HYDROXYCHLOROQUINE 200 mg 30 TABLETS

Specifications

Active ingredients Hydroxychloroquine

Manufacturer's countryRussia

Manufacturer Sintez OJSC

Release formFilm-coated tablets, 200 mg-30 pcs with instructions for use vu up

Store in a dark place

Keep away from children

Dosage form

Round biconvex tablets, film-coated, white in color. Slight surface roughness is acceptable. The color of the tablets on the break is white or white with a yellowish tinge.

Composition

1 tablet contains:

active ingredient: hydroxychloroquine sulfate-200 mg;

excipients: calcium hydrophosphate dihydrate-99.86 mg, prosolv [microcrystalline cellulose-98%, colloidal silicon dioxide-2%] - 126.79 mg, hypromellose (hydroxypropylmethylcellulose) - 24.25 mg, croscarmellose sodium-19.40 mg, colloidal silicon dioxide (aerosil) - 4.85 mg, magnesium stearate-4.85 mg;

shell composition: hypromellose (hydroxypropylmethylcellulose) - 2.972 mg, titanium dioxide (E171) - 1.363 mg, macrogol (polyethylene glycol) (E1521) - 0.665 mg.

Pharmacotherapy group

antimalarial medicine

Storage temperature

2℃ to 25℃

Special conditions

Common

Toxic effects on the retina are largely dose-dependent. The incidence of retinopathy at doses up to 6.5 mg / kg of "ideal" body weight is low. Exceeding the recommended daily dose dramatically increases the risk of retinopathy.

Before starting a long course of treatment with the drug, a thorough examination of both eyes should be performed. The examination should include determination of visual acuity, fundus examination, assessment of color vision and visual fields. During therapy, such an examination should be carried out at least once every 6 months.

The examination should be more frequent in the following situations::

- at a daily dose exceeding 6.5 mg / kg of "ideal" body weight (in patients with increased body weight, using absolute body weight to calculate the dose may lead to overdose);

- in case of renal failure;

- with a total dose of more than 200 g;

- in the elderly;

- if the patient has a decrease in visual acuity of any severity before starting treatment.

If any visual disturbances (decreased visual acuity, changes in color vision) occur, the drug should be discontinued immediately and the patient's vision condition should be carefully monitored, as retinal changes (and visual disorders) can progress even after the drug is discontinued (see the section "Side effects").

Cases of cardiomyopathy leading to heart failure have been reported in patients receiving Hydroxychloroquine (see section "Side effects"). Hydroxychloroquine has been shown to cause severe hypoglycaemia (including loss of consciousness), which can be life-threatening in patients taking or not taking hypoglycaemic medications. Patients taking hydroxychloroquine should be warned about the risk of hypoglycemia and associated clinical signs and symptoms. In patients who experience clinical symptoms during treatment with hydroxychloroquine that indicate the development of hypoglycemia, the blood glucose concentration should be determined and, if necessary, therapy should be reviewed.

Caution is recommended when using hydroxychloroquine in patients with liver and kidney diseases, who may need to reduce the dose of the drug, as well as in patients taking medications that can cause adverse effects on these organs.

In patients taking hydroxychloroquine for a long time, a complete blood test should be performed periodically (if hematological disorders occur, hydroxychloroquine should be discontinued).

Children are particularly sensitive to the toxic effects of 4-aminoquinolines, so care should be taken to keep hydroxychloroquine out of the reach of children.

All patients taking the drug for a long time should be periodically examined by a neurologist for skeletal muscle function and the severity of tendon reflexes. If muscle weakness occurs, the drug should be discontinued.

In very rare cases, suicidal behavior has been reported in patients taking hydroxychloroquine. When using the drug Hydroxychloroquine, extrapyramidal disorders may develop (see the section "Side effects").

For malaria

Hydroxychloroquine is not effective against chloroquine-resistant strains of P. falciparum, nor is it active against non-erythrocytic forms of P. vivax, P. malariae, and P. ovale, and therefore cannot prevent infection with these microorganisms when used for preventive purposes, nor can it prevent relapse of the disease caused by these pathogens.

