Quetiapine 400 mg Tablet, Film Coated, Extended Release, 100-count — NDC 68180-616-01 (Billing 68180-0616-01)
This is a package of 100 tablets of Quetiapine 400 mg Tablet, Film Coated, Extended Release from Lupin Pharmaceuticals, Inc., marketed since Aug 2017 and currently FDA-listed.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GPI-14 (Medi-Span): 59153070107540
- RxCUI (RxNorm): 721791
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Atypical Antipsychotic class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Quetiapine is used to treat schizophrenia (a mental illness that affects how a person thinks, feels and behaves), bipolar disorder (a disease that causes depression, mania, and other abnormal moods) and major depressive disorder. Quetiapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.
Read the full MedlinePlus article ↗- It treats schizophrenia and bipolar disorder, including manic and depressive episodes. Extended-release versions can also be added to an antidepressant for major depressive disorde...
- Regular tablets can be taken with or without food. Extended-release tablets are taken once daily, usually in the evening, without food or with a light meal, and must be swallowed w...
- Sleepiness, dry mouth, dizziness, constipation, increased appetite and weight gain are the most common. Many people notice these early on. Tell your doctor if they bother you.
- Call right away for suicidal thoughts, worsening mood, fever with stiff muscles and confusion, uncontrolled movements, fainting, seizures, signs of infection, or high blood sugar s...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Quetiapine — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 3, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 68180-0616-01 You're viewing this | 100 TABLET, EXTENDED RELEASE in 1 BOTTLE | — | — | 2017-08-22 | — | Active |
| 68180-0616-07 68180-616-07 Main listing | 60 TABLET, EXTENDED RELEASE in 1 BOTTLE | $0.3174 / ea | $19.05 | 2017-08-22 | — | Active |
You're viewing the largest of 2 pack sizes for this product.
This pack shows little to no recent Medicaid volume — the 60 tablets pack carries most fills. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 68180-0616-07?
What NDC number is used to bill for this package of Quetiapine 400 mg Tablet, Film Coated, Extended Release?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Quetiapine 400 mg 00904-6805-61 | Major | 1 tablet | $0.317 | AB | Availability likely | — |
| Quetiapine 400 mg 29300-0312-16 | Unichem | 60 tablets | $0.317 | AB | Availability likely | — |
| Quetiapine 400 mg 33342-0137-09 | Macleods | 60 tablets | $0.317 | AB | Availability likely | — |
| Quetiapine 400 mg 68001-0602-06 | BluePoint | 60 tablets | $0.317 | AB | Availability likely | — |
| Quetiapine Fumarate 400 mg 16729-0097-12 | Accord | 60 tablets | $0.323 | AB | Availability likely | — |
| Quetiapine Extended Release 400 mg 71093-0139-02 | ACI | 60 tablets | $0.323 | AB | Availability likely | — |
| Seroquel Xr 400 mg 00310-0284-60 | AstraZeneca | 60 tablets | $23.975 | AB | FDA listed | — |
| Seroquel Xr 400 mg 61269-0274-60 | H2-Pharma, | 60 tablets | $26.358 | AB | Availability likely | — |
| Quetiapine 400 mg 43547-0023-06 | Solco | 60 tablets | — | AB | FDA listed | — |
| Quetiapine Extended Release 400 mg 50228-0384-05 | ScieGen | 500 tablets | — | AB | FDA listed | — |
| Quetiapine Fumarate 400 mg 50742-0639-10 | Ingenus | 1000 tablets | — | AB | FDA listed | — |
| Quetiapine Extended Release 400 mg 51407-0803-60 | Golden | 60 tablets | — | AB | FDA listed | — |
| Quetiapine 400 mg 63629-5944-01 | Bryant | 60 tablets | — | AB | FDA listed | — |
| Quetiapine Fumarate 400 mg 65862-0877-01 | Aurobindo | 100 tablets | — | AB | FDA listed | — |
| Quetiapine 400 mgthis 68180-0616-01 | Lupin | 100 tablets | — | AB | FDA listed | — |
| Quetiapine 400 mg 70518-4437-00 | REMEDYREPACK | 30 tablets | — | AB | FDA listed | — |
| Quetiapine 400 mg 71335-2641-01 | Bryant | 60 tablets | — | AB | FDA listed | — |
| Quetiapine Fumarate ER 400 mg 72189-0483-30 | Direct_Rx | 30 tablets | — | AB | FDA listed | — |
| Quetiapine Fumarate ER 400 mg 72189-0642-30 | Direct_Rx | 30 tablets | — | AB | FDA listed | — |
| Quetiapine 400 mg 70518-4700-00 | REMEDYREPACK | 30 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII Z78RG6M2N2
Hypromellose 2208 is a plant-derived thickening agent used as a binder and film-coating material in tablets and capsules. It helps hold ingredients together and creates a protective coating that controls how quickly the medicine dissolves.
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UNII 0WZ8WG20P6
Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII B697894SGQ
Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII B22547B95K
A salt derived from citric acid that helps maintain the proper acid-base balance in the medicine. It's used as a buffer to keep the product stable and at the right pH level.
9 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death [see WARNINGS AND PRECAUTIONS ( 5.1 )]. Quetiapine extended-release tablet is not approved for the treatment of patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS ( 5.1 )]. Suicidal Thoughts and Behavior Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies.
These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see WARNINGS AND PRECAUTIONS ( 5.2 )]. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber [see WARNINGS AND PRECAUTIONS ( 5.2 )] Quetiapine extended-release tablet is not approved for use in pediatric patients under ten years of age [see USE IN SPECIFIC POPULATIONS ( 8.4 )].
See full prescribing information for complete boxed warning. Increased Mortality in Elderly Patients with Dementia-Related Psychosis • Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Quetiapine extended-release tablet is not approved for elderly patients with dementia-related psychosis.
( 5.1 ) Suicidal Thoughts and Behaviors • Increased risk of suicidal thoughts and behavior in children, adolescents and young adults taking antidepressants. ( 5.2 ) • Monitor for worsening and emergence of suicidal thoughts and behaviors. ( 5.2 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Quetiapine extended-release tablet is an atypical antipsychotic indicated for the treatment of: Schizophrenia ( 1.1 ) Bipolar I disorder, manic or mixed episodes ( 1.2 ) Bipolar disorder, depressive episodes ( 1.2 ) Major depressive disorder, adjunctive therapy with antidepressants ( 1.3 )
1.1Schizophrenia Quetiapine extended-release tablet USP is indicated for the treatment of schizophrenia. The efficacy of quetiapine extended-release tablet USP in schizophrenia was established in one 6-week and one maintenance trial in adults with schizophrenia. Efficacy was supported by three 6-week trials in adults with schizophrenia and one 6-week trial in adolescents with schizophrenia (13 to 17 years) treated with SEROQUEL [see CLINICAL STUDIES ( 14.1 )] .
1.2Bipolar Disorder Quetiapine extended-release tablet USP is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder, both as monotherapy and as an adjunct to lithium or divalproex. The efficacy of quetiapine extended-release tablet USP in manic or mixed episodes of bipolar I disorder was established in one 3-week trial in adults with manic or mixed episodes associated with bipolar I disorder. Efficacy was supported by two 12-week monotherapy trials and one 3-week adjunctive trial in adults with manic episodes associated with bipolar I disorder as well as one 3-week monotherapy trial in children and adolescents (10 to 17 years) with manic episodes associated with bipolar I disorder treated with SEROQUEL [see CLINICAL STUDIES ( 14.2 )] .
