Composition, form of production and packaging
The tablets covered with a film cover of pink color with a brownish shade, round, biconcave, with the extruded inscriptions "QE" on one side and "25" - on the other;on a cross section - a homogeneous mass of white or almost white color.
1 tab.
quetiapine fumarate 28.784 mg,
which corresponds to the content of quetiapine 25 mg
Excipients: lactose monohydrate 7.24 mg, microcrystalline cellulose 8.776 mg, calcium hydrophosphate dihydrate 4.2 mg, giprolose 2.4 mg, sodium carboxymethyl starch 4.2 mg, talc 2.9 mg, colloidal silicon dioxide 0.9 mg, magnesium stearate 0.6 mg .
The composition of the film shell: opadrai II pink 31F34566 - 1.8 mg (lactose monohydrate - 36%, hypromellose - 28%, titanium dioxide - 23.7%, macrogol 4000 - 10%, dye sunset yellow - 1.3%, iron dye oxide red 1% ).
10 pieces. - blisters (6) - packs of cardboard.
The tablets covered with a film cover of yellow color with a brownish tinge, round, biconcave, with the extruded inscriptions "QE" on one side and "100" - on the other; on a cross section - a homogeneous mass of white or almost white color.
1 tab.
quetiapine fumarate 115.136 mg,
which corresponds to the content of quetiapine 100 mg
Auxiliary substances: lactose monohydrate - 28.96 mg, microcrystalline cellulose 35.104 mg, calcium hydrogen phosphate dihydrate 16.8 mg, giprolase 9.6 mg, sodium carboxymethyl starch 16.8 mg, talc 11.6 mg, colloidal colloidal silicon 3.6 mg, magnesium stearate 2.4 mg .
The composition of the film shell: opadrai II yellow 31F32561 - 7.2 mg (lactose monohydrate - 36%, hypromellose - 28%, titanium dioxide - 23.18%, macrogol 4000 - 10%, iron oxide oxide yellow - 2.82%).
10 pieces. - blisters (6) - packs of cardboard.
The tablets covered with a film cover of white color, round, biconcave, with the extruded inscriptions "QE" on one side and "200" - on the other; on a cross section - a homogeneous mass of white or almost white color.
1 tab.
quetiapine fumarate 230.272 mg,
which corresponds to the content of quetiapine 200 mg
Excipients: lactose monohydrate - 57.92 mg, cellulose microcrystalline - 70.208 mg, calcium hydrophosphate dihydrate 33.6 mg, giprolase 19.2 mg, sodium carboxymethyl starch 33.6 mg, talc 23.2 mg, silicon dioxide colloid 7.2 mg, magnesium stearate 4.8 mg .
The composition of the film shell: opadrai II white OY-L-28900 - 14.4 mg (lactose monohydrate - 36%, hypromellose - 28%, titanium dioxide - 26%, macrogol 4000 - 10%).
10 pieces. - blisters (6) - packs of cardboard.
Combi-package contains one blister of each dosage:
Tablets covered with a film membrane (6 pcs in a blister) 1 tab.
quetiapine (in the form of fumarate) 25 mg
Tablets covered with a film membrane (3 pieces in a blister) 1 tab.
quetiapine (in the form of fumarate) 100 mg
Tablets covered with a film membrane (1 piece in a blister) 1 tab.
quetiapine (in the form of fumarate) 200 mg
Blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Atypical antipsychotic drug (neuroleptic), which interacts with various types of neurotransmitter receptors. Has a higher affinity for serotonin (5-HT 2 ) receptors than for dopamine receptors (D 1 and D 2 ) of the brain. Has also a higher affinity for histamine and? 1- adrenoreceptors and less - in relation to? 2- adrenoreceptors. There was no significant affinity for quetiapine for m-cholinergic receptors and benzodiazepine receptors.
Quetiapine causes a selective decrease in the activity of mesolimbic A10 dopaminergic neurons in comparison with A9 nigrostriate neurons involved in motor function. Do not cause a prolonged increase in the concentration of prolactin in the blood plasma. Clinical studies have shown efficacy for both positive and negative symptoms of schizophrenia.
The effect of quetiapine on the receptors of 5-HT 2 and D 2 continues up to 12 hours after taking the drug.
PHARMACOKINETICS
Suction and distribution
When administered orally, quetiapine is well absorbed from the digestive tract. The intake of food does not significantly affect the bioavailability of quetiapine.Approximately 83% of quetiapine binds to plasma proteins.
Metabolism
It is actively metabolized in the liver. The main metabolites in the plasma do not have a pronounced pharmacological activity. It was found that CYP3A4 is the key enzyme of quetiapine metabolism, mediated by cytochrome P450.
Quetiapine and some of its metabolites have weak inhibitory activity against cytochrome P450 1A2, 2C9, 2C19, 2D6 and 3A4 enzymes, but only at a concentration 10-50 times higher than that observed at the usual effective dose of 300-450 mg / day .
Excretion
T 1/2 is about 7 hours. Approximately 73% of the quetiapine dose administered is excreted by the kidneys and 21% by the intestine, while less than 5% of the quetiapine is unchanged in kidney or intestine.
