Plaquenil

Plaquenil – the drug having antimalarial properties and having immunodepressive and antiinflammatory effect.

Form of release and structure

Dosage form of Plaquenil – a tablet, film coated: biconvex, round, white color, on one of the parties an engraving - "HCQ", on other party – "200" (on 10 pieces in blisters, on 6 blisters in cardboard packs).

Contains in 1 tablet:

• Active ingredient: hydroxychloroquine sulfate – 200 mg;
• Auxiliary components: magnesium stearate, K25 povidone, lactoses monohydrate, starch corn, опадрай OY-L-28900 (macrogoal 4000, gipromelloza, titanium dioxide (E171), lactoses monohydrate).

Indications to use

Plaquenil is applied to treatment of a pseudorheumatism, a juvenile pseudorheumatism, a system lupus erythematosus, a diskoidny lupus erythematosus.

At malaria (except for caused chloroquine - resistant strains of Plasmodium falciparum) drug is used for the purpose of prevention and for therapy of bad attacks of the malaria caused by Plasmodium ovale, Plasmodium vivax and Plasmodium malariae and sensitive strains of Plasmodium falciparum, and also at radical treatment of the malaria caused by Plasmodium falciparum strains, sensitive to hydroxychloroquine.

Contraindications

Absolute:

• Retinopathy;
• Hereditary insufficiency of lactase, lactose intolerance, galactosemia or sprue of a glucose/galactose (as a part of drug there is a lactose);
• The pregnancy period (an exception – cases when the potential advantage of therapy for mother is significantly higher than risk of development of pathologies of a fruit);
• Children's age up to 6 years (it is not applied at children with ideal body weight less than 31 kg) (in case of need performing long therapy at children is more senior than 6 years the probability of toxic effects is increased);
• Hypersensitivity to components of drug and other derivatives 4 aminoquinolines.

Relative (Plaquenil should be applied with care because of the increased probability of side effects):

• Visual frustration: disturbance of color sight, decrease in visual acuity, narrowing of fields of vision, and also a concomitant use of the drugs promoting emergence of adverse ophthalmologic reactions (in connection with danger of progressing of visual frustration and retinopathies);
• Hematologic diseases (including data in the anamnesis);
• Serious neurologic illness, psychoses (including data in the anamnesis);
• Late skin porphyria (risk of an aggravation), psoriasis (risk of aggravation of skin manifestations), concomitant use of the drugs promoting emergence of skin reactions;
• Renal and/or liver failure, hepatitis, concomitant use of the drugs capable to exert adverse impact on function of kidneys and/or a liver (in case of heavy abnormal liver functions or kidneys the dose is required to be selected, exercising control of concentration in hydroxychloroquine plasma);
• Deficit glyukozo-6-fosfatdegidrogenazy;
• Serious illness of the digestive tract (DT);
• Hypersensitivity to quinine (cross allergic reactions are possible).

When breastfeeding (lactation) it is required to estimate carefully need of use of Plaquenil as in small amounts hydroxychloroquine is emitted with breast milk, and children about one year have considerably a hypersensitivity to toxic effects of 4 aminoquinolines.

Route of administration and dosage

The tablets Plaquenil are intended for oral administration, accept them along with food or between meals, washing down with 1 glass of milk.

It is important to consider cumulative activity of hydroxychloroquine: its therapeutic action begins to be shown several weeks later from the beginning of regular administration of drug, at the same time side effects can arise relatively early. The required therapeutic effect develops several months later. In the absence of objective improvement of a condition of the patient within half a year of treatment by hydroxychloroquine, use of Plaquenil should be stopped.

Therapy of the pseudorheumatism (P):

• Adults, including elderly patients: the minimal effective dose to 6,5 mg/kg of body weight a day (calculation is made on ideal body weight, but not on real) can make 200 mg (1 tablet) or 400 mg (2 tablets) a day; at an initial dose of 400 mg it is divided into several receptions; on reaching obvious improvement the dose can be lowered to 200 mg, in case of efficiency reduction it is possible to increase a maintenance dose to 400 mg;
• Children: a minimal effective dose – to 6,5 mg/kg of body weight a day (calculation is made on ideal weight) therefore tablets of 200 mg are not intended for children with ideal body weight up to 31 kg.

The combined use of Plaquenil with glucocorticosteroids (GKS), a methotrexate, salicylates, non-steroidal anti-inflammatory drugs (NPVS), other therapeutic substances / drugs of the second row safely. Several weeks later from the beginning of reception of medicine of a dose of salicylates and GKS can be reduced, or the termination of reception of these drugs is possible. At the same time doses of GKS need to be reduced gradually, reducing the accepted amount of substances once in 4-5 days: a cortisone – ≤ 5-15 mg, a hydrocortisone – ≤ 5-10 mg, Prednisolonum and Prednisonum – ≤ 1-2,5 mg, Methylprednisolonum and Triamcinolonum – ≤ 1-2 mg, dexamethasone – ≤ 0,25-0,5 mg.

