Hydroxychloroquine (Hydroxychloroquine)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceHydroxychloroquineHydroxychloroquine
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    • Dosage form: & nbspfilm-coated tablets
    Composition:
    1 tablet, film-coated, contains:
    active substance - Hydroxychloroquine sulfate - 200 mg;
    Excipients: croscarmellose sodium 3.0 mg, magnesium stearate 4.0 mg, silicon dioxide colloid 0.5 mg, cellulose microcrystalline (PH 102) 92.5 mg;
    film sheath: giprolase (hydroxypropylcellulose), LF - 2.4 mg, hypromelose 2910 (hydroxypropylmethylcellulose) 0.6 mg, macrogol (polyethylene glycol) 8000 1.8 mg, titanium dioxide (E 171) 2.4 mg.
    Description:White or almost white capsular shaped, biconvex, beveled to the edge of a tablet covered with a film sheath, engraved with "ARO" on one side and engraved "HCQ 200" on the other.
    View in fracture: the core is white or almost white, surrounded by a white or almost white shell.
    Pharmacotherapeutic group:Anti-malarial drug
    ATX: & nbsp

    P.01.B.A.02   Hydroxychloroquine

    Pharmacodynamics:
    Hydroxychloroquine by chemical structure and pharmacological action is close to chloroquine (hingamine).
    Hydroxychloroquine has several pharmacological effects, which determine its therapeutic effect: it interacts with sulfhydryl groups, changes the activity of enzymes (including phospholipase, NADH-cytochrome C-reductase, cholinesterase, proteases and stabilizes lysosomal membranes, inhibits the formation of prostaglandins, inhibits chemotaxis and phagocytosis polymorphonuclear cells.
    Malaria
    Hydroxychloroquine actively suppresses erythrocyte forms, as well as gametes of R. vivax and R. malariae, which disappear from the blood almost simultaneously with asexual forms, does not affect the gametes of R. Falciparum. Hydroxychloroquine does not prevent repeated attacks of malaria caused by P. vivax and P. malariae, since it is ineffective against the exoerythrocytic forms of the causative agent of P. vivax, R. malariae and P.ovale, and also does not protect against infection by these microorganisms in preventive reception. At the same time, it reduces the severity of attacks, stops seizures and significantly lengthens the interval between the treatment course and the next attack in the disease caused by these pathogens. With malaria caused by P. falciparum, it eliminates acute attacks and leads to complete cure, unless it is a question of stable variants of the parasite.The frequency of resistant to the derivatives of 4-aminoquinoline forms P. falciparum depends on the geographical location, most often observed in some areas of I, South Asia, Central and South America, East Africa, Oceania.
    Rheumatoid arthritis and lupus erythematosus
    Hydroxychloroquine has immunosuppressive and anti-inflammatory discoid and systemic forms) and with acute and chronic rheumatoid arthritis. The exact mechanism of action for these diseases is unknown.
    Pharmacokinetics:
    Being a weak ground, hydroxychloroquine quickly and completely absorbed in the small intestine of the gastrointestinal tract (GIT). The speed and completeness of absorption can vary from person to person, but they do not depend on food intake. In blood hydroxychloroquine approximately 40 - 45% is associated with plasma proteins (albumin and a 1-glycoprotein), the degree of availability is about 74% (from 70 to 80%). After a single oral intake of 200 mg of hydroxychloroquine sulfate (1 tablet) in a healthy subject, the average peak concentration (Cmax) is 244 ng / ml (188-427 ng / ml) after 2-4.5 h after administration (Tmax). The concentration of the drug in plasma is 7-8 times lower than in whole blood.
    The preparation 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 when calculated 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. how 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 μg in 48 hours) were found in 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 this sequence:
    • a secondary amine, deethyl hydrochloroquine or deethylchloroquine;
    • a primary amine, bisdeethyl chloroquine;
    • 4 '- aldehyde derivative, a small part is restored further to alcohol;
    • 4 'is a carboxy derivative. The main product of decomposition is deethylhydrochloroquine, which also possesses anti-plasmodial activity. Hydroxychloroquine, conjugated with glucuronic acid, found in bile.
