PLAKVENIL 200 mg

Composition

Active ingredient: hydroxychloroquine sulfate 200 mg,

Excipients: lactose monohydrate, povidone K25, corn starch, magnesium stearate, opadry OY-L-28900 (hypromellose, macrogol 4000, titanium dioxide (E171), lactose monohydrate).

Pharmacokinetics

Plaquenil has:

antiprotozoal action - they suppress the vital activity of protozoa that cause infectious diseases, first of all, it concerns pathogens of malaria, therefore, the main effect of the drug is antimalarial,

immunosuppressive effect - suppresses an over-expressed reaction of the immune system, including allergy to the patient's own tissues,

anti-inflammatory action - suppresses inflammatory reactions.

Plaquenil belongs to the group of antimalarial and immunosuppressive drugs from the group of 4-aminoquinoline derivatives. The mechanism of its action is not well understood, but it is believed that it is associated with the following properties of this drug:

The ability to suppress the action of toxic free radicals formed during the metabolic process (antioxidant effect).

The ability to inhibit the action of enzymes that cause the breakdown of cartilage tissue.

The ability to suppress the synthesis of prostaglandins - biologically active substances involved in inflammatory processes.

The ability to concentrate in leukocytes and strengthen the membranes of lysosomes - cell structures containing enzymes that can break down nutrients entering the cell. Lysosomes are also involved in the digestion of bacteria captured by leukocytes.

The ability to suppress the synthesis of those types of cytokines (hormone-like proteins synthesized by cells to affect other cells) that activate the immune system. It also helps to reduce autoimmune processes (destruction of the body's own tissues by immune processes).

The ability to suppress the activity of lymphocytes involved in immune responses.

The ability to suppress the formation of rheumatoid factor - immunoglobulins (antibodies), which perceive the body's own tissues as foreign structures (antigens) and destroy them.

The antimalarial properties of Plaquenil consists in suppressing the activity of pathogens of three-day malaria, four-day malaria, malaria-oval, as well as forms of tropical malaria pathogens that are sensitive to it (most pathogens of tropical malaria are insensitive to Plaquenil).

After taking the Plaquenil tablet, its active ingredient is rapidly and almost completely absorbed and enters the bloodstream, and then accumulates in high concentrations in various organs and tissues. The maximum concentration of the active substance in the blood plasma is reached within approximately 100 minutes. The drug is decomposed in the liver into active and inactive metabolic products (metabolites) and is excreted in the urine, but partially in the feces. The active substance Plaquenil crosses the placenta and is excreted in human milk. The drug is excreted slowly, it disappears from the blood plasma no earlier than a month later.

Indications for use

rheumatoid arthritis,

juvenile rheumatoid arthritis,

lupus erythematosus (systemic and discoid),

malaria (excluding those caused by chloroquine-resistant Plasmodium falciparum)

for the prevention and treatment of acute attacks of malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, as well as susceptible strains of Plasmodium falciparum,

for the radical treatment of malaria caused by susceptible strains of Plasmodium falciparum.

Contraindications

eye diseases

cardiac arrhythmias

hypersensitivity to the drug.

Application during pregnancy and lactation

Hydroxychloroquine crosses the placenta. Limited data are available for its use in pregnancy. It should be noted that 4-aminoquinolines in therapeutic doses can cause intrauterine damage to the central nervous system, incl. auditory nerve (hearing and vestibular disorders, congenital deafness), retinal hemorrhages and abnormal retinal pigmentation. Therefore, the use of hydroxychloroquine during pregnancy should be avoided, unless the potential benefit to the mother outweighs the risk to the fetus.

The need to use the drug during breastfeeding should be carefully weighed. it has been shown that it is excreted in small quantities in breast milk, and young children are especially sensitive to the toxic effects of 4-aminoquinolines.

Side effects

From the side of the organ of vision: may develop, although rarely, retinopathy with changes in pigmentation and defects in the fields of vision. In its early form, these events are usually reversible after discontinuation of hydroxychloroquine. If the condition remains undiagnosed and retinal lesions continue to develop further, there may be a risk of their progression even after the drug is discontinued.

Retinal changes may initially be asymptomatic, or manifest as paracentral or pericentral scotomas, transient scotomas, and color vision disorders.

Changes in the cornea, including edema and opacity, are possible. They may be asymptomatic or cause visual disturbances such as halos, blurred vision, or photophobia. When treatment is discontinued, these changes may be reversed.

There may also be visual impairments associated with accommodation impairments, which are dose-dependent and reversible.

From the side of the skin: sometimes skin rashes occur, itching, changes in pigmentation of the skin and mucous membranes, discoloration of hair and alopecia are also described. These changes usually go away quickly after stopping treatment. The development of bullous rash has been reported, including very rare cases of erythema multiforme and Stevens-Johnson syndrome, photosensitivity, and isolated cases of exfoliative dermatitis.

