Hydroxychloroquine, 200 mg 30 pcs

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). Its mechanism of action in malaria, lupus erythematosus and rheumatoid arthritis is not fully known.

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

The efficacy in SLE and RA is associated with the following anti-inflammatory and immunomodulatory effects of hydroxychloroquine: increasing intracellular pH leads to slower antigenic response and reduces binding of peptides of the main histocompatibility complex (HCG) receptors. Fewer antigen-HCG receptors reach the cell surface, resulting in a reduced autoimmune response; decreased activity of phospholipase A2 at high concentrations, lysosomal enzymes; reduced concentrations of cytokines IL-1 and IL-6, leading to reduced clinical and laboratory parameters of autoimmune response. Since there is no disruption of interferon gamma synthesis, these effects may be associated with a selective effect on cytokines; inhibition of pre- and/or post-transcriptional DNA and RNA.

Hydroxychloroquine actively suppresses asexual erythrocytic forms as well as gametes of P. vivax and P. malariae, which disappear from the blood almost simultaneously with the asexual forms. Hydroxychloroquine has no effect on R. falciparum gametes. Hydroxychloroquine is ineffective against chloroquine-resistant strains of P. falciparum, and inactive against extra-erythrocytic forms of P. vivax, P. malariae and P. ovale, and therefore cannot prevent infection with these microorganisms when administered for prophylactic purposes, and cannot prevent relapse of the disease caused by these pathogens.

Pharmacokinetics

Hydroxychloroquine is rapidly and almost completely absorbed after oral administration. The binding to plasma proteins is 45%. Mean T_1/2 from plasma varies with time since hydroxychloroquine administration as follows: 5.9 h (from reaching C_max to 10 h), 26.1 h (10 to 48 h), and 299 h (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 high levels of metabolism (in the liver, kidneys, lungs, spleen – in these organs the concentration exceeds the plasma concentration by 200-700 times; CNS, red blood cells, leukocytes), as well as in the retina and melanin-rich tissues. Hydroxychloroquine and its metabolites are excreted mainly in the urine and to a lesser extent in the bile. Excretion of hydroxychloroquine is slow, the terminal T_1/2 is about 50 days (from whole blood) and 32 days (from plasma). In 24 hours 3% of the administered dose of hydroxychloroquine is excreted in the urine. Hydroxychloroquine penetrates the placental barrier and is detected in small amounts in breast milk.

Indications

Active ingredient

Composition

How to take, the dosage

Ingestion.

Only the lowest effective dose should be used.

The dose should not exceed 6.5 mg/kg/day (calculated by “ideal” body weight, not real body weight) and may be 200 mg or 400 mg per day.

The regimen and duration of therapy are determined individually, depending on the indication, clinical situation, and age of the patient.

Interaction

Caution should be exercised when prescribing hydroxychloroquine to patients receiving medications that prolong the QT interval (eg, antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, antipsychotics, some antimicrobials [eg, moxifloxacin]), because of the increased risk of ventricular arrhythmias.

There are reports that hydroxychloroquine can increase plasma concentrations of digoxin, so to avoid glycoside intoxication with their concomitant use, the dose of digoxin should be reduced – with monitoring of plasma concentrations.

Hydroxychloroquine may increase the effects of insulin and oral hypoglycemic agents; doses of these drugs may need to be reduced at the beginning of hydroxychloroquine administration.

The antacids may decrease the absorption of hydroxychloroquine. Therefore, when concomitant use of antacids and hydroxychloroquine the interval between their intake should be at least 4 hours.

Hydroxychloroquine also cannot be ruled out the following interactions with other medications 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 inhibits the metabolism of protomalarials, which may increase their plasma concentrations and increase the risk of their side effects, especially toxic.

With neostigmine and pyridostigmine – antagonism of action.

With any human intradermal diploid cell rabies vaccine – reduced antibody formation in response to primary immunization with that vaccine.