    After administration of 200 mg of hydroxychloroquine sulphate orally to adult volunteers, the half-life of the drug (t1/2) is according to the data for whole blood 50 ± 16 days (about 32 days in plasma).
    Elimination of hydroxychloroquine from the body proceeds in 2 stages. In the liver, about 30-60% of the drug is metabolized. A small amount is allocated by the kidneys - from 15 to 25% of the total; even a few months after the end of treatment in the urine, traces of medication are found. After a single intake of 200 mg of hydroxychloroquine sulfate, the total excretion in the urine of unchanged substance and its metabolites after 86 days is 16% and 1.3% of the administered dose, respectively. The non-sucked substance (up to 15-24%) is secreted through the digestive tract. An unidentified amount is deposited in the cells of the epithelium and excreted during their exfoliation. Some of the accepted dose is eliminated by hepatic metabolism, followed by excretion with bile, as well as when updating pigmented epithelial tissues, for example, the skin. In a number of works it is indicated that from 21 to 47% of the drug is excreted unchanged.
    Indications:
    - Malaria - for relief of acute attacks and prevention of malaria caused by Plasmodium vivax, R. ovale and R. malariae, as well as sensitive strains of P. falciparum; for the radical treatment of malaria caused by sensitive strains of R. 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 derivatives of 4-aminoquinoline or any other component of the drug
    - Maculopathy
    - Previous maculopathy
    - Children under 6 years of age (200 mg tablets are not adapted for use in children weighing less than 31 kg).
    - Child age if necessary long-term therapy (increased risk of toxic effects)
    - Pregnancy (possible for life use)
    - Lactation period
    - Congenital abnormalities, such as galactose intolerance, lactase deficiency or glucose malabsorption / galactose syndrome.
    Carefully:
    With retinopathy, visual disturbances (changes in the visual fields,reduction in visual acuity), simultaneous administration of medications that can cause visual disturbances, oppression of bone marrow hematopoiesis, psychoses (including in anamnesis), porphyria, psoriasis, simultaneous administration of medications that can cause skin reactions, glucose-6- phosphate dehydrogenase, with renal or hepatic insufficiency (if necessary, the doses of hydroxychloroquine are selected for control of plasma concentrations), hepatitis, severe gastrointestinal diseases.
    Dosing and Administration:
    Assign inside. Tablets are taken with food or washed down with a glass of milk. All doses are given for hydroxychloroquine sulphate and are not equivalent to doses of hydroxychloroquine base!
    Malaria
    Suppression of malaria: for adults: 400 mg every seventh day.
    For children over the age of 6 years, the weekly dose is 6.5 mg / kg, but, regardless of body weight, it should not exceed the dose for adults. If conditions permit, preventive treatment should be started 2 weeks before the trip to the endemic zone. If this is not possible, adults can be given an initial double dose of 800 mg, children - 12.9 mg / kg (but not more than 800 mg), divided into 2 divided doses at intervals of 6 hours.Preventative treatment should continue for 8 weeks after leaving the endemic area.
    Treatment for acute malaria attacks: the initial dose for adults is 800 mg, then 400 mg after 6 or 8 hours and 400 mg 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 taking into account the body weight (see below).
    For children over the age of 6, the total dose of 32 mg / kg (but not exceeding 2 g) is applied for more than three days as follows:
    - the first dose is 12.9 mg / kg (but not more than 800 mg per reception);
    - the second dose is 6.5 mg / kg (but not more than 400 mg) 6 hours after the first dose;
    - the third dose is 6.5 mg / kg (but not more than 400 mg) 18 hours after the second dose;
    - the fourth dose is 6.5 mg / kg (but not more than 400 mg) 24 hours after the 3rd dose.
    Rheumatoid diseases
    The drug has a cumulative effect, and several weeks are necessary to achieve its therapeutic effect, while side effects can occur 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, maintaining a dose of 200 to 400 mg / day.
    Systemic and discoid lupus erythematosus
    Doses should not exceed 6.5 mg / kg body weight (calculated according to the "ideal body weight") or 400 mg / day, the minimum effective dose or 200-400 mg / day should be given. In light-sensitive dermatological diseases treatment should be limited to periods maximum exposure to light.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 canceled on time, there is a risk of progression of retinopathy even after the drug is discontinued. Changes in the retina may be asymptomatic at first, or may be manifested by a paracentral, pericentral, or transient scotoma and color vision disorders.