Quetiapine extended-release tablet USP is indicated for the acute treatment of depressive episodes associated with bipolar disorder. The efficacy of quetiapine extended-release tablet was established in one 8-week trial in adults with bipolar I or II disorder and supported by two 8-week trials in adults with bipolar I or II disorder treated with SEROQUEL [see CLINICAL STUDIES ( 14.2 )]. Quetiapine extended-release tablet USP is indicated for the maintenance treatment of bipolar I disorder, as an adjunct to lithium or divalproex.
Efficacy was extrapolated from two maintenance trials in adults with bipolar I disorder treated with SEROQUEL. The effectiveness of monotherapy for the maintenance treatment of bipolar I disorder has not been systematically evaluated in controlled clinical trials [see CLINICAL STUDIES ( 14.2 )].
1.3Adjunctive Treatment of Major Depressive Disorder (MDD) Quetiapine extended-release tablet USP is indicated for use as adjunctive therapy to antidepressants for the treatment of MDD. The efficacy of quetiapine extended-release tablet as adjunctive therapy to antidepressants in MDD was established in two 6-week trials in adults with MDD who had an inadequate response to antidepressant treatment [see CLINICAL STUDIES ( 14.3 )] .
1.4Special Considerations in Treating Pediatric Schizophrenia and Bipolar I Disorder Pediatric schizophrenia and bipolar I disorder are serious mental disorders, however, diagnosis can be challenging. For pediatric schizophrenia, symptom profiles can be variable, and for bipolar I disorder, patients may have variable patterns of periodicity of manic or mixed symptoms. It is recommended that medication therapy for pediatric schizophrenia and bipolar I disorder be initiated only after a thorough diagnostic evaluation has been performed and careful consideration given to the risks associated with medication treatment.
Medication treatment for both pediatric schizophrenia and bipolar I disorder is indicated as part of a total treatment program that often includes psychological, educational and social interventions.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Swallow tablets whole and do not split, chew or crush ( 2.1 ) Take without food or with a light meal (approx. 300 calories) ( 2.1 ) Administer once daily, preferably in the evening ( 2.1 ) Geriatric Use: Consider a lower starting dose (50 mg/day), slower titration, and careful monitoring during the initial dosing period in the elderly. ( 2.3 , 8.5 ) Hepatic Impairment: Lower starting dose (50 mg/day) and slower titration may be needed ( 2.4 , 8.7 , 12.3 ) Indication Initial Dose Recommended Dose Maximum Dose Schizophrenia- Adults ( 2.2 ) 300 mg/day 400 to 800 mg/day 800 mg/day Schizophrenia-Adolescents (13 to 17 years) ( 2.2 ) 50 mg/day 400 to 800 mg/day 800 mg/day Bipolar I Disorder manic or mixed-Acute monotherapy or adjunct to lithium or divalproex-Adults ( 2.2 ) 300 mg/day 400 to 800 mg/day 800 mg/day Bipolar I Disorder, manic Acute monotherapy -Children and Adolescents (10 to 17 years) ( 2.2 ) 50 mg/day 400 to 600 mg/day 600 mg/day Bipolar Disorder, Depressive Episodes-Adults ( 2.2 ) 50 mg/day 300 mg/day 300 mg/day Major Depressive Disorder, Adjunctive Therapy with Antidepressants-Adults ( 2.2 ) 50 mg/day 150 to 300 mg/day 300 mg/day
2.1Important Administration Instructions Quetiapine extended-release tablets USP should be swallowed whole and not split, chewed, or crushed. It is recommended that quetiapine extended-release tablet USP be taken without food or with a light meal (approximately 300 calories) [see CLINICAL PHARMACOLOGY ( 12.3 )]. Quetiapine extended-release tablet USP should be administered once daily, preferably in the evening.
2.2Recommended Dosing The recommended initial dose, titration, dose range and maximum Quetiapine extended-release tablet USP dose for each approved indication is displayed in Table 1 below. After initial dosing, adjustments can be made upwards or downwards, if necessary, depending upon the clinical response and tolerability of the patient [see CLINICAL STUDIES ( 14.1 , 14.2 and 14.3 )]. Table 1: Recommended Dosing for Quetiapine extended-release tablet USP Indication Initial Dose and Titration Recommended Dose Maximum Dose Schizophrenia-Adults Day 1: 300 mg/day Dose increases can be made at intervals as short as 1 day and in increments of up to 300 mg/day 400 to 800 mg/day 800 mg/day Schizophrenia-Adolescents (13 to 17 years) Day 1: 50 mg/day Day 2: 100 mg/day Day 3: 200 mg/day Day 4: 300 mg/day Day 5: 400 mg/day 400 to 800 mg/day 800 mg/day Schizophrenia Maintenance-Monotherapy-Adults Not applicable 400 to 800 mg/day 800 mg/day Bipolar I Disorder manic or mixed-Acute monotherapy or adjunct to lithium or divalproex-Adults Day 1: 300 mg/day Day 2: 600 mg/day Day 3: between 400 and 800 mg/day 400 to 800 mg/day 800 mg/day Bipolar I Disorder, manic -Acute monotherapy -Children and Adolescents (10 to 17 years) Day 1: 50 mg/day Day 2: 100 mg/day Day 3: 200 mg/day Day 4: 300 mg/day Day 5: 400 mg/day 400 to 600 mg/day 600 mg/day Bipolar Disorder, Depressive Episodes-Adults Day 1: 50 mg/day Day 2: 100 mg/day Day 3: 200 mg/day Day 4: 300 mg/day 300 mg/day 300 mg/day Bipolar I Disorder Maintenance-Adjunct to lithium or divalproex-Adults Not applicable 400 to 800 mg/day 800 mg/day Major Depressive Disorder- Adjunctive Therapy with Antidepressants-Adults Day 1: 50 mg/day Day 2: 50 mg/day Day 3: 150 mg/day 150 to 300 mg/day 300 mg/day Maintenance Treatment for Schizophrenia and Bipolar I Disorder Maintenance Treatment: Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see CLINICAL STUDIES ( 14.1 , 14.2 )].
2.3Dose Modifications in Elderly Patients Consideration should be given to a slower rate of dose titration and a lower target dose in the elderly and in patients who are debilitated or who have a predisposition to hypotensive reactions [see USE IN SPECIFIC POPULATIONS ( 8.5 , 8.7 ), and CLINICAL PHARMACOLOGY ( 12.3 )]. When indicated, dose escalation should be performed with caution… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Quetiapine extended-release tablets USP, 50 mg are peach to red colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K71" on the other side. Quetiapine extended-release tablets USP, 150 mg are white colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K72" on the other side. Quetiapine extended-release tablets USP, 200 mg are yellow colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K73" on the other side.
