Farm effect Hydroxychloroquine:
antimalarials, actively inhibits erythrocytic forms (gematoshizotropny drug). Compacts lysosomal membranes and prevents the lysosomal enzyme, breaks replication of DNA, RNA synthesis and utilization of hemoglobin erythrocyte forms of Plasmodium. Is also immunosuppressive and anti-inflammatory action, suppresses free radical processes, reduces the activity of proteolytic enzymes (protease and collagenase), leukocyte chemotaxis of lymphocytes.
Pharmacokinetics Hydroxychloroquine:
Absorption – variable. Period poluabsorbtsii – 3.6 h (1.9-5.5 h). Bioavailability – 74%. Relationship to plasma proteins – 45%. TSmax -3.2 h (2-4.5 h), Smah after oral 155 mg – 948 ng / ml after oral 310 mg-1895 ng / ml. Accumulates in tissues with high levels of metabolism (liver, kidney, lung, spleen – in these organs over plasma concentrations of 200-700 times, the CNS, erythrocyte, leukocyte) and in tissues rich in melanin. At very low concentrations found in the walls of the gastrointestinal tract. Crosses the placental barrier in small amounts determined in breast milk. The volume of distribution: measured in blood – 5,522 liters of plasma – 44,257 liters. Partially metabolized in the liver with the formation of active metabolites dezetilirovannyh. T1 / 2 of blood – 50 days from the plasma – 32 days. Excreted by the kidneys (23-25% unchanged) and bile (less than 10%). Excretion is very slow and long can be determined in urine after cessation of treatment.
Indications Hydroxychloroquine:
Rheumatoid arthritis, lupus (systemic and discoid). Juvenile arthritis. Hypercalcemia on the background of sarcoidosis. Malaria: treatment of acute attacks and suppressive therapy of malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae (excluding гидроксихлорохинрезистентные cases) and sensitive strains of Plasmodium falciparum; radical treatment of malaria caused by susceptible strains of Plasmodium falciparum. Photodermatitis. Late cutaneous porphyria, chronic cutaneous vasculitis.
Contraindications Hydroxychloroquine:
Hypersensitivity, pregnancy (possible use in “real life” condition), lactation, children’s age (continuous therapy). With caution. Retinopathy, changing fields of view, inhibition of bone marrow hematopoiesis, psychosis (including history), porphyria, psoriasis, deficiency of glucose-6-phosphate dehydrogenase, hepatitis, hepatic and / or kidney failure.
Dosage Hydroxychloroquine:
Orally, during a meal or with a glass of milk. 200 mg of hydroxychloroquine sulfate equivalent to 155 mg hydroxychloroquine base. Rheumatoid arthritis: the initial dose in adults – 400-600 mg / day., Maintenance – 200-400 mg / day. Juvenile arthritis: dose should not exceed 6.5 mg / kg or 400 mg / day. (Choose the lowest dose). Discoid and systemic lupus erythematosus: an initial dose for adults – 400-800 mg / day., Which support – 200-400 mg / day. Photodermatosis: up to 400 mg / day. Treatment should be limited to periods of maximum solar exposure. Malaria: suppressive therapy in adults – 400 mg / day. Every day 7; children (including infants) weekly overwhelming dose – 6.5 mg / kg, but regardless of the weight should not exceed adult dose (400 mg). If conditions permit, suppressive therapy is prescribed for 2 weeks prior to the action, otherwise, you can assign an initial double dose: 800 mg – for adults and 12.9 mg / kg (but not exceeding 800 mg) – children, dividing it into 2 doses with an interval of 6 h. suppressive therapy should continue for 8 weeks after leaving endemic area. Treatment of acute attacks of malaria: an initial dose for adults – 800 mg, then 400 mg every 6-8 hours, then 400 mg in next 2 days (total 2 g hydroxychloroquine sulfate). An alternative method may be an effective dose of 800 mg dose. For children the total dose – 32 mg / kg (but not more than 2 g) shall be appointed for 3 days: the first dose – 12.9 mg (but not exceeding a single dose of 800 mg), a second dose – 6.5 mg / kg (but not exceeding 400 mg ) 6 h after the first, third dose – 6.5 mg / kg (but not exceeding 400 mg) 18 h after the second dose, the fourth dose – 6.5 mg / kg (but not exceeding 400 mg) 24 h after the third dose. The dose for adults may also be calculated for 1 kg of body weight, as well as for children.
Side effects Hydroxychloroquine:
On the part of the musculoskeletal and nervous systems: myopathy or neuromyopathy, leading to growing infants and atrophy of proximal muscle groups, sensory impairments, reduced tendon reflexes, abnormal nerve conduction, headache, dizziness, nervousness, psychosis, emotional lability, seizures . From the senses: tinnitus, deafness, photophobia, impaired visual acuity, accommodation disturbance, edema, and corneal opacity, scotoma, with prolonged use of high doses – retinopathy (including violation of pigmentation and defects in visual fields), atrophy optic nerve, keratopathy, dysfunction of the ciliary muscle. From the CAS: ILC, AV block, decreased myocardial contractility, myocardial hypertrophy. From the digestive system: nausea, vomiting (rare), decreased appetite, abdominal pain spastic character, diarrhea, hepatotoxicity (liver dysfunction, liver failure). For part of the blood: Neutropenia, aplastic anemia, agranulocytosis, thrombocytopenia, hemolytic anemia (in patients with deficiency of glucose-6-phosphate dehydrogenase). For the skin: skin rash (including bullous and generalized pustular), pruritus, impaired pigmentation of the skin and mucous membranes, hair discoloration, alopecia, photosensitivity, mnogomofornaya exudative erythema), exacerbation of psoriasis (including those with fever and hyperskeocytosis).
Overdose Hydroxychloroquine:
Symptoms: cardiac toxicity (conduction disturbances in bundle branch block (chronic intoxication – myocardial hypertrophy of both ventricles), decreased blood pressure, neurotoxicity (dizziness, headache, irritability, convulsions, coma), visual disturbances, respiratory arrest and heart. Overdosage especially dangerous in young children, even the use of 2.1 grams of the drug can be fatal. Treatment: gastric lavage, the appointment of activated charcoal (at a dose 5 times higher than the dose), forced diuresis and alkalinization of urine (eg, ammonium chloride until the pH of urine – 5.5-6.5) increases the urinary excretion of 4-aminohinolina, symptomatic therapy (including the appointment in convulsions – diazepam, antishock therapy). is necessary to monitor the concentration of sodium in blood serum and constant medical supervision for at least 6 h after the relief of symptoms.
Interactions Hydroxychloroquine:
Increases plasma digoxin. Increases the plasma concentrations of penicillamine and the risk of its side-effects of blood, urinary tract and skin reactions. Alkaline fluids and alkalis accelerate excretion.
Cautions:
Before and during therapy should be carried out at least 1 time in 6 months. ophthalmologic examination. During therapy requires constant monitoring of blood cell composition, state of skeletal muscles (including tendon reflexes). During the period of treatment must be careful when driving vehicles and occupation of other potentially hazardous activities that require high concentration of attention and quickness of psychomotor reactions.
