral, or transient scotoma and color vision disorders. Changes in the cornea, including edema and opacity, are possible. They may be asymptomatic or cause disturbances such as halos, blurred vision, or photophobia. These changes can be temporary or reversible when treatment is stopped. Blurred vision is caused by a violation of accommodation, it is dose-dependent and reversible. With prolonged use of large doses, optic nerve atrophy, keratopathy, and ciliary muscle dysfunction may be possible.On the part of the hearing organs: tinnitus, hearing loss, hearing loss. On the part of the skin: rarely - skin rash, itching, changes in the pigmentation of the skin and mucous membranes, discoloration of the hair and alopecia. These changes usually resolve quickly after stopping treatment. Bullous rash may occur, including very rare cases of erythema polymorphism and Stevens-Johnson syndrome, photosensitivity, and isolated cases of exfoliative dermatitis. Very rarely - acute generalized exanthematous pustular rash, which must be distinguished from psoriasis, although the drug can exacerbate psoriasis. This can be associated with fever and leukocytosis. After discontinuation of the drug, the prognosis is usually good. From the side of the central nervous system:occasionally dizziness, headache, nervousness, emotional lability, psychosis, convulsions, ataxia, irritability are noted. From the side of the cardiovascular system: cardiomyopathy (rarely), atrioventricular block (AV block), decreased myocardial contractility, myocardial hypertrophy; with long-term therapy with large doses - myocardial dystrophy. If conduction disturbances (AV block, Giss bundle block) and hypertrophy of both ventricles are detected, chronic intoxication should be suspected. On the part of the hematopoietic organs: rarely - inhibition of bone marrow hematopoiesis, aplastic anemia, agranulocytosis, thrombocytopenia, hemolytic anemia (in patients with glucose-6-phosphate dehydrogenase deficiency), aggravation of porphyria.On the part of the musculoskeletal and nervous system: skeletal muscle myopathy or neuromyopathy is likely, leading to progressive weakness and atrophy of the proximal muscle groups. Myopathy is usually reversible after discontinuation of the drug, but it may take several months for full recovery. Mild sensory changes, suppression of the tendon reflex, and abnormal nerve conduction may occur. After discontinuation of the drug, conductivity is usually restored. From the digestive system: nausea, vomiting (rarely), loss of appetite, abdominal pain of a spastic nature, diarrhea. From the liver:hepatotoxicity (impaired liver function, liver failure). In some cases, there may be changes in the indicators of functional liver function tests, several cases of suddenly developed liver failure have been reported. Others: weight loss.

Overdose

Overdose is especially dangerous in young children, even taking 1-2 g of the drug can be fatal!

Symptoms: headache, drowsiness, stupor, coma, ataxia, insomnia, agitation, hyperreflexia, muscle rigidity, choreoathetosis, convulsions, decreased blood pressure, tachycardia, arrhythmias, intraventricular block, AV block, heart failure, cyanosis, fever, body temperature, midriasis oliguria, depression of the respiratory center, respiratory arrest. Symptoms develop 4 hours after overdose, reach a maximum after 24 hours and last 4 to 6 days. Treatment:gastric lavage (to clean wash water); the appointment of activated carbon (in a dose 5 times higher than the dose of the drug); forced diuresis and alkalinization of urine (for example, ammonium chloride to a urine pH of 5.5 - 6.5) increase the excretion of 4-aminoquinoline in the urine; symptomatic therapy (including the appointment for convulsions - diazepam; anti-shock therapy). It is necessary to control the concentration of sodium in the blood serum and constant medical supervision for at least 6 hours after the relief of symptoms. Monitoring of cardiovascular activity (ECG) for 5 days is indicated, since a relapse can occur after 48 hours or later. Administration of physostigmine is contraindicated due to the increased risk of seizures. Hemodialysis and forced diuresis are ineffective.

