Expiration date: 03/2026

Active substance: Hydroxychloroquine

Analogue: Immard

The composition and form of issue:

Tablets, film-coated 1 tablet contains:

of hydroxychloroquine sulfate 200 mg

excipients: lactose monohydrate povidone (K25) corn starch magnesium stearate Opadry OY-L-28900 (hypromellose, macrogol-4000, titanium dioxide (E171), lactose monohydrate) 

blistere in 10 PCs. in cartons of 6 blister packs.

Description pharmaceutical form:

Round biconvex tablets, film-coated white color is engraved with the "HCQ" on one side and "200" on the other.

Pharmacokinetics:

After ingestion hydroxychloroquine is rapidly and almost completely absorbed. In healthy volunteers after a single dose of 400 mg of hydroxychloroquine Cmax in plasma achieved through of 1.83 h and ranged from 53 to 208 ng/ml the plasma protein Binding is 45%. The average value of T1/2 from plasma varies depending on the time elapsed after taking the drug as follows: 5,9 h (from reaching Cmax to 10 hours) 26.1 hrs (from 10 to 48 h) and 299 mph (48 to 504 h ). In the liver it is partially converted into active metabolites leaded. Unchanged drug and its metabolites are well distributed in the body. The volume of distribution 5-10 l/kg. the Drug accumulates in tissues with high metabolism (in the liver, kidneys, lungs, spleen — these organs the concentration exceeds plasma in 200-700 times the Central nervous system, erythrocytes, leukocytes), as well as in the retina and tissues rich in melanin. Hydroxychloroquine and its metabolites are excreted mainly with urine and to a lesser extent, — with bile. Allocation of the drug slow terminal T1/2 is about 50 days (whole blood) and 32 days (plasma). 24 h urine output of 3% of the administered dose.

Hydroxychloroquine crosses the placental barrier and in small quantities found in breast milk.

Description pharmacological action:

Plaquenil possesses antimalarial properties and also exerts anti-inflammatory and immunosuppressive effect in chronic discoidal or systemic lupus erythematosus (SLE) and acute and chronic rheumatoid arthritis (RA). Its mechanism of action in malaria, SLE and RA are not fully known.

Hydroxychloroquine has the properties of moderate immunosuppressant, inhibiting the synthesis of rheumatoid factor and of the reaction components of the acute phase. It also accumulates in leukocytes, stabilizing lysosomal membranes and inhibits the activity of many enzymes, including collagenases and proteases that cause the breakdown of cartilage.

Efficacy in SLE and RA is associated with the following anti-inflammatory and immunomodulatory effects of hydroxychloroquine:

• increase in intracellular pH leads to slower antigenic response and reduces the binding of peptide receptors major histocompatibility complex (MHC). Fewer receptors antigen-MHC reaches the cell surface, which leads to a reduction of the autoimmune response
  
• decrease the activity of phospholipase A2 in high concentrations of lysosomal enzymes
  
• reduced concentrations of cytokines IL-1 and IL-6, leading to reduction of clinical and laboratory indicators of autoimmune response. As there is no violation of the synthesis of interferon gamma, these effects may be associated with selective effects on cytokines
  
• inhibition of pre - and/or posttranscription DNA and RNA.
  

The drug actively suppresses the asexual erythrocytic forms and the gametes of Plasmodium vivax and Plasmodium malariae, which disappear from the blood almost simultaneously with the asexual forms. Plaquenil does not act on gametes of Plasmodium falciparum. Plaquenil is not effective against chloroquine-resistant strains of Plasmodium falciparum and inactive against neitronakh forms of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, and therefore cannot prevent infection by these organisms when administered prophylactically and also may not prevent recurrence of disease caused by these pathogens.

Indications:

• rheumatoid arthritis
  
• juvenile rheumatoid arthritis
  
• lupus erythematosus (systemic and diskoidna)
  
• malaria (with the exception caused by chloroquine-resistant strains of Plasmodium falciparum):
  
• for the prevention and treatment of acute attacks of malaria due to Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, and sensitive strains of Plasmodium falciparum
  
• for the radical treatment of malaria caused by sensitive strains of Plasmodium falciparum.
  

