Quetiapine Fumarate

QUETIAPINE FUMARATE- quetiapine fumarate tablet
RedPharm Drug, Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use QUETIAPINE TABLETS safely and effectively. See full prescribing information for QUETIAPINE TABLETS.
QUETIAPINE tablets, for oral use
Initial U.S. Approval: 1997

WARNING: INCREASEDMORTALITYINELDERLYPATIENTS WITHDEMENTIA-RELATEDPSYCHOSIS;ANDSUICIDAL THOUGHTSANDBEHAVIORS

SEEFULLPRESCRIBING INFORMATIONFORCOMPLETEBOXEDWARNING.

IncreasedMortalityin ElderlyPatientswithDementia-Related Psychosis

· Elderly patients withdementia-relatedpsychosis treatedwith antipsychoticdrugsareatanincreasedriskofdeath.Quetiapine tablets is not approved forelderlypatients with dementia-relatedpsychosis(5.1)

SuicidalThoughtsandBehaviors

· Increasedriskofsuicidalthoughtsandbehaviorin children, adolescentsandyoungadultstakingantidepressants (5.2)
· Monitor for worsening and emergence of suicidal thoughts and behaviors (5.2)

RECENT MAJOR CHANGES

WarningsandPrecautions,CerebrovascularAdverseReactions,Including Stroke,inElderlyPatientswithDementia-Related Psychosis(5.3) 4/2013

INDICATIONS AND USAGE

Quetiapineis an atypical antipsychotic indicated forthetreatmentof:

· Schizophrenia (1.1)

· BipolarIdisordermanicepisodes(1.2)

· Bipolar disorder, depressive episodes (1.2)

DOSAGE AND ADMINISTRATION

Quetiapine tablets, USP can betakenwithor without food (2.1)

Indication Initial Dose Recommended Dose Maximum Dose
Schizophrenia-Adults (2.2) 25 mg twice daily 150 to 750 mg/day 750 mg/day
Schizophrenia-Adolescents (13 to 17 years)(2.2) 25 mg twice daily 400 to 800 mg/day 800 mg/day
Bipolar Mania- Adults Monotherapy or as an adjunct to lithium or divalproex (2.2) 50 mg twice daily 400 to 800 mg/day 800 mg/day
Bipolar Mania- Children and Adolescents (10 to 17 years), Monotherapy(2.2) 25 mg twice daily 400 to 600 mg/day 600 mg/day
Bipolar Depression-Adults (2.2) 50 mg once daily at bedtime 300 mg/day 300 mg/day

GeriatricUse: Consider alower starting dose (50mg/day),slower titration and carefulmonitoring duringthe initialdosingperiod in the elderly(2.3, 8.5)
HepaticImpairment: Lower startingdose (25mg/day) andslower titrationmaybeneeded(2.4, 8.7, 12.3)

DOSAGE FORMS AND STRENGTHS

Tablets: 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 300 mg, and 400 mg (3)

CONTRAINDICATIONS

Known hypersensitivity to quetiapine or any components in the formulation. (4)

WARNINGS AND PRECAUTIONS

· CerebrovascularAdverseReactions:Increasedincidence of cerebrovascularadverseevents(e.g.,stroke,transientischemicattack) has beenseenin elderlypatientswith dementia-relatedpsychoses treatedwithatypical antipsychotic drugs (5.3)

· NeurolepticMalignantSyndrome (NMS):Managewithimmediatediscontinuationandclosemonitoring(5.4)

· MetabolicChanges: Atypical antipsychoticshavebeenassociatedwithmetabolicchanges.Thesemetabolicchanges includehyperglycemia, dyslipidemia,andweightgain (5.5)

· HyperglycemiaandDiabetes Mellitus:Monitorpatientsforsymptomsof hyperglycemiaincludingpolydipsia,polyuria, polyphagia,andweakness.Monitorglucose regularlyinpatientswithdiabetesoratriskfor diabetes

· Dyslipidemia: Undesirablealterationshavebeenobservedin patients treatedwithatypicalantipsychotics.Appropriateclinical monitoring isrecommended,including fastingbloodlipidtesting atthebeginning of,andperiodically,duringtreatment

· WeightGain:Gain in bodyweighthas beenobserved;clinical monitoringof weightisrecommended

· TardiveDyskinesia:Discontinueifclinicallyappropriate 432 (5.6)