With arrhythmogenic drugs – increased risk of ventricular arrhythmia when chloroquine is used concomitantly 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 – use of chloroquine may decrease the seizure threshold. Co-administration of chloroquine with other known antimalarial drugs that lower the seizure threshold (e.g., mefloquine) may increase the risk of seizures.

With cyclosporine – there have been reports of increased plasma concentrations of cyclosporine when cyclosporine and chloroquine are used together.

With antiepileptic drugs – the effectiveness of antiepileptic drugs may be insufficient when chloroquine is used together.

With praziquantel – A study of the interaction between chloroquine and praziquantel reported decreased bioavailability of praziquantel. Because of the similarity in structure and pharmacokinetic parameters between hydroxychloroquine and chloroquantel, a similar effect can be expected when hydroxychloroquine and praziquantel are used together.

With agalsidase – there is a theoretical risk of inhibition of intracellular a-galactosidase when hydroxychloroquine is coadministered with agalsidase.

Special Instructions

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

Before starting long-term 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. This examination should be done at least once every 6 months during therapy.

If the daily dose is greater than 6.5 mg/kg of “ideal” body weight (using absolute weight to calculate dose in overweight patients can lead to overdose), if there is renal failure, if the cumulative dose is greater than 200 g, in elderly patients, if there is any decrease in visual acuity before treatment.

In the event of any visual disturbances (decreased visual acuity, changes in color vision), hydroxychloroquine should be discontinued immediately and the patient’s visual status closely monitored, since retinal changes (and visual disturbances) can progress even after discontinuation of hydroxychloroquine.

In patients taking hydroxychloroquine, cases of cardiomyopathy leading to heart failure have been reported. It has been shown that hydroxychloroquine can cause severe hypoglycemia (including loss of consciousness), which can be life-threatening in patients both on and off hypoglycemic medications. Patients taking hydroxychloroquine should be warned about the risk of hypoglycemia and associated clinical signs and symptoms. Patients who experience clinical symptoms suggestive of hypoglycemia during treatment with hydroxychloroquine should have their blood glucose concentrations determined and, if necessary, the therapy should be revised.

We recommend caution when using hydroxychloroquine in patients with liver and kidney disease, in which doses may need to be reduced, as well as in patients taking medications that can have adverse effects on these organs.

In patients taking hydroxychloroquine for a long time, a complete blood count should be performed periodically (if hematological abnormalities occur, hydroxychloroquine should be stopped).

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

All patients taking hydroxychloroquine for a long time should be periodically evaluated by a neurologist for skeletal muscle function and 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 the development of extrapyramidal disorders is possible.

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

Influence on driving and operating ability

When treating with hydroxychloroquine, caution should be exercised when performing potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

Hypersensitivity to hydroxychloroquine and 4-aminoquinoline derivatives; retinopathy (including maculopathy in anamnesis); childhood, if long-term therapy is necessary (children have an increased risk of developing toxic effects); children under 6 years of age (tablets of 200 mg are not intended for children with an “ideal” body weight less than 31 kg); pregnancy.

With caution: in visual disorders (decreased visual acuity, color vision disorder, narrowing of the visual fields), with concomitant use of drugs that can cause adverse ophthalmic reactions (risk of progression of retinopathy and visual disorders). In hematological diseases (including in the anamnesis).

In neurological diseases, psychosis (including history).

In late cutaneous porphyria (risk of exacerbation), psoriasis (risk of increased skin manifestations of the disease), when concomitant use of drugs that may cause skin reactions.

In renal and/or hepatic insufficiency, hepatitis, concomitant use of drugs that may adversely affect liver function and/or renal function (in severe renal or hepatic impairment, the dose should be adjusted under control of plasma concentrations of hydroxychloroquine). In glucose-6-phosphate dehydrogenase deficiency.

In gastrointestinal diseases. In hypersensitivity to quinine (possibility of cross-allergic reactions).