Influence on the ability to drive vehicles and mechanisms

During treatment with the drug, care should be taken when performing potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interaction

With digoxin

It has been reported that hydroxychloroquine can increase plasma concentrations of digoxin, therefore, in order to avoid the development of glycosidic intoxication with simultaneous administration of these drugs, it is necessary to reduce the dose of digoxin under the control of its plasma concentrations.

With medications used to treat diabetes mellitus

Hydroxychloroquine may increase the effects of insulin and oral hypoglycemic agents, and it may be necessary to reduce the doses of these drugs when starting hydroxychloroquine.

With antacids

Antacids may reduce the absorption of hydroxychloroquine. Therefore, with the simultaneous use of antacids and hydroxychloroquine, the interval between their intake should be at least 4 hours.

Hydroxychloroquine also cannot be excluded from the interactions listed below with other drugs that have been described for chloroquine, but have not yet been observed with hydroxychloroquine.

With aminoglycosides

Potentiation of the direct blocking effect of aminoglycosides on neuromuscular transmission.

With cimetidip

Cimetidine suppresses the metabolism of antimalarial drugs, which can lead to an increase in their plasma concentrations and increase the risk of side effects, especially toxic ones.

With neostigmine and pyridostigmine-antagonism of action.

With any intradermal human diploid cell rabies vaccine

Reduction of antibody production in response to primary immunization with intradermal human diploid cell rabies vaccine.

With halofantrine and other arrhythmogenic drugs

Halofantrine prolongs the QT interval and in combination with hydroxychloroquine can cause arrhythmias (this combination is not recommended). In addition, there is an increased risk of ventricular arrhythmia when using hydroxychloroquine concomitantly with other arrhythmogenic drugs (such as amiodarone and moxifloxacin).

With other antimalarial drugs that lower the seizure threshold

The use of hydroxychloroquine may lead to a decrease in the seizure threshold. Co-administration of hydroxychloroquine with other known anti-malarial drugs that lower the seizure threshold (for example, mefloquine) may increase the risk of seizures.

With cyclosporine

An increase in the concentration of cyclosporine in blood plasma has been reported with the combined use of cyclosporine and hydroxychloroquine.

With antiepileptic drugs

When combined with antiepileptic drugs, the effectiveness of the latter may be insufficient.

With praziquantel

A study of the interaction of chloroquine and praziquantel reported a decrease in the bioavailability of praziquantel. Due to the similarity in structure and pharmacokinetic parameters between hydroxychloroquine and chloroquine, a similar effect can be expected with the combined use of hydroxychloroquine and praziquantel.

With agalsidase

There is a theoretical risk of inhibition of intracellular plex NANOLEX Tel. +7 (495) 648-26-87.?- galactosidases in the combined use of hydroxychloroquine with agalsidase.

Pharmacodynamics

Hydroxychloroquine has antimalarial properties, and also has anti-inflammatory and immunosuppressive effects in chronic discoid or systemic lupus erythematosus( SLE), acute and chronic rheumatoid arthritis (RA). The mechanism of its action in malaria, lupus erythematosus and rheumatoid arthritis is not fully known.

Hydroxychloroquine has the properties of a moderate immunosuppressor, suppressing the synthesis of rheumatoid factor and components of the acute phase reaction. It also accumulates in white blood cells, stabilizing lysosomal membranes, and suppresses the activity of many enzymes, including collagenase and proteases, which cause cartilage breakdown.

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

- an increase in intracellular pH slows down the antigenic response and reduces the binding of peptides of the main histocompatibility complex (GKG) receptors. Fewer antigen-GKG receptors reach the cell surface, which leads to a reduced autoimmune response;

- reduced activity of phospholipase A2 at high concentrations of lysosomal enzymes;

- a decrease in the concentrations of cytokines IL-1 and IL-6, leading to a decrease in clinical and laboratory parameters of the autoimmune response. Since there is no disruption in the synthesis of interferon gamma, these effects may be associated with a selective effect on cytokines;

- inhibition of pre - and / or post-transcription of DNA and RNA.

The drug actively suppresses asexual erythrocyte forms, as well as P. vivax and P. malariae gametes, which disappear from the blood almost simultaneously with asexual forms. Hydroxychloroquine does not affect the gametes of P. falciparum. Hydroxychloroquine is ineffective against chloroquine-resistant strains of P. falciparum, as well as inactive against non-erythrocytic forms of P. vivax, P. malariae and P. ovale, and therefore cannot prevent infection with these microorganisms when it is prescribed for preventive purposes, and also cannot prevent relapse of the disease caused by these pathogens.

