Pharmacological Effects Plaquenil
Antimalarial. Plaquenil Hydroxychloroquine has a number of different pharmacological properties that may make it a therapeutic effect: the interaction with sulfhydryl groups, changes in the activity of enzymes (including phospholipase, sodium adenosine-H-cytochrome (NAD-H-cytochrome) c-reductase, cholinesterase, protease and hydrolases) binding to DNA, stabilizing lysosomal membranes, inhibition of prostaglandin synthesis, chemotaxis and phagocytosis polimorfoyadernyh cells, reducing the synthesis of monocyte interleukin-1 and release suleroksidaniona neutrophils.
Intracellular concentration and increasing pH in the lysosomes explains how antiprotozoynoy and antirheumatic activity of hydroxychloroquine. The drug, actively suppresses asexual erythrocytic forms, as well as gametes Plasmodium vivax and Plasmodium malariae, which disappear from the blood almost simultaneously with asexual forms. On Plasmodium falciparum gametes Plaquenil does not work. The drug has also immunosuppressive and antiinflammatory effects.
Pharmacokinetics Plaquenil
Suction
After oral hydroxychloroquine rapidly and almost completely absorbed from the gastrointestinal tract. Tmax is 2-4.5 h, Cmax after oral administration at a dose of 155 mg – 948 ng / ml, after oral administration at a dose of 310 mg – 1895 ng / ml.
Distribution
Plasma protein binding – 45%. Vd is 5.10 L / kg. Well distributed in the body, accumulating in the blood cells in the liver, lungs, kidneys, the retina. Accumulates in tissues with high levels of exchange – in the liver, kidneys, lungs, spleen, these organs over plasma concentrations of 200-700 times; in the CNS, erythrocyte, leukocyte and tissues that are rich in melanin. Crosses the placental barrier. In minor amounts determined in breast milk.
Metabolism and Elimination
In the liver, hydroxychloroquine is partially converted into active metabolites of ethyl and displayed in the kidneys, and also – in the bile. Excretion of the drug slow. T1 / 2 is about 50 days (whole blood) and 32 days (plasma).
Indications Plaquenil
• rheumatoid arthritis;
• juvenile chronic arthritis;
• Lupus (systemic and discoid);
• photodermatitis.
Malaria (with the exception of chloroquine-resistant cases):
• for the treatment of acute attacks and suppression of malaria caused by Plasmodium vivax, P.ovale and P.malariae, as well as sensitive strains of P.falciparum;
• for radical treatment of malaria due to susceptible strains of P. falciparum.
Plaquenil Dosage
Plaquenil is only intended for oral use. Take medication with meals or a glass of milk. All doses are given on the basis of hydroxychloroquine sulfate, and are not equivalent doses of the base. In rheumatic diseases therapeutic activity is observed at the accumulation of the drug.
For the development of the therapeutic effect of the drug must be taken within a few weeks, while side effects may occur relatively early. Adequate therapeutic effect develops after several months of treatment. If objective improvement in the patient’s condition is not observed within 6 months of treatment, the drug should be discontinued.
Rheumatoid arthritis: For adults the initial dose is 400-600 mg / day maintenance dose – 200-400 mg / day. Juvenile chronic arthritis: dose should not exceed 6.5 mg / kg or 400 mg / day (must choose the lowest effective dose). Systemic and discoid lupus erythematosus: adult starting dose is 400-800 mg / day maintenance dose – 200-400 mg / day. Photodermatitis: treatment should be limited to periods of maximum exposure light. For adults can be quite 400 mg / day.
Malaria
For malaria prevention drug prescribed to adults at a dose of 400 mg in one and the same day of the week.
For the vast majority of children weekly dose is 6.5 mg / kg body weight (for calculation shall be the “ideal” body weight), but, regardless of body weight should not exceed adult dose. If conditions allow, the preventive therapy should begin 2 weeks of entry in the endemic zone. If it is not possible, then an adult, you can assign an initial double dose of 800 mg for children – 12.9 mg / kg (maximum 800 mg), and dividing by 2 doses with an interval of 6 hours prophylactic therapy should continue for 8 weeks after departure from endemic zone.
For treatment of acute attacks of malaria drug is prescribed to adults in an initial dose of 800 mg, then 400 mg every 6 or 8 hours, then – to 400 mg over next 2 days, total dose – 2 grams in a single application of 800 mg was also found to be effective .
The dose for adults as for children, can be calculated taking into account body weight.
Children drug prescribed a total dose of 32 mg / kg (maximum 2 g) for 3 days as follows: first dose – 12.9 mg / kg (maximum single dose 800 mg), the second dose – 6.5 mg / kg (not more than 400 mg) 6 h after the first dose, third dose – 6.5 mg / kg (maximum 400 mg) 18 h after the second dose, the fourth dose – 6.5 mg / kg (not to exceed 400 mg) 24 h after the third dose .
For maintenance therapy to use the minimum effective dose, not exceeding 6.5 mg / kg / day (values are taken to calculate the ideal body weight).
Side effects of Plaquenil
• On the part of the vision: rarely – Retinopathy with changes in pigmentation and visual field defects. In an early form of retinopathy is reversible with cessation of hydroxychloroquine treatment. If retinopathy is conserved, then there is a risk of irreversible retinal lesions, even after withdrawal of treatment. Retinal changes may be asymptomatic or manifest scotoma. Describes the changes of the cornea, including swelling and clouding.
They may be asymptomatic or cause such conditions as the emergence of “veil” in front of the eyes or photophobia. These changes may be reversible with cessation of treatment. Possible decrease in vision due to violations of accommodation, which depends on the dose and is reversible.
Dermatological reactions: possible skin rash, itching, changes in pigmentation of the skin and mucous membrane lesions, discoloration of hair and alopecia. These reactions usually pass quickly at the termination of treatment. Possible exacerbation of psoriasis, rarely – photosensitivity, very rare cases of pemphigus (which should be distinguished from psoriasis), sometimes accompanied by fever and hyperskeocytosis. After discontinuation side effects are usually reversible. Allergic reactions: possible bullous eruption, including the very rare cases of erythema multiforme and Stevens-Johnson syndrome.
• From the digestive system: nausea, diarrhea, anorexia, abdominal pain and, rarely, vomiting. These reactions are usually held immediately after the dose reduction or discontinuation of treatment.
With prolonged use and high doses of possible hepatotoxicity, there have been reports of sporadic cases of liver damage, a few cases suddenly developed liver failure. In some cases – liver function abnormalities, and in rare cases – suddenly developed liver failure.
• From the side of the central nervous system and peripheral nervous system: rarely – dizziness, tinnitus, hearing loss, headache, irritability, emotional instability, psychosis, convulsions, muscle weakness, ataxia, and in some cases – myopathy of skeletal muscle or neuromyopathy, leading to progressive weakness and atrophy of proximal muscle groups. Myopathy may be reversible after discontinuation of the drug, but full recovery may take several months. There are weak sensory changes, suppression of tendon reflexes and reduction of nerve conduction.
• Cardio-vascular system: rarely – cardiomyopathy, decrease in conductivity and myocardial contractility, prolonged use at high doses – myocardiodystrophy.
In case of detection of myocardial hypertrophy and ventricular conduction disturbances (AV-block) should be borne in mind the possibility of chronic intoxication (in these situations require removal of the drug).
• With the hemopoietic system: rare – bone marrow suppression of hematopoiesis. Hydroxychloroquine may aggravate porphyria.
Contra Plaquenil
• maculopathy in history;
• Children’s age when necessary long-term therapy;
• Children under the age of 6 years (200 mg tablets are not designed for children weighing less than 35 kg);
• Hypersensitivity to the derivative 4-aminohinolina.
Precautions should be taken in the preparation of retinopathy (maculopathy when the drug is contraindicated), breach of bone marrow hematopoiesis, psychosis (including history), porphyria, psoriasis, deficiency of glucose-6-phosphate dehydrogenase, and hepatic and / or renal failure, hepatitis.
Pregnancy and lactation
Data on the use of the drug during pregnancy are limited. Hydroxychloroquine crosses the placental barrier. It should be noted that the 4-aminohinoliny in therapeutic doses can cause damage to the CNS, including ototoxicity (auditory and vestibular toxicity, congenital deafness), retinal bleeding and abnormal pigmentation of the retina.
Given this, it should avoid the use of hydroxychloroquine during pregnancy except in cases when the potential benefits of therapy to the mother justifies the potential risk to the fetus. Should carefully weigh the need of the drug during lactation (breastfeeding) because shown that hydroxychloroquine in small amounts excreted in breast milk, and it is known that infants are particularly susceptible to the toxic effects of 4-aminohinolinov.