In patients with cardiac conduction disorders (Gis pedicle/AV blockade) and in hypertrophy of both ventricles. In cardiomyopathy.

In congenital or acquired prolongation of the QT interval and/or a history of the following risk factors for QT interval prolongation: cardiac disease (e.g., heart failure, myocardial infarction); proarrhythmic conditions (e.g., bradycardia with a heart rate less than 50 BPM); ventricular arrhythmias (e.g., arrhythmias with a heart rate less than 50 BPM); and cardiac arrhythmias.); ventricular arrhythmias; uncorrected hypokalemia and/or hypomagnesemia; concomitant use of QT prolonging agents (increased risk of ventricular arrhythmias).

Because of the risk of hypoglycemia, hydroxychloroquine should be prescribed with caution in patients both taking and not taking hypoglycemic drugs.

Side effects

Hematopoietic system: frequency unknown – suppression of medullary hematopoiesis, anemia, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

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

Metabolism: frequent – anorexia; frequency unknown – hypoglycemia, possible exacerbation of porphyria.

Psychiatric: often – affective lability; infrequent – nervousness; frequency unknown – psychosis, suicidal behavior.

Nervous system disorders: frequent – headache; infrequent – dizziness; frequency unknown – seizures, extrapyramidal disorders such as muscular dystonia, dyskinesia and tremor.

Overlooking organ: often – blurred vision associated with accommodation disorder, which is dose-dependent and reversible; infrequent – retinopathy with pigmentation changes and visual field defects. In case of timely withdrawal of hydrochloroquine these phenomena are reversible. If the condition remains undiagnosed and retinal lesions continue to develop, there is a risk of their progression even after withdrawal of hydrochloroquine. Retinal changes may initially be asymptomatic or manifest as paracentral or pericentral scotomas, transient scotomas, and color vision abnormalities. Corneal changes, including edema and clouding, may occur. They may be asymptomatic or cause visual disturbances such as halos, blurred vision, or photophobia. These changes may be transient or reversible. Frequencies unknown are maculopathy and macular degeneration, which may be irreversible.

Hearing and labyrinth disorders: infrequent – vertigo, tinnitus; frequency unknown – hearing loss.

Cardiovascular system disorders: frequency unknown – prolongation of the QT interval in patients with risk factors, which may lead to the development of cardiac rhythm disturbances (ventricular pirouette arrhythmia, ventricular tachycardia), cardiomyopathy, which can lead to heart failure and, in some cases, death. The detection of cardiac conduction abnormalities (such as Gis pedicle block/ AV conduction abnormalities) and hypertrophy of both ventricles may indicate chronic cardiac toxicity. When hydrochloroquine is withdrawn, reversal of these changes is possible.

Digestive system disorders: very often – abdominal pain, nausea; often – diarrhea, vomiting. These symptoms usually go away immediately after reducing the dose or discontinuing hydrochloroquine.

Hepatic and biliary tract disorders: infrequent – abnormal liver function tests; frequency unknown – fulminant liver failure.

Skin and subcutaneous tissue disorders: common – skin rash, itching; infrequent – changes in skin and mucous membrane pigmentation, hair discoloration and alopecia (these changes usually go away quickly after stopping treatment); common 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 must be distinguished from psoriasis, although hydroxychloroquine can provoke an exacerbation of psoriasis. OGEP may be accompanied by fever and hyperleukocytosis. After withdrawal of hydroxychloroquine, the outcome is usually favorable.

Muscular system disorders: infrequent – sensory-motor disorders; frequency unknown – skeletal muscle myopathy or neuromyopathy leading to progressive weakness and atrophy of proximal muscle groups (myopathy may be reversible after hydrochloroquine withdrawal, but it may take several months for complete recovery), suppression of tendon reflexes and reduced nerve conduction.

Pregnancy use

It is contraindicated in pregnancy.

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

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