Pharmacokinetics

After oral administration, hydroxychloroquine is rapidly and almost completely absorbed. In healthy volunteers, after a single dose of 400 mg, the maximum plasma concentration of hydroxychloroquine was reached after 1.83 hours and ranged from 53 to 208 ng/ml. Binding to plasma proteins is 45%. The average plasma half-life varies depending on the time elapsed after taking the drug as follows: 5.9 hours (from reaching the maximum plasma concentration (Ctax) to 10 hours), 26.1 hours (from 10 to 48 hours) and 299 hours (from 48 to 504 hours). In the liver, it is partially converted to active ethylated metabolites. The unchanged drug and its metabolites are well distributed in the body. The volume of distribution is 5-10 l/kg. The drug accumulates in tissues with a high level of metabolism (in the liver, kidneys, lungs, spleen - in these organs the concentration exceeds plasma by 200-700 times; CNS, red blood cells, white blood cells), as well as in the retina of the eye and tissues rich in melanin. Hydroxychloroquine and its metabolites are mainly excreted in the urine and to a lesser extent in the bile. Excretion of the drug is slow, with a terminal half-life of about 50 days (from whole blood) and 32 days (from plasma). Within 24 hours, 3% of the administered dose of the drug is excreted in the urine.

Hydroxychloroquine penetrates the placental barrier and is found in small amounts in breast milk.

Indications

Malaria (excluding chloroquine-resistant strains of P. falciparum): prevention and management of acute attacks of malaria caused by Plasmodium vivax, P. ovale and P. malariae, as well as sensitive strains of P. falciparum; radical treatment of malaria caused by sensitive strains of P. Falciparum; rheumatoid arthritis; juvenile rheumatoid arthritis; lupus erythematosus (systemic and discoid); photodermatitis.

Contraindications

- Hypersensitivity to hydroxychloroquine and 4-aminoquinoline derivatives or to other components of the drug.

- Retinopathy (including a history of maculopathy).

- Children's age if long-term therapy is necessary (children have an increased risk of developing toxic effects).

- Children under 6 years of age (200 mg tablets are not intended for children with an "ideal" body weight of less than 31 kg).

- Pregnancy (see "Pregnancy and lactation").

With caution

- With visual disorders (decreased visual acuity, impaired color vision, narrowing of visual fields), while taking medications that can cause adverse ophthalmic reactions (risk of progression of retinopathy and visual disorders).

- With hematological diseases (including in the anamnesis).

- With neurological diseases, psychoses (including in the anamnesis).

- With late skin porphyria (risk of exacerbation), psoriasis (risk of increased skin manifestations of the disease), simultaneous use of drugs that can cause skin reactions.

- In case of renal insufficiency and/or hepatic insufficiency, hepatitis, simultaneous administration of drugs that can adversely affect the function of the liver and / or kidneys (in case of severe renal or hepatic dysfunction, the dose should be selected under the control of plasma concentrations of hydroxychloroquine).

- With a deficiency of glucose-6-phosphate dehydrogenase.

- For gastrointestinal diseases.

- Hypersensitivity to quinine (possibility of cross-allergic reactions).

- With impaired cardiac conduction (bundle branch block/atrioventricular block) and with hypertrophy of both ventricles.

- For cardiomyopathy.

- Due to the risk of hypoglycemia, the drug should be prescribed with caution to patients who are taking or not taking hypoglycemic drugs (see the sections "Side effects", "Interaction with other drugs", "Special instructions").

Use during pregnancy and lactation

Hydroxychloroquine passes through the placenta. Data are limited on its use during pregnancy. It should be noted that 4-aminoquinolines in therapeutic doses can cause intrauterine damage to the central nervous system, including the auditory nerve (hearing and vestibular disorders, congenital deafness), retinal hemorrhages and abnormal retinal pigmentation.

The need to use the drug during breast-feeding should be carefully weighed, as it has been shown that it is excreted in small amounts in mother's milk, and young children are especially sensitive to the toxic effects of 4-aminoquinolines.

