Quetiapine Fumarate Er (quetiapine fumarate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Quetiapine fumarate is an atypical antipsychotic agent.
Quetiapine fumarate is a dibenzothiazepine-derivative antipsychotic agent. The drug is pharmacologically similar to clozapine, but differs pharmacologically from other currently available first-generation (typical) antipsychotic agents (e.g., phenothiazines, butyrophenones). Because of these pharmacologic differences, quetiapine is considered an atypical or second-generation antipsychotic agent.
The exact mechanism of quetiapine's action in the treatment of schizophrenia and bipolar disorder has not been fully elucidated but may involve antagonism at dopamine type 2 (D2) and serotonin type 2 (5-hydroxytryptamine (5-HT2)) receptors. The active metabolite, norquetiapine, has similar activity at D2 receptors but greater activity at 5-HT2A compared to quetiapine.
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.
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.
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.
Following oral administration, quetiapine conventional tablets are rapidly absorbed and reach peak plasma concentrations in 1.5 hours. The extended-release tablets reach peak concentrations after 6 hours. Although the absorption of the conventional tablets is marginally affected by food, administration of the extended-release tablets with a high-fat (approximately 800-1000 calories) meal produces significant increases in quetiapine exposure.
In contrast, when the extended-release tablets are taken with a light meal (approximately 300 calories), quetiapine exposure is not significantly affected. It is recommended to take the extended-release tablets without food or with a light meal. 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 and the active metabolite, norquetiapine. The mean terminal half-life of quetiapine conventional tablets is about 6 hours. The mean terminal half-life of quetiapine extended-release tablets is about 7 hours for quetiapine, and about 12 hours for the active metabolite norquetiapine.
Following oral administration of a single dose of quetiapine, approximately 73 and 20% of the dose is excreted in urine and feces, respectively; less than 1% of the dose is excreted unchanged. 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. Pharmacokinetics of quetiapine at steady state are similar in children and adolescents 10-17 years of age compared to adults; however, when adjusted for weight, AUC and peak plasma concentrations of quetiapine are 41% and 39% lower in pediatric patients compared to adults.
The pharmacokinetics of the active metabolite norquetiapine were similar.
Quetiapine fumarate conventional (immediate-release) tablets (Seroquel(R)) are used orally for the treatment of schizophrenia in adults and pediatric patients 13-17 years of age, for the acute treatment of manic episodes associated with bipolar I disorder (as monotherapy and as an adjunct to lithium or divalproex) in adults and pediatric patients 10-17 years of age, for the acute treatment of depressive episodes associated with bipolar disorder (as monotherapy) in adults, and for the maintenance treatment of bipolar I disorder (as an adjunct to lithium or divalproex) in adults. Quetiapine fumarate extended-release tablets (Seroquel XR(R)) are used orally for the acute treatment of schizophrenia in adults and pediatric patients 13-17 years of age, for the acute treatment of manic or mixed episodes associated with bipolar I disorder (as monotherapy and as an adjunct to lithium or divalproex) in adults and pediatric patients 10-17 years of age, for the acute treatment of depressive episodes associated with bipolar disorder in adults, for the maintenance treatment of bipolar I disorder (as an adjunct to lithium or divalproex) in adults, and for the treatment of major depressive disorder (as adjunctive therapy to antidepressants) in adults.
Generic name: quetiapine fumarate
Pronunciation: (kweh-TIE-ah-peen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Quetiapine Fumarate Er
Indications
The following indications are listed for Quetiapine Fumarate Er:
- Bipolar Disorder
- Depression Associated With Bipolar Disorder
- Major Depressive Disorder Treatment Adjunct
- Schizophrenia
Also known as: Adjunctive Treatment Of Major Depressive Disorder, Augmentation Therapy For Major Depressive Disorder, Bipolar Affective Disorder, Bipolar Affective Illness, Bipolar Mood Disorder, Dementia Praecox, Depression Associated With Bipolar Affective Disorder, Depression Associated With Manic Depressive Disorder, Depressive Episode Associated With Bipolar Disorder, Depressive Phase Of Bipolar Disorder, Major Depressive Disorder Treatment Augmentation, Manic-Depressive Illness, Parergasia.
Dosing
Dosage of quetiapine fumarate is expressed in terms of quetiapine. The dosage may be carefully adjusted upward or downward, if necessary, after initial dosing according to clinical response and tolerability.
The manufacturer states that if quetiapine therapy is reinitiated after a drug-free period of <1 week, dosage titration is not necessary. However, if quetiapine therapy is reinitiated after a drug-free period of >1 week, dosage generally should be titrated as with initial therapy.
Patients who are receiving quetiapine conventional tablets can be switched to quetiapine extended-release tablets at the equivalent daily dosage given once daily. Individual dosage adjustments may be necessary.
Quetiapine fumarate is administered orally. Quetiapine conventional (immediate-release) tablets are administered 2-3 times daily without regard to food, while the extended-release tablets should be administered once daily, preferably in the evening, without food or with a light meal (<300 calories). Quetiapine extended-release tablets should be swallowed whole, and not split, chewed, or crushed.