Very rare cases of acute generalized exanthematous pustulosis (OGEP) must be distinguished from psoriasis, although hydroxychloroquine can also exacerbate psoriasis. OGEB can be accompanied by fever and hyperleukocytosis. After discontinuation of the drug, the outcome is usually favorable.

From the gastrointestinal tract: nausea, diarrhea, anorexia, abdominal pain and rarely vomiting. These symptoms usually resolve immediately after dose reduction or drug withdrawal.

From the side of the hepatobiliary system: with prolonged use in large doses, the development of hepatotoxic action is possible. There are reports of isolated cases of liver dysfunction and several cases of suddenly developed liver failure.

From the side of the central nervous system: infrequently, dizziness, tinnitus, hearing loss, headache, irritability, emotional instability, psychosis, convulsions, muscle weakness, ataxia.

From the peripheral nervous system and muscles: there have been cases of skeletal muscle myopathy or neuromyopathy, leading to progressive weakness and atrophy of the proximal muscle groups. Myopathy may be reversible after discontinuation of the drug, but it may take several months for full recovery. At the same time, weak sensory changes, suppression of tendon reflexes and a decrease in nerve conduction can be observed.

From the side of the cardiovascular system: there are rare reports of the development of cardiomyopathy.

Chronic cardiac toxicity may be suspected when conduction abnormalities (bundle branch block / AV conduction abnormalities) or hypertrophy of both ventricles are found. When the drug is discontinued, the reverse development of these changes is possible.

From the side of the hematopoietic organs: cases of inhibition of bone marrow hematopoiesis were rarely observed. Rare cases of anemia have been reported, incl. aplastic, agranulocytosis, leukopenia and thrombocytopenia.

Hydroxychloroquine can provoke or exacerbate porphyria.

From the immune system: urticaria, angioedema, bronchospasm.

Interaction

Digoxin. It has been reported that hydroxychloroquine is able to increase plasma concentrations of digoxin, therefore, in order to avoid the development of glycosidic intoxication while taking these drugs, it is necessary to reduce the dose of digoxin under the control of its plasma concentrations.

Medications used to treat diabetes. Because hydroxychloroquine can potentiate the effects of insulin and oral hypoglycemic agents, it may be necessary to reduce the dose of these hypoglycemic agents when starting hydroxychloroquine.

Antacids. May decrease absorption of hydroxychloroquine. Therefore, with the simultaneous use of antacids and hydroxychloroquine, the interval between their intake should be at least 4 hours.

In hydroxychloroquine, the following interactions with other drugs that have been described for chloroquine, but have not yet been observed with hydroxychloroquine, cannot be ruled out.

Aminoglycosides. Potentiation of their direct blocking action on neuromuscular transmission.

Cimetidine. Suppresses the metabolism of antimalarial drugs, which can lead to an increase in their plasma concentrations and increase the risk of developing their side effects, especially toxic ones.

Neostigmine and pyridostigmine. Antagonism of action.

Any intradermal human diploid cell rabies vaccine. Decreased antibody production in response to primary immunization with intradermal human diploid cell rabies vaccine.

Method of administration and dosage

Note: All doses are for hydroxychloroquine sulfate, and are not equivalent to base.

Inside, during meals or with a glass of milk.

RA treatment. Hydroxychloroquine has cumulative activity. For the manifestation of its therapeutic effect, several weeks of taking the drug are required, while side effects can appear relatively early. The required therapeutic effect develops after several months of taking the drug. If there is no objective improvement in the patient's condition within 6 months of taking hydroxychloroquine, the drug should be discontinued.

Adults (including the elderly) should take the minimum effective dose. They should not exceed 6.5 mg / kg / day (calculated from ideal body weight, not real body weight) and can be either 200 or 400 mg / day.

In patients capable of taking 400 mg daily

Initially 400 mg daily in divided doses. When an obvious improvement is achieved, the dose can be reduced to 200 mg. With a decrease in the effect, the maintenance dose can be increased to 400 mg.

Children. The minimum effective dose should be used. The dose should not exceed 6.5 mg / kg (based on ideal body weight). Therefore, 200 mg tablets are not suitable for children with an ideal body weight of less than 31 kg.

Use of the drug Plaquenil for combination therapy of RA. Plaquenil can be safely used in combination with GCS, salicylates, NSAIDs, methotrexate and other second-line therapeutic agents. After several weeks of using the drug Plaquenil, the doses of corticosteroids and salicylates may be reduced or these drugs may be discontinued. Doses of GCS should be reduced gradually every 45 days: the dose of cortisone by no more than 515 mg, the dose of hydrocortisone by no more than 510 mg, the dose of prednisolone and prednisone by no more than 12.5 mg, the dose of methylprednisolone and triamcinolone by no more than 12 mg and dexamethasone by no more than 0.250.5 mg.

SLE treatment. The initial average dose in adults is 400 mg 1 or 2 times a day. It should be administered over several weeks or months, depending on the patient's response. For long-term maintenance therapy, it is sufficient to use the drug in a lower dose of 200 to 400 mg.