Pharmacokinetics in special clinical cases
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 in patients with severe renal failure and in patients with liver disease (stabilized alcoholic cirrhosis) is approximately 25% lower (QC less than 30 ml / min / 1.73 m 2 ), however, individual clearance rates are within the range corresponding to healthy people .
INDICATIONS
- schizophrenia;
- manic episodes of moderate and severe degree in the structure of bipolar disorder. It does not prevent the development of manic and depressive episodes.
DOSING MODE
Is inside 2 times / day, regardless of food intake.
Treatment of schizophrenia
The daily dose for the first 4 days of therapy is: Day 1 - 50 mg, Day 2 - 100 mg, Day 3 - 200 mg, Day 4 - 300 mg.
Starting from the 4th day, the dose is selected individually until an effective dose is reached, usually 300-450 mg / day. Depending on the clinical effect and individual patient tolerance, the dose can vary between 150 and 750 mg / day.
The maximum recommended daily dose is 750 mg.
Treatment of manic disorders
The daily dose for the first 4 days of therapy is: the 1st day - 100 mg, the second day - 200 mg, the third day - 300 mg, the 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. The increase in the daily dose should not be more than 200 mg / day.
Depending on the clinical effect and individual tolerability, the dose may vary from 200 to 800 mg / day. Usually the effective dose is from 400 to 800 mg / day.
The maximum recommended daily dose is 800 mg / day.
In elderly patients, the initial dose is 25 mg / day. The dose should be increased daily by 25-50 mg until an effective dose, which is usually less than in young patients.
In renal and / or liver failure, it is recommended to start therapy with a dose of 25 mg / day, followed by a daily increase of 25-50 mg to achieve an effective dose.
SIDE EFFECT
Determination of the frequency of adverse reactions: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely - (> 1/10 000 and < 1/1000), very rarely (<1/10 000).
From the side of the central nervous system: very often - dizziness, drowsiness, headache; often syncope; infrequently - convulsions; rarely - tardive dyskinesia; with an unidentified frequency, there are anxiety, hostility, agitation, insomnia, akathisia, tremor, depression, paresthesia.
From the cardiovascular system: often - tachycardia, orthostatic hypotension, cases of thromboembolism of venous vessels, incl. thromboembolism of pulmonary vessels and deep veins.
On the part of the respiratory system: pharyngitis, rhinitis.
From the digestive system: often - dry mouth, constipation, indigestion; rarely - jaundice, nausea, vomiting, abdominal pain; very rarely - hepatitis.
On the part of the hematopoiesis system: often - leukopenia; infrequently - eosinophilia; very rarely - neutropenia.
Laboratory indicators: often - increased activity of serum transaminases (ALT, ACT); infrequently - increase in GGT activity; an increase in the concentration of total cholesterol and triglycerides in the blood serum.
From the endocrine system: very rarely - hyperglycemia, diabetes mellitus.
Allergic reactions: infrequently - hypersensitivity, angioedema, Stevens-Johnson syndrome, skin rash.
From the side of the reproductive organs: rarely - priapism.
Other: often - moderate asthenia, swelling, weight gain; rarely - back pain, chest pain, subfebrile condition, myalgia, dry skin, weak eyesight.
During treatment with quetiapine, there is a slight dose-dependent decrease in thyroid hormone levels, in particular total and free T4. The maximum decrease in total and free T4 is recorded during the first 2-4 weeks of quetiapine therapy, without further lowering of the hormone levels during long-term treatment. There were no signs of clinically significant changes in the concentration of thyroid stimulating hormone.
In almost all cases, the level of total and free T4 returned to the baseline after quetiapine therapy ceased, regardless of the duration of treatment.
Quetiapine, like other antipsychotics, can cause prolongation of the QT interval, but in clinical studies, there was no correlation between the use of quetiapine and the constant QT interval elongation.
With a sharp withdrawal of the drug, there were registered cases of withdrawal syndrome, accompanied by nausea, vomiting; rarely - insomnia.
CONTRAINDICATIONS
- concurrent use of cytochrome P450 3A4 inhibitors (eg, HIV protease inhibitors, azole antifungal agents, erythromycin, clarithromycin, nefazodone);
- Children's age (effectiveness and safety not established);
- Pregnancy (effectiveness and safety not established);
- lactation period (efficacy and safety not established);
- Hypersensitivity to the components of the drug.
With caution , the drug should be prescribed for arterial hypotension, heart failure, cardiac hypertrophy, cardiovascular and cerebrovascular diseases, or other conditions predisposing to arterial hypotension, elderly patients, liver failure, epilepsy, convulsive seizures in the anamnesis, while prescribing drugs that extend the interval QT, patients with congenital QT interval increase or family predisposition to its increase, with hypocalcemia, hypomag in the presence of risk factors for venous thromboembolism.
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and during lactation, tk. effectiveness and safety of its use in these periods are not established.
APPLICATION FOR FUNCTIONS OF THE LIVER
In renal failure, it is recommended to start therapy with a dose of 25 mg / day, followed by a daily increase of 25-50 mg to achieve an effective dose.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution should prescribe the drug for liver failure.
