hydroxychloroquine Plaquenil | 200 mg, 60 pcs. tablets

Latin name

Plaquenil  - hydroxychloroquine

Packing

10 pcs. - blisters (6) - packs of cardboard.

Pharmacological action

Plaquenil has antimalarial properties and also has anti-inflammatory and immunosuppressive effects in chronic discoid or systemic lupus erythematosus (SLE) and acute and chronic rheumatoid arthritis. The mechanism of its action in malaria, SLE and rheumatoid arthritis is not fully known.

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

Efficacy for SLE and rheumatoid arthritis is associated with the following anti-inflammatory and immunomodulating effects of hydroxychloroquine: an increase in intracellular pH slows down the antigenic response and decreases the binding of peptides of the main histocompatibility complex (HCH) receptors to a lower number of antigen-HCH receptors and leads to a decrease in the cell surface, which leads to a decrease in

response decreased phospholipase A2 activity at high concentrations, lysosomal enzymes

decreased concentration IL-1 and IL-6 s cytokines leading to a reduction of clinical and laboratory parameters as autoimmune response there is no violation of the synthesis of interferon gamma, these effects may be associated with the selective effect of

cytokines inhibition of pre- and / or post-transcription of DNA and RNA.

The drug actively suppresses asexual erythrocyte forms, as well as the gametes Plasmodium vivax and Plasmodium malariae, which disappear from the blood almost simultaneously with asexual forms. Plaquenil does not affect Plasmodium falciparum gametes.

Not effective against chloroquine-resistant strains of Plasmodium falciparum, and also not active against extra-erythrocytic forms of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale and therefore cannot prevent infection with these microorganisms when prescribed for prophylactic purposes, and is also not able to prevent relapse caused by these pathogens.

Pharmacokinetics

Absorption

After oral administration, hydroxychloroquine is rapidly and almost completely absorbed from the digestive tract. In healthy volunteers, after a single dose of 400 mg of Cmax hydroxychloroquine in blood plasma was reached after 1.83 hours and ranged from 53 to 208 ng / ml.

Distribution of

Plasma Protein Binding - 45%.

Unchanged drug and its metabolites are well distributed in the body. Vd is 5-10 l / kg. Hydroxychloroquine accumulates in tissues with a high level of metabolism - in the liver, kidneys, lungs, spleen (in these organs the concentration exceeds the plasma by 200-700 times), in the central nervous system, erythrocytes, leukocytes, as well as in the retina and tissues rich in melanin.

Hydroxychloroquine crosses the placental barrier and is found in small amounts in breast milk.

Metabolism

In the liver, hydroxychloroquine is partially converted into active leaded metabolites.

Excretion of

The average T1 / 2 value from plasma varies depending on the time elapsed after taking the drug as follows: 5.9 hours (from reaching Cmax to 10 hours), 26.1 hours (from 10 to 48 hours) and 299 hours (from 48 to 504 h).

Hydroxychloroquine and its metabolites are excreted mainly in the urine and to a lesser extent with bile. Withdrawal of the drug is slow, terminal T1 / 2 is about 50 days (from whole blood) and 32 days (from plasma). For 24 hours with urine, 3% of the administered dose of the drug is excreted.

Indications

rheumatoid arthritis

juvenile rheumatoid arthritis

lupus erythematosus and systemic and discoid Plasmodium falciparum

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

Contraindications

hypersensitivity to 4-aminoquinoline derivatives

retinopathy

pregnancy (see “Pregnancy and lactation”)

hereditary lactose intolerance, lactase deficiency, galactosemia or glucose / galactose malabsorption syndrome (due to the presence of lactose in the preparation).

children's age if prolonged therapy is necessary (children have an increased risk of developing toxic effects)

children's age up to 6 years (200 mg tablets are not intended for children with an "ideal" body weight of less than 31 kg).

Precautions: visual disturbances (decreased visual acuity, color vision impairment, narrowing of visual fields), concomitant use of drugs that can cause adverse ophthalmic reactions (danger of progression of retinopathy and visual disturbances)

hematologic diseases (including and a history of)

severe neurological diseases, psychoses (including a history of)

late skin porphyria (risk of exacerbation), psoriasis (risk of increased skin manifestations of the disease), simultaneous administration of drugs that can cause skin reactions

renal failure and / or liver failure, hepatitis, concomitant use of drugs that can adversely affect the function of the liver and / or kidneys (for severe impairment of renal or hepatic function, the dose should be selected under the control of plasma concentrations of hydroxychlo ohineyu)

deficiency of glucose-6-phosphate dehydrogenase

severe gastrointestinal disease

hypersensitivity to quinine (possibility of cross allergic reactions).

Use during pregnancy and lactation

Hydroxychloroquine crosses the placenta. With regard to its use during pregnancy, data are limited. It should be noted that 4-aminoquinolines in therapeutic doses can cause intrauterine damage to the central nervous system, including auditory nerve (impaired hearing and vestibular apparatus, 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, as it is shown that it is excreted in small amounts in breast milk, and young children are especially sensitive to the toxic effects of 4-aminoquinolines.

