Quetiapine Fumarate Tablets

Schizophrenia

Quetiapine tablets USP are indicated for the treatment of schizophrenia. The efficacy of quetiapine tablets USP in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents (13 to 17 years). The effectiveness of quetiapine tablets USP for the maintenance treatment of schizophrenia has not been systematically evaluated in controlled clinical trials [see CLINICAL STUDIES (14.1)].

Bipolar Disorder

Quetiapine tablets USP are indicated for the acute treatment of manic episodes associated with bipolar I disorder, both as monotherapy and as an adjunct to lithium or divalproex. Efficacy was established in two 12-week monotherapy trials in adults, in one 3-week adjunctive trial in adults, and in one 3-week monotherapy trial in pediatric patients (10 to 17 years) [see CLINICAL STUDIES (14.2)].

Quetiapine tablets USP are indicated as monotherapy for the acute treatment of depressive episodes associated with bipolar disorder. Efficacy was established in two 8-week monotherapy trials in adult patients with bipolar I and bipolar II disorder [see CLINICAL STUDIES (14.2)].

Quetiapine tablets USP are indicated for the maintenance treatment of bipolar I disorder, as an adjunct to lithium or divalproex. Efficacy was established in two maintenance trials in adults. The effectiveness of quetiapine tablets USP as monotherapy for the maintenance treatment of bipolar disorder has not been systematically evaluated in controlled clinical trials  [see CLINICAL STUDIES (14.2)].

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.

Important Administration Instructions

Quetiapine tablets USP can be taken with or without food.

Recommended Dosing

The recommended initial dose, titration, dose range and maximum quetiapine dose for each approved indication is displayed in Table 1. 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 and 14.2)].

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 (14.2)].

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 CLINICAL PHARMACOLOGY (12.3)]. When indicated, dose escalation should be performed with caution in these patients.

Elderly patients should be started on quetiapine 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 25 mg/day. The dose should be increased daily in increments of 25 mg/day to 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.

Dose Modifications when used with CYP3A4 Inhibitors

Quetiapine 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 quetiapine should be increased by 6 fold [see CLINICAL PHARMACOLOGY (12.3) and DRUG INTERACTIONS (7.1)].

Dose Modifications when used with CYP3A4 Inducers

Quetiapine 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 to 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 tolerability of the individual patient. When the CYP3A4 inducer is discontinued, the dose of quetiapine should be reduced to the original level within 7 to 14 days [see CLINICAL PHARMACOLOGY (12.3) and DRUG INTERACTIONS (7.1)].

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 quetiapine for more than one week, the initial dosing schedule should be followed. When restarting patients who have been off quetiapine for less than one week, gradual dose escalation may not be required and the maintenance dose may be re-initiated.

Switching from Antipsychotics

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

Human 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 reactions. 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 and sedation, tachycardia and hypotension. 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. There were also very rare reports of overdose of quetiapine alone resulting in death or coma.

Management of Overdosage

In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizure or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients with acute overdosage of quetiapine. Similarly it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of quetiapine, resulting in problematic hypotension.

There is no specific antidote to quetiapine. Therefore, appropriate supportive measures should be instituted. The possibility of multiple drug involvement should be considered. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of quetiapine-induced alpha blockade). In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.

See FDA-approved patient labeling (MEDICATION GUIDE)

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with quetiapine and should counsel them in its appropriate use. A patient Medication Guide about "Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions" is available for quetiapine. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

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 [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 and Nursing

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with quetiapine [see USE IN SPECIFIC POPULATIONS (8.1) and (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)].

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States.

MADE IN INDIA. 

Rev: October 2017                                                                                         ID#: 253002

MEDICATION GUIDE

Quetiapine (kwe-TYE-a-peen) Tablets USP

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 tablets?

Quetiapine tablets 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 tablets are 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:
  • all risks and benefits of treatment with antidepressant medicines.
  • 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?
  • 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.
  • Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
  • 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 tablet?