Malaria treatment

Prevention of acute attacks of malaria caused by P. malariae and susceptible strains of Plasmodium falciparum

Adults 400 mg weekly on the same day of the week.

For children, the weekly dose is 6.5 mg / kg (for the calculation, the ideal body weight is taken), however, regardless of body weight, it should not exceed the adult dose.

If conditions permit, then preventive therapy should be started 2 weeks before entering the endemic area. If this is not possible, then an initial double (loading) dose can be prescribed: adults 800 mg, children 12.9 mg / kg of ideal body weight (but not more than 800 mg), divided into two doses with a 6-hour interval. Prophylactic treatment should be continued for 8 weeks after leaving the endemic area.

Treatment of acute attacks of malaria

For adults, an initial dose of 800 mg is followed by a dose of 400 mg every 6 or 8 hours, followed by 400 mg every 2 consecutive days (a total of 2 g of hydroxychloroquine sulfate).

Alternative treatment: A single dose of 800 mg has also been proven to be effective.

Doses for adults can also be calculated based on ideal body weight, similar to calculating doses for children (see below).

For children, a total dose of 32 mg / kg of ideal body weight (but not more than 2 g) is prescribed for 3 days as follows:

the first dose of 12.9 mg / kg (single dose of no more than 800 mg), the second dose of 6.5 mg / kg (no more than 400 mg) 6 hours after the first, the third dose of 6.5 mg / kg (no more than 400 mg ) 18 hours after the second dose, the fourth dose of 6.5 mg / kg (no more than 400 mg) 24 hours after the third dose.

Radical treatment of Plasmodium malariae and Plasmodium vivax malaria

For the radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax, the simultaneous administration of 8-aminoquinolone derivatives is necessary.

Overdose

An overdose of 4-aminoquinolines is especially dangerous in children; even 12 g of the drug can be fatal.

Symptoms: headache, visual disturbances, collapse, seizures, hypokalemia, rhythm and conduction disturbances, followed by cardiac arrest and respiratory arrest.

Treatment: t. these effects can develop very quickly after taking a large dose of the drug, in these cases, appropriate measures should be started immediately. Induction of vomiting or gastric lavage through a tube should be performed immediately. To slow down absorption, the appointment of activated carbon in a dose at least 5 times higher than the taken dose of the drug. Parenteral administration of diazepam is advisable (a decrease in the cardiotoxicity of chloroquine against its background is described).

If necessary, artificial ventilation of the lungs and anti-shock therapy should be carried out.

After the relief of symptoms of an overdose, continued medical supervision is required for at least 6 hours.

special instructions

The toxic effect on the retina is highly dose-dependent. The incidence of retinopathy with doses up to 6.5 mg / kg of ideal body weight is low. Exceeding the recommended daily dose dramatically increases the risk of developing retinopathy and accelerates its appearance.

Before starting a long course of drug treatment, a thorough examination of both eyes should be carried out. The examination should include the determination of visual acuity, examination of the fundus, 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 more frequent in the following situations:

at a daily dose exceeding 6.5 mg / kg of ideal body weight (in obese patients, the use of absolute body weight to calculate the dose can lead to an overdose),

with renal failure,

with a total dose of more than 200 g,

in the elderly,

with reduced visual acuity.

In the event of any visual disturbances (decreased visual acuity, change in color vision), the drug should be immediately discontinued and the patient's visual condition should be closely monitored. retinal changes (and visual disturbances) may progress even after drug withdrawal.

It is recommended to be careful when prescribing hydroxychloroquine to patients with liver and kidney disease, which may require a decrease in the dose of the drug, as well as due to the possibility of the drug's effect on the function of these organs (in severely impaired renal or liver function, the dose should be selected under the control of plasma concentrations of hydroxychloroquine) ...

In patients receiving long-term treatment, a complete blood count should be performed periodically; if hematological disorders occur, hydroxychloroquine should be canceled.

Children are especially sensitive to the toxic effects of 4-aminoquinolines, so care should be taken to keep hydroxychloroquine out of the reach of children.

All patients receiving the drug for a long time should be periodically examined by a neurologist regarding the functions of skeletal muscles and the severity of tendon reflexes. If muscle weakness occurs, the drug should be discontinued.

NS and malaria

Plaquenil is ineffective against chloroquine-resistant strains of Plasmodium falciparum, and is also inactive against extra-erythrocytic forms of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale and therefore cannot prevent infection with these microorganisms when administered to prevent acute attacks of malaria, but also cannot prevent relapse diseases caused by these pathogens.

Influence on the ability to drive vehicles and control mechanisms

Patients should be careful when driving vehicles or performing work requiring increased attention, because hydroxychloroquine can interfere with accommodation and vision clarity. If this condition does not go away on its own, the dose may be temporarily reduced.

Conditions of dispensing from pharmacies

Dispensed by prescription

Storage conditions

At a temperature not higher than 25 C

Shelf life

3 years