Quetiapine extended-release tablets USP, 300 mg are pale yellow colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K74" on the other side. Quetiapine extended-release tablets USP, 400 mg are white colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K75" on the other side. Extended-Release Tablets: 50 mg, 150 mg, 200 mg, 300 mg, and 400 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Hypersensitivity to quetiapine or to any excipients in the quetiapine extended-release tablet formulation. Anaphylactic reactions have been reported in patients treated with quetiapine extended-release tablet. Known hypersensitivity to quetiapine extended-release tablet or any components in the formulation. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) has been seen in elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs ( 5.3 ) Neuroleptic Malignant Syndrome (NMS): Manage with immediate discontinuation and close monitoring ( 5.4 ) Metabolic Changes: Atypical antipsychotics have been associated with metabolic changes. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain ( 5.5 ) Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.
Monitor glucose regularly in patients with diabetes or at risk for diabetes Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of, and periodically, during treatment Weight Gain: Gain in body weight has been observed; clinical monitoring of weight is recommended Tardive Dyskinesia: Discontinue if clinically appropriate ( 5.6 ) Hypotension: Use with caution in patients with known cardiovascular or cerebrovascular disease ( 5.7 ) Increased Blood Pressure in Children and Adolescents: Monitor blood pressure at the beginning of, and periodically during treatment in children and adolescents ( 5.9 ) Leukopenia, Neutropenia and Agranulocytosis: Monitor complete blood count frequently during the first few months of treatment in patients with a pre-existing low white cell count or a history of leukopenia/neutropenia and discontinue quetiapine extended-release tablet at the first sign of a decline in WBC in absence of other causative factors ( 5.10 ) Cataracts: Lens changes have been observed in patients during long-term quetiapine treatment.
Lens examination is recommended when starting treatment and at 6-month intervals during chronic treatment ( 5.11 ) Anticholinergic (antimuscarinic) Effects: Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, or constipation ( 5.20 ).
5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analysis of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Quetiapine extended-release tablet is not approved for the treatment of patients with dementia-related psychosis [see BOXED WARNING ].
5.2Suicidal Thoughts and Behaviors in Adolescents and Young Adults Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strong… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Increased mortality in elderly patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS ( 5.1 )] Suicidal thoughts and behaviors in adolescents and young adults [see WARNINGS AND PRECAUTIONS ( 5.2 )] Cerebrovascular adverse reactions, including stroke in elderly patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS ( 5.3 )] Neuroleptic Malignant Syndrome (NMS) [see WARNINGS AND PRECAUTIONS ( 5.4 )] Metabolic changes (hyperglycemia, dyslipidemia, weight gain) [see WARNINGS AND PRECAUTIONS ( 5.5 )] Tardive dyskinesia [see WARNINGS AND PRECAUTIONS ( 5.6 )] Hypotension [see WARNINGS AND PRECAUTIONS ( 5.7 )] Falls [see WARNINGS AND PRECAUTIONS ( 5.8 )] Increases in blood pressure (children and adolescents) [see WARNINGS AND PRECAUTIONS ( 5.9 )] Leukopenia, neutropenia and agranulocytosis [see WARNINGS AND PRECAUTIONS ( 5.10 )] Cataracts [see WARNINGS AND PRECAUTIONS ( 5.11 )] QT Prolongation [see WARNINGS AND PRECAUTIONS ( 5.12 )] Seizures [see WARNINGS AND PRECAUTIONS ( 5.13 )] Hypothyroidism [see WARNINGS AND PRECAUTIONS ( 5.14 )] Hyperprolactinemia [see WARNINGS AND PRECAUTIONS ( 5.15 )] Potential for cognitive and motor impairment [see WARNINGS AND PRECAUTIONS ( 5.16 )] Body temperature regulation [see WARNINGS AND PRECAUTIONS ( 5.17 )] Dysphagia [see WARNINGS AND PRECAUTIONS ( 5.18 )] Discontinuation Syndrome [see WARNINGS AND PRECAUTIONS ( 5.19 )] Anticholinergic (antimuscarinic) Effects [see WARNINGS AND PRECAUTIONS, ( 5.20 )] Most common adverse reactions (incidence ≥5% and twice placebo): Adults: somnolence, dry mouth, constipation, dizziness, increased appetite, dyspepsia, weight gain, fatigue, dysarthria, and nasal congestion ( 6.1 ) Children and Adolescents: somnolence, dizziness, fatigue, increased appetite, nausea, vomiting, dry mouth, tachycardia, weight increased ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adults The information below is derived from a clinical trial database for quetiapine extended-release tablet consisting of approximately 3400 patients exposed to quetiapine extended-release tablet for the treatment of Schizophrenia, Bipolar Disorder, and Major Depressive Disorder in placebo-controlled trials.
This experience corresponds to approximately 1020.1 patient-years. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, body weights, laboratory analyses and ECG results. The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, an adverse reaction of the type listed.
Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials: Schizophrenia There were no adverse reactions leading to discontinuation that occurred at an incidence of ≥ 2% for quetiapine extended-release tablet in schizophrenia trials. Bipolar I Disorder, Manic or Mixed Episodes There were no adverse reactions leading to discontinuation that occurred at an incidence of ≥ 2% for quetiapine extended-release tablet in the bipolar mania trial. Bipolar Disorder, Depressive Episode In a single clinical trial in patients with bipolar depression, 14% (19/137) of patients on quetiapine extended-release tablet discontinued due to an adverse reaction compared to 4% (5/140) on placebo.
Somnolence was the only adverse reaction leading to discontinuation that occurred at an incidence of ≥ 2% in quetiapine extended-release tablet in the bipolar depressio… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Concomitant use of strong CYP3A4 inhibitors: Reduce quetiapine dose to one sixth when coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) ( 2.5 , 7.1 , 12.3 ) Concomitant use of strong CYP3A4 inducers: Increase quetiapine dose up to 5 fold when used in combination with a chronic treatment (more than 7 to 14 days) of potent CYP3A4 inducers (e.g. phenytoin, rifampin, St. John's wort) ( 2.6 , 7.1 , 12.3 ) Discontinuation of strong CYP3A4 inducers: Reduce quetiapine dose by 5 fold within 7 to 14 days of discontinuation of CYP3A4 inducers ( 2.6 , 7.1 , 12.3 )
7.1Effect of Other Drugs on Quetiapine The risks of using quetiapine extended-release tablet in combination with other drugs have not been extensively evaluated in systematic studies. Given the primary CNS effects of quetiapine extended-release tablet, caution should be used when it is taken in combination with other centrally acting drugs. Quetiapine potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine.
Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.) and decreased by the prototype of CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, avasimibe, St. John's wort etc.). Dose adjustment of quetiapine will be necessary if it is co-administered with potent CYP3A4 inducers or inhibitors.
CYP3A4 inhibitors Coadministration of ketoconazole, a potent inhibitor of cytochrome CYP3A4, resulted in significant increase in quetiapine exposure. The dose should be reduced to one sixth of the original dose in patients coadministered with a strong CYP3A4 inhibitor [see DOSAGE AND ADMINISTRATION ( 2.5 ) and CLINICAL PHARMACOLOGY ( 12.3 )]. CYP3A4 inducers Coadministration of quetiapine and phenytoin, a CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
Increased doses of quetiapine extended-release tablet up to 5 fold may be required to maintain control of symptoms of schizophrenia in patients receiving quetiapine and phenytoin, or other known potent CYP3A4 inducers [see DOSAGE AND ADMINISTRATION ( 2.6 ) and CLINICAL PHARMACOLOGY ( 12.3 )]. When the CYP3A4 inducer is discontinued, the dose of quetiapine extended-release tablet should be reduced to the original level within 7 to 14 days [see DOSAGE AND ADMINISTRATION ( 2.6 )]. Anticholinergic Drugs Concomitant treatment with quetiapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility.
