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

Excipients: calcium hydrophosphate anhydrous 12.567 mg, lactose monohydrate 1 mg, microcrystalline cellulose 12 mg, sodium carboxymethyl starch 2.75 mg, povidone 2 mg, magnesium stearate 0.9 mg;

film sheath: Opadrai® pink 03B84929 2 mg: hypromellose 1.25 mg, titanium dioxide 0.567 mg, macrogol 400 0.125 mg, iron oxide dye yellow 0.03 mg, iron oxide red oxide 0.028 mg.

Dosage of 100 mg

active substance: Quetiapine fumarate 115.130 mg is equivalent to 100 mg quetiapine;

Excipients: calcium hydrophosphate anhydrous 50.27 mg, lactose monohydrate 4 mg, microcrystalline cellulose 48 mg, sodium carboxymethyl starch 11 mg, povidone 8 mg, magnesium stearate 3.6 mg;

film sheath: Opadrai® yellow 03B82923 6 mg: hypromellose 3.75 mg, titanium dioxide 1.695 mg, macrogol 400 0.375 mg,dye iron oxide yellow 0.18 mg.

Dosage 200 mg

active substance: Quetiapine fumarate 230.260 mg is equivalent to 200 mg quetiapine;

Excipients: calcium hydrophosphate anhydrous 100.54 mg, lactose monohydrate 8 mg, microcrystalline cellulose 96 mg, sodium carboxymethyl starch 22 mg, povidone 16 mg, magnesium stearate 7.2 mg;

film sheath: Opadrai® white Y-1-7000 12 mg: hypromellose 7.5 mg, titanium dioxide 3.75 mg, macrogol 400 0.75 mg.

Dosage of 300 mg

active substance: Quetiapine fumarate 345.390 mg is equivalent to 300 mg quetiapine;

Excipients: calcium hydrophosphate anhydrous 150.81 mg, lactose monohydrate 12 mg, cellulose micrometercrystalline 144 mg, sodium carboxymethyl starch 33 mg, povidone 24 mg, magnesium stearate 10.8 mg;

film sheath: Opadrai® white Y-1-7000 18 mg: hypromellose 11.25 mg, titanium dioxide 5.625 mg, macrogol 400 1.125 mg.

Description:

Nantaride® tablets 25 mg, film-coated. Round biconvex tablets covered with a film coating of yellow-pink color.

Nantarid® tablets 100 mg, film-coated. Round biconvex tablets covered with a film membrane, yellow with a risk on one side.

Nantaride® tablets 200 mg, film-coated. Round biconvex tablets, covered with a film coat from white to almost white.

Nantaride® tablets 300 mg, film-coated. Tablets in the form of capsules, coated with a film shell from white to almost white with a risk on one side.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.04 Quetiapine

Pharmacodynamics:

Antipsychotic agent (antipsychotic). Has a higher affinity for serotonin (5-HT2) receptors than for dopamine receptors D1 and D2 of the brain. Has an affinity for histamine and alpha1-adrenoreceptors, less active with respect to alpha2-adrenergic receptors. There was no selective affinity for cholinergic muscarinic and benzodiazepine receptors. Reduces the activity of mesolimbic A10-dopaminergic neurons, in comparison with A9-nigrostriate neurons involved in motor functions. Does not cause a prolonged increase in the concentration of prolactin. The duration of communication with 5-HT2-serotonin and D2-dopamine receptors is less than 12 hours after taking the drug.

Pharmacokinetics:

Suction

When administered orally, it is well absorbed from the gastrointestinal tract. Absorption is high, food intake does not affect bioavailability.

Distribution

Quetiapine approximately 83% binds to plasma proteins. The pharmacokinetics of quetiapine are linear, and do not differ between men and women.

Metabolism

Actively metabolized in the liver with the formation of pharmacologically inactive metabolites under the influence of isoenzyme CYP3A4 cytochrome P450. Quetiapine and some of its metabolites have a weak inhibitory effect on cytochrome isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, but only in concentrations 10-50 times higher than those that occur at the usual dose of 300-450 mg / day.

Excretion

It is excreted by the kidneys 73%, through the intestines - 21%. The half-life (T_1/2) about 7 hours. Less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys or through the intestine.

Pharmacokinetics in special clinical cases

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

Patients with cirrhosis of the liver T_1/2 slightly increases, and the bioavailability of the drug decreases (dosage adjustment may be required).

The mean plasma clearance of quetiapine was approximately 25% less in patients with severe renal dysfunction (creatinine clearance less than 30 ml / min / 1.73 m²) and in patients with liver damage (alcohol cirrhosis in the stage of compensation), but the individual clearance levels were within the limits corresponding to healthy people.

Indications:

Acute and chronic psychoses, including schizophrenia.

Manic episodes in bipolar disorder.

