Pharmacological properties Seroquel:
Seroquel atypical antipsychotic drug, interacts with different types of neurotransmitter receptors. Seroquel exhibits a high affinity for serotonin receptors (5NT2) than to the dopamine receptors D1 and D2 in the brain, as well as a high affinity for histamine and α1 adrenergic receptors and lower – to the α2-adrenoreceptors. Has no affinity for the M-cholinergic receptors and benzodiazepine receptors, exhibits antipsychotic activity.
In the study of extrapyramidal symptoms in the experiment found that Seroquel produces only weak catalepsy when used in doses that effectively blocking dopamine D2-receptors. Quetiapine causes a selective decrease in activity of mesolimbic A10 dopaminergic neurons compared with A9 nigrostriatalnymi motor neurons and has minimal effect on muscle tone in monkeys are sensitive to neuroleptics. Quetiapine does not cause increase prolactin levels in serum.
The drug effectively eliminates both the positive and negative symptoms of schizophrenia.
If ingestion is well absorbed and is actively metabolized. Food intake did not significantly affect the bioavailability of quetiapine. The main metabolites do not possess a pronounced pharmacological activity. The half-life of about 7 h. About 83% of Seroquel binds to plasma proteins. Effective at taking 2 times a day. Effect of Seroquel on receptors 5NT2 and D2 can be extended to 12 h, which was confirmed by positron emission tomography. The pharmacokinetics of Seroquel is linear, the differences pharmacokinetics in males and females. The average clearance of quetiapine in elderly patients is 30-50% lower than in patients aged 18-65 years. Clearance of Seroquel was reduced by 25% in patients with severely impaired renal function (creatinine clearance less than 30 ml/min/1, 73 m2) and in patients with liver disease (compensated alcoholic cirrhosis), but individual levels of clearance within the limits of the healthy people. Less than 5% of the Seroquel is not metabolized and excreted unchanged in the urine or feces. Approximately 73% of quetiapine is excreted in the urine and 21% in feces. Key enzyme metabolism of quetiapine is CYP 3A4, mediated by cytochrome P450. Quetiapine and some of its metabolites have a weak inhibitory effect on cytochrome P450 1A2, 2S9, 2S19, 2D6 and ZA4, but only at concentrations 10-50 times higher than the concentration that is achieved using a conventional dose (300-450 mg / day). In vitro is not established the ability of quetiapine to cause significant inhibition of cytochrome P450 and the influence of mediated metabolism of other drugs.
INDICATIONS Seroquel:
acute and chronic psychoses, schizophrenia, manic episodes associated with bipolar disorder.
APPLICATION Seroquel:
adults inside 2 times daily with meals or between meals.
Treatment for schizophrenia
Daily dose of adult first 4 days of therapy leaves: 1-day treatment – 50 mg / day, 2-day-100 mg / day, third day – 200 mg / day, 4-th day – 300 mg / day. Starting from 4-day dose titrated to achieve the desired clinical effect in the range of 300 to 450 mg / day. Depending on the clinical efficacy and tolerability the dose can vary from 150 to 750 mg / day.
Treatment of manic episodes associated with bipolar disorder
Daily dose of the first 4 days of treatment is: 1 day – 100 mg / day, 2-day – 200 mg / day, third day – 300 mg / day, 4-th day – 400 mg / day. Further increase the dose by no more than 200 mg daily until a dose of 800 mg / day starting from 6-day treatment. Depending on the clinical efficacy and tolerability the dose can vary from 200 to 800 mg / day.
Elderly patients
Like other antipsychotics, Seroquel should be used with caution in elderly patients, especially in the initial phase of therapy. In these patients, the initial dose should be 25 mg / day. Further dose increases every day to 25-50 mg to achieve an effective dose, which is usually lower than in young patients.
Human liver or kidney disease
In patients with impaired renal function or hepatic clearance of Seroquel for oral administration is reduced by approximately 25%. Quetiapine is actively metabolized in the liver and therefore should be used with caution in patients with impaired liver function. Such patients the drug is prescribed in an initial dose of 25 mg / day. Then increase the dose every day for 25-50 mg to achieve an effective dose.
CONTRAINDICATIONS Seroquel:
hypersensitivity to the drug.
SIDE EFFECTS Seroquel:
The most frequently reported side effects such as drowsiness, dizziness, dry mouth, asthenia, constipation, tachycardia, orthostatic hypotension, dyspepsia. As in the treatment of other antipsychotics, Seroquel mentioned in the application of neuroleptic malignant syndrome, leucopenia, peripheral edema.
Seroquel therapy is sometimes accompanied by a slight dose-dependent decrease in thyroid hormone levels in blood (total T4 and unbound T4). Maximum reduction of total and unbound T4 noted during the first 2-4 weeks of therapy Seroquel without further reduction in hormone levels during prolonged treatment. In virtually all cases, cessation of treatment leads to normalization of the levels of total T4 and free T4, irrespective of the duration of treatment. The slight decrease in the level of total T3 noted only when using the drug in high dose. The level of thyroxine binding globulin did not change, increased thyroid-stimulating hormone were observed. When receiving a quetiapine did not observe any signs of hypothyroidism. Very rarely reported on the development of hyperglycemia and decompensation of diabetes mellitus in the treatment of quetiapine. As with other antipsychotics, quetiapine therapy may be associated with increased body weight, mainly in the first weeks of treatment. Like other antipsychotics, quetiapine may cause an increase in Q-Tc interval on the ECG, but in clinical studies the relationship between drug use and constant increase in Q-Tc is not revealed.
