Pharmacological properties

Pharmacodynamics. anti-malarial means, such as chloroquine and hydroxychloroquine, possess several pharmacological actions causing their therapeutic effect at treatment of rheumatic diseases though the role of each of these mechanisms is unknown. these actions include interaction with sulfhydryl groups, change of activity of enzymes (including phospholipases, nadn-cytochrome with - reductases, cholinesterases, proteases and hydrolases); linking with DNA; stabilization of lizosomalny membranes; oppression of formation of prostaglandin; inhibition of a chemotaxis and phagocytosis of polymorphonuclear cells; participation in synthesis by interleukin-1 monocytes (silt-1) and inhibition of release by superoxide neutrophils is probable.

Pharmacokinetics. The action mechanism, pharmacokinetics and metabolism of hydroxychloroquine is similar to chloroquine. After oral administration, hydroxychloroquine quickly and almost is completely absorbed. In one of researches the average peak concentration of hydroxychloroquine after reception by healthy volunteers of a single dose of 400 mg fluctuated within 53–208 ng/ml, at the same time average concentration made 105 ng/ml. Average time before achievement With _max in blood plasma made 1.83 h. Average T _½ from plasma varied depending on time which passed after reception, as follows: 5.9 h (at With _max 10 h), 26.1 h (at 10–48 h) and 299 h (at 48–504 h). Related connection and its metabolites are widely distributed on all organism, removed mainly with urine, at the same time in one research was shown that in 24 h only 3% of the entered dose were removed.

Indication

Pseudorheumatism, a juvenile pseudorheumatism, a diskoidny and system lupus erythematosus, dermatitis, the cause or deterioration in the course of which is impact of sunlight.

Malaria: for treatment of bad attacks and preventive treatment of the malaria caused by Plasmodium vivax, P. ovale and P. malariae and also sensitive strains of P. alciparum; for radical treatment of the malaria caused by sensitive strains of P. falciparum.

Use Immard is intended to

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for oral administration.

Adults and patients of advanced age. It is necessary to apply a minimal effective dose. This dose should not exceed 6.5 mg/kg of body weight (per the ideal, but not the actual body weight of the patient) in day and has to make 200 mg or 400 mg a day.

For patients who can apply a dose of 400 mg/days. The initial daily dose of 400 mg is distributed on 2 receptions. The dose can be reduced to 200 mg if obvious improvement of a condition of the patient is not observed. The maintenance dose has to be raised to 400 mg a day in case of decrease in efficiency of drug.

Children. It is necessary to apply minimum effective dose which should not exceed 6.5 mg/kg of ideal body weight a day. Therefore tablets on 200 mg cannot be applied to treatment of children with ideal body weight less than 31 kg.

Preventive treatment of malaria

Adult: 400 mg in the same day of the week.

Children with ideal body weight more than 31 kg. The week preventive dose makes 6.5 mg/kg of body weight, however, irrespective of body weight, it should not exceed the dose recommended for adults.

If are allowed by circumstances, then preventive therapy needs to be begun for 2 weeks prior to a trip to an endemic zone. However if it is impossible, then adults can appoint an initial double (load) dose of 800 mg, and to children — 12.9 mg/kg of body weight (but no more than 800 mg), distributed on 2 receptions at an interval of 6 h. Preventive therapy needs to be continued for 8 weeks after departure from an endemic zone.

Treatment of a bad attack of malaria

Adult. The initial dose makes 800 mg, then in 6–8 h 400 mg and on 400 mg within 2 next days (only 2 g of hydroxychloroquine of sulfate). As the alternative method which also proved the efficiency, perhaps single use of medicament in a dose of 800 mg. The dose for adults can be calculated taking into account body weight, as well as for children (see below).

Children with ideal body weight more than 31 kg. The general dose of 32 mg/kg of body weight (but not 2 g) is applied within 3 days, as shown below.

First dose: 12.9 mg/kg of body weight (but without exceeding a single dose of 800 mg).

Second dose: 6.5 mg/kg of body weight (but not 400 mg) in 6 h after reception of the first dose.

Third dose: 6.5 mg/kg of body weight (but not 400 mg) in 18 h after reception of the second dose.

Fourth dose: 6.5 mg/kg of body weight (but not 400 mg) in 24 h after reception of the third dose.

Each dose needs to be accepted at meal time and to wash down with a glass of milk.

