Quetiapine

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals -> Antipsychotics

Breast Feeding; Lactation; Milk, Human; Antipsychotic Agents

Medicines for bipolar disorders

188.6 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID3044201]

192.9 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

190.58 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

191.1 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated]

191.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P304+P340, P305+P354+P338, P317, P319, P330, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 4 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H225: Highly Flammable liquid and vapor [Danger Flammable liquids]

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including quetiapine fumarate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Quetiapine fumarate/

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. Use water spray to cool unopened containers.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature -20 °C

ACCIDENTAL RELEASE MEASURES. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Evacuate personnel to safe areas. Beware of vapours accumulating to form explosive concentrations. Vapours can accumulate in low areas.; Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.; Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid inhalation of vapour or mist. Use explosion-proof equipment.Keep away from sources of ignition - No smoking.Take measures to prevent the build up of electrostatic charge.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Body Protection: Complete suit protecting against chemicals, Flame retardant antistatic protective clothing., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Skin protection: Handle with gloves.

Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

... The quetiapine mean and range of concentrations found in each tissue are as follows: peripheral blood, 7.7 mg/L (0.14-37 mg/L, n = 17); heart blood, 23.63 mg/L (0.53-76 mg/L, n = 4); liver, 91 mg/Kg (1.1-510 mg/Kg, n = 19); bile, 44 mg/L (6.0-96 mg/L, n = 4); urine, 15 mg/L (1.9-37 mg/L, n = 8); gastric, 897 mg total (3.5-3960 mg, n = 7); and vitreous, 1.4 mg/L (0.2-3.2 mg/L, n = 5). The average of all blood concentrations in 18 cases in which quetiapine contributed to the cause of death was 7.95 mg/L (0.4-76 mg/L). The manner of death in 13 of those cases was suicide, two were undetermined, and three were accidents. In two cases in which quetiapine was an incidental finding, the blood concentrations were 0.14 and 1.0 mg/L. ...

Coadministration of quetiapine (250 mg) and phenytoin (100 mg) increased the mean oral clearance of quetiapine by 5-fold. Increased doses of quetiapine may be required to maintain control of symptoms of schizophrenia in patients receiving quetiapine and phenytoin, or other hepatic enzyme inducers (e.g., carbamazepine, barbiturates, rifampin, glucocorticoids). Caution should be taken if phenytoin is withdrawn and replaced with a non-inducer (e.g., valproate)

Coadministration of quetiapine (150 mg) and divalproex (500 mg) increased the mean maximum plasma concentration of quetiapine at steady state by 17% without affecting the extent of absorption or mean oral clearance.

Thioridazine (200 mg) increased the oral clearance of quetiapine (300 mg) by 65%.

Administration of multiple daily doses of cimetidine (400 mg) resulted in a 20% decrease in the mean oral clearance of quetiapine (150 mg).

For more Interactions (Complete) data for QUETIAPINE (10 total), please visit the HSDB record page.

Liver test abnormalities may occur in up to 30% of patients on long term therapy with quetiapine, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury have been reported due to quetiapine, but they are rare. The onset of jaundice is within 1 to 4 weeks of starting the drug, and the pattern of serum enzyme elevations is typically hepatocellular. Signs of immunoallergic manifestations (fever, rash and eosinophilia) are rare, as are autoantibodies. Most cases are mild-to-moderate in severity and self-limited in course. Instances of DRESS syndrome and acute liver failure have been reported but not vanishing bile duct syndrome or chronic liver injury.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3.2X10+4(SRC), determined from a structure estimation method(2), indicates that quetiapine is expected to be immobile in soil(SRC). The estimated pKa values of quetiapine are 2.78 and 7.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of quetiapine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.5X10-18 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Quetiapine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2015).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3.2X10+4(SRC), determined from a structure estimation method(2), indicates that quetiapine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.5X10-18 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 31(SRC), from an estimated log Kow of 3.17(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2015).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), quetiapine, which has an estimated vapor pressure of 5.4X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase quetiapine may be removed from the air by wet and dry deposition(SRC). Quetiapine contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may to be susceptible to direct photolysis by sunlight(SRC).