APPLICATION FOR CHILDREN
Contraindication: child age (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
In elderly patients, the initial dose is 25 mg / day. The dose should be increased daily by 25-50 mg until an effective dose, which is usually less than in young patients.
SPECIAL INSTRUCTIONS
In the initial period of dose selection, orthostatic hypotension may be observed. In this case, you should return to the previously taken dose. Particular attention should be paid to patients with cardiovascular diseases, cerebrovascular diseases and other conditions predisposing to arterial hypotension.
Antipsychotic drugs (antipsychotics), incl. quetiapine, contribute to the development of thromboembolic complications in patients with a predisposition to the formation of thrombi. Prior to the initiation of quetiapine therapy, all possible risk factors for the development of venous thromboembolism should be identified and appropriate measures should be taken to prevent the development of thromboembolic complications.
There was no correlation between the drug intake in the recommended regimen and the increase in the QT interval. However, an increase in the QT interval was noted with an overdose of the drug. Caution should be exercised in appointing quetiapine concomitantly with drugs that extend the QTc interval, especially in the elderly, in patients with congenital QT syndrome, in heart failure, cardiac hypertrophy, hypocalcemia, or hypomagnesemia, and in the presence of a family predisposition to prolong the QT interval.
It should be used with caution in combination with other drugs that have a depressing effect on the central nervous system, as well as alcohol.
Care must be taken when treating patients with seizures in the anamnesis.
In the treatment with quetiapine, the development of ZNS is possible, the clinical manifestations of which include hyperthermia, altered mental status, muscle rigidity, vegetative nervous system instability, and an increase in the level of CK. In such cases, it is necessary to cancel the drug and appropriate treatment.
It should also consider the possibility of developing tardive dyskinesia with prolonged use of quetiapine. In this case, you should reduce the dose of the drug or consider the question of its cancellation.
With a sharp cancellation of treatment with high doses, the following acute reactions (withdrawal syndrome) can occur: nausea, vomiting, rarely insomnia. It may also exacerbate the symptoms of mental illness and the occurrence of involuntary motor disorders (akathisia, dystonia, dyskinesia). In connection with this, the elimination of the drug is recommended to be carried out gradually.
Lakvel is not intended for the treatment of patients suffering from psychosis accompanying senile dementia.
There is evidence of an increased risk of developing cerebrovascular complications in patients with senile dementia when using atypical antipsychotics.
Caution should be exercised when assigning Lakvel to patients with risk factors for stroke.
The drug Lakvel contains lactose, therefore it is not prescribed for patients with lactase deficiency or impaired absorption of glucose and galactose.
Impact on the ability to drive vehicles and manage mechanisms
The drug may cause drowsiness, so during the treatment, patients are not recommended to drive vehicles and work with mechanisms that are dangerous.
OVERDOSE
Symptoms: drowsiness and excessive sedation, tachycardia and lowering blood pressure.
Treatment: there is no specific antidote. In cases of serious intoxication - symptomatic treatment (maintenance of respiratory function, cardiovascular system, adequate oxygenation and ventilation). Careful medical supervision and supervision are necessary until the patient fully recovers.
DRUG INTERACTION
CYP3A4 is the key enzyme involved in the metabolism of quetiapine. With simultaneous administration of drugs with a strong inhibitory effect on the isoenzyme CYP3A4 (antifungal agents of the azole group and macrolide antibiotics), the concentration of quetiapine in plasma can be significantly increased. Thus, with simultaneous administration of quetiapine and ketoconazole, the increase in quetiapine AUC is 5-8 times. For this reason, such combinations of drugs are contraindicated. Also during treatment, Lackwell is not recommended to use grapefruit juice.
With the simultaneous administration of lakvel with drugs that induce the enzyme system of the liver, such as carbamazepine or phenytoin, the concentration of quetiapine in the plasma decreases. Care should be taken to weigh the risk and benefit of concomitant administration of Lakvel and inducers of hepatic enzymes (other than those mentioned above, barbiturates, rifampicin). It may be necessary to increase the dose of Lakvel, which is carried out gradually; should also consider replacing Lakvel with a drug that does not induce microsomal liver enzymes (eg, valproic acid).
The pharmacokinetics of lithium preparations does not change with the simultaneous administration of Lakvel.
Simultaneous administration of antipsychotic drugs risperidone or haloperidol does not significantly affect the pharmacokinetics of quetiapine. However, simultaneous administration of thioridazine leads to an increase in clearance of quetiapine by approximately 70%.
The pharmacokinetics of quetiapine does not change significantly with the simultaneous use of cimetidine, an inhibitor of cytochrome P450 isoenzymes, as well as in combination with imipramine or fluoxetine.
With the simultaneous administration of lakvel and preparations of valproic acid, their pharmacokinetic parameters did not change significantly.
Drugs that depress the central nervous system, as well as ethanol, increase the risk of side effects.
Caution should be exercised when administering Lakvel in combination with drugs that extend the QT interval (antipsychotics, antiarrhythmics, halofantrine, mesoridazine, thioridazine, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, dolasetron, mefloquine, sertindole, cisapride), as well as with medications that cause electrolyte balance disorders (thiazide diuretics).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
