What antiepileptic medication might the nurse Administer to treat bipolar disorder

What is Seroquel and how is it used?

Seroquel is a prescription medicine used to treat the symptoms of Schizophrenia, Bipolar I Disorder, Mania; Bipolar Disorder, Depressive Episodes; Bipolar I Disorder, Maintenance; and Major Depressive Disorder. Seroquel may be used alone or with other medications.

Seroquel belongs to a class of drugs called Antipsychotics, 2nd Generation; Antimanic Agents.

It is not known if Seroquel is safe and effective in children younger than 12 years of age.

What are the possible side effects of Seroquel?

Seroquel may cause serious side effects including:

• uncontrolled muscle movements in your face [chewing, lip smacking, frowning, tongue movement, blinking or eye movement],
• mask-like appearance of the face,
• trouble swallowing,
• problems with speech,
• lightheadedness,
• severe constipation,
• painful or difficult urination,
• blurred vision,
• tunnel vision,
• eye pain,
• seeing halos around lights,
• very stiff [rigid] muscles,
• high fever,
• sweating,
• confusion,
• fast or uneven heartbeats,
• tremors,
• fainting,
• increased thirst,
• increased urination,
• dry mouth,
• fruity breath odor,
• fever,
• chills,
• mouth sores,
• skin sores,
• sore throat,
• cough, and
• trouble breathing

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Seroquel include:

• speech problems,
• dizziness,
• drowsiness,
• tiredness,
• lack of energy,
• fast heartbeats,
• stuffy nose,
• increased appetite,
• weight gain,
• upset stomach,
• vomiting,
• constipation,
• dry mouth, and
• abnormal liver function test

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Seroquel. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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]. SEROQUEL is not approved for the treatment of patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS].

Suicidal Thoughts and Behaviors

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].

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].

SEROQUEL is not approved for use in pediatric patients under ten years of age [see Use In Specific Populations].

DESCRIPTION

SEROQUEL® [quetiapine fumarate] is a psychotropic agent 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 C42H50N6O4S2•C4H4O4 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.

SEROQUEL is supplied for oral administration as 25 mg [round, peach], 50 mg [round, white], 100 mg [round, yellow], 200 mg [round, white], 300 mg [capsule-shaped, white], and 400 mg [capsule-shaped, yellow] tablets.

Inactive ingredients are povidone, dibasic dicalcium phosphate dihydrate, microcrystalline cellulose, sodium starch glycolate, lactose monohydrate, magnesium stearate, hypromellose, polyethylene glycol and titanium dioxide.

The 25 mg tablets contain red ferric oxide and yellow ferric oxide and the 100 mg and 400 mg tablets contain only yellow ferric oxide.

3 pharmacies near 95014 have coupons for SEROquel [Brand Names:Seroquel for 25MG]

INDICATIONS

Schizophrenia

SEROQUEL XR is indicated for the treatment of schizophrenia. The efficacy of SEROQUEL XR 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 [13-17 years] treated with SEROQUEL [see Clinical Studies].

Bipolar Disorder

SEROQUEL XR 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 SEROQUEL XR 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 - 17 years] with manic episodes associated with bipolar I disorder treated with SEROQUEL [see Clinical Studies].

SEROQUEL XR is indicated for the acute treatment of depressive episodes associated with bipolar disorder. The efficacy of SEROQUEL XR 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].

SEROQUEL XR 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].

Adjunctive Treatment Of Major Depressive Disorder [MDD]

SEROQUEL XR is indicated for use as adjunctive therapy to antidepressants for the treatment of MDD. The efficacy of SEROQUEL XR 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].

Special 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.

SLIDESHOW

DOSAGE AND ADMINISTRATION

Important Administration Instructions

SEROQUEL XR tablets should be swallowed whole and not split, chewed, or crushed.

It is recommended that SEROQUEL XR be taken without food or with a light meal [approximately 300 calories] [see CLINICAL PHARMACOLOGY].

SEROQUEL XR should be administered once daily, preferably in the evening.

Recommended Dosing

The recommended initial dose, titration, dose range and maximum SEROQUEL XR 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].

Table 1: Recommended Dosing for SEROQUEL XR

Maintenance Treatment

Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies].

