Quetaz

Quetaz 25: Peach coloured, round, film coated tablets debossed with "F71" on one side and plain on the other side.
Each tablet contains Quetiapine fumarate 28.78 mg equivalent to quetiapine 25 mg.
Quetaz 100: Yellow coloured, round, film coated tablets debossed with "F73" on one side and plain on the other side.
Each tablet contains Quetiapine fumarate 115.12 mg equivalent to quetiapine 100 mg.
Quetaz 200: White coloured, round, film coated tablets debossed with "F75" on one side and plain on the other side.
Each tablet contains Quetiapine fumarate 230.24 mg equivalent to quetiapine 200 mg.

Pharmacology: Pharmacodynamics: Quetiapine fumarate is a psychotropic agent belonging to a chemical class, the dibenzothiapine derivatives. The chemical name is 2-[2-(4-dibenzo [b,f] [1,4]thiazepin-11-yl-1-piperazinyl) ethoxy]-ethanol fumarate (2:1) (salt). It has an empirical formula of C₄₂H₅₀N₆O₄S₂.C₄H₄O₄.
Quetiapine is an antagonist at multiple neurotransmitter receptors in the brain: Serotonin 5-HT1A and 5-HT2, dopamine D1 and D2, histamine H1, adrenergic α1 and α2 receptors. Quetiapine has no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors.
Quetiapine blocks the action of dopamine agonists, measured either behaviorally or electrophysiologically, and elevates dopamine metabolite concentrations, a neurochemical index of D2-receptor blockade.
Pharmacokinetics: Absorption: Quetiapine fumarate is rapidly absorbed after oral administration and throughout the body, reaching peak plasma concentration in 1.5 hours.
Distribution: Quetiapine is widely distributed throughout the body. It is about 83% bound to plasma protein.
Metabolism: Quetiapine is extensively metabolized by the liver. The major metabolic pathways are sulfoxidation to the sulfoxide metabolite and oxidation to the parent acid metabolite; both metabolites are pharmacologically inactive. In vitro studies using human liver microsomes revealed that the cytochrome P450 3A4 isoenzyme is involved in the metabolism of quetiapine to its major, but inactive, sulfoxide metabolite and in the metabolism of its active metabolite N-desalkyl quetiapine.
Elimination: Following a single oral dose of 14C-quetiapine, less than 1% of the administered dose was excreted as unchanged drug, indicating that quetiapine is highly metabolized. Approximately 73% and 20% of the dose was recovered in the urine and feces, respectively.

Quetiapine fumarate is indicated for the treatment of: Schizophrenia; Bipolar Disorder including Manic episodes associated with bipolar disorder, Depressive episodes associated with bipolar disorder, Maintenance treatment of bipolar I disorder (manic, mixed or depressed episode) in combination with mood stabilizers (lithium or valproate).