SEROQUEL should be used with caution in patients receiving medications having anticholinergic (antimuscarinic) effects [ see WARNINGS AND PRECAUTIONS ( 5.20 )]. The potential effects of several concomitant medications on quetiapine pharmacokinetics were studied studied [see CLINICAL PHARMACOLOGY ( 12.3 ) ].
7.2Effect of Quetiapine on Other Drugs Because of its potential for inducing hypotension, quetiapine extended-release tablet may enhance the effects of certain antihypertensive agents. Quetiapine extended-release tablet may antagonize the effects of levodopa and dopamine agonists. There are no clinically relevant pharmacokinetic interactions of SEROQUEL on other drugs based on the CYP pathway.
SEROQUEL and its metabolites are non-inhibitors of major metabolizing CYP's (1A2, 2C9, 2C19, 2D6 and 3A4).
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including quetiapine extended-release tablet, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including quetiapine extended-release tablet, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see CLINICAL CONSIDERATIONS).
Overall available data from published epidemiologic studies of pregnant women exposed to quetiapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). There are risks to the mother associated with untreated schizophrenia, bipolar I, or major depressive disorder, and with exposure to antipsychotics, including, quetiapine extended-release tablet during pregnancy (see CLINICAL CONSIDERATIONS). In animal studies, embryo-fetal toxicity occurred including delays in skeletal ossification at approximately 1 and 2 times the maximum recommended human dose (MRHD) of 800 mg/day in both rats and rabbits, and an increased incidence of carpal/tarsal flexure (minor soft tissue anomaly) in rabbit fetuses at approximately 2 times the MRHD.
In addition, fetal weights were decreased in both species. Maternal toxicity (observed as decreased body weights and/or death) occurred at 2 times the MRHD in rats and approximately 1 to 2 times the MRHD in rabbits. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or fetal risk: There is a risk to the mother from untreated schizophrenia, or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide.
Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy.
The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Fetal/neonatal adverse reactions: Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including quetiapine extended-release tablet, during the third trimester of pregnancy.
These symptoms varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.
Data Human Data: Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. A retrospe… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including quetiapine extended-release tablet, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including quetiapine extended-release tablet, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see CLINICAL CONSIDERATIONS).
Overall available data from published epidemiologic studies of pregnant women exposed to quetiapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). There are risks to the mother associated with untreated schizophrenia, bipolar I, or major depressive disorder, and with exposure to antipsychotics, including, quetiapine extended-release tablet during pregnancy (see CLINICAL CONSIDERATIONS). In animal studies, embryo-fetal toxicity occurred including delays in skeletal ossification at approximately 1 and 2 times the maximum recommended human dose (MRHD) of 800 mg/day in both rats and rabbits, and an increased incidence of carpal/tarsal flexure (minor soft tissue anomaly) in rabbit fetuses at approximately 2 times the MRHD.
In addition, fetal weights were decreased in both species. Maternal toxicity (observed as decreased body weights and/or death) occurred at 2 times the MRHD in rats and approximately 1 to 2 times the MRHD in rabbits. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or fetal risk: There is a risk to the mother from untreated schizophrenia, or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide.
Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy.
The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Fetal/neonatal adverse reactions: Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including quetiapine extended-release tablet, during the third trimester of pregnancy.
These symptoms varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.
Data Human Data: Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of quetiapine extended-release tablet is supported by studies of SEROQUEL for schizophrenia in adolescent patients 13 to 17 years of age and in bipolar mania in children and adolescent patients 10 to 17 years of age [see CLINICAL STUDIES ( 14.1 and 14.2 )]. In general, the adverse reactions observed in children and adolescents during the clinical trials with SEROQUEL were similar to those in the adult population with few exceptions. Increases in systolic and diastolic blood pressure occurred in children and adolescents and did not occur in adults.
Orthostatic hypotension occurred more frequently in adults (4 to 7%) compared to children and adolescents (< 1%) [see WARNINGS AND PRECAUTIONS ( 5.7 ) and ADVERSE REACTIONS ( 6.1 )]. Bipolar Depression The effectiveness of quetiapine extended-release tablet for the treatment of bipolar depression in patients under the age of 18 years has not been established. One 8-week trial was conducted to evaluate the safety and efficacy of quetiapine extended-release tablet in the treatment of bipolar depression in pediatric patients 10 to 17 years of age.
The primary objective of the study was to evaluate whether quetiapine extended-release tablet at a dose of 150 to 300 mg/day demonstrated superior efficacy (as measured by change in CDRS-R total score from baseline to end of 8 weeks) compared to placebo in children and adolescents 10 to 17 years of age with bipolar depression. A total of 193 patients with bipolar depression were randomized to placebo or quetiapine extended-release tablet. The primary results of this study did not show a difference between quetiapine extended-release tablet and placebo in decreasing depression symptoms in children and adolescents with bipolar disorder.
In this study, patients treated with quetiapine extended-release tablet exhibited metabolic changes, weight gain, increases in blood pressure and increases in heart rate [see WARNINGS AND PRECAUTIONS ( 5.5 , 5.9 ) and ADVERSE REACTIONS ( 6.1 )]. Some differences in the pharmacokinetics of quetiapine were noted between children/adolescents (10 to 17 years of age) and adults. When adjusted for weight, the AUC and C max of quetiapine were 41% and 39% lower, respectively, in children and adolescents compared to adults.
The pharmacokinetics of the active metabolite, norquetiapine, were similar between children/adolescents and adults after adjusting for weight [see CLINICAL PHARMACOLOGY ( 12.3 )]. Schizophrenia The efficacy and safety of quetiapine extended-release tablet in the treatment of schizophrenia in adolescents aged 13 to 17 years is supported by one 6-week, double-blind, placebo-controlled trial with SEROQUEL [see INDICATIONS AND USAGE ( 1.1 ), DOSAGE AND ADMINISTRATION ( 2.2 ), ADVERSE REACTIONS ( 6.1 ), and CLINICAL STUDIES ( 14.1 )].
Safety and effectiveness of quetiapine extended-release tablet in pediatric patients less than 13 years of age with schizophrenia have not been established. The safety and effectiveness of quetiapine extended-release tablet in the maintenance treatment of schizophrenia has not been established in patients less than 18 years of age. Bipolar Mania The efficacy and safety of quetiapine extended-release tablet in the treatment of bipolar mania in children and adolescents ages 10 to 17 years is supported by one 3-week, double-blind, placebo controlled trial with SEROQUEL [see INDICATIONS AND USAGE ( 1.2 ), DOSAGE AND ADMINISTRATION ( 2.2 ), ADVERSE REACTIONS ( 6.1 ), and CLINICAL STUDIES ( 14.2 )].
Safety and effectiveness of quetiapine extended-release tablet in pediatric patients less than 10 years of age with bipolar mania have not been established. The safety and effectiveness of quetiapine extended-release tablet in the maintenance treatment of bipolar disorder has not been established in patients less than 18 years of age.