For therapy of the system lupus erythematosus (SLE) the average initial dose of 400 mg (2 tablets) 1-2 times a day, a course of treatment – from several weeks to several months, depending on reaction of the patient is recommended to adult patients; a long maintenance therapy – 200-400 mg a day.

Prevention of bad attacks of malaria, owing to infection of Plasmodium malariae and sensitive strains of Plasmodium falciparum, once a week, in the same day:

• Adults – on 400 mg;
• Children – on 6,5 mg/kg of ideal body weight of the child, but (irrespective of weight) no more dose for adults.

Preventive therapy is recommended to be begun in 2 weeks prior to entrance to an endemic zone if it is impossible, the double (load) dose is appointed: for adults – 800 mg, for children – 12,9 mg/kg of ideal body weight (but ≤ 800 mg), divided into two receptions at an interval of 6 hours. It is necessary to continue administration of drug for prevention of a disease for 8 weeks after escape of an endemic zone.

At bad attacks of malaria at adults: 800 mg (4 tablets) once, then 400 mg (2 tablets) later 6-8 h, further – on 400 mg 2 more days (totally 2000 mg of hydroxychloroquine of sulfate).

Also efficiency, as an alternative way, a single dose of Plaquenil in a dose of 800 mg was proved.

The dose for children – 3,2 mg/kg of ideal weight (but ≤ 2000 mg), is expected 3 days of reception according to the following scheme:

• The I dose (at the beginning of an attack) – 12,9 mg/kg, but ≤ 800 mg;
• The II dose (after the I dose in 6 hours) – 6,5 mg/kg, but ≤ 400 mg;
• The III dose (after the II dose in 18 hours) – 6,5 mg/kg, but ≤ 400 mg;
• The IV dose (after the III dose in 24 hours) – 6,5 mg/kg, but ≤ 400 mg.

Radical treatment of the malaria caused by Plasmodium vivax and Plasmodium malariae: it is required to accept derivative 4 aminoquinolines along with derivatives of a 8-aminokhinolon.

The given doses of Plaquenil are expected hydroxychloroquine sulfate and are not equivalent to basis doses.

For adults the dose can be calculated taking into account ideal body weight as well as for children.

Side effects

• Blood and lymphatic system: frequency is unknown – aplastic anemia, anemia, oppression of a marrowy hemopoiesis, an agranulocytosis, thrombocytopenia, a leukopenia;
• Immune system: frequency is unknown – a Quincke's disease, a small tortoiseshell, a bronchospasm;
• Metabolism and food: often – anorexia; frequency is unknown – probability of an aggravation of a porphyria, a hypoglycemia;
• Disturbances of mentality: often – affective lability; infrequently – nervousness; frequency is unknown – suicide behavior, psychoses;
• Central and peripheral nervous system: often – a headache; infrequently – dizziness; frequency is unknown – spasms;
• Organ of sight: often – the sight illegibility connected with accommodation disturbances (dozozavisimy and reversible); infrequently – a retinopathy with defects of fields of vision and changes in pigmentation (reversible in an early form after the treatment termination by hydroxychloroquine; preservation of not diagnosed retinopathy increases risk of an irreversible damage of a retina of an eye even after drug withdrawal; in the beginning changes of a retina can be asymptomatic, be shown by scotomas of pericentral or paracentral types, passing scotomas, and also disturbances of color sight), changes of a cornea, including swelled also opacification (can be asymptomatic or cause emergence of changes, reversible after the termination of a course of therapy, such as a sight illegibility, photophobia, auras); frequency is unknown – a macular degeneration and a maculopathia (can be irreversible);
• Acoustic organ and labyrinth disturbances: infrequently – a sonitus, вертиго; frequency is unknown – deafness;
• Cardiovascular system: frequency is unknown – a cardiomyopathy owing to which heart failure up to a fatal outcome can develop (chronic cardial toxicity should be taken into account in case of detection of disturbances of conductivity (blockade of legs of a ventriculonector and/or disturbances of atrioventricular conductivity) or at a hypertrophy of both ventricles (involution of such changes is possible with drug withdrawal));
• GIT (symptoms usually at once pass after reduction of a dose or drug withdrawal): very often – nausea, an abdominal pain; often – vomiting, diarrhea;
• Gepatobiliarny system: infrequently – aberrations of laboratory indicators of functional hepatic trials; frequency is unknown – a fulminantny liver failure;
• Skin and hypodermic fabrics: often – an itch, skin rash; infrequently – disturbances of pigmentation of mucous membranes and skin, an alopecia, decolouration of hair (after the therapy termination usually these changes quickly take place); frequency is unknown – violent rash (including a multiformny erythema, Stephens-Johnson's syndrome, exfoliative dermatitis, photosensitivity, a toxic epidermal necrolysis), DRESS syndrome (the medicinal skin reaction which is followed by system manifestations and an eosinophilia), OGEP (acute generalized exanthematous пустулез; can be followed by a hyperleukocytosis and temperature increase; it is necessary to distinguish from psoriasis; after the treatment termination an outcome usually favorable);
• Skeletal and muscular and connecting fabrics: infrequently – sensomotor disturbances; frequency is unknown – the neuromyopathy or a myopathy of skeletal muscles leading to the progressing weakness with an atrophy of proximal muscular groups (can be reversible after the termination of administration of drug, but several months can be necessary for full rehabilitation), decrease in nerve conduction, suppression of tendon jerks.