· Hypotension: Usewith cautionin patientswithknowncardiovascularor cerebrovascular disease (5.7)

· Increased Blood Pressure in ChildrenandAdolescents:Monitorblood pressureat thebeginning of,andperiodicallyduringtreatment inchildren andadolescents(5.8)

· Leukopenia,NeutropeniaandAgranulocytosis:Monitor completeblood countfrequentlyduring the first fewmonthsoftreatment in patientswith apre-existinglow whitecellcountorahistoryofleukopenia/neutropenia and discontinue quetiapineatthe firstsignofadeclineinWBCinabsence of othercausative factors (5.9)

· Cataracts: Lens changeshavebeenobservedin patients during long-term quetiapinetreatment.Lensexaminationisrecommendedwhenstarting treatment and at6-month intervalsduring chronictreatment (5.10)

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥ 5% and twice placebo):

Adults:somnolence, dry mouth, dizziness, constipation, asthenia, abdominal pain,postural hypotension, pharyngitis, weight gain, lethargy, ALT increased,dyspepsia (6.1)

Childrenand Adolescents: somnolence, dizziness, fatigue, increased appetite, nausea,vomiting, dry mouth, tachycardia, weight increased (6.1)

To report SUSPECTED ADVERSE REACTIONS, contactAscend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

· ConcomitantuseofstrongCYP3A4 inhibitors: Reducequetiapinedoseto onesixthwhencoadministeredwithstrong CYP3A4inhibitors(e.g., ketoconazole, ritonavir)(2.5,7.1,12.3)

· ConcomitantuseofstrongCYP3A4 inducers:Increasequetiapinedose upto5foldwhen used incombinationwithachronictreatment (more than7-14 days)of potentCYP3A4inducers(e.g.,phenytoin, rifampin, St.John’s wort)(2.6, 7.1,12.3)

· Discontinuation ofstrongCYP3A4 inducers:Reduce quetiapinedoseby5foldwithin7-14 daysofdiscontinuationofCYP3A4inducers (2.6,7.1,12.3)

USE IN SPECIFIC POPULATIONS

Pregnancy: Limited human data.Basedonanimaldata,maycause fetal harm. Quetiapineshould beusedonlyif thepotentialbenefit justifiesthe potential risk (8.1)
Nursing Mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother’s health (8.3)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 12/2015

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; AND SUICIDAL THOUGHTS AND BEHAVIORS
1 INDICATIONS & USAGE
1.1 Schizophrenia
1.2 Bipolar Disorder
1.3 Special Considerations in Treating Pediatric Schizophrenia and Bipolar I Disorder
2 DOSAGE & ADMINISTRATION
2.1 Important Administration Instructions
2.2 Dose Modifications in Elderly Patients
2.3 Dose Modifications in Elderly Patients
2.4 Dose Modifications in Hepatically Impaired Patients
2.5 Dose Modifications when used with CYP3A4 Inhibitors
2.6 Dose Modifications when used with CYP3A4 Inducers
2.7 Reinitiation of Treatment in Patients Previously Discontinued
2.8 Switching from Antipsychotics
3 DOSAGE FORMS & STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis
5.2 Suicidal Thoughts and Behaviors in Adolescents and Young Adults
5.3 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis
5.4 Neuroleptic Malignant Syndrome(NMS)
5.5 Metabolic Changes
5.6 Tardive Dyskinesia
5.7 Hypotension
5.8 Increases in Blood Pressure(Children and Adolescents)
5.9 Leukopenia, Neutropenia and Agranulocytosis
5.10 Cataracts
5.11 QT Prolongation
5.12 Seizures
5.13 Hypothyroidism
5.14 Hyperprolactinemia
5.15 Potential for Cognitive and Motor Impairment
5.16 Body Temperature Regulation
5.17 Dysphagia
5.18 Discontinuation Syndrome
6 ADVERSE REACTIONS
6.1 Clinical Study Experience
6.2 Post Marketing Experience
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on quetiapine
7.2 Effect of Quetiapine on Other Drugs
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
9.2 Abuse
10 OVERDOSAGE
10.1 Human Experience
10.2 Management of Overdosage
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
14.1 Schizophrenia
14.2 Bipolar Disorder
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION

*
Sections or subsections omitted from the full prescribing information are not listed.