Hydroxychloroquine pills 200 mg, 30 pcs.

Composition

1 film-coated tablet contains:Active ingredient:hydroxychloroquine sulfate-200 mg; excipients:croscarmellose sodium – 3.0 mg, magnesium stearate – 4.0 mg, silicon dioxide colloid – 0.5 mg, microcrystalline cellulose (PH 102) with 92.5 mg;film shell: hyprolose (hydroxypropyl cellulose), LF – 2.4 mg, hypromellose 2910 (hydroxypropyl methylcellulose) – 0.6 mg, macrogol (polyethylene glycol) 8000 – 1.8 mg, titanium dioxide (E 171) and 2.4 mg

Pharmacological action

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-HCG receptors reach the cell surface, which leads to a decrease in the autoimmune response; a decrease in the activity of phospholipase a2 at high concentrations, 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 selective effects on cytokines; inhibition of pre – and/or post-transcription of DNA and RNA.

Hydroxychloroquine 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. Binding to plasma proteins is 45%. The mean value of T_1/2 from plasma varies depending on the time elapsed after taking hydroxychloroquine as follows: 5.9 h (from reaching C_max to 10 h),26.1 h (from 10 to 48 h) and 299 h (from 48 to 504 h). In the liver, hydroxychloroquine is partially converted to active ethylated metabolites. Unchanged hydroxychloroquine and its metabolites are well distributed in the body. The volume of distribution is 5-10 l/kg. Hydroxychloroquine 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. The release of hydroxychloroquine is slow, with a terminal T_1/2 of about 50 days (from whole blood) and 32 days (from plasma). Within 24 hours,3% of the administered dose of hydroxychloroquine is excreted in the urine. Hydroxychloroquine penetrates the placental barrier and is found in small amounts in breast milk.

Indications

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

Use during pregnancy and lactation

It is contraindicated for use during pregnancy.

If it is necessary to use it during breastfeeding, the ratio of the expected benefit of therapy for the mother and the potential risk for the children should be carefully evaluated, taking into account the indications for use and the duration of therapy.

Contraindications

Hypersensitivity to hydroxychloroquine and 4-aminoquinoline derivatives; retinopathy (including maculopathy in the anamnesis); children’s age if long-term therapy is required (children have an increased risk of 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.

With caution: in case of 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). In case of hematological diseases (including in the anamnesis).

For neurological diseases, psychoses (including in the anamnesis).

With late cutaneous porphyria (risk of exacerbation), psoriasis (risk of increased skin manifestations of the disease), while taking medications that can cause skin reactions.

In case of renal and/or hepatic insufficiency, hepatitis, while taking medications that may adversely affect liver and/or kidney function (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).

In violation of cardiac conduction (bundle branch block / AV block) and hypertrophy of both ventricles. For cardiomyopathy.

In cases of congenital or acquired QT prolongation and / or the following risk factors for QT prolongation in the anamnesis: heart disease (for example, heart failure, myocardial infarction); proarrhythmic conditions (for example, bradycardia with a heart rate of less than 50 beats / min); ventricular arrhythmias; uncorrected hypokalemia and / or hypomagnesemia; concomitant use of drugs that prolong the QT interval (increased risk of ventricular arrhythmias.

Because of the risk of hypoglycaemia, hydroxychloroquine should be administered with caution in patients who are taking or not taking hypoglycaemic medications.

Side effects

from the hematopoietic system: frequency unknown-bone marrow hematopoiesis suppression, anemia, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

From the immune system: frequency unknown – urticaria, angioedema, bronchospasm.

From the side of metabolism: often – anorexia; frequency unknown-hypoglycemia, possible exacerbation of porphyria.

From the side of the psyche: 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.

From the side of the visual organ: often – blurred vision associated with a dose-dependent and reversible accommodation disorder; infrequently-retinopathy with pigmentation changes and visual field defects. In the case of timely withdrawal of hydrochloroquine, these phenomena are reversible. If the condition remains undiagnosed and retinal lesions continue to develop, there is a possible risk of their progression even after discontinuation of hydrochloroquine. 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.

