Immard^® (Tablets) Instructions for Use

Marketing Authorization Holder

Ipca Laboratories Ltd. (India)

ATC Code

P01BA02 (Hydroxychloroquine)

Active Substance

Hydroxychloroquine (Rec.INN registered by WHO)

Dosage Form

Immard®

Film-coated tablets, 200 mg: 10, 20, 30 or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex, with an engraving “HCQS” on one side.

Excipients: corn starch, calcium hydrogen phosphate, talc, colloidal silicon dioxide, polysorbate 80, magnesium stearate.

Shell composition titanium dioxide, macrogol, hypromellose, talc.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.

Clinical-Pharmacological Group

A 4-aminoquinoline derivative. An antimalarial and amoebicidal drug. An immunosuppressant

Pharmacotherapeutic Group

Antimalarial agent

Pharmacological Action

An antimalarial drug that actively suppresses erythrocytic forms (hematoschizotropic drug). It condenses lysosomal membranes and prevents the release of lysosomal enzymes, disrupts DNA replication, RNA synthesis, and hemoglobin utilization by erythrocytic forms of plasmodium.

It also has an immunosuppressive and anti-inflammatory effect, suppresses processes in which free radicals are formed, weakens the activity of proteolytic enzymes (proteases and collagenases), leukocytes, and lymphocyte chemotaxis.

Pharmacokinetics

Absorption

Drug absorption is variable. The half-absorption period is 3.6 h (1.9-5.5 h). Bioavailability is 74%.

T_max in blood plasma is 3.2 h (2-4.5 h). After oral administration of the drug at a dose of 155 mg, C_max in blood plasma is 948 ng/ml, at a dose of 310 mg – 1895 ng/ml.

Distribution

Plasma protein binding is 45%. It accumulates in tissues with a high level of metabolism (in the liver, kidneys, lungs, spleen – in these organs the concentration exceeds the plasma concentration by 200-700 times; in the CNS, erythrocytes, leukocytes) and in tissues rich in melanin. It is found in very low concentrations in the walls of the gastrointestinal tract. It penetrates the placental barrier and is detected in small amounts in breast milk. V_d in blood is 5,522 L, in plasma – 44,257 L.

Metabolism

It is partially metabolized in the liver with the formation of active deethylated metabolites.

Excretion

T_1/2 is 50 days, from plasma – 32 days. It is excreted by the kidneys (23-25% unchanged) and with bile (less than 10%). It is excreted very slowly and can be detected in the urine for a long time after the end of treatment.

Indications

• Malaria: treatment of acute attacks and suppressive therapy of malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae (excluding Hydroxychloroquine-resistant cases) and sensitive strains of Plasmodium falciparum; radical treatment of malaria caused by sensitive strains of Plasmodium falciparum;
• Rheumatoid arthritis;
• Systemic lupus erythematosus, discoid lupus erythematosus;
• Photodermatosis;
• Bronchial asthma;
• Sjögren’s syndrome.

ICD codes

Dosage Regimen

Take orally during meals or with a glass of milk.

200 mg of hydroxychloroquine sulfate is equivalent to 155 mg of hydroxychloroquine base.

For malaria as suppressive therapy, adults are prescribed at a dose of 400 mg/day every 7th day; children – 6.5 mg/kg weekly, but regardless of body weight, the dose for children should not exceed the dose for adults (400 mg). If conditions allow, suppressive therapy is prescribed 2 weeks before possible infection. Otherwise, an initial double dose can be prescribed: adults – 800 mg, children – 12.9 mg/kg (but not more than 800 mg), dividing the dose into 2 doses with an interval of 6 hours. Suppressive therapy should be continued for 8 weeks after leaving the endemic area.

Treatment of an acute attack of malaria for adults initial dose – 800 mg, then after 6-8 hours – 400 mg and 400 mg on the 2nd and 3rd days of treatment (total – 2 g of hydroxychloroquine sulfate). As an alternative method, a single dose of 800 mg may be effective.

For children, the total dose is 32 mg/kg (but not more than 2 g) and is prescribed over 3 days: first dose – 12.9 mg/kg (but not more than a single dose of 800 mg), second dose – 6.5 mg/kg (but not more than 400 mg) 6 hours after the first, third dose – 6.5 mg/kg (but not more than 400 mg) 18 hours after the second dose, fourth dose – 6.5 mg/kg (but not more than 400 mg) 24 hours after the third dose.

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

Rheumatoid arthritis for adults initial dose – 400-600 mg/day, maintenance – 200-400 mg/day.