As with any antipsychotic drug, quetiapine is associated with an increased risk of death in dementia-related psychosis in elderly patients. Alongside this risk, neuroleptic malignant syndrome should be a consideration due to its D2 receptor blockage. It is the least likely of atypical antipsychotics to cause extrapyramidal symptoms. There is an increased risk for suicidal thoughts and behavior associated with drug treatment in major depressive disorder patients. Somnolence, orthostatic hypotension, and dizziness are the most common side effects of quetiapine. Somnolence and dizziness are due to the nature of quetiapine’s antagonism of H1 receptors, while antagonism causes hypotension for alpha-1 receptors. Stroke, myocarditis, and coronary heart disease have also correlated with the use of this drug.

Quetiapine appears to be distributed into milk in humans in relatively small amounts.

EXPERIMENTAL: Quetiapine is distributed into milk in animals. Not known whether quetiapine is distributed into milk in humans.

IDENTIFICATION AND USE: Quetiapine fumarate is used for the symptomatic management of psychotic disorders. Short-term efficacy of quetiapine for the management of schizophrenia has been established by placebo-controlled studies of 6 weeks' duration principally in hospitalized patients with schizophrenia. Quetiapine is used alone or in conjunction with lithium or divalproex sodium for the management of acute manic episodes associated with bipolar I disorder. Quetiapine also is used for the treatment of depressive episodes associated with bipolar disorder. HUMAN EXPOSURE AND TOXICITY: The most common adverse 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. 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 occurred in 0.6% of patients receiving quetiapine in controlled clinical trials. Geriatric patients with dementia-related psychosis treated with atypical antipsychotic drugs appear to be at an increased risk of death compared with that among patients receiving placebo. Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric patients with major depressive disorder and other psychiatric disorders, whether or not they are taking antidepressants. Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported in patients receiving antipsychotic agents, including quetiapine. Contact dermatitis, maculopapular rash, and photosensitivity reactions were reported infrequently during clinical trials. Anaphylaxis and Stevens-Johnson syndrome have been reported during postmarketing surveillance. Quetiapine appears to be distributed into human milk in relatively small amounts. The effect of quetiapine on labor and delivery is unknown. Safety and efficacy of quetiapine in pediatric patients younger than 18 years of age with bipolar depression have not been established. Quetiapine overdose causes central nervous system depression and sinus tachycardia. In large overdoses, patients may require intubation and ventilation for associated respiratory depression. Although a prolonged QTc occurs, its clinical significance is unclear because it is most likely caused by an overcorrection caused by the tachycardia. No evidence of clastogenic potential was obtained in an in vitro chromosomal aberration assay in cultured human lymphocytes. ANIMAL STUDIES: Quetiapine caused a dose-related increase in pigment deposition in thyroid gland in a mouse 2 year carcinogenicity study. Doses were 75-750 mg/kg. The identity of the pigment could not be determined, but was found to be co-localized with quetiapine in thyroid gland follicular epithelial cells. The functional effects and the relevance of this finding to human risk are unknown. In dogs receiving quetiapine for 6 or 12 months, but not for 1 month, focal triangular cataracts occurred at the junction of posterior sutures in the outer cortex of the lens at a dose of 100 mg/kg. This finding may be due to inhibition of cholesterol biosynthesis by quetiapine. Quetiapine caused a dose related reduction in plasma cholesterol levels in repeat-dose dog and monkey studies; however, there was no correlation between plasma cholesterol and the presence of cataracts in individual dogs. The appearance of delta-8-cholestanol in plasma is consistent with inhibition of a late stage in cholesterol biosynthesis in these species. There also was a 25% reduction in cholesterol content of the outer cortex of the lens observed in a special study in quetiapine treated female dogs. The teratogenic potential of quetiapine was studied in rats and rabbits dosed during the period of organogenesis. No evidence of a teratogenic effect was detected in rats at doses of 25 to 200 mg/kg or in rabbits at 25 to 100 mg/kg. There was, however, evidence of embryo/fetal toxicity. Delays in skeletal ossification were detected in rat fetuses at doses of 50 and 200 mg/ kg and in rabbits at 50 and 100 mg/kg. Fetal body weight was reduced in rat fetuses at 200 mg/kg and rabbit fetuses at 100 mg/kg. There was an increased incidence of a minor soft tissue anomaly (carpal/tarsal flexure) in rabbit fetuses at a dose of 100 mg/kg. Evidence of maternal toxicity (i.e., decreases in body weight gain and/or death) was observed at the high dose in the rat study and at all doses in the rabbit study. In a peri/ postnatal reproductive study in rats, no drug-related effects were observed at doses of 1, 10, and 20 mg/kg. However, in a preliminary peri/postnatal study, there were increases in fetal and pup death, and decreases in mean litter weight at 150 mg/kg. The mutagenic potential of quetiapine was tested in six in vitro bacterial gene mutation assays and in an in vitro mammalian gene mutation assay in Chinese Hamster Ovary cells. However, sufficiently high concentrations of quetiapine may not have been used for all tester strains. Quetiapine did produce a reproducible increase in mutations in one Salmonella typhimurium tester strain in the presence of metabolic activation. No evidence of clastogenic potential was obtained in the in vivo micronucleus assay in rats.

