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

Excipientslactose monohydrate 7,240 mg / 28,960 mg / 57,920 mg, microcrystalline cellulose 8,776 mg / 35,104 mg / 70,208 mg, calcium hydrophosphate dihydrate 4,200 mg / 16,800 mg / 33,600 mg, giprolose 2,400 mg / 9,600 mg / 19,200 mg, sodium carboxymethyl starch 4,200 mg / 16,800 mg / 33,600 mg, talc 2,900 mg / 11,600 mg / 23,200 mg, silicon dioxide colloid 0,900 mg / 3,600 mg / 7,200 mg, magnesium stearate 0,600 mg / 2,400 mg / 4,800 mg;

film sheath:

for tablets 25 mg: Opadrai II pink 31F34566 1,800 mg (lactose monohydrate 36,000%, hypromellose 28,000%, titanium dioxide 23,700%, macrogol-4000 10,000%, coloring sunset sunset yellow 1,300%; iron dye oxide red 1,000%); for tablets 100 mg: Opadrai II yellow 31F32561 7,200 mg (lactose monohydrate 36,000%, hypromellose 28,000%, titanium dioxide 23,180%, macrogol-4000 10,000%, iron dye oxide yellow 2,820%); for tablets 200 mg: Opadrai II white OY-L-28900 14,400 mg (lactose monohydrate 36,000%, hypromellose 28,000%, titanium dioxide 26,000%, macrogol 4000 10,000%).

Description:

Tablets 25 mg: pink with a brownish hint of round, biconvex tablets, covered with a film shell, with embossed inscriptions "QE"on one side and" 25 " - another.

Tablets 100 mg: yellow with a brownish shade of round, biconvex tablets, covered with a film shell, with the embossed inscriptions "QE"on one side and" 100 " - another.

Tablets 200 mg: white round, biconvex tablets, covered with a film shell, with the embossed inscriptions "QE"on one side and" 200 "on the other.

For all dosages: a cross-sectional view is a homogeneous mass of white or almost white color.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.04 Quetiapine

Pharmacodynamics:

Atypical antipsychotic drug (neuroleptic), which interacts with various types of neurotransmitter receptors. Has a higher affinity for serotonin receptors (5-HT₂) than to dopamine receptors (D₁ and D₂) brain. It also has a higher affinity for histamine and α₁-adrenoceptors and less - in relation to α₂adrenoreceptors. There was no significant affinity for quetiapine for cholinergic muscarinic and benzodiazepine receptors.

Quetiapine causes a selective decrease in the activity of mesolimbic A10-dopaminergic neurons in comparison with A9-nigrostri- neal neurons involved in motor function.Does not cause a prolonged increase in the concentration of prolactin in

blood plasma. Clinical studies have shown efficacy for both positive and negative symptoms of schizophrenia.

The effect of quetiapine on 5-HT receptors₂ and D₂ lasts up to 12 hours after taking the drug.

Pharmacokinetics:

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

The intake of food does not significantly affect the bioavailability of quetiapine. Half-life is about 7 hours. Approximately 83% of quetiapine binds to plasma proteins. The pharmacokinetics of quetiapine is linear, there is no difference 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 (creatinine clearance less than 30 ml / min / 1.73 m²), however, individual clearance rates are within the limits corresponding to healthy people.

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 the kidney or intestine. Determined that CYP3A4 is the key enzyme of quetiapine metabolism, mediated by cytochrome P450.

Quetiapine and some of its metabolites have a weak inhibitory activity against cytochrome P450 1A2, 2C9, 2C19, 2D6 and 4A4, but only at concentrations 10-50 times higher than the concentrations observed at the usual effective dosage of 300-450 mg / day.

Indications:

Schizophrenia.

Maniac episodes of moderate and severe degree in the structure of bipolar disorder. Does not prevent the development of manic and depressive episodes.

Contraindications:

Hypersensitivity to any of the components of the drug.

Simultaneous use of cytochrome P 450 3A4 inhibitors (eg, HIV protease inhibitors, azole antifungal agents, erythromycin, clarithromycin, nefazodone).

Child age (effectiveness and safety not established).

Pregnancy and lactation (efficacy and safety not established).

Carefully:

Arterial hypotension, heart failure, cardiac hypertrophy, cardiovascular and cerebrovascular diseases, or other conditions predisposing to arterial hypotension, elderly age, hepatic insufficiency, epilepsy, seizures in the anamnesis, simultaneous administration of drugs prolonging the QT-interval, patients with congenital QT- interval or family predisposition to its increase, hypocalcemia, hypomagnesemia, risk factors for thromboembolism of venous vessels.