Dose 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, and CLINICAL PHARMACOLOGY]. When indicated, dose escalation should be performed with caution in these patients.

Elderly patients should be started on SEROQUEL XR 50 mg/day and the dose can be increased in increments of 50 mg/day depending on the clinical response and tolerability of the individual patient.

Dose Modifications In Hepatically Impaired Patients

Patients with hepatic impairment should be started on SEROQUEL XR 50 mg/day. The dose can be increased daily in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.

Dose Modifications When Used With CYP3A4 Inhibitors

SEROQUEL XR dose should be reduced to one sixth of original dose when co-medicated with a potent CYP3A4 inhibitor [e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.]. When the CYP3A4 inhibitor is discontinued, the dose of SEROQUEL XR should be increased by 6-fold [see CLINICAL PHARMACOLOGY and DRUG INTERACTIONS].

Dose Modifications When Used With CYP3A4 Inducers

SEROQUEL XR dose should be increased up to 5-fold of the original dose when used in combination with a chronic treatment [e.g., greater than 7-14 days] of a potent CYP3A4 inducer [e.g., phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.]. The dose should be titrated based on the clinical response and tolerance of the individual patient. When the CYP3A4 inducer is discontinued, the dose of SEROQUEL XR should be reduced to the original level within 7-14 days [see CLINICAL PHARMACOLOGY and DRUG INTERACTIONS].

Re-Initiation Of Treatment In Patients Previously Discontinued

Although there are no data to specifically address re-initiation of treatment, it is recommended that when restarting therapy of patients who have been off SEROQUEL XR for more than one-week, the initial dosing schedule should be followed. When restarting patients who have been off SEROQUEL XR for less than oneweek, gradual dose escalation may not be required and the maintenance dose may be re-initiated.

Switching Patients From SEROQUEL Tablets To SEROQUEL XR Tablets

Patients who are currently being treated with SEROQUEL [immediate release formulation] may be switched to SEROQUEL XR at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary.

Switching From Antipsychotics

There are no systematically collected data to specifically address switching patients from other antipsychotics to SEROQUEL XR, or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. When switching patients from depot antipsychotics, if medically appropriate, initiate SEROQUEL XR therapy in place of the next scheduled injection. The need for continuing existing extrapyramidal syndrome medication should be re-evaluated periodically.

HOW SUPPLIED

Dosage Forms And Strengths

• 50 mg extended-release tablets are peach, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 50” on one side and plain on the other side
• 150 mg extended-release tablets are white, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 150” on one side and plain on the other side
• 200 mg extended-release tablets are yellow, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 200” on one side and plain on the other side
• 300 mg extended-release tablets are pale yellow, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 300” on one side and plain on the other side
• 400 mg extended-release tablets are white, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 400” on one side and plain on the other side

Storage And Handling

50 mg Tablets [NDC 0310-0280-60] peach, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 50” on one side and plain on the other are supplied in bottles of 60 tablets.

150 mg Tablets [NDC 0310-0281-60] white, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 150” on one side and plain on the other are supplied in bottles of 60 tablets.

200 mg Tablets [NDC 0310-0282-60] yellow, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 200” on one side and plain on the other are supplied in bottles of 60 tablets.

300 mg Tablets [NDC 0310-0283-60] pale yellow, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 300” on one side and plain on the other are supplied in bottles of 60 tablets.

400 mg Tablets [NDC 0310-0284-60] white, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 400” on one side and plain on the other are supplied in bottles of 60 tablets.

Store SEROQUEL XR at 25°C [77°F]; excursions permitted to 15-30°C [59-86°F] [See USP].

Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850. Revised: Mar 2020

SIDE EFFECTS

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]
• Suicidal thoughts and behaviors in adolescents and young adults [see WARNINGS AND PRECAUTIONS]
• Cerebrovascular adverse reactions, including stroke in elderly patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS]
• Neuroleptic Malignant Syndrome [NMS] [see WARNINGS AND PRECAUTIONS]
• Metabolic changes [hyperglycemia, dyslipidemia, weight gain] [see WARNINGS AND PRECAUTIONS]
• Tardive dyskinesia [see WARNINGS AND PRECAUTIONS]
• Hypotension [see WARNINGS AND PRECAUTIONS]
• Falls [see WARNINGS AND PRECAUTIONS]
• Increases in blood pressure [children and adolescents] [see WARNINGS AND PRECAUTIONS]
• Leukopenia, neutropenia and agranulocytosis [see WARNINGS AND PRECAUTIONS]
• Cataracts [see WARNINGS AND PRECAUTIONS]
• QT Prolongation [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Hypothyroidism [see WARNINGS AND PRECAUTIONS]
• Hyperprolactinemia [see WARNINGS AND PRECAUTIONS]
• Potential for cognitive and motor impairment [see WARNINGS AND PRECAUTIONS]
• Body temperature regulation [see WARNINGS AND PRECAUTIONS]
• Dysphagia [see WARNINGS AND PRECAUTIONS]
• Discontinuation Syndrome [see WARNINGS AND PRECAUTIONS]
• Anticholinergic [antimuscarinic] Effects [see WARNINGS AND PRECAUTIONS]

Clinical Study Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Adults

The information below is derived from a clinical trial database for SEROQUEL consisting of over 4300 patients. This database includes 698 patients exposed to SEROQUEL for the treatment of bipolar depression, 405 patients exposed to SEROQUEL for the treatment of acute bipolar mania [monotherapy and adjunct therapy], 646 patients exposed to SEROQUEL for the maintenance treatment of bipolar I disorder as adjunct therapy, and approximately 2600 patients and/or normal subjects exposed to 1 or more doses of SEROQUEL for the treatment of schizophrenia.

Of these approximately 4,300 subjects, approximately 4000 [2300 in schizophrenia, 405 in acute bipolar mania, 698 in bipolar depression, and 646 for the maintenance treatment of bipolar I disorder] were patients who participated in multiple dose effectiveness trials, and their experience corresponded to approximately 2400 patient-years. The conditions and duration of treatment with SEROQUEL varied greatly and included [in overlapping categories] open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations.

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

Overall, there was little difference in the incidence of discontinuation due to adverse reactions [4% for SEROQUEL vs. 3% for placebo] in a pool of controlled trials. However, discontinuations due to somnolence [0.8% SEROQUEL vs. 0% placebo] and hypotension [0.4% SEROQUEL vs. 0% placebo] were considered to be drug related [see WARNINGS AND PRECAUTIONS].

Bipolar Disorder

Overall, discontinuations due to adverse reactions were 5.7% for SEROQUEL vs. 5.1% for placebo in monotherapy and 3.6% for SEROQUEL vs. 5.9% for placebo in adjunct therapy.

Overall, discontinuations due to adverse reactions were 12.3% for SEROQUEL 300 mg vs. 19.0% for SEROQUEL 600 mg and 5.2% for placebo.

In the acute therapy of schizophrenia [up to 6 weeks] and bipolar mania [up to 12 weeks] trials, the most commonly observed adverse reactions associated with the use of SEROQUEL monotherapy [incidence of 5% or greater] and observed at a rate on SEROQUEL at least twice that of placebo were somnolence [18%], dizziness [11%], dry mouth [9%], constipation [8%], ALT increased [5%], weight gain [5%], and dyspepsia [5%].

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the side effect incidence in the population studied.

Table 9 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy of schizophrenia [up to 6 weeks] and bipolar mania [up to 12 weeks] in 2% or more of patients treated with SEROQUEL [doses ranging from 75 to 800 mg/day] where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Table 9: Adverse Reaction Incidence in 3-to 12-Week Placebo-Controlled Clinical Trials for the Treatment of Schizophrenia and Bipolar Mania [Monotherapy]

In the acute adjunct therapy of bipolar mania [up to 3 weeks] studies, the most commonly observed adverse reactions associated with the use of SEROQUEL [incidence of 5% or greater] and observed at a rate on SEROQUEL at least twice that of placebo were somnolence [34%], dry mouth [19%], asthenia [10%], constipation [10%], abdominal pain [7%], postural hypotension [7%], pharyngitis [6%], and weight gain [6%].