Quetiapine can be life-threatening if abused or misused. Toxicity is associated with levels greater than 1500 ng/mL in serum or plasma. Supportive care is the mainstay of treatment. In acute toxicity, measures are necessary to maintain the airway and ensure adequate oxygenation and ventilation. Gastric lavage and activated charcoal administration alongside a laxative to prevent further drug absorption are used if time appropriate. Plasma concentrations of quetiapine reach maximal levels within 1 to 2 hours of oral administration. ECG is a recommendation to monitor for possible Torsades de pointes or another arrhythmia due to QT-interval prolongation. Treat extrapyramidal effects with anticholinergic and hypotension with intravenous fluids and sympathomimetic agents such as A1 agonists. Management/treatment of neuroleptic malignant syndrome is possible by immediate withdrawal of quetiapine, followed by the management of symptoms.

The mechanism of action of quetiapine, as with other drugs used to treat schizophrenia, is unknown. However, it is thought that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT₂) receptor antagonism. Although quetiapine is known to bind other receptors with similar affinity, only the dopamine D2 and serotonin 5HT₂ receptor binding is responsible for quetiapine's therapeutic activity in schizophrenia.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of quetiapine can be estimated to be 3.2X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that quetiapine is expected to be immobile in soil. The estimated pKa values of quetiapine are 2.78 and 7.46(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including quetiapine fumarate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Quetiapine fumarate/

N05AH04

N - Nervous system

QN - Nervous system

N05AH04

Quetiapine improves the positive and negative symptoms of schizophrenia and major depression by acting on various neurotransmitter receptors, such as the serotonin and dopamine receptors. In bipolar disorder, it improves both depressive and manic symptoms. **A note on suicidality in young patients and administration in the elderly** Quetiapine can cause suicidal thinking or behavior in children and adolescents and should not be given to children under 10 years of age. It is important to monitor for suicidality if this drug is given to younger patients. In addition, this drug is not indicated for the treatment of psychosis related to dementia due to an increased death rate in elderly patients taking this drug.

Although the mechanism of action of quetiapine is not fully understood, several proposed mechanisms exist. In schizophrenia, its actions could occur from the antagonism of dopamine type 2 (D2) and serotonin 2A (5HT2A) receptors. In bipolar depression and major depression, quetiapine's actions may be attributed to the binding of this drug or its metabolite to the norepinephrine transporter. Additional effects of quetiapine, including somnolence, orthostatic hypotension, and anticholinergic effects, may result from the antagonism of H1 receptors, adrenergic α1 receptors, and muscarinic M1 receptors, respectively.