Juvenile arthritis maximum dose – 6.5 mg/kg or 400 mg/day (the lower dose should be chosen).

Systemic lupus erythematosus and discoid lupus erythematosus for adults initial dose – 400-800 mg/day, maintenance – 200-400 mg/day.

Photodermatosis up to 400 mg/day. Treatment should be limited to periods of maximum sun exposure.

Adverse Reactions

Musculoskeletal system myopathy or neuromyopathy, leading to increasing myasthenia and atrophy of proximal muscle groups.

Central and peripheral nervous system sensory disturbances, decreased tendon reflexes, abnormal nerve conduction; headache, dizziness, nervousness, psychosis, emotional lability, convulsions.

Sensory organs tinnitus, hearing loss, photophobia, impaired visual acuity, impaired accommodation, corneal edema and clouding, scotoma; with long-term use in high doses – retinopathy (including with pigmentation disorders and visual field defects), optic nerve atrophy, keratopathy, ciliary muscle dysfunction.

Cardiovascular system with long-term therapy with the drug in high doses – myocardial dystrophy, cardiomyopathy, AV block, decreased myocardial contractility, myocardial hypertrophy.

Digestive system nausea, vomiting (rarely), decreased appetite, abdominal pain of a spasmodic nature, diarrhea, hepatotoxicity (impaired liver function, liver failure).

Hematopoietic system neutropenia, aplastic anemia, agranulocytosis, thrombocytopenia, hemolytic anemia (in patients with glucose-6-phosphate dehydrogenase deficiency).

Metabolism weight loss, exacerbation of porphyria.

Dermatological reactions skin rash (including bullous and generalized pustular), itching, impaired pigmentation of the skin and mucous membranes, hair discoloration, alopecia, photosensitivity, Stevens-Johnson syndrome (multiform exudative erythema), exacerbation of psoriasis (including with fever and hyperleukocytosis).

Contraindications

• Pregnancy;
• Lactation period;
• Children under 3 years of age;
• Long-term therapy in childhood;
• Hypersensitivity to the components of the drug.

With caution should be used in patients with retinopathy (including a history of maculopathy), impaired bone marrow hematopoiesis, diseases of the central nervous system and cardiovascular system, with psychosis (including in history), porphyria, psoriasis, glucose-6-phosphate dehydrogenase deficiency, with hepatic and/or renal insufficiency.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

The drug should be used with caution in hepatic and/or renal insufficiency.

Use in Renal Impairment

The drug should be used with caution in hepatic and/or renal insufficiency.

Pediatric Use

Contraindicated in children under 3 years of age, as well as for long-term therapy in children of any age.

Special Precautions

Before starting and during therapy, an ophthalmological examination should be performed at least once every 6 months.

During therapy, constant monitoring of the cellular composition of the blood, the condition of skeletal muscles (including tendon reflexes) is necessary.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, caution must be exercised when driving vehicles and other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms cardiotoxicity (impaired conduction along the bundle of His; with chronic intoxication – hypertrophy of the myocardium of both ventricles), decreased blood pressure, neurotoxicity (dizziness, headache, increased excitability, convulsions, coma), visual impairment, respiratory and cardiac arrest.

Overdose is especially dangerous in young children; even taking 1-2 g of the drug can be fatal.

Treatment gastric lavage, administration of activated charcoal (in a dose 5 times the dose of the drug), forced diuresis and urine alkalinization (for example, with ammonium chloride to urine pH – 5.5-6.5) increase the urinary excretion of 4-aminoquinoline, symptomatic therapy (including the administration of diazepam for convulsions, anti-shock therapy). Control of serum sodium concentration and constant medical supervision for at least 6 hours after the symptoms have been relieved are necessary.

Drug Interactions

With simultaneous use, Hydroxychloroquine increases the plasma concentration of digoxin; aminoglycosides enhance the blocking effect on neuromuscular conduction.

Hydroxychloroquine enhances the effect of hypoglycemic drugs (a dose reduction of the latter is required).

With simultaneous use with antacids, the absorption of hydroxychloroquine is reduced (the interval between taking the antacid and the drug Immard^® should be at least 4 hours).

Alkaline drinks and alkalis accelerate the excretion of hydroxychloroquine from the body.

Hydroxychloroquine increases the plasma concentrations of penicillamine and increases the risk of side effects from the hematopoietic system, urinary system and skin reactions.

Hydroxychloroquine enhances the side effects of corticosteroids, salicylates, class IA antiarrhythmic drugs, hematotoxic, hepatotoxic and neurotoxic agents.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.