Recommended dose: Adults: For the treatment of schizophrenia: For the treatment of schizophrenia, quetiapine should be administered twice a day with or without food. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). From Day 4 onwards, the dose should be titrated to the usual effective dose of 300 to 450 mg/day. Depending on the clinical response and tolerability of the individual patient, the dose may be adjusted within the range 150 to 750 mg/day.
For treatment of manic episodes associated with bipolar disorder: Quetiapine should be administered twice a day with or without food. The total daily dose for the first four days of therapy is 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3), and 400 mg (Day 4). Further dosage adjustment up to 800 mg/day by Day 6 should be in increments of no greater than 200 mg/day.
The dose may be adjusted depending on clinical response and tolerability of the individual patient, within the range of 200-800 mg/day. The usual effective dose is in the range of 400 to 800 mg/day.
For treatment of depressive episodes associated with bipolar disorder: Quetiapine should be administered once daily at bedtime with or without food. Quetiapine should be titrated as follows: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). Quetiapine can be titrated to 400 mg on Day 5 and up to 600 mg by Day 8.
Antidepressant efficacy was demonstrated with quetiapine at 300 mg and 600 mg however no additional benefit was seen in the 600 mg group during short-term treatment.
For the maintenance treatment of bipolar I disorder in combination with mood stabilizers (lithium or valproate): Patients who have responded to quetiapine in combination therapy to a mood stabilizer (lithium or valproate) for acute treatment of bipolar disorder should continue on quetiapine therapy at the same dose. Quetiapine dose can be re-adjusted depending on clinical response and tolerability of the individual patient. Efficacy was demonstrated with quetiapine (administered twice daily totaling 400 mg to 800 mg a day) as combination therapy to mood stabilizer (lithium or valproate).
Elderly: As with other antipsychotics, quetiapine should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration may need to be slower, and the daily therapeutic dose lower, than that used in younger patients, depending on the clinical response and tolerability of the individual patient. The mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared with younger patients.
Children and adolescents: The safety and efficacy of quetiapine have not been evaluated in children and adolescents.
Renal impairment: Dosage adjustment is not necessary.
Hepatic impairment: Quetiapine is extensively metabolized by the liver. Therefore, Quetiapine should be used with caution in patients with known hepatic impairment, especially during the initial dosing period. Patients with known hepatic impairment should be started with 25 mg/day. The dosage should be increased daily with increments of 25-50 mg/day to an effective dose, depending on the clinical response and tolerability of the individual patient.
Mode of administration: Quetiapine is oral tablet and can be administered with or without food.

Symptoms: In general, reported signs and symptoms were those resulting from an exaggeration of the active substance's unknown pharmacological effect, i.e., drowsiness and sedation, tachycardia, hypotension and anticholinergic effects.
Overdose could lead to QT-prolongation, patients with pre-existing severe cardiovascular disease may be at an increased risk of the effects of overdose.
Treatment: There is no specific antidote to quetiapine. The prevention of absorption in overdose has not been investigated, gastric lavage can be indicated in severe poisonings and if possible to perform within one hour of ingestion. The administration of activated charcoal should be considered.

Quetiapine is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients of this product formulation.