Hydroksikhlorokhin possesses cumulative action therefore achievement of therapeutic effect requires several weeks whereas insignificant side effects can arise early enough. If at treatment of a rheumatic disease the condition of the patient does not improve within 6 months, treatment needs to be stopped. In the diseases connected with hypersensitivity to light, treatment has to be limited by the periods of the maximum exposure by light.

Contraindication

Hypersensitivity to derivatives 4 aminoquinolines. preliminary maculopathia, retinopathy, maculopathia, disease of kidneys, liver, central nervous system, blood, porphyria. patients with rare congenital conditions of intolerance of a galactose, deficiency of lactase a paw or a glucose galactose sprue. period of pregnancy and feeding by a breast. children with the ideal body weight of 31 kg.

Side effects

from an organ of sight: developing of a retinopathy with change of pigmentation and emergence of defects of a field of vision is possible, however, if not to exceed the recommended daily dose, then this phenomenon arises seldom. at an early stage the retinopathy is reversible after medicament withdrawal. if immard in due time not to cancel drug, there is a risk of progressing of a retinopathy even after medicament withdrawal.

at first can be

Change of a retina asymptomatic or can be shown by paracentral, pericentral or temporal scotoma or disturbance of color sight.

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changes of a cornea, including hypostasis and turbidity Can be observed. They can be asymptomatic or cause such disturbances as emergence of an aura around objects, illegibility of sight or photophobia. These changes can be temporary and reversible at the treatment termination.

Illegibility of sight can be caused by accommodation disturbance, depends on a dose of medicament and is reversible.

from skin: seldom — skin rash, an itching, change of xanthopathy and mucous membranes, decolouration of hair and an alopecia. These changes usually quickly disappear after the treatment termination. Bullous rashes, including isolated cases of a multiformny erythema and Stephens's syndrome — Johnson, photosensitivity and separate cases of exfoliative dermatitis are possible; very seldom — acute generalized exanthematous pustulous rashes which need to be distinguished from psoriasis though hydroxychloroquine can cause exacerbation of psoriasis. It can be followed by fervescence and a hyperleukocytosis. After medicament withdrawal the forecast usually favorable.

from a GIT: nausea, diarrhea, anorexia, abdominal pain; seldom — vomiting. These symptoms, as a rule, disappear right after a dose decline or the termination of treatment.

from central nervous system: dizziness, vertigo, sonitus, a hearing loss, a headache, nervousness, emotional lability, psychosis against the background of toxicosis and a spasm.

from the musculoskeletal system: a myopathy of skeletal muscles or a neuromyopathy that results in the progressing weakness and an atrophy of proximal groups of muscles. The myopathy can be reversible after medicament withdrawal, but several months can be necessary for an absolute recovery.

moderate touch disturbances, oppression of tendon jerks and disturbance of nerve conduction Can be observed by

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from a cardiovascular system: in isolated cases — a cardiomyopathy.

Emergence of disturbances of conductivity (blockade ventriculonector / AV blockade) and also hypertrophies of both ventricles testify to chronic intoxication. Drug withdrawal can lead to recovery of conductivity.

from the system of blood: seldom — oppression of function of marrow; in isolated cases — anemia, aplastic anemia, an agranulocytosis, a leukopenia and thrombocytopenia.

Hydroksikhlorokhin can cause aggravation or worsen a porphyria course.

Gepatobiliarny disturbances: changes of indicators of functional trials of a liver, it was reported about several cases of a fulminantny liver failure.

Hypersensitivity reaction: urticaria, Quincke's disease and bronchospasm.

Special instructions

General

Frequency of developing of a retinopathy if the recommended daily dose, small is not exceeded. Exceeding the recommended daily dose increases risk of developing of a retinopathy and accelerates this process.

before a course of treatment the medicament Immard all patients have to undergo ophthalmologic inspection. Further it is necessary to perform such examination at least each 12 months

during ophthalmologic inspection needs to check visual acuity, to carry out a careful oftalmoskopiya and a fundoskopiya and also a research of the central field of vision with a red target and color sight.

needs to perform Examination more often, having adapted it to features of the certain patient, in the following cases:

— the daily dose of medicament exceeds 6.5 mg/kg of the ideal (not increased) body weight; use of an indicator of the actual body weight during calculation of a dose of medicament for patients with excessive body weight can lead to overdose;

— a renal failure;

— visual acuity 6–8 D;

— age of 65 years;

— a cumulative dose of 200 g

Immard Drug treatment needs to be cancelled immediately if at the patient note pigmentary disturbances, defects of a field of vision or other aberrations which cannot be explained with disturbance of accommodation or existence of turbidity of a cornea. It is necessary to continue observation of a condition of such patients as these changes can progress.

in case of any disturbances from an organ of sight, including at disturbance of color sight, to patients needs to advise to stop immediately administration of medicament and to see a doctor.

needs to use the Drug Immard with care for treatment of the patients taking the accompanying medicaments which can cause side reactions from an organ of sight or skin.