Interaction

Increases the side effects of glucocorticoids, salicylates, quinidine-like antiarrhythmics, hemato-, hepato- and neurotoxic drugs. The simultaneous use of hydroxychloroquine and digoxin can cause an increase in the level of digoxin in the blood serum, therefore, in patients receiving combination therapy, the level of digoxin in serum, if necessary, reduce the dose of digoxin. Increases the plasma concentration of penicillamine and the risk of its side effects from the hematopoietic organs, urinary system and skin reactions. May enhance the effect of hypoglycemic agents, as a result of which it may be necessary to reduce the dose of insulin and antidiabetic drugs. Hydroxychloroquine can enter into some of the known interactions of chloroquine, ie, it is possible to enhance: - the blocking effect of aminoglycoside antibiotics on neuromuscular transmission; suppression of its metabolism with cimetidine, which can increase the concentration of the drug in the blood plasma; - antagonism of the action of neostigmine and pyridostigmine ; - decrease in the formation of antibodies in response to primary immunization with a diploid cell vaccine against rabies. With the simultaneous use of hydroxychloroquine and antacids, the interval between doses should be at least 4 hours (decrease in absorption).Alkaline drinks and alkalis accelerate the elimination of hydroxychloroquine from the body.

special instructions

ѕеред началом и во врем¤ терапии необходимо проводить не реже 1 раза в 6 мес¤цев офтальмологическое обследование (применение суточных доз более 6,5 мг/кг увеличивает риск повреждени¤ сетчатки).ѕри возникновении неблагопри¤тных реакций со стороны зрени¤ (снижение остроты зрени¤, изменение цветовоспри¤ти¤ и др.) препарат следует немедленно отменить (изменени¤ сетчатки могут прогрессировать даже после отмены препарата).ѕревышение рекомендуемой суточной дозы повышает риск повреждени¤ сетчатки и ускор¤ет этот процесс. ѕеред началом курса лечени¤ препаратом следует провести офтальмоскопию обоих глаз дл¤ исследовани¤ остроты зрени¤, цветового зрени¤ и оптического пол¤. ¬последствии такое обследование необходимо повтор¤ть, как минимум, ежегодно. ?сли зрение ухудшаетс¤ (острота зрени¤, цветовое зрение и др.), следует немедленно отменить препарат. Ѕольные должны находитьс¤ под наблюдением, так как изменени¤ сетчатки и нарушение зрени¤ могут прогрессировать даже после отмены лечени¤. ѕрименение при беременности возможно только по жизненным показани¤м (в терапевтических дозах может вызывать у плода или младенца повреждени¤ ?Ќ— (в т.ч. ототоксичность, слуховую и вестибул¤рную, вплоть до глухоты), ретинальное кровотечение и патологическую пигментацию ретины (младенцы особенно чувствительны к токсическим эффектам 4-аминохоли- нов).–екомендуетс¤ соблюдать осторожность при лечении пациентов с заболевани¤ми печени и почек. ћожет возникнуть необходимость в снижении дозы препарата дл¤ уменьшени¤ его токсического воздействи¤ на эти органы.— осторожностью примен¤ют препарат при лечении пациентов с желудочно- кишечными, неврологическими или гематологическими заболевани¤ми; больных, чувствительных к хинину и страдающих дефицитом глюкозо-6- фосфат-дегидрогеназы, порфирией и псориазом. Ѕольным, принимающим препарат в течение длительного времени, следует периодически проводить развернутый анализ крови. ѕри вы¤влении отклонений от нормы препарат отмен¤ют. ” больных, длительно принимающих препарат, необходимо периодически проводить исследование функции скелетных мышц и сухожильных рефлексов. ?сли при приеме препарата возникает мышечна¤ слабость, препарат следует отменить. ќбследование должно быть более частым и в таких ситуаци¤х: суточна¤ доза препарата превышает 6,5 мг/кг идеальной (не повышенной) массы тела; реальна¤ масса, используема¤ дл¤ установки дозы дл¤ тучных больных, может привести к передозировке; почечна¤ недостаточность; обща¤ доза превышает 200 мг; больные пожилого возраста (старше 65 лет); сниженна¤ острота зрени¤.

Impact on the ability to drive vehicles. Wed and fur.

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in a dry, dark place at a temperature of 15 to 30 ? C,

Keep out of the reach of children.

Shelf life

3 years.

Do not use after the expiration date stated on the package.

Conditions of dispensing from pharmacies

On prescription