Store quetiapine conventional and extended-release tablets at 25degreesC; excursions permitted from 15-30degreesC.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to quetiapine or any ingredients in the formulation. Anaphylactic reactions have occurred in quetiapine-treated patients.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects reported in >=5% of adult patients receiving quetiapine therapy 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 most common adverse effects reported in >=5% of children and adolescents receiving quetiapine therapy and at a frequency twice that reported among patients receiving placebo in clinical trials include somnolence, dizziness, fatigue, increased appetite, nausea, vomiting, dry mouth, tachycardia, and weight gain.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of quetiapine have been established in pediatric patients 13-17 years of age with schizophrenia. Safety and efficacy of quetiapine for schizophrenia in patients 13-17 years of age have been established in a placebo-controlled study of 6 weeks' duration.
Safety and efficacy of quetiapine have been established in pediatric patients 10-17 years of age with manic episodes associated with bipolar I disorder. Safety and efficacy of quetiapine for the treatment of mania in patients 10-17 years of age with bipolar I disorder have been established in a placebo-controlled study of 3 weeks' duration.
Safety and efficacy of quetiapine for schizophrenia in pediatric patients <13 years of age are not established.
Safety and efficacy of quetiapine for bipolar mania in pediatric patients <10 years of age are not established.
Safety and efficacy of quetiapine have not been established in pediatric patients <18 years of age for the maintenance treatment of bipolar disorder. Safety and efficacy of quetiapine have not been established in pediatric patients <18 years of age for the maintenance treatment of schizophrenia.
Safety and efficacy of quetiapine have not been established in pediatric patients <18 years of age with bipolar depression. A controlled study of extended-release quetiapine was conducted in pediatric patients 10-17 years of age with bipolar depression, and efficacy of the drug was not established.
After adjustment for weight, AUC and peak plasma concentrations of quetiapine are 41% and 39% lower in pediatric patients 10-17 years of age compared to adults; however, pharmacokinetics of the active metabolite norquetiapine were similar.
Generally, adverse effects observed in clinical studies were similar in children and adolescents compared to adults, except for systolic and diastolic blood pressure increases that were not observed in adults. Additionally, orthostatic hypotension occurred less frequently in children (<1%) compared to adults (4-7%).
Based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (selective serotonin-reuptake inhibitors (SSRIs) and other antidepressants), a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders. No suicides occurred in these pediatric trials. It is unclear if the risk of suicidality extends to longer-term use (i.e., beyond several months).
A pregnancy exposure registry is available that monitors outcomes in women exposed to atypical antipsychotics, including quetiapine, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at https://womensmentalhealth.org/research/pregnancyregistry/.
Neonates exposed to antipsychotic agents during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Symptoms reported to date have included agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Neonates exhibiting such symptoms should be monitored and symptoms managed appropriately. The complications have varied in severity; some neonates recovered within hours to days without specific treatment, while others have required prolonged hospitalization.
Available data from epidemiologic studies of pregnant women exposed to quetiapine have not indicated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are risks associated with untreated schizophrenia, bipolar I disorder, or major depressive disorder, and with exposure to antipsychotic agents during pregnancy. In animal studies, embryofetal toxicity (e.g., delays in skeletal ossification, carpal/tarsal flexure, decreased fetal weights) and maternal toxicity were reported.
Quetiapine appears to be distributed into human milk at a relative infant dose of <1% of the maternal weight-adjusted dosage. No consistent adverse effects have been reported in infants exposed to quetiapine through maternal breast milk. It is not known if quetiapine affects milk production. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for the drug and the potential for adverse effects on the breastfed infant from exposure to quetiapine through the breast milk or from the mother's underlying condition.
Geriatric or debilitated patients and patients predisposed to hypotension or in whom hypotension would pose a risk (e.g., patients with dehydration or hypovolemia, those receiving antihypertensive drugs, patients with known cardiovascular or cerebrovascular disease) should have a slower rate of dosage titration and should receive lower target dosages of quetiapine. The risk of orthostatic hypotension can be minimized by limiting the initial dosage of quetiapine conventional tablets to 25 mg twice daily. Additionally, dosage of the extended-release tablets should be limited to 50 mg once daily. Subsequent dosage adjustments of the conventional or extended-release tablets generally should be made in increments of 50 mg daily. If orthostatic hypotension occurs during titration to the target dosage, the manufacturer recommends a return to the previous dosage in the titration schedule.
In clinical studies of quetiapine conventional tablets, approximately 7% of 3400 patients were >=65 years of age. In clinical studies of quetiapine extended-release tablets, approximately 68 patients were >=65 years of age. While no substantial differences in safety relative to younger adults were observed, factors that decrease pharmacokinetic clearance, increase the pharmacodynamic response, or cause poorer tolerance (e.g., orthostasis) may be present in geriatric patients.
ICD codes
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Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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