Classification of frequency of undesirable side effects:> 1/10 – very often; ≥ 1/100-<1/10 – it is frequent; ≥ 1/1000-<1/100 – infrequently; ≥ 1/10 000-<1/1000 – it is rare; <1/10 000 – in isolated cases; it is not possible to determine frequency by the available data – frequency is unknown.

Symptoms of overdose of hydroxychloroquine are: vision disorders, a headache, a collapse, a hypopotassemia, spasms, disturbances of conductivity and a rhythm which involve an apnoea and hearts. As such reactions can directly develop after acceptance of an overdose of Plaquenil, it is necessary to carry out emergency treatment – to take measures for removal of drug from a stomach (to cause artificially vomiting, to carry out washing), to accept absorbent carbon in a dose, at least by 5 times exceeding the accepted hydroxychloroquine dose. Reasonablly parenteral administration of diazepam, is data on decrease on its background of cardiotoxicity of chloroquine.

For further treatment in case of need carry out antishock therapy and the artificial ventilation of the lungs (AVL). The patient has to be under constant medical control not less than 6 hours after stopping of symptoms of overdose.

The overdose of 4 aminoquinolines at children is especially dangerous, even in case of use of drug in a dose of 1000-2000 mg the lethal outcome is possible.

Special instructions

Toxic impact of hydroxychloroquine on a retina of an eye is considerably dozozavisimy. At use of means in doses to 6,5 mg on kg of ideal body weight the frequency of developing of a retinopathy small. In case of exceeding of the recommended daily doses the risk of development of a retinopathy sharply increases, and its emergence accelerates.

Prior to long therapy it is required to undergo the careful inspection of eyes including survey of an eyeground, visual acuity definition, assessment of fields and color sight. Further in the course of treatment such inspection is recommended to be undergone at least 1 time in half a year.

The following states / situations are the reason for more frequent inspection of patients:

• The daily dose of hydroxychloroquine exceeds 6,5 mg on kg of ideal body weight (at patients with an excess weight the overdose is possible);
• Renal failure;
• The total accepted dose for the expired period more than 200 000 mg;
• Advanced age;
• Reduced visual acuity.

Any visual frustration (change of color sight, decrease in visual acuity) are an indicator for immediate drug withdrawal and ensuring careful observation of a condition of sight of the patient as such changes of a retina are capable to progress even after cancellation of means.

In case of a long course of therapy it is periodically necessary to do full laboratory blood test; hydroxychloroquine is cancelled at emergence of hematologic disturbances.

As children are especially sensitive to toxic effects of 4 aminoquinolines, especially carefully it is required to meet storage conditions and to remove Plaquenil from places, available to children.

The patients receiving drug long time periodically have to undergo inspection of functions of skeletal muscles and expressiveness of a tendon jerk at the neurologist. At observation of muscular weakness drug stops being accepted.

In the relation chloroquine - resistant strains of Plasmodium falciparum, and also the vneeritrotsitny Plaquenil forms Plasmodium malariae, Plasmodium ovale, Plasmodium vivax is not effective therefore it cannot prevent infection with these microorganisms when using as means for prevention of bad attacks of malaria as means for prevention of a recurrence of the diseases caused by these activators.

It is necessary to be careful, managing vehicles and difficult mechanisms as hydroxychloroquine can break accommodation owing to what the clearness of visual perception worsens. If this state does not pass in itself over time, the dose of drug should be reduced temporarily.

Medicinal interaction

• Digoxin – increase in its concentration in serum is possible (it is recommended to reduce a digoxin dose under control of plasma concentration);
• Hypoglycemic drugs, insulin – decrease in their dose in connection with possible strengthening of effects at the beginning of therapy by hydroxychloroquine can be required;
• Antacids – can reduce hydroxychloroquine absorption therefore it is necessary to observe an interval not less than 4 hours between receptions.

Terms and storage conditions

To store in the place unavailable to children, at a temperature not above 25 °C.

Period of validity – 3 years.