Quetitex^® Prolong (Tablets) Instructions for Use

Marketing Authorization Holder

Aliym, JSC (Russia)

ATC Code

N05AH04 (Quetiapine)

Active Substance

Quetiapine (Rec.INN registered by WHO)

Dosage Forms

	Quetitex® Prolong	Prolonged-release film-coated tablets, 150 mg: 10 or 60 pcs.
		Prolonged-release film-coated tablets, 200 mg: 10 or 60 pcs.
		Prolonged-release film-coated tablets, 300 mg: 10 or 60 pcs.
		Prolonged-release film-coated tablets, 400 mg: 10 or 60 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release film-coated tablets white or almost white, biconvex, oblong in shape, with rounded ends; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate, microcrystalline cellulose type 101, sodium citrate dihydrate, hypromellose (hydroxypropyl methylcellulose), colloidal anhydrous silica, magnesium stearate.

Excipients for the coating: Opadry II 85F48105 white [polyvinyl alcohol, partially hydrolyzed, macrogol, talc, titanium dioxide].

10 pcs. – blister packs (1) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.

Prolonged-release film-coated tablets from yellow to yellow-brown, biconvex, oblong in shape, with rounded ends; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate, microcrystalline cellulose type 101, sodium citrate dihydrate, hypromellose (hydroxypropyl methylcellulose), colloidal anhydrous silica, magnesium stearate.

Excipients for the coating: Opadry II 85F38111 yellow [polyvinyl alcohol, partially hydrolyzed, macrogol, titanium dioxide, talc, iron oxide yellow dye, iron oxide red dye, iron oxide black dye].

10 pcs. – blister packs (1) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.

Prolonged-release film-coated tablets from yellow to yellow-brown, biconvex, oblong in shape, with rounded ends; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate, microcrystalline cellulose type 101, sodium citrate dihydrate, hypromellose (hydroxypropyl methylcellulose), colloidal anhydrous silica, magnesium stearate.

Excipients for the coating: Opadry II 85F38111 yellow [polyvinyl alcohol, partially hydrolyzed, macrogol, titanium dioxide, talc, iron oxide yellow dye, iron oxide red dye, iron oxide black dye].

10 pcs. – blister packs (1) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.

Prolonged-release film-coated tablets white or almost white, biconvex, oblong in shape, with rounded ends; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate, microcrystalline cellulose type 101, sodium citrate dihydrate, hypromellose (hydroxypropyl methylcellulose), colloidal anhydrous silica, magnesium stearate.

Excipients for the coating: Opadry II 85F48105 white [polyvinyl alcohol, partially hydrolyzed, macrogol, talc, titanium dioxide].

10 pcs. – blister packs (1) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Antipsychotic agent (neuroleptic)

Pharmacological Action

Antipsychotic agent (neuroleptic). It exhibits higher affinity for serotonin 5HT₂ receptors compared to dopamine D₁ and D₂ receptors in the brain.

It also has high affinity for histamine and α₁-adrenergic receptors and less pronounced affinity for α₂-adrenergic receptors.

It has no affinity for muscarinic cholinergic receptors and benzodiazepine receptors.

Quetiapine, at a dose that effectively blocks dopamine D₂ receptors, causes only weak catalepsy.

It selectively reduces the activity of mesolimbic A₁₀ dopamine neurons compared to A₉ nigrostriatal neurons involved in motor function.

It does not cause a prolonged increase in prolactin levels.

According to positron emission tomography results, the effect of quetiapine on serotonin 5HT₂ and dopamine D₂ receptors lasts up to 12 hours.

Pharmacokinetics

After oral administration, it is well absorbed from the gastrointestinal tract. Food intake does not significantly affect the bioavailability of quetiapine.

The pharmacokinetics of quetiapine are linear.

Plasma protein binding is about 83%.

It undergoes intensive metabolism. In vitro studies have established that the key enzyme for quetiapine metabolism is CYP3A4.

The main metabolites detected in plasma do not have significant pharmacological activity.

The elimination half-life (T_1/2) is about 7 hours.

Less than 5% of quetiapine is excreted unchanged by the kidneys or through the intestines.

Approximately 73% of metabolites are excreted by the kidneys and 21% through the intestines.

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

The mean plasma clearance of quetiapine was approximately 25% lower in patients with severe renal impairment (creatinine clearance less than 30 ml/min/1.73 m²) and in patients with liver damage (compensated alcoholic cirrhosis), but individual clearance levels were within the range corresponding to healthy individuals.

Indications

Acute and chronic psychoses (including schizophrenia).