    There may be changes in the cornea, including swelling and turbidity. They can
    Be asymptomatic, or cause such abnormalities as halos, blurred vision or photophobia. These changes may be temporary or reversible upon discontinuation of treatment. 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, dysfunction of the ciliary muscle can occur.
    From the organs of hearing: noise in the ears, deafness, hearing loss.
    From the skin: rarely - skin rash, itching, changes in pigmentation of the skin and mucous membranes, hair discoloration and alopecia. These changes usually quickly pass after discontinuation of treatment. Bullous rash is possible, including very rare cases of polymorphic erythema and Stevens-Johnson syndrome, photosensitivity and isolated cases of exfoliative dermatitis. Very rarely - acute generalized exanthematous pustular eruptions, which must be distinguished from psoriasis, although the drug may cause an exacerbation of psoriasis. This may be associated with an increase in temperature and leukocytosis. After the withdrawal of the drug, the prognosis is usually favorable.
    From the central nervous system: occasionally there are dizziness, headache, nervousness, emotional lability, psychoses, convulsions, ataxia, irritability.
    From the cardiovascular system: cardiomyopathy (rarely), atrioventricular blockade (AV blockade), decreased myocardial contractility, myocardial hypertrophy; with prolonged therapy with large doses - myocardial dystrophy.If there are conduction disturbances (AV blockade, Gissa beam blockade) and hypertrophy of both ventricles, chronic intoxication should be suspected.
    From the hematopoiesis: rarely - oppression of bone marrow hematopoiesis, aplastic anemia, agranulocytosis, thrombocytopenia, hemolytic anemia (in patients with deficiency of glucose-6-phosphate dehydrogenase), porphyria aggravation.
    From the musculoskeletal and nervous system: likely myopathy of skeletal muscles or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups. Myopathy is usually reversible after drug withdrawal, but it may take several months for complete recovery. There may be mild sensory changes, suppression of the tendon reflex and abnormal nerve conduction. After the drug is discontinued, conduction is usually restored.
    From the digestive system: nausea, vomiting (rarely), decreased appetite, abdominal pain of a spastic nature, diarrhea.
    From the side of the liver: hepatotoxicity (a violation of liver function, liver failure).In some cases, there may be changes in indicators of liver function tests have been reported on several occasions suddenly developed liver failure.
    Other: decrease in body weight.
    Overdose:
    Overdose is especially dangerous in young children, even reception 1-2 g of the drug can be fatal!
    Symptoms: headache, drowsiness, stupor, coma, ataxia, insomnia, agitation, hyperreflexia, muscle rigidity, choreoathetosis, convulsions, decrease blood pressure, tachycardia, arrhythmia, intraventricular block, AV block, heart failure, cyanosis, fever, mydriasis, oliguria, depression of the respiratory center, respiratory arrest. Symptoms develop after 4 hours after the overdose, reaching a maximum after 24 hours and the last 4 - 6 days.
    Treatment: gastric lavage (to clean washings); the purpose of activated carbon (in a dose of 5 times the dose of the drug); diuresis and alkalinization of the urine (e.g., ammonium chloride to the urine pH 5.5 - 6.5) increase urinary excretion of 4-aminoquinoline; symptomatic therapy (including the appointment of convulsions - diazepam, anti-shock therapy).It is necessary to monitor the concentration of sodium in the blood serum and constant medical control for at least 6 hours after the relief of symptoms. Monitoring of cardiovascular activity (ECG) for 5 days is shown, since a relapse may occur after 48 hours and later.
    The introduction of physostigmine is contraindicated because of the increased risk of seizures. Hemodialysis and forced diuresis are ineffective.
    Interaction:
    Enhances side effects glucocorticoids, salicylates, quinidine-like antiarrhythmics, hemato-, hepato- and neurotoxic medicines.
    Simultaneous use of hydroxychloroquine and digoxin can cause an increase in the level of digoxin in the serum, so patients receiving combination therapy should regularly monitor the level of digoxin in the blood serum, if necessary reduce the dose of digoxin.