Table 10 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during therapy [up to 3 weeks] of acute mania in 2% or more of patients treated with SEROQUEL [doses ranging from 100 to 800 mg/day] used as adjunct therapy to lithium and divalproex where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Table 10: Adverse Reaction Incidence in 3-Week Placebo-Controlled Clinical Trials for the Treatment of Bipolar Mania [Adjunct Therapy]

In bipolar depression studies [up to 8 weeks], the most commonly observed adverse reactions associated with the use of SEROQUEL [incidence of 5% or greater] and observed at a rate on SEROQUEL at least twice that of placebo were somnolence [57%], dry mouth [44%], dizziness [18%], constipation [10%], and lethargy [5%].

Table 11 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during therapy [up to 8 weeks] of bipolar depression in 2% or more of patients treated with SEROQUEL [doses of 300 and 600 mg/day] where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Table 11: Adverse Reaction Incidence in 8-Week Placebo-Controlled Clinical Trials for the Treatment of Bipolar Depression

Explorations for interactions on the basis of gender, age, and race did not reveal any clinically meaningful differences in the adverse reaction occurrence on the basis of these demographic factors.

Dose Dependency of Adverse Reactions in Short-Term, Placebo-Controlled Trials

Spontaneously elicited adverse reaction data from a study of schizophrenia comparing five fixed doses of SEROQUEL [75 mg, 150 mg, 300 mg, 600 mg, and 750 mg/day] to placebo were explored for dose-relatedness of adverse reactions. Logistic regression analyses revealed a positive dose response [p3 times the upper limits of the normal reference range in a pool of 3-to 12-week placebo-controlled trials were approximately 1% for both SEROQUEL [3/560] and placebo [3/294]. These hepatic enzyme elevations usually occurred within the first 3 weeks of drug treatment and promptly returned to pre-study levels with ongoing treatment with SEROQUEL. In bipolar depression trials, the proportions of patients with transaminase elevations of >3 times the upper limits of the normal reference range in two 8-week placebo-controlled trials was 1% [5/698] for SEROQUEL and 2% [6/347] for placebo.

Adults

In short-term placebo-controlled trials, decreases in hemoglobin to ≤13 g/dL males, ≤12 g/dL females on at least one occasion occurred in 8.3% [594/7155] of quetiapine-treated patients compared to 6.2% [219/3536] of patients treated with placebo. In a database of controlled and uncontrolled clinical trials, decreases in hemoglobin to ≤13 g/dL males, ≤12 g/dL females on at least one occasion occurred in 11% [2277/20729] of quetiapine-treated patients.

There have been literature reports suggesting false positive results in urine enzyme immunoassays for methadone and tricyclic antidepressants in patients who have taken quetiapine. Caution should be exercised in the interpretation of positive urine drug screen results for these drugs, and confirmation by alternative analytical technique [e.g., chromatographic methods] should be considered.

Adults

Between-group comparisons for pooled placebo-controlled trials revealed no statistically significant SEROQUEL/placebo differences in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc, and PR intervals. However, the proportions of patients meeting the criteria for tachycardia were compared in four 3-to 6-week placebo-controlled clinical trials for the treatment of schizophrenia revealing a 1% [4/399] incidence for SEROQUEL compared to 0.6% [1/156] incidence for placebo. In acute [monotherapy] bipolar mania trials the proportions of patients meeting the criteria for tachycardia was 0.5% [1/192] for SEROQUEL compared to 0% [0/178] incidence for placebo. In acute bipolar mania [adjunct] trials the proportions of patients meeting the same criteria was 0.6% [1/166] for SEROQUEL compared to 0% [0/171] incidence for placebo. In bipolar depression trials, no patients had heart rate increases to >120 beats per minute. SEROQUEL use was associated with a mean increase in heart rate, assessed by ECG, of 7 beats per minute compared to a mean increase of 1 beat per minute among placebo patients. This slight tendency to tachycardia in adults may be related to SEROQUEL's potential for inducing orthostatic changes [see WARNINGS AND PRECAUTIONS].