Use in hepatic dysfunction
Precautions should be used in the preparation for liver failure.
Use in renal impairment
Precautions should be used in the preparation of renal failure.
Cautions
The frequency of retinopathy, if not higher than the recommended daily intake is low. Exceeding the recommended daily dose increases the risk of retinal damage and accelerates the process. Before starting treatment drug, a thorough examination of both eyes. The survey should include a definition of visual acuity, color vision and visual field examination. During therapy, the survey should be conducted at least 1 time in 6 months. More frequent screening should be conducted in the following cases: – a daily dose exceeding 6.5 mg / kg ideal (not high) body weight (in calculating the dose, taking into account the absolute body weight is possible overdosing in obese patients) – kidney failure – the total dose of more than 200 r – elderly patients – reduced visual acuity.
If there are adverse changes in vision (including reduced visual acuity, changes in color vision), you should immediately remove the drug. Patients require prolonged observation since possible progression of these disorders. Retinal changes may progress even after drug withdrawal.
Caution is recommended to use the drug for patients with diseases of the liver and kidneys. Because the drug affects the liver and kidney function may require dose reduction. It is to be careful when using the drug in patients suffering from gastro-intestinal, neurological, or hematological diseases, hypersensitivity to quinine, with a deficit of glucose-6-phosphate dehydrogenase, porphyria and psoriasis.
Long-term therapy should periodically complete blood count, with the appearance of violations of hydroxychloroquine should be repealed. Should not be prescribed to patients with congenital intolerance galactose lactase deficiency Lappa or malabsorption syndrome with glucose-galactose. Children are particularly susceptible to the toxic effects of 4-aminohinolinov, so patients should be particularly careful to monitor so as to remove hydroxychloroquine of places available for children.
All patients receiving long-term medication should be periodically examined by a neurologist on the functions of skeletal muscles and the severity of tendon reflexes. If there is weakness, the drug should be discontinued. Malaria. Hydroxychloroquine is ineffective against chloroquine-resistant strains of P. faiciparum, as well as inactive for Forms vneeritrotsitnyh P.vivax, P.ovale and P.malariae and therefore can not prevent infection by these microorganisms in appointing him as a preventive measure and may not prevent recurrence of the disease caused by them.
Effects on ability to drive vehicles and management mechanisms
Patients should use caution when driving vehicles or performing activities requiring increased attention, because hydroxychloroquine may interfere with the accommodation and cause blurred vision. If this condition persists by itself, then the dose can be temporarily reduced.
Plaquenil Overdose
4-aminohinolinov overdose is especially dangerous in children, even when using the drug at a dose of 1-2 g can be fatal. Symptoms: headache, visual disturbances, collapse, seizures, hypokalemia, cardiac arrhythmias and conduction, followed by cardiac arrest and breathing. Because These effects may develop immediately after taking an overdose of the drug required an emergency treatment.
Should take immediate steps to remove the drug from the stomach, activated charcoal to appoint a dose of at least 5 times the accepted dose of a drug that can stop further absorption (with the introduction of coal into the stomach through a tube for 30 minutes after taking the drug).
The advisability of a parenteral diazepam (described reduction of cardiotoxicity of chloroquine against it). Treatment: If necessary, should be ventilated and anti shock therapy. Requires constant medical supervision for at least 6 hours after arresting symptoms of overdose.
Drug Interactions Plaquenil
With the simultaneous application of hydroxychloroquine and digoxin may increase digoxin concentration in serum (for this combination should be closely monitored in the serum concentration of digoxin). As hydroxychloroquine may enhance the effects of hypoglycemic agents may need to decrease the dose of insulin or hypoglycemic drugs.
It is also possible the interaction of hydroxychloroquine sulfate in aminoglycoside antibiotics (inhibition of neuromuscular transmission) with cimetidine (inhibition of metabolism of hydroxychloroquine sulfate, which can lead to an increase in its concentration in blood plasma); antagonistic actions against neostigmine and pyridostigmine, a reduction of antibody response the primary immunization intradermal human diploid-cell rabies vaccine.
With the simultaneous use of antacids interval between doses must be at least 4 h, because may reduce absorption of the drug.
Conditions and terms of Plaquenil
List B. The drug should be kept away from children at a temperature below 25 ° C. Shelf life – 3 years.
