Quetiapine, 300 mg 60 pcs

Quetiapine is an atypical antipsychotic that has a higher affinity for serotonin (hydroxytryptamine) receptors (5NT2) than for brain dopamine D1 and D2 receptors. Quetiapine also has greater affinity for histamine and alpha1 adrenoreceptors and less affinity for alpha2 adrenoreceptors. No significant affinity of quetiapine for muscarinic and benzodiazepine receptors was found. In standard tests, quetiapine exhibits antipsychotic activity.

Pharmacokinetics

Quetiapine is well absorbed from the gastrointestinal tract and is actively metabolized in the liver when administered orally. The major plasma metabolites have no pronounced pharmacological activity.

The bioavailability of quetiapine is not significantly affected by food intake. The T1/2 is about 7 hours. About 83% of quetiapine is bound to plasma proteins.

The pharmacokinetics of vetiapine are linear; there are no differences in pharmacokinetics between men and women.

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

The mean plasma clearance of quetiapine is about 25% lower in patients with severe renal impairment (creatinine clearance less than 30 mL/min/1.73 m2) and in patients with liver damage, but interindividual clearance rates are within limits consistent with healthy volunteers. Approximately 73% of quetiapine is excreted in the urine and 21% in the feces. Less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys or in the feces. CYP3A4 has been found to be a key isoenzyme of cytochrome P450-mediated metabolism of quetiapine.

In a study of the pharmacokinetics of quetiapine at various doses, administration of quetiapine prior to or concomitantly with ketoconazole resulted in an average increase in Cmax and area under the concentration-time curve (AUC) of quetiapine of 235% and 522%, respectively, and a decrease in quetiapine clearance of 84%, on average. The T1/2 of quetiapine increased, but the Tmax was unchanged.

Quetiapine and some of its metabolites have weak inhibitory activity against cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and ZA4, but only at concentrations 10-50 times greater than those observed at the commonly used effective dose of 300-450 mg/day.

Based on in vitro results, concomitant use of quetiapine with other drugs should not be expected to result in clinically significant inhibition of cytochrome P450-mediated metabolism of other drugs.

Indications

Acute and chronic psychosis, including schizophrenia.

Active ingredient

Composition

Active substances:

quetiapine fumarate (quetiapine hemifumarate), in terms of quetiapine 300 mg;

Auxiliary substances:

Hyprolose (Clucel LF hydroxypropylcellulose),

calcium hydrophosphate dihydrate,

Pregelatinized starch,

magnesium stearate,

sodium carboxymethyl starch (sodium starch glycolate; primogel),

cellulose microcrystalline;

Composition of the film coating:

AquaPolish D 8107 [hypromellose (hydroxypropyl methyl cellulose), glycerol (glycerol), microcrystalline cellulose, talc, candurin silver luster dye ([potassium aluminosilicate E555, titanium dioxide E171]), indigo carmine dye-based aluminum varnish].

How to take, the dosage

Treatment of acute and chronic psychosis, including schizophrenia.

The daily dose for the first 4 days of therapy is 50 mg (day 1), 100 mg (day 2), 200 mg (day 3), 300 mg (day 4). Starting on day 4, the dose should be titrated to effective, ranging from 300 to 450 mg/day, up to 750 mg/day if necessary.

The treatment of manic episodes in the structure of bipolar disorder.

Quetiapine is used as monotherapy or as adjuvant therapy for mood stabilization.

The daily dose for the first 4 days of therapy is 100 mg (day 1), 200 mg (day 2), 300 mg (day 3), 400 mg (day 4). Further, by the 6th day of therapy the daily dose of the drug can be increased to 800 mg. Increase in the daily dose should not exceed 200 mg per day.

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

For treatment of schizophrenia, the maximum recommended daily dose of quetiapine is 750 mg; for treatment of manic episodes as part of bipolar disorder, the maximum recommended daily dose of quetiapine is 800 mg/day.

In renal and/or hepatic impairment and in elderly patients, the initial dose is 25 mg/day, with daily increases of 25-50 mg thereafter until an effective dose is achieved.

Interaction

In concomitant administration of drugs with strong inhibitory effect on CYP3A4 (such as antifungal agents of azole group and macrolide antibiotics), plasma concentration of quetiapine may increase.

In such cases lower doses of vetiapine should be used. Particular attention should be paid to elderly and frail patients. The risk-benefit ratio for each patient must be evaluated individually.

Hepatic microsomal systems inducers (phenytoin, etc.) and thioridazine increase the risk-benefit ratio.), thioridazine increase clearance of quetiapine, hepatic microsomal system inhibitors decrease it; at the same time simultaneous administration of quetiapine and antidepressants – imipramine (CYP2D6 inhibitor) or fluoxetine (CYP3A4 and CYP2D6 inhibitor) has no significant effect on its pharmacokinetics.

The pharmacokinetics of quetiapine are not significantly altered by concomitant administration with the antipsychotic drugs risperidone or haloperidol.

It does not cause induction of liver enzyme systems involved in antipyrine metabolism.

The pharmacokinetics of lithium preparations are not altered by concomitant administration of quetiapine.

There are no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine when divalproex sodium (sodium valproate and valproic acid in a molar ratio of 1:1) and Quetiapine are co-administered.

Drugs that depress the central nervous system and ethanol increase the risk of side effects.

Special Instructions

No correlation between quetiapine administration and QTc interval prolongation has been found. However, caution should be exercised when using vetiapine concomitantly with drugs that prolong the QTc interval.

In children, adolescents, and young adults (younger than 24 years) with depression, other psychiatric disorders, antidepressants, compared with placebo, increase the risk of suicidal ideation and suicidal behavior. Therefore, when prescribing antidepressants in children, adolescents, and young adults (younger than 24 years), the risk of suicide and the benefits of their use should be weighed.

In short-term studies, people over the age of 24 had no increased risk of suicide, and people over the age of 65 had a slightly decreased risk of suicide. Any depressive disorder itself increases the risk of suicide. Therefore, all patients should be monitored during antidepressant treatment for early detection of impairment or behavioral changes as well as suicidal tendencies.

During treatment, caution should be exercised when driving motor vehicles and engaging in other potentially hazardous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

Hypersensitivity

Side effects

Nervous system disorders: drowsiness, dizziness, headache, anxiety, asthenia, hostility, agitation, insomnia, akathisia, tremors, convulsions, depression, paresthesias, malignant neuroleptic syndrome (hyperthermia, muscle rigidity, altered mental status, labile autonomic nervous system, increased creatine phosphokinase activity).

Cardiovascular system disorders: orthostatic hypotension (accompanied by dizziness), tachycardia, syncope, prolongation of QT interval (no relationship of quetiapine use with continuous QTc prolongation has been found).

Gastrointestinal system disorders: dry mouth, nausea, vomiting, abdominal pain, diarrhea or constipation, increased liver transaminase activity.

Respiratory system: pharyngitis, rhinitis.

Allergic reactions: skin rash, eosinophilia.

Laboratory parameters: leukopenia, hypercholesterolemia, hypertriglyceridemia, decreased concentration of thyroxine (the first 4 weeks).

Others: low back pain, chest pain, subfebrile fever, weight gain (mostly in the first weeks of treatment), myalgia, dry skin, visual impairment.

Pregnancy use

The safety and efficacy of quetiapine in pregnant women have not been established.

Therefore, during pregnancy, quetiapine should only be used if the expected benefit justifies the potential risk.

The extent to which quetiapine is excreted with the female milk is not known.

Women should be advised to avoid breastfeeding while taking quetiapine.

Similarities