Dosing and Administration:

Inside, 2 times a day, regardless of food intake.

Treatment of schizophrenia

The daily dose for the first 4 days of therapy is: the 1st day - 50 mg, the second day - 100 mg, the third day - 200 mg, the 4th day - 300 mg.

Starting from the 4th day, the dose is selected individually until an effective dosage is reached, usually 300-450 mg / day. Depending on the clinical effect and individual patient tolerance, the dose may 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, 6The 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 per 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.

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.

Renal and / or hepatic impairment

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 effects:

Very often more than 10/100, often more than 1/100 and less than 1/10, infrequently more than 1/1000 and less than 1/100, rarely more than 1/10000 and less than 1/1000, very rarely less than 1 / 10000.

From the central nervous system: very often - dizziness, drowsiness,headache; often - syncopation; 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, including thromboembolism of pulmonary vessels and deep veins.

From the respiratory system: pharyngitis, rhinitis.

From the digestive system: often - dry mouth, constipation, indigestion; rarely - jaundice, nausea, vomiting, abdominal pain; very rarely - hepatitis.

From the blood and lymphatic system: often - leukopenia; infrequently - eosinophilia; very rarely - neutropenia.

Laboratory indicators: often - increased activity of serum transaminases (ALT, ACT); infrequently - increased activity of gamma-glutamate transaminase; 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 - malignant neuroleptic syndrome, 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. Maximum reduction in total and free T₄ registered 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 practically all cases, the level of total and free T₄ returned to the baseline after quitting Quetiapine therapy, 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.

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.

Interaction:

Cytochrome P450 CYP3A4 is a key enzyme involved in the metabolism of quetiapine. With the simultaneous administration of drugs that have a strong inhibitory effect on cytochrome P450 CYP3A4 (antifungal agents of the azole group and macrolide antibiotics), the concentration of quetiapine in plasma can be significantly increased. Thus, with the simultaneous administration of quetiapine and ketoconazole, an increase in the area under the curve (AUC) quetiapine 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 is reduced. Care must be taken to weigh the risk and benefit of concomitant administration of Lakvel and inductors of liver 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 simultaneous use of cimetidine, which is an inhibitor of P450, and also when administered together 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 used when administering Lakvel in combination with drugs that extend the interval QT (neuroleptics, antiarrhythmics, halofantrine, mesoridazine, thioridazine, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, dolasetron, mesylate, mefloquine, sertindole, cisapride), as well as with drugs that cause electrolyte imbalances (thiazide diuretics).

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 hypotension.

Antipsychotic drugs (antipsychotics), including quetiapine, promote the development of thromboembolic complications in patients with a predisposition to the formation of thrombi. Prior to initiation of quetiapine therapy, it is necessary to identify all possible risk factors for venous thromboembolism and to take appropriate measures to prevent the development of thromboemboliccomplications.

There was no correlation between drug intake in the recommended regimen and an increase in QT-interval. However, an increase in the QT-interval was noted with an overdose of the drug. Caution should be exercised when administering quetiapine concomitantly with drugs that extend the QT 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 an increase in the QT interval .

It should be used with caution in combination with other drugs that have an inhibitory 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 of quetiapine, a malignant neuroleptic syndrome may develop, the clinical manifestations of which include hyperthermia, altered mental status, muscle rigidity, vegetative nervous system instability, and increased levels of creatine phosphokinase. 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, and rarely insomnia. There may also be an exacerbation of the symptoms of a psychotic illness and the appearance 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 cerebro-vascular 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, so it is not prescribed for patients with lactase deficiency or impaired absorption of glucose and galactose

Effect on the ability to drive transp. cf. and fur:

The drug may cause drowsiness, so during the period of treatment, patients are not recommended to drive vehicles, work with mechanisms, which are dangerous.

Form release / dosage:

Tablets, film-coated, 25 mg, 100 mg, 200 mg.

Packaging:

For 10 tablets in a blister of PVC / PVDC / aluminum foil.

For 6 blisters together with instructions for use in a cardboard box.

Combi pack: 6 tablets each 25 mg each in a blister of PVC / PVDC / aluminum foil, 3 tablets each for 100 mg in the blister of PVC / PVDC / aluminum foil, 1 tablet 200 mg in a blister of PVC / PVDC / aluminum foil.

For 1 blister with tablets of each dosage together with instructions for use in a cardboard pack.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009007/09

Date of registration:10.11.2009 / 02.11.2012

Expiration Date:Unlimited

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Representation: & nbspTeva Teva Israel

Information update date: & nbsp09.02.2018

Illustrated instructions

Instructions

Lakvel (Lacvel)