From the cardiovascular system: the frequency is unknown – prolongation of the QT interval in patients with risk factors, which can lead to the development of cardiac arrhythmias (ventricular arrhythmia of the “pirouette” type, ventricular tachycardia), cardiomyopathy, which can lead to heart failure and, in some cases, to death. Detection of cardiac conduction disorders (such as bundle branch block / AV conduction disorders) and hypertrophy of both ventricles may indicate chronic cardiac toxicity. With the withdrawal of hydrochloroquine, these changes may reverse.

From the digestive system: very often-abdominal pain, nausea; often-diarrhea, vomiting. These symptoms usually resolve immediately after reducing the dose or discontinuing hydrochloroquine.

Liver and biliary tract disorders: infrequently-abnormal liver function tests; frequency unknown-fulminant liver failure.

Skin and subcutaneous tissue disorders: often – skin rash, pruritus; infrequently – changes in pigmentation of the skin and mucous membranes, 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 hydrochloroquine, the outcome is usually favorable.

Musculoskeletal 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 hydrochloroquine, but it may take several months for complete recovery), suppression of tendon reflexes and decreased nerve conduction.

Interaction

Caution should be exercised when prescribing hydroxychloroquine to patients receiving medications that prolong the QT interval (for example, Class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, certain antimicrobials [for example, moxifloxacin]), because of the increased risk of ventricular arrhythmias.

There are reports that hydroxychloroquine can increase plasma concentrations of digoxin, therefore, in order to avoid the development of glycosidic intoxication with their simultaneous use, it is necessary to reduce the dose of digoxin – under the control of its concentration in plasma.

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

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 cimetidine, cimetidine suppresses the metabolism of protvomalarial 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, a reduction in the formation of antibodies in response to primary immunization with this vaccine.

With arrhythmogenic drugs – increased risk of ventricular arrhythmia when using chloroquine simultaneously with other arrhythmogenic drugs (such as amiodarone and moxifloxacin).

Halofantrine prolongs the QT interval and in combination with chloroquine may cause arrhythmias (this combination is not recommended).

With other antimalarial drugs that lower the seizure threshold – the use of chloroquine may lead to a decrease in the seizure threshold. Concomitant use of chloroquine with other known antimalarial drugs that lower the seizure threshold (for example, mefloquine) may increase the risk of seizures.

With cyclosporine – there are reports of an increase in the concentration of cyclosporine in blood plasma with the combined use of cyclosporine and chloroquine.

With antiepileptic drugs – with the combined use of chloroquine, the effectiveness of antiepileptic drugs may not be sufficient.

With praziquantel-in a study of the interaction of chloroquine and praziquantel, a decrease in the bioavailability of praziquantel was reported. 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 a-galactosidase when hydroxychloroquine is co-administered with agalsidase.

How to take, course of administration and dosage

Inside.

Only the minimum effective dose should be used.

The dose should not exceed 6.5 mg / kg / day (calculated according to the “ideal” body weight, not the actual body weight) and can be 200 mg or 400 mg per day.

The scheme of application, the duration of therapy is determined individually, depending on the indications, clinical situation and age of the patient.

Special instructions

The toxic effect of hydroxychloroquine on the retina is 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 hydroxychloroquine, 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 performed more frequently in the following situations: with 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); with 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, color vision changes) occur, hydroxychloroquine should be discontinued immediately and the patient’s vision condition should be carefully monitored, as retinal changes (and visual disorders) can progress even after hydroxychloroquine is discontinued.

Cases of cardiomyopathy leading to heart failure have been reported in patients receiving hydroxychloroquine. 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 their doses, as well as in patients taking medications that may 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 hydroxychloroquine for a long time should be periodically examined by a neurologist regarding skeletal muscle function and the severity of tendon reflexes. If muscle weakness occurs, hydroxychloroquine should be discontinued.

In very rare cases, suicidal behavior has been reported in patients taking hydroxychloroquine. When using hydroxychloroquine, extrapyramidal disorders may develop.

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 it 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 hydroxychloroquine, caution should be exercised when performing potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Active ingredient

Hydroxychloroquine

Conditions of release from pharmacies

By prescription

Dosage form

of the tablet

Weight

Weight: 33 gr.