With care to use drug:

— at treatment of patients with a disease of a liver or kidneys and also if patients accept medicines which can negatively influence function of these bodies. At patients with a heavy renal failure or a liver it is necessary to determine hydroxychloroquine level in blood plasma and as appropriate to adjust a medicament dose;

— at patients with a serious gastrointestinal, neurologic and hematologic illness.

Though risk of oppression of function of marrow low, is recommended to carry out periodically control of a gemogramma as there can be anemia, aplastic anemia, an agranulocytosis, a leukopenia and thrombocytopenia. At identification of pathological changes from blood the use of medicament should be stopped.

With care to use medicament for treatment of the patients sensitive to quinine having deficiency of glyukozo-6-phosphate-dehydrogenase, the patient with a chronic hematoporphyria as the course of these diseases under the influence of hydroxychloroquine can worsen and also sick psoriasis as the risk of aggravation of skin reactions increases.

Children of younger age are especially sensitive

to toxic action of 4-aminokhinolon; therefore patients should be warned about what Immard needs to be stored out of children's reach.

At the patients taking the medicament for an appreciable length of time needs to conduct periodically a research of function of skeletal muscles and tendon jerks. When developing muscle weakness, medicament should be cancelled.

Malaria. Hydroksikhlorokhinin is inefficient rather chlorokhinrezistentny strains of P. falciparum, is inactive rather ekzoeritrotsitarny P. vivax, P. ovale and P. forms malariae. Therefore Immard does not prevent infection with these microorganisms at use in the preventive purposes, a recurrence of the disease caused by them.

Use during pregnancy and feeding by a breast. Administration of medicament is contraindicated during pregnancy and feeding by a breast.

Children. It is necessary to apply minimum effective dose which should not exceed 6.5 mg/kg of ideal body weight a day. Therefore tablets on 200 mg cannot be applied to treatment of children with ideal body weight less than 31 kg.

Ability to influence speed of response at control of vehicles or work with other mechanisms. As after an initiation of treatment there can soon be an accommodation disturbance, patients have to be careful at control of vehicles and the performance of work requiring special attention. If this state does not pass independently, it disappears at a dose decline or the termination of treatment.

Interaction

Hydroksikhlorokhin's

sulfate can cause increase in level of digoxin in blood plasma therefore at the patients receiving combination therapy it is regularly necessary to control digoxin level in blood serum.

Hydroksikhlorokhin's

sulfate can enter some of the known interactions of chloroquine even if about it there are no publications. Treat them: strengthening of the direct blocking action of aminoglikozidny antibiotics on neuromuscular synapses; inhibition of his metabolism under the influence of Cimetidinum that leads to increase in concentration of anti-malarial medicament in blood plasma; antagonism of action of a neostigmin and pyridostigmine; decrease in antibody formation in response to primary immunization by the intradermal human diploid and cellular vaccine against rage. As well as in a case with chloroquine, reception of antiacid means can reduce hydroxychloroquine absorption therefore the interval between Immard's reception and antiacid means has to be not to a mensha of 4 h

As hydroxychloroquine can enhance effect of gipoglikemiziruyushchy means, there can be a need of a dose decline of insulin or antidiabetic drugs.

Overdose

Overdose of 4-aminokhinolon is especially dangerous by

to babies as reception can even lead 1–2 g to a lethal outcome.

Symptoms: the headache, a disorder of vision, cardiovascular collapse, spasms, a hypopotassemia, disturbance of a rhythm and conductivity, can be a consequence of what a sudden apnoea and hearts.

Treatment. As these effects can develop at once after reception of a considerable dose of drug, it is necessary to carry out symptomatic treatment immediately. To immediately remove stomach contents by its washing or to cause vomiting. Activated carbon in quantity, at least by 5 times the exceeding amount of the taken drug, can stop its further absorption if activated carbon is entered into a stomach via the probe after washing and no later than in 30 min. after administration of drug.

in case of overdose needs to consider the possibility of parenteral administration of diazepam. It is proved that this medicament can reduce the cardiotoxicity phenomena caused by chloroquine.

If necessary should take measures for maintenance of breath and antishock therapy.

Storage conditions

At a temperature not above 25 °C.