25 mg tab: Each film coated tablet contains: Quetiapine Fumarate Eq. to Quetiapine 25 mg.
100 mg tab: Each film coated tablet contains: Quetiapine Fumarate Eq. to Quetiapine 100 mg.
200 mg tab: Each film coated tablet contains: Quetiapine Fumarate Eq. to Quetiapine 200 mg.
Chemistry: 2-[2-(4-dibenzo [b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol fumarate.
Pharmacotherapeutic Group: Antipsychotic Agent.
Pharmacology: Pharmacodynamics: Quetiapine is an antagonist at multiple neurotransmitter receptors in the brain: serotonin 5HT1A and 5HT2 (IC50s = 717 & 148 nM, respectively), dopamine D1 and D2 (IC50s = 1268 & 329 nM, respectively), histamine H1 (IC50=30 nM), and adrenergic a1 and a2 receptors (IC50s=94 & 271 nM, respectively). Quetiapine has no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors (IC50s>5000 nM). The mechanism of action of Quetiapine, as with other antipsychotic drugs, is unknown. However, it has been proposed that this drug's antipsychotic activity is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonism. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other effects of Quetiapine.
Mechanism of action: The mechanism of action of Quetiapine, as with other antipsychotic drugs, is unknown. However, it has been proposed that this drug's antipsychotic activity is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonism. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other effects of Quetiapine. Quetiapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Quetiapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
Pharmacokinetics: Quetiapine is well absorbed following oral administration and widely distributed throughout the body. It is about 83% bound to plasma proteins. Quetiapine is extensively metabolized in the liver by sulfoxidation mediated mainly by the cytochrome P450 isoenzyme CYP34A4 and by oxidation. It is excreted mainly as inactive metabolites, about 73% of a dose appearing in the urine and about 20% in the faeces.
The elimination half life has been reported to be about 6 to 7 hours.
Absorption: Quetiapine fumarate is rapidly absorbed after oral administration, reaching peak plasma concentrations in 1.5 hours. The tablet formulation is 100% bioavailable relative to solution. The bioavailability of quetiapine is marginally affected by administration with food, with Cmax and AUC values increased by 25% and 15%, respectively.
Distribution: Quetiapine is widely distributed throughout the body with an apparent volume of distribution of 10±4 L/kg. It is 83% bound to plasma proteins at therapeutic concentrations. In vitro, quetiapine did not affect the binding of warfarin or diazepam to human serum albumin. In turn, neither warfarin nor diazepam altered the binding of quetiapine.
Metabolism and 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 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.
Quetiapine is indicated for the management of the manifestations of psychotic disorders. The antipsychotic efficacy of Quetiapine was established in short-term (6-week) controlled trials of schizophrenic inpatients. It is given in the treatment of schizophrenia.
Quetiapine should generally be administered with an initial dose of 25 mg of the base twice daily on day one, 50 mg twice daily on day two. 100 mg twice daily on day three and 150 mg twice daily on day four. The dosage is then adjusted according to response to usual range of 300 mg to 450 mg daily given in 2 divided doses, although 150 mg daily may be adequate for some patients. The maximum recommended dose is 750 mg daily. Quetiapine should be given in reduced doses to the elderly patients with impaired hepatic or renal function; a recommended starting dose is 25 mg daily increased in steps of 25 to 50 mg daily according to response.
Hypotension, tachycardia and somnolence were the main clinical events observed in a patient who have ingested an overdose of 3 g of quetiapine. Tachycardia of an unexpected long duration was also noted. Management was symptomatic, including maintenance of fluids. Asymptomatic prolongation of the QT interval was observed in another patient who had ingested a 2 g overdose of quetiapine. The treatment regimen also included risperidone, and the authors warned that considerable QT interval prolongation may occur when patients overdose on quetiapine while taking therapeutic doses of risperidone.
Quetiapine is contraindicated in individuals with a known hypersensitivity to this medication or any of its ingredients. Contraindicated with coma or severe CNS depression, allergy to quetiapine, lactation.
It is recommended that patients should have an eye examination to detect cataract formation before starting therapy with quetiapine and every 6 months during treatment.
Use in Children: No information is available on the relationship of age to the effects of quetiapine in pediatric patients. Safety and efficacy have not been established.
Use in Elderly: No geriatrics-specific problems that would limit the usefulness of quetiapine in the elderly were seen in studies that included subjects 65 years of age and older. However, the mean plasma clearance of quetiapine in elderly patients was 30 to 50% less than in younger patients reduced initial and target dosages, and slower dosage titration may be necessary in elderly patients.
Use in Pregnancy: Adequate and well-controlled studies in humans have not been done. Quetiapine showed no teratogenic potential in rats and rabbits dosed at 0.3 to 2.4 and 0.6 to 2.4 times the MRHD on a mg/m2 basis, respectively, during the period of organogenesis. However, in rats, delays in skeletal ossification were seen in the fetuses at all doses. Also, reduced fetal body weight and reduced maternal weight gain and/or increased maternal deaths were seen at the highest dose used. In rabbits. reduced maternal weight gain and/or increased maternal deaths were seen at all doses, delays in skeletal ossification in the fetuses were seen at doses of 1.2 and 2.4 times the MRHD on a mg/m2 basis, and reduced fetal body weight and an increased incidence of minor soft tissue anomaly in the fetuses were seen at the highest dose used.
Use in Lactation: Quetiapine is distributed into the milk of animals. It is not known whether quetiapine is distributed into breast milk, but breast-feeding while taking quetiapine is not recommended.
Quetiapine has been associated with a low incidence of extrapyramidal symptoms. Rises in prolactin concentrations may be less than with chlorpromazine. Other adverse effect have included mild asthenia, anxiety, dizziness, myalgia, rhinitis, dyspepsia, rises in plasma triglyceride and cholesterol concentrations, and reduced plasma thyroid hormone concentrations. There have been a rare reports of priapism or peripheral oedema. Asymptomatic changes in the lens of the eye have occurred in patients during long term treatment with quetiapine; cataracts have developed in dogs during chronic dosing studies.
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate) not necessarily inclusive (>> = major clinical significance): Antihypertensive agents (hypotensive effects of these medications may be enhanced.
Cimetidine (oral clearance of quetiapine was decreased by 20% when coadministered with cimetidine 400 mg three times a day.
Cytochrome P450 3A (CYP3A) isoenzyme inhibitors, such as: Clarithromycin, Diltiazem, Erythromycin, Fluconazole, Itraconazole, Ketoconazole, Nefazodone, Verapamil (although there is no experience with the combination of quetiapine and a potent CYP3A enzyme inhibitor, caution is advised since quetiapine's major route of metabolism involves CYP3A4, Dopamine agonists or Levodopa) effects of these medications may be antagonized by quetiapine. Enzyme inducers, hepatic, cytochrome P450 mean oral clearance of quetiapine was increased five-fold in patients receiving phenytoin higher doses of quetiapine may be required during concomitant therapy with an enzyme-inducing medication; a decrease in quetiapine dosage may be required when enzyme-inducer therapy is discontinued.
Store at temperature not exceeding 30°C.
N05AH04 - quetiapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.
FC tab 25 mg x 50's. 100 mg x 50's. 200 mg x 50's.