Side effects

The frequency of adverse reactions is presented according to the World Health Organization (WHO) classification: very common (> 1/10), common (>>1/100 and >>< 1/10), infrequent (> 1/1000 and < 1/10), infrequent (>< 1/100), rare (> 1/10000 and < 1/100), rare (>< 1/1000), very rare (

Disorders of the blood and lymphatic system: frequency unknown - inhibition of bone marrow hematopoiesis, anemia, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Immune system disorders: frequency unknown - urticaria, angioedema, bronchospasm.

Metabolic and nutritional disorders: often - anorexia; frequency unknown-hypoglycemia, possible exacerbation of porphyria.

Mental disorders: often-affective lability; infrequently-nervousness; frequency unknown-psychosis, suicidal behavior.

Nervous system disorders: often-headache; infrequently-dizziness; frequency unknown-convulsions, extrapyramidal disorders such as muscular dystonia, dyskinesia and tremor.

Visual organ disorders: often-blurred vision associated with a dose-dependent and reversible accommodation disorder; infrequently-retinopathy with pigmentation changes and visual field defects. In case of timely withdrawal of the drug, these phenomena are reversible. If the condition remains undiagnosed and retinal lesions continue to develop, there may be a risk of their progression even after discontinuation of the drug. Retinal changes may initially be asymptomatic or manifest as paracentral or pericentral scotomas, transient scotomas, and color vision disorders. Corneal changes may occur, including swelling and opacity. They may be asymptomatic or cause visual disturbances such as ghosting, blurred vision, or photophobia. These changes may be temporary or reversible. The frequency is unknown-maculopathy and macular degeneration, which may be irreversible.

Hearing disorders and labyrinth disorders: infrequently-vertigo, tinnitus; frequency unknown-hearing loss.

Disorders of the cardiovascular system: frequency unknown-cardiomyopathy, which can lead to heart failure and, in some cases, to death. Detection of cardiac conduction disorders (such as bundle branch block / atrioventricular conduction disorders) and hypertrophy of both ventricles may indicate chronic cardiac toxicity. If the drug is discontinued, these changes may reverse.

Gastrointestinal disorders: very often - abdominal pain, nausea; often-diarrhea, vomiting. These symptoms usually resolve as soon as the dose is reduced or the drug is discontinued.

Disorders of the liver and biliary tract: infrequently-deviations from the norm of functional "liver" tests; frequency unknown-fulminant liver failure.

Subcutaneous tissue disorders: often - skin rash, pruritus; infrequently: changes in skin and mucosal pigmentation, hair discoloration and alopecia (these changes usually disappear quickly after discontinuation of treatment); frequency unknown - bullous rash including erythema multiforme; Stevens - Johnson syndrome; toxic epidermal necrolysis; photosensitization; exfoliative dermatitis; drug-induced skin reaction accompanied by eosinophilia and systemic manifestations (DRESS syndrome); acute generalized exanthematous pustulosis (OGEP). OGEP should be distinguished from psoriasis, although hydroxychloroquine can provoke an exacerbation of psoriasis. OGEP may be accompanied by fever and hyperleukocytosis. After discontinuation of the drug, the outcome is usually favorable.

Musculoskeletal and connective tissue disorders: infrequently-sensory-motor disorders; frequency unknown-skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of the proximal muscle groups (myopathy may be reversible after discontinuation of the drug, but it may take several months for complete recovery), suppression of tendon reflexes and decreased nerve conduction.

Overdose

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

Symptoms

Symptoms of overdose include headache, visual disturbances, collapse, seizures, hypokalemia, rhythm and conduction disturbances, followed by cardiac and respiratory arrest.

Treatment

Since overdose symptoms can develop very quickly after taking a large dose of the drug, in these cases, appropriate measures should be taken immediately. Artificial vomiting or gastric lavage through a probe should be performed immediately. Activated carbon in a dose at least 5 times higher than the dose of the drug taken can slow down absorption. Parenteral administration of diazepam is advisable, which will reduce the cardiotoxicity of chloroquine. If necessary, artificial ventilation and anti-shock therapy should be performed.

After stopping the symptoms of overdose, continuous medical supervision is required for at least 6 hours.

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