The therapeutic effects of antipsychotic drugs are thought to be mediated by dopaminergic blockade in the mesolimbic and mesocortical areas of the CNS, while antidopaminergic effects in the neostriatum appear to be associated with extrapyramidal effects. The apparently low incidence of extrapyramidal effects associated with quetiapine therapy suggests that the drug is more active in the mesolimbic than in the neostriatal dopaminergic system. In contrast to typical antipsychotic agents (e.g., chlorpromazine) but like other atypical antipsychotic drugs (e.g., clozapine), quetiapine does not cause sustained elevations in serum prolactin concentrations and therefore is unlikely to produce adverse effects such as amenorrhea, galactorrhea, and impotence.

The exact mechanism of antipsychotic action of quetiapine has not been fully elucidated but may involve antagonism at serotonin type 1 (5-hydroxytryptamine [5- HT1A]) and type 2 (5-HT2A, 5-HT2C) receptors, and at dopamine (D1, D2) receptors. Current evidence suggests that the clinical potency and antipsychotic efficacy of both typical and atypical antipsychotic drugs generally are related to their affinity for and blockade of central dopamine D2 receptors; however, antagonism at dopamine D2 receptors does not appear to account fully for the antipsychotic effects of quetiapine. Results of in vivo and in vitro studies indicate that quetiapine is a comparatively weak antagonist at dopamine D2 receptors. Receptor binding studies show quetiapine is a weak antagonist at D1 receptors. Although their role in eliciting the pharmacologic effects of antipsychotic agents remains to be fully elucidated, dopamine D3, D4, and D5 receptors also have been identified; quetiapine possesses no affinity for the dopamine D4 receptor.

Quetiapine exhibits alpha1- and alpha2-adrenergic blocking activity; blockade of alpha1-adrenergic receptors may explain the occasional orthostatic hypotension associated with the drug. Quetiapine also blocks histamine H1 receptors, which may explain the sedative effects associated with the drug. Quetiapine possesses little or no affinity for beta-adrenergic, gamma-aminobutyric acid (GABA), benzodiazepine, or muscarinic receptors.

Recent neuroimaging and postmortem studies have reported abnormalities in white matter of schizophrenic brains, suggesting the involvement of oligodendrocytes in the etiopathology of schizophrenia. This view is being supported by gene microarray studies showing the downregulation of genes related to oligodendrocyte function and myelination in schizophrenic brain compared to control subjects. However, there is currently little information available on the response of oligodendrocytes to antipsychotic drugs (APDs), which could be invaluable for corroborating the oligodendrocyte hypothesis. In this study we found: (1) quetiapine (QUE, an atypical APD) treatment in conjunction with addition of growth factors increased the proliferation of neural progenitors isolated from the cerebral cortex of embryonic rats; (2) QUE directed the differentiation of neural progenitors to oligodendrocyte lineage through extracellular signal-related kinases; (3) addition of QUE increased the synthesis of myelin basic protein and facilitated myelination in rat embryonic cortical aggregate cultures; (4) chronic administration of QUE to C57BL/6 mice prevented cortical demyelination and concomitant spatial working memory impairment induced by cuprizone, a neurotoxin. These findings suggest a new neural mechanism of antipsychotic action of QUE, and help to establish a role for oligodendrocytes in the etiopathology and treatment of schizophrenia.

The average terminal half-life of quetiapine is about 6-7 hours.

The mean terminal half-life of quetiapine is about 6 hours.