Contraindications:

- Hypersensitivity to quetiapine or other components of the drug;

- the period of breastfeeding;

- children and adolescents under 18 years of age (efficacy and safety not established);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption (in the drug form of the drug contains lactose).

Carefully:

Cardiovascular and cerebrovascular diseases, arterial hypotension, congenital syndrome of lengthening the interval QT or the presence of conditions potentially capable of causing lengthening of the interval QT (simultaneous administration of drugs that extend the interval QT, congestive heart failure, hypokalemia, hypomagnesemia),in patients with the risk of venous thromboembolism, hypothyroidism, diabetes mellitus, elderly age, hepatic insufficiency, epilepsy, convulsive fits in the anamnesis, pregnancy.

Pregnancy and lactation:

Safety and effectiveness of use in pregnancy is not established. Therefore, in pregnancy, Nantaride® can only be used if the expected benefit to the mother exceeds the potential risk to the fetus.

The degree of excretion of quetiapine with human milk is not known. If it is necessary to use the drug Nantaride® it is recommended to stop breastfeeding during lactation.

Dosing and Administration:

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

Treatment of acute and chronic psychoses, including schizophrenia

The daily dose for the first 4 days of therapy is 50 mg (1 day), 100 mg (2 day), 200 mg (3 day), 300 mg (4 day). Starting from 4 days, the dose should be selected up to an effective dose ranging from 300 to 450 mg / day. Depending on the clinical effect and tolerability of the drug, the dose may vary from 150 to 750 mg / day.

Treatment of manic episodes with bipolar disorder

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.Further, within 6 days, the daily dose is increased to 800 mg, but not more than 200 mg per day. Depending on the clinical effect and tolerability of the drug, the dose may vary from 200 to 800 mg / day. The effective dose is from 400 to 800 mg / day.

Elderly age

The plasma clearance of quetiapine in elderly people is reduced by 30-50% compared to young patients, so the drug should be administered with caution, especially at the beginning of treatment. The starting dose is 25 mg / day, followed by an increase of 25-50 mg / day until the effective dose is reached.

Renal and hepatic impairment

In renal and / or liver failure, quetiapine should be treated with 25 mg / day, followed by a daily increase of 25-50 mg to achieve an effective dose.

Safety and efficacy of the drug in children and adolescents not investigated.

Side effects:

Side effects observed with the use of the drug are classified into categories depending on the frequency of their occurrence: very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10 000, <1/1000); very rarely (<1/10 000), including individual messages.

On the part of the hematopoiesis system: often - leukopenia, infrequently - eosinophilia, thrombocytopenia; very rarely - neutropenia.

Metabolic and nutritional disorders: often - weight gain (mainly in the first weeks of treatment), hyperglycemia or decompensation of diabetes mellitus; very rarely - diabetes.

From the nervous system: very often - dizziness, drowsiness, headache; often syncope, unusual and nightmarish dreams, fainting, extrapyramidal symptoms, anorexia; infrequently - anxiety, hostility, agitation, insomnia, akathisia, tremor, convulsions, depression, dysarthria, paresthesia; rarely - malignant neuroleptic syndrome (hyperthermia, muscle rigidity, altered mental status, lability in the autonomic nervous system, increased activity of creatine phosphokinase); very rarely - tardive dyskinesia.

From the side of the cardiovascular system: often - orthostatic hypotension, palpitations, tachycardia, increased blood pressure, prolongation of the QT interval on the ECG, separate reports - the risk of venous thromboembolism.

From the digestive system: very often - dry mouth, often - nausea, vomiting, diarrhea or constipation, dyspepsia; infrequently - dysphagia; rarely - pain in the abdomen, jaundice, very rarely - hepatitis.

From the respiratory system: often pharyngitis, rhinitis.

Allergic reactions: infrequently - skin rash, hypersensitivity reactions, very rarely - angioedema, Stevens-Johnson syndrome.

From the side of the reproductive system: rarely - priapism (painful erection).

From the side of the organ of vision: often - blurred vision

From the immune system: infrequently - hypersensitivity reactions; very rarely - angioedema, Stevens-Johnson syndrome.

Laboratory indicators: very often - hypercholesterolemia, hypertriglyceridemia; often - an increase in the activity of "liver" transaminases, infrequently - an increase in the activity of HTT, a decrease in the concentration of total and free T₄ (the first 4 weeks), as well as the general T₃ and reversible T₃ (only with high doses of quetiapine), an increase in the activity of creatine phosphokinase, not associated with a malignant neuroleptic syndrome.

Other: very often - withdrawal syndrome; often - peripheral edema, asthenia, increased sweating; rarely - back pain, chest pain, subfebrile condition, myalgia, dry skin, weak eyesight.

Overdose:Dunnth the drug overdose is limited. The cases of taking quetiapine in a dose exceeding 20 g without fatal outcomes are described and the coping of side effects without consequences. Very rarely reported cases of quetiapine overdose, leading to lengthening of the interval QT, coma or death.

