Quetiapine - instructions for use, dose, side effects, contraindications

Pharmacodynamics:The mechanism of action is not fully understood. A dopamine D antagonist₂ and serotonin 5-HT₂receptors. Affinity profile (affinity for receptors): 5-HT2 = D2 = α1 = α2 = H1.

Pharmacological effects: antipsychotic, antiemetic, sedative, hypnotic (drowsiness), blockade of histamine H₁-receptor, hypotensive (orthostatic hypotension), blockade α₁-adrenoreceptors, a decrease in the concentration of free thyroxine (T4), hyperprolactinemia.

Pharmacokinetics:Absorption is fast, complete (increases with eating). The volume of distribution is 10 ± 4 l / kg. The connection with plasma proteins is 83%. Biotransformed in the liver by oxidative enzyme systems involving CYP3A4 (to a lesser extent - 2D6, 2C9) to two active metabolites. The half-life of both metabolites is 6-7 hours. The time for obtaining the maximum plasma concentration is 2 hours. The maximum concentration in the plasma is 25% of the initial dose, the area under the "concentration-time" curve is 15%. Displayed quetiapine kidneys (73% in the form of metabolites) and with feces unchanged (20%).

Indications:Acute and chronic psychoses, including schizophrenia.

ICD-10

V.F20-F29.F20.1 Gebefrenic schizophrenia

V.F20-F29.F20 Schizophrenia

Contraindications:Hypersensitivity, pregnancy, breast-feeding, children's age (efficacy and safety not established).

Carefully:Arterial hypotension, convulsive syndrome (in the anamnesis), a violation of liver function (the metabolic rate decreases by about 25%) and kidneys (a 25% decrease in clearance).

Pregnancy and lactation:Recommendations FDA category C. During pregnancy and lactation, the application is possible in cases where the expected benefit to the mother exceeds the potential risk to the fetus. It is not known whether quetiapine with breast milk. If it is necessary to use lactation, breastfeeding should be discontinued.

Dosing and Administration:Inside 2 times a day, regardless of food intake. Daily doses: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3), 300 mg (Day 4). Further titrated to the effective dose (450 mg per day, if necessary up to 750 mg per day, with schizophrenia of 25-750 mg per day).

For elderly patients, the daily dose is 25 mg per day.

In patients with impaired liver and / or kidney function, the initial dose is 25 mg per day.

Daily dose increase should be 25-50 mg until optimal effect is achieved.

Side effects:From the side of the central nervous system: drowsiness, dizziness, headache, anxiety; rarely - malignant neuroleptic syndrome.

From the cardiovascular system: arterial hypertension, orthostatic hypotension, tachycardia.

From the musculoskeletal system: myalgia.

From the digestive system: constipation, dyspepsia, diarrhea, dry mouth, transient increase in hepatic enzyme activity, abdominal pain.

From the hematopoiesis: asymptomatic leukopenia and / or neutropenia; rarely - eosinophilia.

From the sides of metabolism: a slight increase in the content of cholesterol and triglycerides in the blood.

From the respiratory system: rhinitis.

Dermatological reactions: skin rash, dry skin.

From the organ of hearing: earache.

From the genitourinary system: urinary tract infection.

From the endocrine system: a small dose-dependent reversible decrease in thyroid hormone levels (in particular, total and free T4).

Other: asthenia, back pain, weight gain, fever, chest pain.

Overdose:Drowsiness, cardiac blockade, hypotension, hypokalemia, tachycardia. Treatment is symptomatic. Do not use disopyramide, procainamide, quinidine, brethility, epinephrine, dopamine. ECG monitoring is required (arrhythmias are possible).

Interaction:Alcohol and other drugs that depress the central nervous system: increased oppression.

Inhibitors of cytochrome P4503A (clarithromycin, erythromycin, fluconazole, itraconazole, ketoconazole, verapamil, diltiazem): the risk of an overdose of quetiapine.

Inductors of cytochrome P4503A: a reduction in the dose of quetiapine is necessary when enzyme inducers are eliminated.

Special instructions:When using the drug, it is necessary to monitor the activity of transaminases (increase with prolonged use of the drug), peripheral blood parameters, cholesterol concentration, serum triglycerides, thyroxine, extrapyramidal reactions. It is necessary to monitor patients with suicidal tendencies, to see the oculist (every 6 months).

It is necessary to refrain from occupations requiring increased concentration of attention and quickness of reactions, avoiding alcohol, overheating and dehydration.

Quetiapine is the least studied atypical neuroleptic.A large number of patients who dropped out of the study do not recommend the widespread use of quetiapine.

Limited evidence suggests that the drug is an antipsychotic agent whose extrapyramidal effects are comparable to placebo, but quetiapine has no advantages over traditional neuroleptics for a global assessment of efficacy, influence on positive and negative symptoms, mental status.

Quetiapine is much more expensive than other antipsychotics, its use must be considered individually from the standpoint of cost effectiveness. In the treatment of schizophrenia, the use of quetiapine is more effective than placebo.

Instructions

Quetiapine (Quetiapinum)