Expiration date: 04/2025

Active substance: Hydroxychloroquine

Analogue: Plaquenil

The composition and form of issue:

Tablets, film-coated 1 tablet contains active substance: 

hydroxychloroquine sulfate 200 mg

excipients: starch maize calcium hydrogen phosphate talc silica colloidal anhydrous Polysorbate 80 magnesium stearate 

shell film: titanium dioxide hypromellose macrogol talc 

in blister al/PVC 10 PCs. in cardboard pack of 3, 6 or 10 blisters.

Description pharmaceutical form:

The tablets are biconvex, round shaped, film-coated white or almost white, engraved with "HCQS" on one side.

Pharmacokinetics:

Absorption — variable. The period of poluabsorbtion — 3,6 h (1.9–5.5 hrs). Bioavailability of 74%. Connection with plasma proteins — 45%. Tmax of the drug in the blood, 3.2 h (2-4,5 h), Cmax is after intake of 155 mg — 948 ng/ml after intake of 310 mg — 1895 ng/ml. are Accumulated in tissues with high metabolism (liver, kidneys, lungs, spleen — these organs the concentration exceeds plasma in 200-700 times the Central nervous system, erythrocytes, leukocytes) and tissues rich in melanin. In very low concentrations found in the walls of the digestive tract. Penetrates through the placental barrier, in small amounts detected in breast milk. Vd, measured in the blood — 5,522 l, in plasma — 44,257 L. is partially Metabolized in the liver to form active metabolites dezetilirovanny. T1/2 from the blood is 50 days, from plasma of 32 days. Excreted by the kidneys (23-25% in unmodified form) and bile (<10%). The very slow excretion: drug and its metabolites may long be determined in urine after cessation of treatment.

Description pharmacological action:

Antimalarial drug that actively inhibits erythrocytic forms (hematocytopenia the drug). Seals the lysosomal membranes and prevents the release of lysosomal enzymes, breaks reduplicatia DNA, RNA synthesis and recycling hemoglobin eritrocitariani forms of Plasmodium.

Also has immunosuppressive and anti-inflammatory effect, inhibits free radical processes, reduces the activity of proteolytic enzymes (proteases and collagenase), leukocytes, chemotaxis of lymphocytes.

Indications:

• malaria: treatment of acute attacks and suppressive treatment of malaria due to Plasmodium vivax, Plasmodium ovale and Plasmodium malariae (excluding hydrochlorothiazideonline cases) and sensitive strains of Plasmodium falciparum radical treatment of malaria caused by sensitive strains of Plasmodium falciparum
  
• rheumatoid arthritis
  
• lupus erythematosus (systemic and diskoidna)
  
• photodermatitis
  
• bronchial asthma
  
• Sjogren's syndrome.
  

Contraindications:

• hypersensitivity to the drug
  
• pregnancy, lactation
  
• children up to age 3 years, as well as long-term therapy in children.
  

Caution: retinopathy (including may in history), impaired bone marrow hematopoiesis, diseases of the CNS and SSS, psychosis (W. in history), porfirii, psoriasis, deficiency of glucose-6-phosphate dehydrogenase, liver and/or kidney failure.

Side effects:

From the musculoskeletal and nervous systems: weight loss, myopathy or neuromyopathy, leading to increasing myasthenia and atrophy of proximal muscle groups sensory disturbance, reduction of tendon reflexes and abnormal nerve conduction, headache, dizziness, nervousness, psychosis, emotional lability, convulsions.

From the sensory organs: tinnitus, hearing loss, photophobia, impaired visual acuity, a violation ccomodation, swelling and clouding of the cornea, scotoma with long-term use of large doses retinopathy, including pigmentation disorders and visual field defects, optic nerve atrophy, keratopathy, dysfunction of the ciliary muscle.

Co the CCC: during prolonged therapy with high doses — myocardiodystrophy, cardiomyopathy, AV block, decrease myocardial contractility, cardiac hypertrophy.

From the digestive system: nausea, vomiting (rarely), loss of appetite, abdominal pain of spastic character, diarrhea, hepatotoxicity (abnormal liver function, liver failure).