🧓 Geriatric Use ▾
8.5Geriatric Use Sixty-eight patients in clinical studies with quetiapine extended-release tablet were 65 years of age or over. In general, there was no indication of any different tolerability of quetiapine extended-release tablet in the elderly compared to younger adults. Nevertheless, the presence of factors that might decrease pharmacokinetic clearance, increase the pharmacodynamic response to quetiapine extended-release tablet, or cause poorer tolerance or orthostasis, should lead to consideration of a lower starting dose, slower titration, and careful monitoring during the initial dosing period in the elderly.
The mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients [see DOSAGE AND ADMINISTRATION ( 2.3 ) and CLINICAL PHARMACOLOGY ( 12.3 )].
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Human Experience In clinical trials, survival has been reported in acute overdoses of up to 30 grams of quetiapine. Most patients who overdosed experienced no adverse reactions or recovered fully from the reported events. Death has been reported in a clinical trial following an overdose of 13.6 grams of quetiapine alone.
In general, reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and anticholinergic toxicity including coma and delirium. Patients with pre-existing severe cardiovascular disease may be at an increased risk of the effects of overdose [see WARNINGS AND PRECAUTIONS ( 5.12 )]. One case, involving an estimated overdose of 9600 mg, was associated with hypokalemia and first degree heart block.
In post-marketing experience, there were cases reported of QT prolongation with overdose.
10.2Management of Overdosage Establish and maintain an airway and ensure adequate oxygenation and ventilation. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. Appropriate supportive measures are the mainstay of management.
For the most up-to-date information on the management of quetiapine extended-release tablet overdosage, contact a certified Regional Poison Control Center (1-800-222-1222). Quetiapine extended-release tablet overdose may lead to gastric bezoar formation and appropriate diagnostic imaging is recommended to further guide patient management. Routine gastric lavage may not be effective in the removal of the bezoar due to gum like sticky consistency of the mass.
Endoscopic pharmacobezoar removal has been performed successfully.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action of quetiapine extended-release tablet in the listed indications is unclear. However, the efficacy of quetiapine in these indications could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2A (5HT 2A ) antagonism. The active metabolite, N-desalkyl quetiapine (norquetiapine), has similar activity at D 2 , but greater activity at 5HT 2A receptors, than the parent drug (quetiapine).
12.2Pharmacodynamics Quetiapine and its metabolite norquetiapine have affinity for multiple neurotransmitter receptors with norquetiapine binding with higher affinity than quetiapine in general. The Ki values for quetiapine and norquetiapine at the dopamine D 1 are 428/99.8 nM, at D 2 626/489nM, at serotonin 5HT 1A 1040/191 nM at 5HT 2A 38/2.9 nM, at histamine H 1 4.4/1.1 nM, at muscarinic M 1 1086/38.3 nM, and at adrenergic α1b 14.6/46.4 nM and, at α 2 receptors 617/1290 nM, respectively. Quetiapine and norquetiapine lack appreciable affinity to the benzodiazepine receptors.
Effect on QT Interval In clinical trials quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE ( 10.1 )], in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval.
12.3Pharmacokinetics Adults Following multiple dosing of quetiapine up to a total daily dose of 800 mg, administered in divided doses, the plasma concentration of quetiapine and norquetiapine, the major active metabolite of quetiapine, were proportional to the total daily dose. Accumulation is predictable upon multiple dosing. Steady-state mean C max and AUC of norquetiapine are about 21 to 27% and 46 to 56%, respectively of that observed for quetiapine.
Elimination of quetiapine is mainly via hepatic metabolism. The mean-terminal half-life is approximately 7 hours for quetiapine and approximately 12 hours for norquetiapine within the clinical dose range. Steady-state concentrations are expected to be achieved within two days of dosing. quetiapine extended-release tablet is unlikely to interfere with the metabolism of drugs metabolized by cytochrome P450 enzymes.
Children and Adolescents At steady state, the pharmacokinetics of the parent compound, in children and adolescents (10 to 17 years of age), were similar to adults. However, when adjusted for dose and weight, AUC and C max of the parent compound were 41% and 39% lower, respectively, in children and adolescents than in adults. For the active metabolite, norquetiapine, AUC and C max were 45% and 31% higher, respectively, in children and adolescents than in adults.
When adjusted for dose and weight, the pharmacokinetics of the metabolite, norquetiapine, was similar between children and adolescents and adults [see USE IN SPECIFIC POPULATIONS ( 8.4 )]. Absorption Quetiapine reaches peak plasma concentrations approximately 6 hours following administration. quetiapine extended-release tablet dosed once daily at steady state has comparable bioavailability to an equivalent total daily dose of SEROQUEL administered in divided doses, twice daily. A high-fat meal (approximately 800 to 1000 calories) was found to produce statistically significant increases in the quetiapine extended-release tablet C max and AUC of 44% to 52% and 20% to 22%, respectively, for the 50 mg and 300 mg tablets.
In comparison, a light meal (approximately 300 calories) had no significant effect on the C max or AUC of quetiapine. It is recommended that quetiapine extended-release tablet be taken without food or with a light meal [see DOSAGE AND ADMINISTRATION ( 2.1 )]. Distribution Quetiapine is widely distributed throughout the body with an apparent volume of distribution of 10±4 L/kg.
It is 83%… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism of action of quetiapine extended-release tablet in the listed indications is unclear. However, the efficacy of quetiapine in these indications could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2A (5HT 2A ) antagonism. The active metabolite, N-desalkyl quetiapine (norquetiapine), has similar activity at D 2 , but greater activity at 5HT 2A receptors, than the parent drug (quetiapine).
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Quetiapine extended-release tablets USP, 50 mg are peach to red colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K71" on the other side Bottle of 60 tablets (NDC 68180-612-07). Quetiapine extended-release tablets USP, 150 mg are white colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K72" on the other side Bottle of 60 tablets (NDC 68180-613-07). Quetiapine extended-release tablets USP, 200 mg are yellow colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K73" on the other side Bottle of 60 tablets (NDC 68180-614-07).
Quetiapine extended-release tablets USP, 300 mg are pale yellow colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K74" on the other side Bottle of 60 tablets (NDC 68180-615-07). Quetiapine extended-release tablets USP, 400 mg are white colored, capsule shaped, biconvex, film coated tablets debossed with "LU" on one side and "K75" on the other side Bottle of 60 tablets (NDC 68180-616-07). Store quetiapine extended-release tablets USP at 25ºC (77ºF); excursions permitted to 15 to 30ºC (59 to 86ºF) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Quetiapine fumarate is an atypical antipsychotic belonging to a chemical class, the dibenzothiazepine derivatives. The chemical designation is 2-[2-(4-dibenzo [ b,f ] [1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol fumarate (2:1) (salt). It is present in tablets as the fumarate salt.
All doses and tablet strengths are expressed as milligrams of base, not as fumarate salt. Its molecular formula is C 42 H 50 N 6 O 4 S 2 . C 4 H 4 O 4 and it has a molecular weight of 883.11 (fumarate salt).
The structural formula is: Quetiapine fumarate is a white to off-white crystalline powder which is moderately soluble in water. Quetiapine extended-release tablets, USP are supplied for oral administration as 50 mg (peach to red), 150 mg (white), 200 mg (yellow), 300 mg (yellow to pale yellow), and 400 mg (white). All tablets are capsule shaped and film coated.