SPECIAL INSTRUCTIONS Seroquel:
The maximum daily dose of Seroquel for the treatment of schizophrenia is 750 mg for the treatment of manic episodes associated with bipolar disorder, this dose should be 800 mg. Prolonged treatment with high-dose possible only if the expected benefit outweighs the potential risk.
Cardiovascular disease
The drug should be used with caution in patients with cerebrovascular diseases, diseases of the cardiovascular system or other conditions that lead to the development of hypotension. The risk of orthostatic hypotension is higher in the initial period of titration, especially in elderly patients. Results of clinical studies have not revealed the relationship between the use of Seroquel and continuous increase of Q-Tc interval. However, like other antipsychotics in the appointment of Seroquel in conjunction with drugs that increase the range of Q-Tc, caution should be exercised, especially in the elderly.
Seizures
It should also be careful when assigning patients with a history of seizures.
Tardive dyskinesia
Prolonged use of Seroquel, as well as other antipsychotics may cause tardive dyskinesia. In this case, you should reduce the dose or stop medicine.
Neuroleptic malignant syndrome
In the application of antipsychotic drugs may develop neuroleptic malignant syndrome. Clinical manifestations of syndrome include hyperthermia, altered mental status, muscle rigidity, unstable autonomic nervous system, increasing the level of CPK in serum. In this case, drug overturned and conduct appropriate treatment.
Sudden discontinuation of medication
Very rarely reported on the development of symptoms such as nausea, vomiting and drowsiness after an abrupt discontinuation of antipsychotic drugs in high doses. It is also possible recurrence of psychotic symptoms. Marked the emergence of involuntary movements (akathisia, dystonia, dyskinesia). Therefore, we recommend gradual discontinuation of the drug.
Children and Teens
Safety and efficacy of Seroquel in children and adolescents has not been established.
During pregnancy and lactation
Safety and efficacy in pregnancy has not been established, so Quetiapine should be prescribed only if the expected benefit outweighs the potential risk. The degree of excretion of quetiapine in breast milk is not known. Should be advised to stop breastfeeding while taking the drug.
Effects on ability to drive vehicles and other mechanisms
Seroquel may cause drowsiness, so patients during treatment is not recommended to drive and work with potentially dangerous machinery.
INTERACTION:
Seroquel should be used with caution in combination with other drugs acting on the CNS. In this regard, during treatment to avoid alcohol.
Pharmacokinetics of lithium, while the appointment of Seroquel did not change.
Pharmacokinetics of sodium valproate and quetiapine during their concomitant use is not changed.
The pharmacokinetics of quetiapine did not significantly change when simultaneous appointment with risperidone or haloperidol. Simultaneous treatment with quetiapine and thioridazine increases the clearance of quetiapine.
Co-administration of quetiapine and carbamazepine (an inductor of microsomal liver enzymes) increases the clearance of quetiapine. Co-administration of Seroquel and phenytoin (or other inducers of liver enzymes, such as barbiturates, rifampin) may significantly reduce the systemic effects of Seroquel, therefore, may need to increase the dose of quetiapine to be applied simultaneously with inducers of liver enzymes, to maintain control of psychotic symptoms. The dose of quetiapine may be reduced by the abolition of phenytoin, carbamazepine or other hepatic enzyme inducers or replacement drug, which has no inducing effect on liver enzymes (eg sodium valproate).
CYP 3A4 is a key enzyme participating in the cytochrome P450-mediated metabolism of quetiapine. The pharmacokinetics of quetiapine are not significantly altered while the application of cimetidine, an inhibitor of cytochrome P450. Co-administration of quetiapine and the antidepressant imipramine (an inhibitor of CYP 2D6) or fluoxetine (an inhibitor of CYP 3A4 and CYP 2D6) did not cause significant changes in the pharmacokinetics of quetiapine. Co-administration of ketoconazole increased the mean peak concentration and AUC of quetiapine by 235 and 522%, respectively, and reduced clearance by 84%. The average half-life of quetiapine increased from 2.6 to 6.8 h, but the average time to reach maximum concentration remained unchanged. Advised to observe caution while using Seroquel, and potential inhibitors of CYP 3A4 (azolovye antifungals and macrolide antibiotics), and should consider lowering the dose of quetiapine.
OVERDOSE Seroquel:
data on drug overdose is limited. There are cases of the drug in doses above 20 grams, deaths have been recorded, carried out an effective symptomatic therapy. After the widespread introduction of the drug in practice there were few reports of cases of Seroquel overdose leading to coma or death.
Symptoms of an overdose of Seroquel – sedation, tachycardia and hypotension were usually a consequence of enhancing the pharmacological effects of the drug. No specific antidote. In cases of severe intoxication is recommended to perform multidirectional intensive care, including rehabilitation and control of upper airway patency, maintenance of adequate oxygenation and ventilation, monitoring and support of the cardiovascular system. Thorough medical supervision and monitoring should be conducted until the patient recovers.