The bodies of the blood: neutropenia, aplastic anemia, agranulocytosis, thrombocytopenia, hemolytic anemia (patients with deficiency of glucose-6-phosphate dehydrogenase).

From the skin: skin rashes, including generalized bullous and pustular, pruritus, pigmentation of skin and mucous membranes, bleaching of hair, alopecia, photosensitivity, Stevens-Johnson syndrome (exudative erythema mnogomernaya), exacerbation of psoriasis, including fever and hyperleukocytosis, aggravation of porphyria.

Drug interactions:

Increases the concentration of digoxin in plasma aminoglycosides enhance the blocking effect on neuromuscular conduction.

Enhances the effect of hypoglycemic drugs: requires dose reduction of the latter.

With simultaneous use of antacids the interval between doses should be at least 4 hours (reduced absorption).

Alkaline water and alkali accelerate the excretion from the body.

Increases plasma concentrations of penicillamine and the risk of its side effects from the blood, urinary system and skin reactions.

Intensifies the side effects of corticosteroids, salicylates, anti-arrhythmic drugs-class 1A, haemato-, hepato - and neurotoxic funds.

Method of application and dose:

Inside.

During a meal or with a glass of milk. 200 mg of hydroxychloroquine sulfate equivalent to 155 mg of hydroxychloroquine base.

Rheumatoid arthritis: the initial dose in adults is 400-600 mg/day, supporting — 200-400 mg/day.

Juvenile arthritis: the dose should not exceed 6.5 mg/kg or 400 mg/day (smaller dose).

Diskoidna and systemic lupus erythematosus: initial dose for adults is 400-800 mg/day, supporting — 200-400 mg/day.

Photodermatosis: up to 400 mg/day treatment should be limited to periods of maximum solar exposure.

Malaria: suppressive therapy in adults is 400 mg/day every 7th day from the kids weekly suppressive dose of 6.5 mg/kg, but irrespective of body weight, should not exceed the adult dose (400 mg). If conditions allow, the overwhelming therapy is prescribed for 2 weeks prior to exposure, otherwise you can assign the initial double dose: 800 mg adults and 12.9 mg/kg (but not exceeding 800 mg) — children, divided into 2 doses with an interval of 6 h. Inhibiting therapy should continue for 8 weeks after left the endemic area.

Treatment of acute attack of malaria: initial dose for adults is 800 mg, then after 6-8 h 400 mg and 400 mg on the 2nd and 3rd day of treatment (total 2 g hydroxychloroquine sulfate). As an alternative method can be effective dose is 800 mg once.

For children the total dose of 32 mg/kg (but not exceeding 2 g) is appointed within 3 days: 1st dose of 12.9 mg/kg (but not exceeding a single dose of 800 mg), 2nd dose of 6.5 mg/kg (but not exceeding 400 mg) through 6 hours after first, 3rd dose of 6.5 mg/kg (but not exceeding 400 mg) through 18 hours after the 2nd dose 4th dose of 6.5 mg/kg (but not exceeding 400 mg) 24 h after 3rd dose.

The dose for adults may be calculated per 1 kg of body weight, as well as for children.

Overdose:

Symptoms: cardiotoxicity (conduction in bundle branch block in chronic intoxication — a hypertrophy of a myocardium of both ventricles), decrease in blood pressure, neurotoxicity (dizziness, headache, irritability, convulsions, coma), blurred vision, respiratory arrest and heart overdose is especially dangerous in young children, even the reception 1-2 g of the drug may lead to death.

Treatment: gastric lavage, the appointment activated charcoal (dose, 5 times higher than the dose of the drug), forced diuresis and alkalinization of urine (e.g., ammonium chloride to the urine pH — 5.5 to 6.5) increase the urinary excretion of 4-aminohinolina, symptomatic therapy, including the appointment in convulsions diazepam, anti-shock therapy was necessary to control the concentration of sodium in blood serum and constant medical supervision for at least 6 h after the relief of symptoms.

Precautions:

Before and during treatment is necessary to spend not less than 1 time in 6 months an eye examination.

During treatment requires constant monitoring of cellular blood, the condition of skeletal muscle, including tendon reflexes.

Effects on ability to drive or to perform work requiring high speed physical and mental reactions. During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and psychomotor speed reactions.