Inactive ingredients for quetiapine extended-release tablets, USP are hypromellose, hypromellose 2208, lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium citrate dihydrate. The film coating for all quetiapine extended-release tablets, USP contain hypromellose 2910, macrogol and titanium dioxide. In addition, red iron oxide (for 50 mg) and yellow iron oxide (for 50 mg, 200 mg and 300 mg) are included in the film coating of specific strengths.
Each 50 mg film-coated tablet contains 58 mg of quetiapine fumarate equivalent to 50 mg quetiapine. Each 150 mg film-coated tablet contains 173 mg of quetiapine fumarate equivalent to 150 mg quetiapine. Each 200 mg film-coated tablet contains 230 mg of quetiapine fumarate equivalent to 200 mg quetiapine.
Each 300 mg film-coated tablet contains 345 mg of quetiapine fumarate equivalent to 300 mg quetiapine. Each 400 mg film-coated tablet contains 461 mg of quetiapine fumarate equivalent to 400 mg quetiapine. Quetiapine extended-release tablets USP meets USP Dissolution Test 13.
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💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking quetiapine extended-release tablet. Increased Mortality in Elderly Patients with Dementia-Related Psychosis Patients and caregivers should be advised that elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs are at increased risk of death compared with placebo.
Quetiapine extended-release tablet is not approved for elderly patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS ( 5.1 )]. Suicidal Thoughts and Behaviors Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down.
Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [see WARNINGS AND PRECAUTIONS ( 5.2 )].
Neuroleptic Malignant Syndrome (NMS) Patients should be advised to report to their physician any signs or symptoms that may be related to NMS. These may include muscle stiffness and high fever [see WARNINGS AND PRECAUTIONS ( 5.4 )]. Hyperglycemia and Diabetes Mellitus Patients should be aware of the symptoms of hyperglycemia (high blood sugar) and diabetes mellitus.
Patients who are diagnosed with diabetes, those with risk factors for diabetes, or those that develop these symptoms during treatment should have their blood glucose monitored at the beginning of and periodically during treatment [see WARNINGS AND PRECAUTIONS ( 5.5 )]. Hyperlipidemia Patients should be advised that elevations in total cholesterol, LDL-cholesterol and triglycerides and decreases in HDL-cholesterol may occur. Patients should have their lipid profile monitored at the beginning of and periodically during treatment [see WARNINGS AND PRECAUTIONS ( 5.5 )].
Weight Gain Patients should be advised that they may experience weight gain. Patients should have their weight monitored regularly [ see WARNINGS AND PRECAUTIONS ( 5.5 )]. Orthostatic Hypotension Patients should be advised of the risk of orthostatic hypotension (symptoms include feeling dizzy or lightheaded upon standing, which may lead to falls) especially during the period of initial dose titration, and also at times of re-initiating treatment or increases in dose [see WARNINGS AND PRECAUTIONS ( 5.7 )].
Increased Blood Pressure in Children and Adolescents Children and adolescent patients should have their blood pressure measured at the beginning of, and periodically during, treatment [see WARNINGS AND PRECAUTIONS ( 5.9 )]. Leukopenia/Neutropenia Patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia should be advised that they should have their CBC monitored while taking quetiapine extended-release tablet. Patients should be advised to talk to their doctor as soon as possible if they have a fever, flu-like symptoms, sore throat, or any other infection as this could be a result of a very low WBC, which may require quetiapine extended-release tablet to be stopped and/or treatment to be given [see WARNINGS AND PRECAUTIONS ( 5.10 )].
Interference with Cognitive and Motor Performance Patients should be advised… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE Quetiapine (kweh-TYE-uh-peen) Extended-Release tablets USP Read this Medication Guide before you start taking quetiapine extended-release tablet and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment.
What is the most important information I should know about quetiapine extended-release tablet? Quetiapine extended-release tablet may cause serious side effects, including: 1. Risk of death in the elderly with dementia: Medicines like quetiapine extended-release tablet can increase the risk of death in elderly people who have memory loss (dementia).
Quetiapine extended-release tablet is not for treating psychosis in the elderly with dementia. 2. Risk of suicidal thoughts or actions (antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions).
Talk to your or your family member's, healthcare provider about: о all risks and benefits of treatment with antidepressant medicines о all treatment choices for depression or other serious mental illness • Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment. • Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions.
These include people who have (or have a family history of) depression, bipolar illness (also called manic-depressive illness), or suicidal thoughts or actions. • How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member? о Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed. о Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. о Keep all follow-up visits with the healthcare provider as scheduled.
Call the healthcare provider between visits as needed, especially if you have concerns about symptoms. Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you: • thoughts about suicide or dying • attempts to commit suicide • new or worse depression • new or worse anxiety • feeling very agitated or restless • panic attacks • trouble sleeping (insomnia) • new or worse irritability • acting aggressive, being angry, or violent • acting on dangerous impulses • an extreme increase in activity and talking (mania) • other unusual changes in behavior or mood What else do I need to know about antidepressant medicines? • Never stop an antidepressant medicine without first talking to your healthcare provider.
Stopping an antidepressant medicine suddenly can cause other symptoms. • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants. • Antidepressant medicines have other side effects.
Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member. • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member take. Keep a list of all medicines to show the healthcare provider.
Do not start new medicines without first checking with your healthcare provider. • Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child's healthcare provider for more information. What is quetiapine extended-release tablet?… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Adults Following multiple dosing of quetiapine up to a total daily dose of 800 mg, administered in divided doses, the plasma concentration of quetiapine and norquetiapine, the major active metabolite of quetiapine, were proportional to the total daily dose. Accumulation is predictable upon multiple dosing. Steady-state mean C max and AUC of norquetiapine are about 21 to 27% and 46 to 56%, respectively of that observed for quetiapine.
Elimination of quetiapine is mainly via hepatic metabolism. The mean-terminal half-life is approximately 7 hours for quetiapine and approximately 12 hours for norquetiapine within the clinical dose range. Steady-state concentrations are expected to be achieved within two days of dosing. quetiapine extended-release tablet is unlikely to interfere with the metabolism of drugs metabolized by cytochrome P450 enzymes.
Children and Adolescents At steady state, the pharmacokinetics of the parent compound, in children and adolescents (10 to 17 years of age), were similar to adults. However, when adjusted for dose and weight, AUC and C max of the parent compound were 41% and 39% lower, respectively, in children and adolescents than in adults. For the active metabolite, norquetiapine, AUC and C max were 45% and 31% higher, respectively, in children and adolescents than in adults.
When adjusted for dose and weight, the pharmacokinetics of the metabolite, norquetiapine, was similar between children and adolescents and adults [see USE IN SPECIFIC POPULATIONS ( 8.4 )]. Absorption Quetiapine reaches peak plasma concentrations approximately 6 hours following administration. quetiapine extended-release tablet dosed once daily at steady state has comparable bioavailability to an equivalent total daily dose of SEROQUEL administered in divided doses, twice daily. A high-fat meal (approximately 800 to 1000 calories) was found to produce statistically significant increases in the quetiapine extended-release tablet C max and AUC of 44% to 52% and 20% to 22%, respectively, for the 50 mg and 300 mg tablets.