ICD codes

Dosage Regimen

When used in adults, the initial dose is 50 mg/day, for elderly patients – 25 mg/day.

The dose is then gradually increased according to the scheme.

Depending on the clinical effect and individual sensitivity, the effective therapeutic dose can range from 150 to 750 mg/day.

In patients with impaired liver and/or kidney function, the initial dose is 25 mg/day.

The daily dose increase should be 25-50 mg until the optimal effect is achieved.

Adverse Reactions

From the nervous system: headache, drowsiness, dizziness, anxiety; rarely – neuroleptic malignant syndrome.

From the cardiovascular system: orthostatic hypotension, tachycardia, arterial hypertension.

From the digestive system: constipation, dry mouth, dyspepsia, diarrhea, transient increase in liver enzyme activity (ALT, AST, GGT), abdominal pain.

From the hematopoietic organs: asymptomatic leukopenia and/or neutropenia; rarely – eosinophilia.

From the musculoskeletal system: myalgia.

From the respiratory system: rhinitis.

Dermatological reactions: skin rash, dry skin.

From the hearing organ: ear pain.

From the genitourinary system: urinary tract infections.

From metabolism: slight increase in blood cholesterol and triglyceride levels.

From the endocrine system: small dose-dependent reversible decrease in thyroid hormone levels (in particular total and free T₄).

Other: asthenia, back pain, weight gain, fever, chest pain.

Contraindications

Hypersensitivity to quetiapine.

Use in Pregnancy and Lactation

During pregnancy and lactation, use is possible in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

It is not known whether Quetiapine is excreted in breast milk.

If it is necessary to use during lactation, breastfeeding should be discontinued.

In experimental studies on animals, no mutagenic or clastogenic effects of quetiapine were detected.

No effect of quetiapine on fertility was detected (decreased male fertility, pseudopregnancy, increased interval between two estrous cycles, increased precocial interval and decreased pregnancy rate), however, these data cannot be directly extrapolated to humans due to specific differences in the hormonal control of reproduction.

Use in Hepatic Impairment

Quetiapine undergoes active metabolism in the liver. In patients with impaired liver function, the clearance of quetiapine is reduced by approximately 25%. Therefore, Quetiapine should be used with caution in patients with impaired liver function.

Use in Renal Impairment

In patients with impaired renal function, the clearance of quetiapine is reduced by approximately 25%. Therefore, Quetiapine should be used with caution in patients with impaired renal function.

Geriatric Use

Use with caution in the elderly, especially when taking drugs that prolong the QT interval concomitantly.

Special Precautions

Use with caution in patients with cardiovascular diseases and other conditions associated with the risk of arterial hypotension, especially at the beginning of treatment and in the elderly; with a history of seizures.

Quetiapine undergoes active metabolism in the liver. In patients with impaired liver and kidney function, the clearance of quetiapine is reduced by approximately 25%. Therefore, Quetiapine should be used with caution in patients with impaired liver and/or kidney function.

Use with caution concomitantly with drugs that prolong the QT interval (especially in the elderly); with drugs that have a depressant effect on the central nervous system, as well as with ethanol; with potential inhibitors of the CYP3A4 isoenzyme (including ketoconazole, erythromycin).

If neuroleptic malignant syndrome develops during treatment, Quetiapine should be discontinued and appropriate treatment prescribed.

With long-term use, there is a possibility of developing tardive dyskinesia. In such cases, it is necessary to reduce the dose of quetiapine or discontinue it.

Use with caution in combination with other drugs that affect the activity of the central nervous system, as well as with ethanol.

In experimental studies on the carcinogenicity of quetiapine, an increased incidence of mammary gland adenocarcinomas was noted in rats (at doses of 20, 75 and 250 mg/kg/day), which is associated with prolonged hyperprolactinemia.

In male rats (250 mg/kg/day) and mice (250 and 750 mg/kg/day), an increased incidence of benign adenomas of thyroid follicular cells was noted, which was associated with a known, rodent-specific mechanism of increased hepatic clearance of thyroxine.

Effect on the ability to drive vehicles and operate machinery

Quetiapine may cause drowsiness, so patients are not recommended to perform work that requires concentration and high speed of psychomotor reactions (including driving vehicles).

Drug Interactions

With simultaneous use with ketoconazole, erythromycin, a theoretical possibility of increasing the plasma concentration of quetiapine and the development of side effects exists.

With simultaneous use with phenytoin, carbamazepine, barbiturates, rifampicin, the clearance of quetiapine increases, and its plasma concentration decreases.

With simultaneous use with thioridazine, an increase in the clearance of quetiapine is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.