Contraindications:

• hypersensitivity to derivatives of 4-aminohinolina
  
• retinopathy
  
• pregnancy (see "Pregnancy and lactation")
  
• hereditary lactose intolerance, lactase deficiency, galactosemia or malabsorption syndrome glucose/galactose (due to the presence in the product is lactose)
  
• children's age when they need long-term therapy (children have an increased risk of toxic effects)
  
• children up to age 6 years (tablets 200mg are not intended for children with "ideal" body weight less than 31 kg).
  

With caution:

• visual disorders (decreased visual acuity, impaired color vision, constriction of visual fields), concomitant use of drugs that can cause adverse ophthalmic reaction (risk of progression of retinopathy and visual disorders)
  
• hematological diseases (including in history)
  
• severe neurological disease, psychosis (including in history)
  
• porphyria cutanea tarda (risk of exacerbation), psoriasis (risk of increasing skin manifestations of the disease), concomitant use of drugs that can cause skin reactions
  
• renal insufficiency and/or hepatic insufficiency, hepatitis, concomitant use of drugs that can adversely affect the function of the liver and/or kidneys (in severe renal impairment or hepatic the dose should be under the control of the plasma concentrations of hydroxychloroquine)
  
• the deficit glukozo-6-fosfatdegidrogenaza
  
• severe gastrointestinal disease
  
• hypersensitivity to quinine (the possibility of cross-allergic reactions).
  

Application of pregnancy and breast-feeding:

Hydroxychloroquine crosses the placenta. Against its use during pregnancy, data are limited. It should be noted that 4-aminohinolina in therapeutic doses can cause prenatal damage to the Central nervous system, including the auditory nerve (disorders of the hearing and vestibular system, congenital deafness), bleeding in the retina and abnormal pigmentation of the retina. Therefore, you should avoid the use of hydroxychloroquine during pregnancy, except in cases where the potential benefit to the mother outweighs risk to the fetus.

You should carefully weigh the need for the use of the drug during lactation, since it is shown that it in small amounts excreted in breast milk, and young children are especially sensitive to the toxic effects of 4-aminohinolina.

Side effects:

Side on view: may develop, though rarely, retinopathy with changes in pigmentation and defects in the visual fields. In the early form, these phenomena are usually reversible after discontinuation of hydroxychloroquine. If the condition remains undiagnosed and retinal lesions continue to develop further, there may be a risk of progression even after discontinuation of the drug.

Retinal changes may initially be asymptomatic, or manifest scotoma paracentral or perigean types, transient scotoma and disturbances in color vision.

Possible changes of the cornea, including swelling and clouding. They can be asymptomatic or cause such visual disturbances like the appearance of ghosting, blurring of vision or photophobia. Upon termination of the treatment, these changes can be subjected to reverse development.

You may also experience visual disturbances associated with disorders of accommodation which is dose-dependent and reversible.

With the skin: sometimes there are skin rashes described as itching, changes in pigmentation of the skin and mucous membranes, bleaching of hair and alopecia. These changes usually quickly pass after the end of treatment. Reported on the development of bullous rash, including rare cases of erythema multiforme and Stevens-Johnson syndrome, photosensitivity and individual cases exfoliative dermatitis.

Very rare cases of acute generalized asantemanso pustulata (OGAP) must be distinguished from psoriasis, although hydroxychloroquine may cause exacerbation of psoriasis. OGAP may be accompanied by fever and hyperleukocytosis. After the drug the outcome is usually favorable.

Gastrointestinal: nausea, diarrhea, anorexia, abdominal pain and rarely vomiting. These symptoms usually disappear immediately after a dose reduction or drug withdrawal.

Hepatobiliary system: long-term use at high doses may develop hepatotoxicity. There are reports of isolated cases of liver dysfunction and several cases of unexpected liver failure.

CNS: rarely — dizziness, tinnitus, hearing loss, headache, irritability, emotional instability, psychosis, convulsions, muscle weakness, ataxia.

From the peripheral nervous system and muscle: cases of myopathy of skeletal muscle or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups. Myopathy may be reversible after discontinuation of the drug, but full recovery may take several months. At the same time may experience a weak sensory changes, suppression of tendon reflexes and reduced nerve conduction.

From the side of cardiovascular system: there are rare reports of development of cardiomyopathy.

Chronic cardiac toxicity can be suspected when it detects violations conductivity (blockade feet beam Guisa/violation of AV conduction) or hypertrophy of both ventricles. If you cancel the drug may reverse development of these changes.

Organs of hematopoiesis: rarely there have been cases of oppression kostnomozgovy blood. It was reported about rare cases of anemia, including aplastic, agranulocytosis, leukopenia and thrombocytopenia.

Hydroxychloroquine can cause or exacerbate porphyria.

The immune system: urticaria, angioedema, bronchospasm.

Drug interactions:

Digoxin. It was reported that hydroxychloroquine may increase the plasma concentrations of digoxin, therefore, to avoid the development of glycoside intoxication while taking these drugs, it is necessary to reduce the dose of digoxin under the control of its plasma concentrations.

The drugs used for the treatment of diabetes. As hydroxychloroquine may enhance the effects of insulin and oral hypoglycemic agents, may need to decrease doses of these hypoglycemic drugs in the beginning of reception of hydroxychloroquine.

Antacids. May reduce the absorption of hydroxychloroquine. Therefore, while the use of antacids and hydroxychloroquine the interval between their reception should make not less than 4 h.

The hydroxychloroquine is also impossible to exclude the following interactions with other drugs, which have been described for chloroquine, but have not yet been observed when taking hydroxychloroquine.

Aminoglycosides. Potentiation of its direct blocking action at the neuromuscular transmission.

Cimetidine. Inhibits the metabolism of anti-malarial drugs, which could lead to increased plasma concentrations and increase the risk of their side effects, especially toxic.

The neostigmine and pyridostigmine. Antagonism of the action.

Any intradermal human diploid-cell rabies vaccine. The decrease in the formation of antibodies in response to primary immunization with intradermal human diploid-cell rabies vaccine.

Method of application and dose:

Note: all doses given for hydroxychloroquine sulfate and is not the equivalent doses for the base.

Inside, during a meal or with a glass of milk.

Treatment of RA. Hydroxychloroquine has a cumulative activity. For the manifestation of its therapeutic effect requires several weeks of taking the drug, whereas side effects may occur relatively early. The desired therapeutic effect develops after several months of taking the drug. In the absence of objective improvement in the patient's condition within 6 months of receiving hydroxychloroquine, the drug should be discontinued.

Adults (including the elderly) should take the minimum effective dose. They should not exceed 6.5 mg/kg/day (calculated for the "ideal" body weight, not actual body weight) and can be either 200 or 400 mg/day.

Patients capable of taking 400 mg daily

Initially 400 mg daily in divided doses. Upon reaching the obvious improvement of a condition the dose can be reduced to 200 mg in the reduction of the maintenance dose may be increased to 400 mg.

Children. You should use the minimum effective dose. The dose should not exceed 6.5 mg/kg (based on the "ideal" body weight). So tablets 200 mg are not suitable for children with the "ideal" body weight less than 31 kg.

The use of the drug Plaquenil for combination therapy of RA. Plaquenil can be safely used in combination with corticosteroids, salicylates, NSAIDs, methotrexate and other therapeutic agents of the second row. After several weeks of use of the drug Plaquenil dose corticosteroids and salicylates may be reduced or may be discontinued taking these drugs. The dose of corticosteroids must be reduced gradually every 4-5 days the dose of cortisone is no more than 5-15 mg, the dose of hydrocortisone is not more than 5-10 mg, the dose of prednisone and the prednisone for no more than 1-2,5 mg dose of methylprednisolone and triamcinolone — no more than 1-2 mg of dexamethasone is not more than 0.25–0.5 mg.

The treatment of SLE. The average initial dose in adults is 400 mg 1 or 2 times a day. It should be administered for several weeks or months depending on patient response. For prolonged maintenance therapy enough use of the drug in a smaller dose, from 200 to 400 mg.

Treatment of malaria

Prevention of acute attacks of malaria caused by P. malariae, and sensitive strains of Plasmodium falciparum

Adults — 400 mg weekly on the same day of the week.

Children's weekly dose of 6.5 mg/kg (for calculation shall be the "ideal" body weight), however, regardless of body mass it should not exceed adult dose.

If circumstances permit, preventive therapy should begin 2 weeks before entering the endemic area. If this is not possible, you can assign the initial double (load) dose: adults — 800 mg, children — 12.9 mg/kg "ideal" body weight (but not more than 800 mg), divided into two doses with 6-hour intervals. Preventive treatment should continue for 8 weeks after departure from endemic areas.

Treatment of acute attacks of malaria

For adults, the initial dose of 800 mg should be dose of 400 mg every 6 or 8 hours, and then 400 mg 2 consecutive days (total 2 g hydroxychloroquine sulfate).

An alternative method of treatment: has been proven the effectiveness of a single dose of 800 mg.

Doses for adults can also be calculated from the "ideal" body weight, similar to the calculation of doses in children (see below).

For children the total dose 32 mg/kg "ideal" body weight (but not more than 2 g) is appointed within 3 days as follows:

the first dose of 12.9 mg/kg (single dose not exceeding 800 mg) second dose of 6.5 mg/kg (no more 400 mg) through 6 hours after first third dose — 6.5 mg/kg (no more 400 mg) through 18 hours after the second dasychira dose of 6.5 mg/kg (no more 400 mg) through 24 hours after the third dose.

Radical treatment of malaria, caused by Plasmodium malariae and Plasmodium vivax

For the radical treatment of malaria due to Plasmodium malariae, and Plasmodium vivax, the necessary simultaneous use of derivatives of 8-aminohinolina.

Overdose:

Overdose of 4-aminohinolina especially dangerous in children, even 1-2 g of the drug can lead to death.

Symptoms: headache, visual disturbances, collapse, convulsions, hypokalemia, rhythm and conduction followed by cardiac arrest and respiratory arrest.

Treatment: because these effects can develop very quickly after taking a large dose of the drug in these cases should immediately initiate the appropriate measures. Should be immediately carried out induction of vomiting or gastric lavage through the probe. To slow absorption, the appointment of activated charcoal in a dose at least 5 times the accepted dose of the drug. Appropriate parenteral administration of diazepam (describes the reduction of the cardiotoxicity of chloroquine in the background).

If necessary, perform artificial respiration and shock treatment.

After the relief of symptoms of overdose requires ongoing medical supervision for at least 6 hours.

Special instructions:

Common

Toxic effects on the retina is largely dose-dependent. The incidence of retinopathy in the application of doses up to 6.5 mg/kg "ideal" body weight is a small. Exceeding the recommended daily dose sharply increases the risk of development of retinopathy, and accelerate its emergence.

Before starting a long course of drug treatment should conduct a thorough examination of both eyes. Examination should include visual acuity testing, fundus examination, assessment of color vision and visual field. During therapy, such examination should be conducted at least 1 time in 6 months.

The examination should be more frequent in the following situations:

• at a daily dose exceeding 6.5 mg/kg "ideal" body weight (in obese patients, the use of absolute body weight to calculate dose can lead to overdose)
  
• in renal failure
  
• when the total dose of 200 g
  
• the elderly
  
• if reduced visual acuity.
  

If you have any visual disorders (decreased visual acuity, change in color vision), the drug should be discontinued immediately and to keep a careful monitoring of the patient's eyesight because of retinal changes (and visual disturbances) may progress even after discontinuation of the drug.

We recommend caution in the appointment of hydroxychloroquine to patients with diseases of the liver and kidneys, which may require lower doses of the drug, as well as in connection with the possible impact of the drug on the function of these organs (in severe renal impairment or hepatic the dose should be under the control of the plasma concentrations of hydroxychloroquine).

Patients receiving long-term treatment, periodically conduct a full analysis of blood, occurrence of hematological disorders hydroxychloroquine should be abolished.

Children are especially sensitive to the toxic effects of 4-aminohinolina, therefore, you should carefully follow in order hydroxychloroquine were kept out of the reach of children.

All patients receiving long-term medication needs periodically to be examined by a neurologist in relation to the functions of skeletal muscle and the severity of tendon reflexes. If you experience weakness in the muscles of the drug should be discontinued.

In malaria

Plaquenil is not effective against chloroquine-resistant strains of Plasmodium falciparum and inactive against neitronakh forms of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, and therefore cannot prevent infection by these organisms when administered as a prophylaxis of acute attacks of malaria, and cannot prevent relapse of the disease caused by these pathogens.

Effects on ability to drive and perform work associated with increased risk. Patients should observe caution while driving a vehicle or performing work requiring attention, since hydroxychloroquine can impair the accommodation and clarity of vision. If this condition persists by itself, the dose may be temporarily reduced.