In comparison, a light meal (approximately 300 calories) had no significant effect on the C max or AUC of quetiapine. It is recommended that quetiapine extended-release tablet be taken without food or with a light meal [see DOSAGE AND ADMINISTRATION ( 2.1 )]. 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 14 C-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. The average dose fraction of free quetiapine and its major active metabolite is <5% excreted in the urine.
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 norquetiapine.
Age Oral clearance of quetiapine was reduced by 40% in elderly patients (≥65 years, n = 9) compared to young patients (n=12), and dosing adjustment may be necessary [see DOSAGE AND ADMINISTRATION ( 2.3 )]. Gender There is no gender effect on the pharmacokinetics of quetiapine. Race There is no race effect on the pharmacokinetics of quetiapine.
Smoking Smoking has no effect on the oral clearance of quetiapine. Renal Insufficiency Patients with seve… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Quetiapine and its metabolite norquetiapine have affinity for multiple neurotransmitter receptors with norquetiapine binding with higher affinity than quetiapine in general. The Ki values for quetiapine and norquetiapine at the dopamine D 1 are 428/99.8 nM, at D 2 626/489nM, at serotonin 5HT 1A 1040/191 nM at 5HT 2A 38/2.9 nM, at histamine H 1 4.4/1.1 nM, at muscarinic M 1 1086/38.3 nM, and at adrenergic α1b 14.6/46.4 nM and, at α 2 receptors 617/1290 nM, respectively. Quetiapine and norquetiapine lack appreciable affinity to the benzodiazepine receptors.
Effect on QT Interval In clinical trials quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE ( 10.1 )], in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Schizophrenia Short-term Trials - Adults The efficacy of quetiapine extended-release tablet in the treatment of schizophrenia was demonstrated in 1 short-term, 6-week, fixed-dose, placebo-controlled trial of inpatients and outpatients with schizophrenia (n=573) who met DSM IV criteria for schizophrenia. Quetiapine extended-release tablet (once daily) was administered as 300 mg on Day 1, and the dose was increased to either 400 mg or 600 mg by Day 2, or 800 mg by Day 3. The primary endpoint was the change from baseline of the Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment (Day 42).
Quetiapine extended-release tablet doses of 400 mg, 600 mg and 800 mg once daily were superior to placebo in the PANSS total score at Day 42 (study 1 in Table 26). Short-term Trials -Adolescents (ages 13 to 17) The efficacy of quetiapine extended-release tablet in the treatment of schizophrenia in adolescents (13 to 17 years of age) was supported by a 6-week, double-blind, placebo-controlled trial. Patients who met DSM-IV diagnostic criteria for schizophrenia were randomized into one of three treatment groups: quetiapine tablet 400 mg/day (n = 73), SEROQUEL 800 mg/day (n = 74), or placebo (n = 75).
Study medication was initiated at 50 mg/day and on day 2 increased to 100 mg/per day (divided and given two or three times per day). Subsequently, the dose was titrated to the target dose of 400 mg/day or 800 mg/day using increments of 100 mg/day, divided and given two or three times daily. The primary efficacy variable was the mean change from baseline in total Positive and Negative Syndrome Scale (PANSS).
SEROQUEL at 400 mg/day and 800 mg/day was superior to placebo in the reduction of PANSS total score (study 2 in Table 26). Table 26: Schizophrenia Short-Term Trials SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval. 1 Doses that are statistically significantly superior to placebo.
2 Difference (drug minus placebo) in least-squares mean change from baseline. 3 Included in the trial for assay sensitivity. Study Number Treatment Group Primary Efficacy Endpoint: PANSS Total Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Difference 2 (95% CI) Study 1 Quetiapine extended-release tablet (400 mg/day) 1 95.8 (13.9) -24.8 (2.5) -6.1 (-11.5, -0.6) Quetiapine extended-release tablet (600 mg/day) 1 96.8 (14.1) -30.9 (2.5) -12.1 (-17.6, -6.7) Quetiapine extended-release tablet (800 mg/day) 1 97.3 (14.7) -31.3 (2.5) -12.5 (-17.9, -7.1) Quetiapine extended-release tablet (400 mg/day) 1,3 96.5 (16) -26.6 (2.4) -7.8 (-13.1, -2.4) Placebo 96.2 (13.3) -18.8 (2.5) -- Study 2 (adolescents) SEROQUEL (400 mg/day) 1 96.2 (17.7) -27.3 (2.6) -8.2 (-16.1, -0.3) SEROQUEL (800 mg/day) 1 96.9 (15.3) -28.4 (1.8) -9.3 (-16.2, -2.4) Placebo 96.2 (17.7) -19.2 (3) Maintenance Trials In a longer-term trial (study 3), clinically stable adult outpatients (n=171) meeting DSM-IV criteria for schizophrenia who remained stable following 16 weeks of open-label treatment with flexible doses of quetiapine extended-release tablet (400 mg/day to 800 mg/day) were randomized to placebo or to continue on their current quetiapine extended-release tablet (400 mg/day to 800 mg/day) for observation for possible relapse during the double-blind continuation (maintenance) phase.
Stabilization during the open-label phase was defined as receiving a stable dose of quetiapine extended-release tablet and having a CGI-S≤4 and a PANSS score ≤60 from beginning to end of this open-label phase (with no increase of ≥10 points in PANSS total score). Relapse during the double-blind phase was defined in terms of a ≥30% increase in the PANSS Total score, or CGI-Improvement score of ≥6, or hospitalization due to worsening of schizophrenia, or need for any other antipsychotic medication. Patients on quetiapine extended-release tablet experienced a statistically significant longer t… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Quetiapine is not a controlled substance.
9.2Abuse Quetiapine extended-release tablet has not been systematically studied in animals or humans for its potential for abuse, tolerance or physical dependence. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of misuse or abuse of quetiapine extended-release tablet (e.g., development of tolerance, increases in dose, drug-seeking behavior).
🔒 Controlled Substance ▾
9.1Controlled Substance Quetiapine is not a controlled substance.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in C57BL mice and Wistar rats. Quetiapine was administered in the diet to mice at doses of 20, 75, 250, and 750 mg/kg and to rats by gavage at doses of 25, 75, and 250 mg/kg for two years. These doses are equivalent to 0.1, 0.5, 1.5, and 4.5 times the MRHD of 800 mg/day based on mg/m 2 body surface area (mice) or 0.3, 1, and 3 times the MRHD based on mg/m 2 body surface area (rats).
There were statistically significant increases in thyroid gland follicular adenomas in male mice at doses 1.5 and 4.5 times the MRHD based on mg/m 2 body surface area and in male rats at a dose of 3 times the MRHD on mg/m 2 body surface area. Mammary gland adenocarcinomas were statistically significantly increased in female rats at all doses tested (0.3, 1, and 3 times the MRHD based on mg/m 2 body surface area). Thyroid follicular cell adenomas may have resulted from chronic stimulation of the thyroid gland by thyroid stimulating hormone (TSH) resulting from enhanced metabolism and clearance of thyroxine by rodent liver.
Changes in TSH, thyroxine, and thyroxine clearance consistent with this mechanism were observed in subchronic toxicity studies in rat and mouse and in a 1-year toxicity study in rat; however, the results of these studies were not definitive. The relevance of the increases in thyroid follicular cell adenomas to human risk, through whatever mechanism, is unknown. Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents.
Serum measurements in a 1-year toxicity study showed that quetiapine increased median serum prolactin levels a maximum of 32- and 13-fold in male and female rats, respectively. Increases in mammary neoplasms have been found in rodents after chronic administration of other antipsychotic drugs and are considered to be prolactin-mediated. The relevance of this increased incidence of prolactin-mediated mammary gland tumors in rats to human risk is unknown [see WARNINGS AND PRECAUTIONS ( 5.15 )].
Mutagenesis Quetiapine was not mutagenic or clastogenic in standard genotoxicity tests. The mutagenic potential of quetiapine was tested in the in vitro Ames bacterial gene mutation assay and in the in vitro mammalian gene mutation assay in Chinese Hamster Ovary cells. The clastogenic potential of quetiapine was tested in the in vitro chromosomal aberration assay in cultured human lymphocytes and in the in vivo bone marrow micronucleus assay in rats up to 500 mg/kg which is 6 times the maximum recommended human dose based on mg/m 2 body surface area.
Impairment of Fertility Quetiapine decreased mating and fertility in male Sprague-Dawley rats at oral doses of 50 and 150 mg/kg or approximately 1 and 3 times the MRHD of 800 mg/day based on mg/m 2 body surface area. Drug-related effects included increases in interval to mate and in the number of matings required for successful impregnation. These effects continued to be observed at 3 times the MRHD even after a two-week period without treatment.
The no-effect dose for impaired mating and fertility in male rats was 25 mg/kg, or 0.3 times the MRHD dose based on mg/m 2 body surface area. Quetiapine adversely affected mating and fertility in female Sprague-Dawley rats at an oral dose approximately 1 times the MRHD of 800 mg/day based on mg/m 2 body surface area. Drug-related effects included decreases in matings and in matings resulting in pregnancy, and an increase in the interval to mate.
An increase in irregular estrus cycles was observed at doses of 10 and 50 mg/kg, or approximately 0.1 and 1 times the MRHD of 800 mg/day based on mg/m 2 body surface area. The no-effect dose in female rats was 1 mg/kg, or 0.01 times the MRHD of 800 mg/day based on mg/m 2 body surface area.
13.2Animal Toxicology and/or Pharmacology Quetiapine caused a dose-related increase in pigment deposition in thyroid gland in rat toxicity studies… [Excerpted — this section continues on DailyMed.]
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Carcinogenicity studies were conducted in C57BL mice and Wistar rats. Quetiapine was administered in the diet to mice at doses of 20, 75, 250, and 750 mg/kg and to rats by gavage at doses of 25, 75, and 250 mg/kg for two years. These doses are equivalent to 0.1, 0.5, 1.5, and 4.5 times the MRHD of 800 mg/day based on mg/m 2 body surface area (mice) or 0.3, 1, and 3 times the MRHD based on mg/m 2 body surface area (rats).
There were statistically significant increases in thyroid gland follicular adenomas in male mice at doses 1.5 and 4.5 times the MRHD based on mg/m 2 body surface area and in male rats at a dose of 3 times the MRHD on mg/m 2 body surface area. Mammary gland adenocarcinomas were statistically significantly increased in female rats at all doses tested (0.3, 1, and 3 times the MRHD based on mg/m 2 body surface area). Thyroid follicular cell adenomas may have resulted from chronic stimulation of the thyroid gland by thyroid stimulating hormone (TSH) resulting from enhanced metabolism and clearance of thyroxine by rodent liver.
Changes in TSH, thyroxine, and thyroxine clearance consistent with this mechanism were observed in subchronic toxicity studies in rat and mouse and in a 1-year toxicity study in rat; however, the results of these studies were not definitive. The relevance of the increases in thyroid follicular cell adenomas to human risk, through whatever mechanism, is unknown. Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents.
Serum measurements in a 1-year toxicity study showed that quetiapine increased median serum prolactin levels a maximum of 32- and 13-fold in male and female rats, respectively. Increases in mammary neoplasms have been found in rodents after chronic administration of other antipsychotic drugs and are considered to be prolactin-mediated. The relevance of this increased incidence of prolactin-mediated mammary gland tumors in rats to human risk is unknown [see WARNINGS AND PRECAUTIONS ( 5.15 )].
Mutagenesis Quetiapine was not mutagenic or clastogenic in standard genotoxicity tests. The mutagenic potential of quetiapine was tested in the in vitro Ames bacterial gene mutation assay and in the in vitro mammalian gene mutation assay in Chinese Hamster Ovary cells. The clastogenic potential of quetiapine was tested in the in vitro chromosomal aberration assay in cultured human lymphocytes and in the in vivo bone marrow micronucleus assay in rats up to 500 mg/kg which is 6 times the maximum recommended human dose based on mg/m 2 body surface area.
Impairment of Fertility Quetiapine decreased mating and fertility in male Sprague-Dawley rats at oral doses of 50 and 150 mg/kg or approximately 1 and 3 times the MRHD of 800 mg/day based on mg/m 2 body surface area. Drug-related effects included increases in interval to mate and in the number of matings required for successful impregnation. These effects continued to be observed at 3 times the MRHD even after a two-week period without treatment.
The no-effect dose for impaired mating and fertility in male rats was 25 mg/kg, or 0.3 times the MRHD dose based on mg/m 2 body surface area. Quetiapine adversely affected mating and fertility in female Sprague-Dawley rats at an oral dose approximately 1 times the MRHD of 800 mg/day based on mg/m 2 body surface area. Drug-related effects included decreases in matings and in matings resulting in pregnancy, and an increase in the interval to mate.
An increase in irregular estrus cycles was observed at doses of 10 and 50 mg/kg, or approximately 0.1 and 1 times the MRHD of 800 mg/day based on mg/m 2 body surface area. The no-effect dose in female rats was 1 mg/kg, or 0.01 times the MRHD of 800 mg/day based on mg/m 2 body surface area.
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 68180-612-07 60 Tablets Quetiapine Extended-Release Tablets USP 50 mg* ONCE DAILY PHARMACIST: Dispense the Medication Guide to each Patient. *Each film-coated tablet contains 58 mg quetiapine fumarate USP equivalent to 50 mg quetiapine Rx only NDC 68180-613-07 60 Tablets Quetiapine Extended-Release Tablets USP 150 mg* ONCE DAILY PHARMACIST: Dispense the Medication Guide to each Patient. *Each film-coated tablet contains 173 mg quetiapine fumarate USP equivalent to 150 mg quetiapine Rx only NDC 68180-614-07 60 Tablets Quetiapine Extended-Release Tablets USP 200 mg* ONCE DAILY PHARMACIST: Dispense the Medication Guide to each Patient. *Each film-coated tablet contains 230 mg quetiapine fumarate USP equivalent to 200 mg quetiapine Rx only NDC 68180-615-07 60 Tablets Quetiapine Extended-Release Tablets USP 300 mg* ONCE DAILY PHARMACIST: Dispense the Medication Guide to each Patient. *Each film-coated tablet contains 345 mg quetiapine fumarate USP equivalent to 300 mg quetiapine Rx only NDC 68180-616-07 60 Tablets Quetiapine Extended-Release Tablets USP 400 mg* ONCE DAILY PHARMACIST: Dispense the Medication Guide to each Patient. *Each film-coated tablet contains 461 mg quetiapine fumarate USP equivalent to 400 mg quetiapine Rx only 01 02 03 04 05
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