Symptoms: excessive sedation, drowsiness, tachycardia, arterial hypotension.

Treatment: there are no specific antidotes to quetiapine. In case of an accidental overdose within the first hour after taking it is necessary to consider the possibility of symptomatic therapy and it is recommended to carry out activities aimed at maintaining the function of respiration, cardiovascular system, ensuring adequate oxygenation and ventilation. Medical supervision and surveillance should be continued until the patient is fully recovered.

Interaction:

With the simultaneous administration of drugs that have a strong inhibitory effect on the isoenzyme CYP3 A4 (such as the azole antifungal agents and macrolide antibiotics), the concentration of quetiapine in the plasma may increase. In such cases, lower doses should be used Nantaride®. Particular attention should be paid to elderly and weakened patients. It is necessary to individually evaluate the relationship between risk and benefit for each patient.

Simultaneous appointment Nantaride® with preparations carbamazepine and phenytoin, inducing microsomal enzymes of the liver, it is possible to reduce the concentration of the drug in the plasma, which may require an increase in the dose Nantaride®, depending on the clinical effect. This should also be considered when removing phenytoin, carbamazepine or other inducer of microsomal liver enzymes or replacing with a drug that does not induce microsomal liver enzymes (for example, valproic acid).

Quetiapine does not induce the induction of microsomal liver enzymes involved in the metabolism of phenazone.

The pharmacokinetics of quetiapine does not change with simultaneous use of cimetidine (inhibitor P450), fluoxetine antidepressants (inhibitor CYP3A4 and CYP2D6) or imipramine (inhibitor CYP2D6).

The pharmacokinetics of quetiapine did not change significantly when taken concomitantly with risperidone, haloperidol, lithium preparations, and valproic acid preparations.However, simultaneous administration of quetiapine with thioridazine led to increased clearance of quetiapine.

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

With the simultaneous administration of quetiapine in a dose of 750 mg / day and lorazepam in a dose of 2 mg, once the clearance of lorazepam is reduced by 20%.

Special instructions:

With a sharp cancellation of high doses of antipsychotic drugs, the following acute reactions (withdrawal syndrome) can occur: nausea, vomiting; rarely insomnia Cases of exacerbation of psychotic symptoms and the appearance of involuntary motor disorders (akathisia, dystonia, dyskinesia) have been reported. In this regard, it is recommended to gradually phase out the drug.

Taking into account that quetiapine, mainly affects the central nervous system, Nantaride® should be used with caution in combination with other drugs that have a depressant effect on the central nervous system. It is recommended to refrain from drinking alcohol.

When symptoms of tardive dyskinesia appear, reduce the dose or stop using quetiapine.

When assigning quetiapine simultaneously with drugs that extend the interval QT, caution should be exercised, especially in the elderly, in patients with congenital lengthening of the interval QT, congestive heart failure, hypertrophy of the myocardium, hypokalemia and hypomagnesemia.

Malignant neuroleptic syndrome can be associated with ongoing antipsychotic treatment. Clinical manifestations of the syndrome include: hyperthermia, altered mental status, muscle rigidity, instability of the autonomic nervous system, increased activity of creatine phosphokinase. With the development of this syndrome quetiapine should be canceled and the appropriate treatment performed.

In patients with prolonged use of quetiapine, cataracts were reported. In this regard, an ophthalmological examination should be conducted before the start of therapy and once every 6 months with prolonged use of the drug.

As with other antipsychotics, caution should be exercised in the treatment of patients with a history of seizures.

There are some reports of the risk of venous thromboembolism in the use of antipsychotic drugs.Before and during quetiapine treatment, all possible risk factors for venous thromboembolism should be identified and preventive measures taken.

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

Nantarid® can cause drowsiness, so patients are not recommended to work with mechanisms that are dangerous, including. it is not recommended to drive and engage in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets, 25 mg, 100 mg, 200 mg and 300 mg.

Packaging:

Tablets 25 mg. For 10 tablets in a blister of PVC / PE / PVDC - aluminum foil. For 3 blisters with instructions for use in a cardboard box.

Tablets 100 mg. For 10 tablets in a blister of PVC / PE / PVDC - aluminum foil. For 3 or 6 blisters with instructions for use in a cardboard box.

Tablets 200 mg. For 10 tablets in a blister of PVC / PE / PVDC - aluminum foil. For 6 blisters with instructions for use in a cardboard box.

Tablets 300 mg. For 10 tablets in a blister of PVC / PE / PVDC - aluminum foil. For 6 blisters with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009347/09

Date of registration:19.11.2009

Expiration Date:Unlimited

Date of cancellation:2018-04-09

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER-RUS, CJSC Russia

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp27.05.2018

Illustrated instructions

Instructions

Nantaride® (Nantarid®)