Children and Adolescents

In the acute [6-week] schizophrenia trial in adolescents, increases in heart rate [>110 bpm] occurred in 5.2% [3/73] of patients receiving SEROQUEL 400 mg and 8.5% [5/74] of patients receiving SEROQUEL 800 mg compared to 0% [0/75] of patients receiving placebo. Mean increases in heart rate were 3.8 bpm and 11.2 bpm for SEROQUEL 400 mg and 800 mg groups, respectively, compared to a decrease of 3.3 bpm in the placebo group [see WARNINGS AND PRECAUTIONS].

In the acute [3-week] bipolar mania trial in children and adolescents, increases in heart rate [>110 bpm] occurred in 1.1% [1/89] of patients receiving SEROQUEL 400 mg and 4.7% [4/85] of patients receiving SEROQUEL 600 mg compared to 0% [0/98] of patients receiving placebo. Mean increases in heart rate were 12.8 bpm and 13.4 bpm for SEROQUEL 400 mg and 600 mg groups, respectively, compared to a decrease of 1.7 bpm in the placebo group [see WARNINGS AND PRECAUTIONS].

In an acute [8-week] SEROQUEL XR trial in children and adolescents [10-17 years of age] with bipolar depression, in which efficacy was not established, increases in heart rate [>110 bpm 10-12 years and 13-17 years] occurred in 0% of patients receiving SEROQUEL XR and 1.2% of patients receiving placebo. Mean increases in heart rate were 3.4 bpm for SEROQUEL XR, compared to 0.3 bpm in the placebo group [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

The following adverse reactions were identified during post approval of SEROQUEL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported since market introduction which were temporally related to quetiapine therapy include anaphylactic reaction, cardiomyopathy, drug reaction with eosinophilia and systemic symptoms [DRESS], hyponatremia, myocarditis, nocturnal enuresis, pancreatitis, retrograde amnesia, rhabdomyolysis, syndrome of inappropriate antidiuretic hormone secretion [SIADH], Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis [TEN], decreased platelet count, serious liver reactions [including hepatitis, liver necrosis, and hepatic failure], agranulocytosis, intestinal obstruction, ileus, colon ischemia, urinary retention, sleep apnea, and acute generalized exanthematous pustulosis [AGEP].

QUESTION

DRUG INTERACTIONS

Effect Of Other Drugs On Quetiapine

The risks of using SEROQUEL in combination with other drugs have not been extensively evaluated in systematic studies. Given the primary CNS effects of SEROQUEL, caution should be used when it is taken in combination with other centrally acting drugs. SEROQUEL 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 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.

Coadministration of ketoconazole, a potent inhibitor of cytochrome CYP3A4, resulted in significant increase in quetiapine exposure. The dose of SEROQUEL should be reduced to one sixth of the original dose if co-administered with a strong CYP3A4 inhibitor [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Coadministration of quetiapine and phenytoin, a CYP3A4 inducer increased the mean oral clearance of quetiapine by 5fold. Increased doses of SEROQUEL 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 and CLINICAL PHARMACOLOGY]. When the CYP3A4 inducer is discontinued, the dose of SEROQUEL should be reduced to the original level within 7-14 days [see DOSAGE AND ADMINISTRATION].

The potential effects of several concomitant medications on quetiapine pharmacokinetics were studied [see CLINICAL PHARMACOLOGY].

Effect Of Quetiapine On Other Drugs

Because of its potential for inducing hypotension, SEROQUEL may enhance the effects of certain antihypertensive agents.

SEROQUEL 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].

Drug Abuse And Dependence

SEROQUEL is not a controlled substance.

SEROQUEL 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 SEROQUEL, e.g., development of tolerance, increases in dose, drug-seeking behavior.

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

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. 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. SEROQUEL is not approved for the treatment of patients with dementia-related psychosis [see BOXED WARNING].

Suicidal 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 strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs [SSRIs and others] showed that these drugs increase the risk of suicidal thinking and behavior [suicidality] in children, adolescents, and young adults [ages 18-24] with major depressive disorder [MDD] and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive-compulsive disorder [OCD], or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials [median duration of 2 months] of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences [drug vs. placebo], however, were relatively stable within age strata and across indications. These risk differences [drug-placebo difference in the number of cases of suicidality per 1000 patients treated] are provided in Table 2.

Table 2: Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated