Quetiapine Fumarate

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS

BOXED WARNING SECTION

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 is not approved for the treatment of patients with dementia-related psychosis [ see Warnings and Precautions (5.1) ]. 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 (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 is not approved for use in pediatric patients under ten years of age [ see Use in Specific Populations (8.4) ].

1 INDICATIONS & USAGE

Indications & Usage Section

2 DOSAGE & ADMINISTRATION

Dosage & Administration Section

3 DOSAGE FORMS & STRENGTHS

Dosage Forms & Strengths Section

Quetiapine Tablets, USP 25 mg are Peach coloured, film coated, round shape, biconvex tablets, debossed with "262" on other side and plain on other side Quetiapine Tablets, USP 50 mg are White coloured, film coated, round shape, biconvex tablets, debossed with"337" on one side and plain on other side Quetiapine Tablets, USP 100 mg are Yellow coloured film coated, round shape, biconvex tablets, debossed with "261" on one side and plain on other side Quetiapine Tablets, USP 150 mg are Off white to light yellow coloured, film coated, round shape, biconvex tablets, debossed with "353" on one side and plain on other side Quetiapine Tablets, USP 200 mg are White coloured, film coated, round shape, biconvex tablets, debossed with "260" on one side and plain on other side Quetiapine Tablets, USP 300 mg are White coloured, film coated, capsule shaped, biconvex tablets, debossed with "259" on one side and plain on other side Quetiapine Tablets, USP 400 mg are Yellow coloured, film coated, capsule shaped, biconvex tablets, debossed with ''336'' on one side and plain on other side

4 CONTRAINDICATIONS

Contraindications Section

Hypersensitivity to quetiapine or to any excipients in the quetiapine formulation. Anaphylactic reactions have been reported in patients treated with quetiapine.

5 WARNINGS AND PRECAUTIONS

Warnings And Precautions Section

6 ADVERSE REACTIONS

Adverse Reactions Section

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 )]

7 DRUG INTERACTIONS

Drug Interactions Section

8 USE IN SPECIFIC POPULATIONS

Use In Specific Populations Section

9 DRUG ABUSE AND DEPENDENCE

Drug Abuse And Dependence Section

10 OVERDOSAGE

Overdosage Section

11 DESCRIPTION

Description Section

Quetiapine 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 USP is a white to off-white crystalline powder which is moderately soluble in water. Quetiapine tablets, USP is supplied for oral administration as 25 mg (round peach), 50 mg (round, white), 100 mg (round yellow), 150 mg (round, off white to light 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 iron oxide and yellow iron oxide and the 100 mg, 150 mg and 400 mg tablets contain only yellow iron oxide. Each 25 mg tablet contains 28.78 mg of quetiapine fumarate USP equivalent to 25 mg quetiapine. Each 50 mg tablet contains 57.56 mg of quetiapine fumarate USP equivalent to 50 mg quetiapine. Each 100 mg tablet contains 115.13 mg of quetiapine fumarate USP equivalent to 100 mg quetiapine. Each 150 mg tablet contains 172.70 mg of quetiapine fumarate USP equivalent to 150 mg quetiapine. Each 200 mg tablet contains 230.27 mg of quetiapine fumarate USP equivalent to 200 mg quetiapine. Each 300 mg tablet contains 345.40 mg of quetiapine fumarate USP equivalent to 300 mg quetiapine. Each 400 mg tablet contains 460.54 mg of quetiapine fumarate USP equivalent to 400 mg quetiapine.

12 CLINICAL PHARMACOLOGY

Clinical Pharmacology Section

13 NONCLINICAL TOXICOLOGY

SPL UNCLASSIFIED SECTION

14 CLINICAL STUDIES

Clinical Studies Section

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied Section

Product: 50090-3333 NDC: 50090-3333-0 30 TABLET in a BOTTLE NDC: 50090-3333-1 90 TABLET in a BOTTLE Product: 50090-3342 NDC: 50090-3342-1 30 TABLET in a BOTTLE