The metabolism of quetiapine occurs mainly in the liver. Sulfoxidation and oxidation are the main metabolic pathways of this drug. According to in vitro studies, cytochrome P450 3A4 metabolizes quetiapine to an inactive sulfoxide metabolite and also participates in the metabolism of its active metabolite, N-desalkyl quetiapine. CYP2D6 also regulates the metabolism of quetiapine. In one study, three metabolites of N-desalkylquetiapine were identified. Two of the metabolites were identified as N-desalkylquetiapine sulfoxide and 7-hydroxy-N-desalkylquetiapine. CYP2D6 has been found to be responsible for metabolism of quetiapine to 7-hydroxy-N-desalkylquetiapine, a pharmacologically active metabolite. Individual differences in CYP2D6 metabolism may be present, which may affect the concentrations of the active metabolite.

Quetiapine is extensively metabolized in the liver principally via sulfoxidation and oxidation to inactive metabolites. In vitro studies suggest that the cytochrome P-450 (CYP) 3A4 isoenzyme is involved in the metabolism of quetiapine to the inactive sulfoxide metabolite, which is the principal metabolite. ... Based on in vitro studies, quetiapine and 9 of its metabolites do not appear likely to inhibit CYP isoenzymes 1A2, 3A4, 2C9, 2C19, or 2D6.

Quetiapine has known human metabolites that include Quetiapine Sulfoxide and 7-Hydroxy Quetiapine.

Hepatic. The major metabolic pathways are sulfoxidation, mediated by cytochrome P450 3A4 (CYP3A4), and oxidation of the terminal alcohol to a carboxylic acid. The major sulfoxide metabolite of quetiapine is inactive. Quetiapine also undergoes hydroxylation of the dibenzothiazepine ring, O-deakylation, N-dealkylation, and phase II conjugation. The 7-hydroxy and 7-hydroxy- N-delakylated metabolites appear to be active, but are present in very low concentrations. Route of Elimination: Elimination of quetiapine is mainly via hepatic metabolism. 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. Half Life: 6 hours

BGL0JSY5SI

QUETIAPINE

Established Pharmacologic Class [EPC] - Atypical Antipsychotic

Quetiapine is an Atypical Antipsychotic.

QUETIAPINE

Atypical Antipsychotic [EPC]

Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

Quetiapine is rapidly and well absorbed after administration of an oral dose. Steady-state is achieved within 48 hours and peak plasma concentrations are achieved within 1.5 hours. The steady-state Cmax of quetiapine in Han Chinese patients with schizophrenia after a 300 mg oral dose of the extended released formulation was approximately 467 ng/mL and the AUC at steady-state was 5094 ng·h/mL. While the absolute bioavailability has not been fully elucidated and is reported to be low, the tablet formulation is 100% bioavailable relative to solution. Absorption of quetiapine is affected by food, with Cmax increased by 25% and AUC increased by 15%.

After an oral dose of radiolabeled quetiapine, less than 1% of unchanged drug was detected in the urine, suggesting that quetiapine is heavily metabolized. About 73% of a dose was detected in the urine, and about 20% in the feces.

Quetiapine distributes throughout body tissues. The apparent volume of distribution of this drug is about 10±4 L/kg.

The clearance of quetiapine healthy volunteers in the fasted state during a clinical study was 101.04±39.11 L/h. Elderly patients may require lower doses of quetiapine, as clearance in these patients may be reduced by up to 50%. Those with liver dysfunction may also require lower doses.

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.

Steady state concentrations are expected to be achieved within two days of dosing.

MEDICATION

Antipsychotic Agents

Use (kg) in Switzerland (2009): >2500

Quetiapine is indicated for the treatment of schizophrenia, depressive episodes associated with bipolar disorder, acute manic episodes associated with bipolar I disorder, and maintenance treatment of bipolar I disorder (L1125).

The cyclic amide, dibenzo[b,f][1,4]thiazepin-11-one is converted to the 11-chloro derivative with phosphorus oxychloride. Nucleophilic displacement of the halogen by 2-[2-(piperazinlyl)ethoxy]ethanol yields the product (base). The salt is prepared by mixing saturated solutions of the base and fumaric acid in ethanol.

Preparation: E. J. Warawa, B. M. Migler, European Patent Office patent 240228; eidem, United States of America patent 4879288 (1987, 1989 both to ICI).