Suicide/suicidal thoughts or clinical worsening: Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-harm and suicide. Physicians should consider the potential risk of suicide-related events after abrupt cessation of quetiapine treatment, due to the known risk factors for the disease being treated.
Patients with a history of suicide related events, or those exhibiting a significant degree of suicidal ideation prior to be a greater risk of suicidal thoughts or suicide attempts, should receive careful monitoring during treatment. A meta-analysis of placebo controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants compared to placebo in patients less than 25 years old.
Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behavior and to seek medical advice immediately if these symptoms present.
Tardive Dyskinesia: If signs and symptoms of tardive dyskinesia (a syndrome of potentially, irreversible, involuntary, dyskinetic movement) appear, dose reduction or discontinuation of quetiapine should be considered.
Neuroleptic Malignant Syndrome: Neuroleptic Malignant Syndrome has been associated with antipsychotic treatment, including quetiapine. Clinical manifestations include hyperthermia, altered mental status, muscular rigidity, autonomic instability, and increased creatinine phosphokinase. In such an event, quetiapine should be discontinued and appropriate medical treatment given.
Hyperglycemia: Hyperglycemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported rarely, including some fatal cases. In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Appropriate clinical monitoring is advisable in accordance with utilized antipsychotic agent including quetiapine, should be observed for signs and symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.
Orthostatic hypotension: Quetiapine treatment has been associated with orthostatic hypotension and related dizziness which, like somnolence has onset usually during the initial dose-titration period. This could increase the occurrence of accidental injury (fall), especially in the elderly population. Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. Dose reduction or more gradual titration should be considered if orthostatic hypotension occurs, especially in patients with underlying cardiovascular disease.
Cardiomyopathy and Myocarditis: Cardiomyopathy and myocarditis have been reported in clinical trials and during the post-marketing experience, however, a causal relationship to quetiapine has not been established. Treatment with quetiapine should be reassessed in patients with suspected cardiomyopathy or myocarditis.
Ocular Effects: The development of cataracts in association with quetiapine was observed in animal studies. Lens changes also have been reported in some patients receiving long-term quetiapine therapy, although a causal relationship has not been established.
Seizures: Seizures occurred in 0.6% of patients receiving quetiapine in controlled clinical trials. Use with caution when treating patients with a history of seizures.
Somnolence and Dizziness: Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation.
Endocrine effect: Dose-related decrease in total and free thyroxine (T₄) of approximately 20% were observed in patients receiving quetiapine dosage at the higher end of the therapeutic dosage range during clinical studies. Increase in TSH were observed in about 0.4% or 12% of patients receiving quetiapine alone or in conjunction with lithium or divalproex sodium, respectively. In patients receiving quetiapine monotherapy, thyroid replacement therapy was necessary in some patients who experienced increase in TSH.
Weight: Weight gain has been reported in patients who have been treated with quetiapine, and should be monitored and managed as clinically appropriate as in accordance with utilized antipsychotic guideline.
Lipids: Increases in LDL and total cholesterol have been observed in clinical trials with quetiapine. Lipid changes should be managed as clinically appropriate.
Hepatic Effects: Asymptomatic, transit, and reversible increases in serum transaminases, principally ALT, have been reported in patients receiving quetiapine; these changes usually occurred within the first 3 weeks and resolved despite continued quetiapine therapy.
Anticholinergic (muscarinic) effects: Norquetiapine, an active metabolite of quetiapine, has moderate to strong affinity for several muscarinic receptor subtypes. Quetiapine should be used with caution in patients receiving medications having anticholinergic (muscarinic) effects. Quetiapine should be used with caution in patients with a current diagnosis or prior history of related disease with cholinergic effect such as urinary retention, priapism, clinically significant prostatic hypertrophy, intestinal obstruction or related conditions, increased intraocular pressure or narrow angle glaucoma.
Extrapyramidal symptoms: Quetiapine is associated with an increased incidence of extrapyramidal symptoms (EPS).
Dysphagia: Dysphagia has been reported with quetiapine. Quetiapine should be used with caution in patients at risk for aspiration pneumonia.
Withdrawal: Acute withdrawal symptoms such as insomnia, nausea, vomiting, dizziness, and irritability have been described after abrupt cessation of quetiapine.
Use in the Elderly: Elderly patients with dementia-related psychosis: Quetiapine is not approved for the treatment of dementia-related psychosis an increased risk of cardiovascular adverse events has been seen in randomized placebo controlled trials with some atypical antipsychotics. The mechanism for this increased risk is not known.

Pregnancy: Pregnancy Category C.
Third trimester: Neonates exposed to antipsychotics (including quetiapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal symptoms and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reported of agitation, hypertonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.
Breast-feeding: Based on very limited data from published reports on quetiapine excretion into human breast milk, quetiapine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

The most common effects reported in 5% or more of patients receiving quetiapine therapy for schizophrenia or bipolar disorder and at a frequency twice that reported among patients receiving placebo in clinical trials include somnolence, sedation, asthenia, lethargy, dizziness, dry mouth, constipation, increased ALT, weight gain, dyspepsia, abdominal pain, postural hypotension, and pharyngitis.

Given the primary central nervous system effects of quetiapine, quetiapine should be used with caution in combination with other centrally acting medicinal products and alcohol.
Caution should be exercised treating patients receiving other medications having anticholinergic (muscarinic) effects.
Cytochrome P450 (CYP) 3A4 is the enzyme that is primarily responsible for the CYP450 mediated metabolism of quetiapine. Concomitant administration of quetiapine with potent inhibitors of CYP3A4 such as erythromycin, fluconazole, itraconazole, and ketoconazole is not recommended, causes an increasing in the AUC of quetiapine. Concomitant administration of quetiapine with potent inducers of CYP3A4 such as carbamazepine, and phenytoin is significantly increased the clearance of quetiapine. As a consequence of this interaction, lower plasma concentrations can occur, which could affect the efficacy of quetiapine therapy.
Antipsychotic: Caution should be exercised when quetiapine is used concomitantly with medicinal products such as risperidone known to cause electrolyte imbalance or to increase QT interval.

Store below 30°C.

Antipsychotics

N05AH04 - quetiapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.

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