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

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. Increased Mortality in Elderly Patients with Dementia-Related Psychosis Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at increased risk of death compared with placebo. Quetiapine 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. 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 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 of the risk of somnolence or sedation (which may lead to falls), especially during the period of initial dose titration. Patients should be cautioned about performing any activity requiring mental alertness, such as operating a motor vehicle (including automobiles) or operating machinery, until they are reasonably certain quetiapine therapy does not affect them adversely [ see Warnings and Precautions ( 5.16 ) ]. Heat Exposure and Dehydration Patients should be advised regarding appropriate care in avoiding overheating and dehydration [ see Warnings and Precautions (5 .17 ) ]. Concomitant Medication As with other medications, patients should be advised to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs. [ see Drug Interactions ( 7.1 ) ]. Pregnancy Advise pregnant women to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with quetiapine. Advise patients that quetiapine may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in a neonate. Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to quetiapine during pregnancy [see Use in Specific Populations ( 8.1 )]. Infertility Advise females of reproductive potential that quetiapine may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversible [see Use in Specific Populations ( 8.3 )]. Need for Comprehensive Treatment Program Quetiapine is indicated as an integral part of a total treatment program for adolescents with schizophrenia and pediatric bipolar disorder that may include other measures (psychological, educational, and social). Effectiveness and safety of quetiapine have not been established in pediatric patients less than 13 years of age for schizophrenia or less than 10 years of age for bipolar mania. Appropriate educational placement is essential and psychosocial intervention is often helpful. The decision to prescribe atypical antipsychotic medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms [ see Indications and Usage ( 1.3 ) ]. Brands listed are the trademarks of their respective owners. For Medication Guide, please visit: http://www.ascendlaboratories.com/mg/quetiapinetab.pdf

MEDICATION GUIDE

SPL Medguide Section

Quetiapine Tablets, USP (kwe-TYE-a-peen) Read this Medication Guide before you start taking quetiapine tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. What is the most important information I should know about quetiapine? Quetiapine may cause serious side effects, including: 1 . risk of death in the elderly with dementia. Medicines like quetiapine can increase the risk of death in elderly people who have memory loss (dementia). Quetiapine 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 : o all risks and benefits of treatment with antidepressant medicines. o all treatment choices for depression or other serious mental illness Antidepressant medications 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? o 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. o Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. o 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? Quetiapine is a prescription medicine used to treat: schizophrenia in people 13 years of age or older bipolar disorder in adults, including: depressive episodes associated with bipolar disorder manic episodes associated with bipolar I disorder alone or with lithium or divalproex long-term treatment of bipolar I disorder with lithium or divalproex manic episodes associated with bipolar I disorder in children ages 10 to 17 years old. It is not known if quetiapine is safe and effective in children under 10 years of age. What should I tell my healthcare provider before taking quetiapine? Before you take quetiapine, tell your healthcare provider if you have or have had: diabetes or high blood sugar in you or your family. Your healthcare provider should check your blood sugar before you start quetiapine, and also during therapy high levels of total cholesterol, triglycerides or LDL-cholesterol, or low levels of HDL-cholesterol low or high blood pressure low white blood cell count cataracts seizures abnormal thyroid tests high prolactin levels heart problems liver problems any other medical condition pregnancy or plans to become pregnant. It is not known if quetiapine will harm your unborn baby. If you become pregnant while receiving quetiapine tablets, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or go to http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ breast-feeding or plans to breast-feed. Quetiapine can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you receive quetiapine tablets. if you have or have had a condition where you cannot completely empty your bladder (urinary retention), have an enlarged prostate, or constipation, or increased pressure inside your eyes Tell the healthcare provider about all the medicines that you take or recently have taken including prescription medicines, over-the-counter medicines, herbal supplements, and vitamins. Quetiapine and other medicines may affect each other causing serious side effects. Quetiapine may affect the way other medicines work, and other medicines may affect how quetiapine works. Tell your healthcare provider if you are having a urine drug screen because quetiapine may affect your test results. Tell those giving the test that you are taking quetiapine. How should I take quetiapine? Take quetiapine exactly as your healthcare provider tells you to take it. Do not change the dose yourself. Take quetiapine by mouth, with or without food. If you feel you need to stop quetiapine, talk with your healthcare provider first . If you suddenly stop taking quetiapine, you may have side effects such as trouble sleeping or trouble staying asleep (insomnia), nausea, and vomiting. If you miss a dose of quetiapine, take it as soon as you remember. If you are close to your next dose, skip the missed dose. Just take the next dose at your regular time. Do not take 2 doses at the same time unless your healthcare provider tells you to. If you are not sure about your dosing, call your healthcare provider. What should I avoid while taking quetiapine? Do not drive, operate machinery, or do other dangerous activities until you know how quetiapine affects you. Quetiapine may make you drowsy. Avoid getting overheated or dehydrated. Do not over-exercise. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much or heavy clothing. Drink plenty of water. Do not drink alcohol while taking quetiapine. It may make some side effects of quetiapine worse. What are possible side effects of quetiapine? Quetiapine can cause serious side effects, including: See “What is the most important information I should know about quetiapine?” stroke that can lead to death can happen in elderly people with dementia who take medicines like quetiapine neuroleptic malignant syndrome (NMS). NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including quetiapine. NMS can cause death and must be treated in a hospital. Call your healthcare provider...

Storage

STORAGE AND HANDLING SECTION

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

Quetiapine Fumarate

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Quetiapine Fumarate

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL