Quetiapine pills 25mg №60

Mechanism of action

Quetiapine is an atypical antipsychotic drug that exhibits a higher affinity for serotonin (hydroxytryptamine) receptors (5HT₂) than to dopamine D receptors₁ and D₂ brain. Quetiapine also has a more pronounced affinity for histamine and alpha.₁-adrenoreceptors and smaller in relation to alpha₂-adrenoreceptors. No significant affinity of quetiapine for muscarinic and benzodiazepine receptors was found. In standard tests, quetiapine exhibits antipsychotic activity.

When administered orally, quetiapine is well absorbed from the gastrointestinal tract and is actively metabolized in the liver. The major metabolites found in plasma do not have pronounced pharmacological activity.

Eating does not significantly affect the bioavailability of quetiapine. T_1/2 about 7 hours. Approximately 83% of quetiapine binds to plasma proteins.

The pharmacokinetics of quetiapine is linear, there are no differences in pharmacokinetic parameters in men and women.

The average clearance of quetiapine in elderly patients is 30-50% less than in patients aged 18 to 65 years.

The average plasma clearance of quetiapine is less by approximately 25% in patients with severe renal failure (creatinine clearance is less than 30ml / min / 1.73 m²) and in patients with liver damage, but interindividual clearance indicators are within the limits corresponding to healthy volunteers. Approximately 73% of quetiapine is excreted in the urine and 21% in feces. Less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys or with feces. It has been established that CYP3A4 is a key isoenzyme of quetiapine metabolism mediated by cytochrome P450.

In a study of the pharmacokinetics of quetiapine at different doses, the use of quetiapine before taking Ketoconazole or simultaneously with ketoconazole resulted in an increase, on average, in_max and the area under the concentration-time curve (AUC) of quetiapine by 235% and 522%, respectively, as well as a decrease in clearance of quetiapine, on average, by 84%. T_1/2 quetiapine increased but T_max did not change.

Quetiapine and some of its metabolites have a weak inhibitory activity against cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and 3A4, but only at a concentration of 10-50 times higher than that observed with the commonly used effective dose of 300-450 mg / day.

Based on in vitro results, one should not expect that simultaneous use of quetiapine with other drugs will lead to clinically pronounced inhibition of cytochrome P450-mediated metabolism of other drugs.

- acute and chronic psychosis, including schizophrenia;

- Manic episodes in the structure of bipolar disorder.

Dosage and administration

Adults:

Acute and chronic psychosis, including schizophrenia

The daily dose for the first 4 days of therapy is: 1st day - 50 mg, 2nd day - 100 mg, 3rd day - 200 mg, 4th day - 300 mg. Starting from the 4th day, the dose should be adjusted to a clinically effective dose, which usually ranges from 300 to 450 mg / day. Depending on the clinical effect and individual tolerance, the dose can vary from 150 to 750 mg / day.

Treatment of manic episodes in the structure of bipolar disorder

Quetiapine is used as monotherapy or as adjuvant therapy to stabilize mood.

The daily dose for the first 4 days of therapy is: 1st day - 100 mg, 2nd day - 200 mg, 3rd day - 300 mg, 4th day - 400 mg. In the future, by the 6th day of therapy, the daily dose of the drug can be increased to 800 mg. Increasing the daily dose should not exceed 200 mg per day.

Depending on the clinical effect and individual tolerance, the dose can vary from 200 to 800 mg / day. Usually the effective dose is from 400 to 800 mg / day.

For treatment schizophrenia The maximum recommended daily dose of quetiapine is 750 mg, for the treatment of manic episodes in the structure of bipolar disorder, the maximum recommended daily dose of quetiapine is 800 mg / day.

In elderly patients The initial dose of Quetiapine is 25 mg / day. The dose should be increased daily by 25-50 mg to achieve an effective dose, which is likely to be less than in younger patients.

In patients with renal or hepatic impairment It is recommended to begin therapy with quetiapine with 25 mg / day. It is recommended to increase the dose daily by 25-50 mg to achieve an effective dose.