    Increases plasma concentrations penicillamine and the risk of its side effects from the organs of hematopoiesis, urinary system and skin reactions.
    Can enhance the effect hypoglycemic agents, which may require a reduction in the dose of insulin and antidiabetic drugs.
    Hydroxychloroquine can enter into some of the known interactions of chloroquine, that is, it is possible to enhance:
    - blocking action aminoglycoside antibiotics neuromuscular transmission; suppression of its metabolism with cimetidine, which can increase the concentration of the drug in the blood plasma;
    - antagonism of action neostigmine and pyridostigmine;
    - decrease in antibody production in response to primary immunization diploid cell vaccine against rabies.
    With the simultaneous use of hydroxychloroquine and antacids the interval between the reception should be at least 4 hours (decrease in absorption).
    Alkaline drinking and alkali accelerate the excretion of hydroxychloroquine from the body.
    Special instructions:Before and during therapy, at least once every 6 months an ophthalmological examination should be performed (the use of daily doses greater than 6.5 mg / kg increases the risk of damage to the retina).
    If adverse reactions from the side of vision (visual acuity, change in color perception, etc.) occur, the drug should be immediately discontinued (changes in the retina may progress even after the drug is discontinued).
    Exceeding the recommended daily dose increases the risk of damage to the retina and speeds up this process. Before the beginning of the course of treatment with the drug, ophthalmoscopy of both eyes should be performed to study visual acuity, color vision and the optical field. Subsequently, such a survey should be repeated, at least annually.
    If vision deteriorates (visual acuity, color vision, etc.), immediately discontinue the drug. Patients should be monitored, since retinal changes and visual impairment may progress even after treatment is discontinued.
    Use in pregnancy is possible only for vital signs (in therapeutic doses can cause damage to the fetus or baby CNS (including ototoxicity, auditory and vestibular, down to deafness), retinal bleeding and pathological pigmentation of the retina (infants are particularly sensitive to toxic effects 4-aminocholine).
    It is advisable to use caution in treating patients with liver and kidney disease. It may be necessary to reduce the dose of the drug to reduce its toxic effects on these organs.
    With caution apply the drug in the treatment of patients with gastrointestinal, neurologic or hematological diseases; patients susceptible to quinine and suffering from deficiency of glucose-6-phosphate dehydrogenase, porphyria and psoriasis. Patients taking the drug for a long time should periodically conduct a detailed blood test. When detecting abnormalities, the drug is canceled.
    In patients who take the drug for a long time, it is necessary to periodically perform an examination of the function of skeletal muscles and tendon reflexes. If a muscle weakness develops when taking the drug, the drug should be discarded.
    The examination should be more frequent in such situations: the daily dose of the drug exceeds 6.5 mg / kg of ideal (not elevated) body weight; the actual mass used to set the dose for obese patients may lead to an overdose; kidney failure; the total dose exceeds 200 mg; elderly patients (over 65 years); decreased visual acuity.
    Effect on the ability to drive transp. cf. and fur:During the treatment period, care must be taken when driving a motor vehicle and doing other activities.potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
    Form release / dosage:
    Tablets, film-coated, 200 mg.
    Packaging:
    For 10, 20, 30, 60 or 100 tablets in a vial of high pressure polyethylene, capped with a lid. 1 bottle with instructions for use in a cardboard box.
    10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil. By 1, 2, 3, 6 or 10 contour packs together with the instruction
    for use in a cardboard bundle.
    For hospitals: For 100 tablets in a bottle of high-density polyethylene, capped with a lid. Vials (20, 25 or 30 bottles) together with instructions for use in a cardboard box.
    Storage conditions:
    Store in a dry, dark place at a temperature of 15 to 30 ° C, Keep out of reach of children.
    Shelf life:
    3 years. Do not use after the expiration date indicated on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-002880/09
    Date of registration:13.04.2009 / 01.11.2012
    Expiration Date:Unlimited
    The owner of the registration certificate:New Farm Inc.New Farm Inc.
    Manufacturer: & nbsp
    Representation: & nbspVECTOR-MEDICA CJSC VECTOR-MEDICA CJSC Russia
    Information update date: & nbsp16.04.2017
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