Composition

1 tab.

hydroxychloroquine sulfate 200 mg

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

Dosage and administration

Note: all doses are for hydroxychloroquine sulfate and are not equivalent to the doses for base.

Inside, with food or with a glass of milk.

Treatment of RA. Hydroxychloroquine has cumulative activity. For the manifestation of its therapeutic effect, several weeks of taking the drug are necessary, while side effects can occur relatively early. The necessary therapeutic effect develops after several months of taking the drug. In the absence of objective improvement in the patient's condition within 6 months of taking hydroxychloroquine, the use of 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 by the "ideal" body weight, and not by actual body weight) and can be either 200 or 400 mg / day.

In patients who are able to take 400 mg daily

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

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

Use of 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, doses of GCS and salicylates may be reduced, or these drugs may be discontinued. GCS doses should be reduced gradually every 4–5 days: the dose of cortisone — no more than 5–15 mg, the dose of hydrocortisone — no more than 5–10 mg, the dose of prednisolone and prednisone — no more than 1–2.5 mg the dose of methylprednisolone and triamcinolone is not more than 1-2 mg and dexamethasone not more than 0.25-0.5 mg.

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

Treatment for malaria

Prevention of acute malaria attacks caused by P. malariae and sensitive 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 (the “ideal” body weight is taken for calculation), however, regardless of body weight, it should not exceed the adult dose.

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

Treatment of acute malaria attacks

For adults, an initial dose of 800 mg should be given in a dose of 400 mg after 6 or 8 hours, and then 400 mg in the next 2 days (a total of 2 g of hydroxychloroquine sulfate).

Alternative treatment: The effectiveness of a single dose of 800 mg has also been proven.

Doses for adults can also be calculated according to the "ideal" body weight, similar to the calculation of doses in children (see below).

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

first dose - 12.9 mg / kg (single dose no more than 800 mg) second dose - 6.5 mg / kg (no more than 400 mg) 6 hours after the first third dose - 6.5 mg / kg (no more 400 mg) 18 hours after the second dose, the fourth dose - 6.5 mg / kg (not more than 400 mg) 24 hours after the third dose.

Radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax

The radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax requires the simultaneous administration of 8-aminoquinolone derivatives.

Side effects

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

Changes in the retina at first may be asymptomatic, or manifest as scotomas of a paracentral or pericentral type, transient scotomas and color vision impairment.

Corneal changes are possible, including swelling and clouding. They may be asymptomatic or cause visual disturbances such as the appearance of halos, blurred vision, or photophobia. Upon termination of treatment, these changes may undergo a reverse development.

Visual disturbances associated with accommodation disorders that are dose-dependent and reversible may also occur.

From the skin: sometimes skin rashes are also described, itching, changes in pigmentation of the skin and mucous membranes, hair bleaching and alopecia. These changes usually pass quickly after discontinuation of treatment. The development of a 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 trigger exacerbation of psoriasis. OHEP may be accompanied by fever and hyperleukocytosis. After drug withdrawal, the outcome is usually favorable.

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

From the hepatobiliary system: with prolonged use in large doses, the development of a hepatotoxic effect is possible. There are reports of isolated cases of impaired liver function 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, cramps, 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 to fully recover. At the same time, weak sensory changes, suppression of tendon reflexes and a decrease in nerve conduction can be observed.

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

Chronic cardiac toxicity may be suspected if conduction abnormalities (blockade of the bundle of the bundle / impairment of AV conduction) or hypertrophy of both ventricles are detected. With the withdrawal of the drug, the reverse development of these changes is possible.

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

Hydroxychloroquine may provoke or cause exacerbation of porphyria.

On the part of the immune system: urticaria, angioedema, bronchospasm.

Drug Interaction

Digoxin. It has been reported that hydroxychloroquine is able to increase plasma concentrations of digoxin, so 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.

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

Antacids. Hydroxychloroquine absorption can be reduced. Therefore, with the simultaneous use of antacids and hydroxychloroquine, the interval between their administration should be at least 4 hours

Hydroxychloroquine also cannot be excluded from the following interactions with other drugs that have been described for chloroquine, but have not yet been observed when taking hydroxychloroquine.

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

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

Neostigmine and pyridostigmine. Antagonism of action.

Any intradermal human diploid rabies vaccine. Reduction of antibody formation in response to primary immunization with an intradermal human diploid-rabies rabies vaccine.

Storage conditions

At a temperature not exceeding 25 РC.

Keep out of the reach of children.

Expiration

3 years.

Do not use after the expiry date stated on the package.

Deystvuyuschee

hydroxychloroquine

Pharmacy

Prescription

dosage form

dosage form

tablets

Sano i-Aventis, France