Adverse reactions

The most common adverse reactions associated with taking the drug: drowsiness (17.5%), dizziness (10%), constipation (9%), dyspepsia (6%), orthostatic hypotension and tachycardia (7%), dry mouth (7% ), an increase in the activity of liver enzymes in the serum (6%), an increase in the concentration of cholesterol and triglycerides in the blood plasma.

Acceptance of quetiapine may be accompanied by the development of moderate asthenia, rhinitis and dyspepsia, and an increase in body weight (mainly in the first weeks of treatment). Quetiapine may cause orthostatic hypotension (accompanied by dizziness), tachycardia, and in some patients fainting; these adverse reactions are mainly found in the initial period of dose selection (see section “Special Instructions”). Quetiapine therapy is associated with a small dose-dependent decrease in the concentration of thyroid hormones, in particular, total T4 and free T4. The maximum decrease in total and free T4 was recorded on the 2nd and 4th week of quetiapine therapy, without further reducing the hormone concentration during long-term treatment. In the future, there were no signs of clinically significant changes in the concentration of thyroid stimulating hormone.

With prolonged use of quetiapine, there is a potential for the development of tardive dyskinesia.If symptoms of tardive dyskinesia occur, reduce the dose or stop further treatment with quetiapine. With the abrupt cancellation of high doses of antipsychotic drugs, the following acute reactions may be observed (“withdrawal” syndrome): nausea, vomiting, rarely insomnia.

There may be cases of exacerbation of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia). In this connection, it is recommended to discontinue the drug gradually.

The following are the side reactions observed with quetiapine and distributed throughout organs and systems:

The nervous systemDrowsiness, dizziness, headache, anxiety, fatigue, hostility, excitement, insomnia, akathisia, tremor, seizures, depression, paresthesia, neuroleptic malignant syndrome (hyperthermia, muscle rigidity, altered mental status, the lability of the autonomic nervous system, increased CPK activity), restless legs syndrome.

Since the cardiovascular system: orthostatic hypotension, tachycardia, prolongation of the Q-T interval.

From the digestive system: dry oral mucosa, nausea, vomiting, abdominal pain, diarrhea or constipation, increased activity of liver transaminases, jaundice, hepatitis.

On the part of the respiratory system: pharyngitis, rhinitis.

Allergic reactions:erythema, eosinophilia, angioedema, Stevens-Johnson syndrome, Anaphylactic reactions.

Laboratory values: leukopenia, neutropenia, hypercholesterolemia, hypertriglyceridemia, decrease in T4 concentration (first 4 weeks), hyperglycemia.

Other: low back pain, chest pain, low-grade fever, weight gain (mainly in the first weeks of treatment), myalgia, dry skin, blurred vision, including blurred vision, decompensation of existing diabetes, priapism, galactorrhea.

- Hypersensitivity to any of the components of the drug;

- simultaneous use with CYP3A4 inhibitors, such as HIV protease inhibitors, azole antifungal drugs, Erythromycin, Clarithromycin, nefazodone;

- children's age up to 18 years;

- lactation period.

Carefully use in patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension; in old age; with liver failure; convulsive seizures in history; of pregnancy.

Use with caution during pregnancy. Contraindicated during lactation.

In patients with hepatic impairment It is recommended to begin therapy with quetiapine with 25 mg / day.It is recommended to increase the dose daily by 25-50 mg to achieve an effective dose.

In patients with renal failure It is recommended to begin therapy with quetiapine with 25 mg / day. It is recommended to increase the dose daily by 25-50 mg to achieve an effective dose.

Contraindicated in children and adolescents under 18 years of age.

In elderly patients The initial dose of Quetiapine is 25 mg / day. The dose should be increased daily by 25-50 mg to achieve an effective dose, which is likely to be less than in younger patients.

Quetiapine may cause orthostatic hypotension, especially in the initial period of dose selection (in older patients it is observed more often than in younger patients). No relationship was found between quetiapine intake and QT increase._with-interval. However, when quetiapine is used simultaneously with drugs that prolong the QT interval_with, care must be taken, especially in the elderly. During the period of treatment with a decrease in the number of neutrophils less than 1000 / μl, quetiapine should be stopped.

With the development of orthostatic hypotension during treatment with a drug, it is necessary to reduce the dose or to titrate the doses more slowly. The drug is not indicated for the treatment of psychoses associated with dementia. In the case of the development of symptoms of tardive dyskinesia, the dose of the drug should be reduced or gradually eliminated. Symptoms of tardive dyskinesia may increase or even appear after stopping the drug.

In the case of the development of malignant neuroleptic syndrome, the drug must be canceled.

Considering that quetiapine mainly affects the central nervous system, the drug should be used with caution in combination with other drugs that depress the central nervous system, or alcohol. In children, adolescents and young people (under 24 years) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing Quetiapine or any other antidepressants in children, adolescents and young people (under 24 years of age), the risk of suicide and the benefits of their use should be correlated. In short-term studies, the risk of suicide was not increased in people over 24 years of age, and in people over 65 years of age it was somewhat reduced. Any depressive disorder itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for the purpose of early detection of abnormalities or behavioral changes, as well as suicidal tendencies.

Influence on ability to drive motor transport and control mechanisms

Quetiapine may cause drowsiness, therefore during the treatment period it is recommended that patients refrain from driving vehicles and practicing activities that require increased concentration of attention and quickness of psychomotor reactions.

Data on quetiapine overdose is limited.There are cases of taking quetiapine at a dose of more than 20 g, without fatal consequences and with full recovery, but there are reports of extremely rare cases of an overdose of quetiapine, leading to death or coma.

Symptoms may be due to the enhancement of known pharmacological effects of the drug, such as drowsiness and excessive sedation, tachycardia and a decrease in blood pressure.

Treatment: no specific antidotes for quetiapine. In cases of overdose, gastric lavage is possible (after intubation, if the patient is unconscious), taking activated charcoal and laxatives to remove unabsorbed quetiapine, however, the effectiveness of these measures has not been studied. Symptomatic therapy and measures aimed at maintaining the respiratory function, cardiovascular system, ensuring adequate oxygenation and ventilation are shown. Medical control and monitoring should be continued until the patient is fully cured.

With the simultaneous use of drugs with a powerful inhibitory effect on the CYP3A4 isoenzyme (such as antifungal agents of the azole group and erythromycin, clarithromycin, nefazodone), the concentration of quetiapine in plasma increases, so their simultaneous intake with quetiapine is contraindicated. With simultaneous use of quetiapine with drugs that induce the enzyme system of the liver, such as Carbamazepine, a decrease in plasma concentration of the drug may be necessary, which may require an increase in the dose of quetiapine, depending on the clinical effect.In a study of the pharmacokinetics of quetiapine in various doses, when applied before or simultaneously with carbamazepine (an inducer of hepatic enzymes) resulted in a significant increase in clearance of quetiapine. This increase in clearance of quetiapine reduced the AUC by an average of 13% compared with the use of quetiapine without carbamazepine. The simultaneous use of quetiapine with another inducer of liver microsomal enzymes, phenytoin, also led to an increase in clearance of quetiapine. With simultaneous use of quetiapine and phenytoin (or other inducers of liver enzymes, such as barbiturates, rifampicin), an increase in the dose of quetiapine may be required. It may also be necessary to lower the dose of quetiapine if you cancel phenytoin or carbamazepine or another inducer of the liver enzyme system or replace it with a drug that does not induce liver microsomal enzymes (for example, valproic acid).

The pharmacokinetics of lithium preparations do not change with simultaneous use of quetiapine.

Quetiapine did not induce hepatic enzyme systems involved in the metabolism of antipyrine. The pharmacokinetics of quetiapine does not change significantly with simultaneous use with antipsychotic drugs - Risperidone or Haloperidol. However, simultaneous administration of quetiapine and thioridazine resulted in increased clearance of quetiapine. CYP3A4 is a key enzyme involved in cytochrome P450-mediated quetiapine metabolism.The pharmacokinetics of quetiapine does not change significantly with the simultaneous use of cimetidine, which is an inhibitor of P450.

The pharmacokinetics of quetiapine did not change significantly with simultaneous use of imipramine (CYP2D6 inhibitor) or Fluoxetine (CYP3A4 and CYP2D6 inhibitor). CNS depressant drugs and ethanol increase the risk of side effects of quetiapine.

Keep out of the reach of children, dry, dark place at temperatures not above 25 ° C.