Quetiapine tablet 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 tablet is safe and effective in children under 10 years of age.

What should I tell my healthcare provider before taking quetiapine tablets?

Before you take quetiapine tablets, 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 tablets 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 tablets will harm your unborn baby.
• Breast-feeding or plans to breast-feed. Quetiapine can pass into your breast milk. You and your healthcare provider should decide if you will take quetiapine tablets or breast-feed. You should not do both.

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 tablets and other medicines may affect each other causing serious side effects. Quetiapine tablets may affect the way other medicines work, and other medicines may affect how quetiapine tablet 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 tablets.

How should I take quetiapine tablets?

• Take quetiapine tablets exactly as your healthcare provider tells you to take it. Do not change the dose yourself.
• Take quetiapine tablets by mouth, with or without food.
• If you feel you need to stop quetiapine tablets, talk with your healthcare provider first. If you suddenly stop taking quetiapine tablets, you may have side effects such as trouble sleeping or trouble staying asleep (insomnia), nausea, and vomiting.
• If you miss a dose of quetiapine tablets, 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 tablets?

• Do not drive, operate machinery, or do other dangerous activities until you know how quetiapine tablet affects you. Quetiapine tablets 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 tablets. It may make some side effects of quetiapine tablets worse.

What are possible side effects of quetiapine tablets?

Quetiapine tablets can cause serious side effects, including:

• See "What is the most important information I should know about quetiapine tablets?"
• stroke that can lead to death can happen in elderly people with dementia who take medicines like quetiapine tablets
• neuroleptic malignant syndrome (NMS). NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including quetiapine tablets. NMS can cause death and must be treated in a hospital. Call your healthcare provider right away if you become severely ill and have some or all of these symptoms:
  • high fever
  • excessive sweating
  • rigid muscles
  • confusion
  • changes in your breathing, heartbeat, and blood pressure
• falls can happen in some people who take quetiapine tablets. These falls may cause serious injuries.
• high blood sugar (hyperglycemia). High blood sugar can happen if you have diabetes already or if you have never had diabetes. High blood sugar could lead to:
  • build up of acid in your blood due to ketones (ketoacidosis)
  • coma
  • death

Increases in blood sugar can happen in some people who take quetiapine tablets. Extremely high blood sugar can lead to coma or death. If you have diabetes or risk factors for diabetes (such as being overweight or a family history of diabetes) your healthcare provider should check your blood sugar before you start quetiapine tablets and during therapy.

Call your healthcare provider if you have any of these symptoms of high blood sugar (hyperglycemia) while taking quetiapine tablets:

• feel very thirsty
• need to urinate more than usual
• feel very hungry
• feel weak or tired
• feel sick to your stomach
• feel confused, or your breath smells fruity

• high fat levels in your blood (increased cholesterol and triglycerides). High fat levels may happen in people treated with quetiapine tablets. You may not have any symptoms, so your healthcare provider may decide to check your cholesterol and triglycerides during your treatment with quetiapine tablets.
• increase in weight (weight gain). Weight gain is common in people who take quetiapine tablets so you and your healthcare provider should check your weight regularly. Talk to your healthcare provider about ways to control weight gain, such as eating a healthy, balanced diet, and exercising.
• movements you cannot control in your face, tongue, or other body parts (tardive dyskinesia). These may be signs of a serious condition. Tardive dyskinesia may not go away, even if you stop taking quetiapine tablets. Tardive dyskinesia may also start after you stop taking quetiapine tablets.
• decreased blood pressure (orthostatic hypotension), including lightheadedness or fainting caused by a sudden change in heart rate and blood pressure when rising too quickly from a sitting or lying position.
• increases in blood pressure in children and teenagers. Your healthcare provider should check blood pressure in children and adolescents before starting quetiapine tablets and during therapy.
• low white blood cell count
• cataracts
• seizures
• abnormal thyroid tests. Your healthcare provider may do blood tests to check your thyroid hormone level.
• increases in prolactin levels. Your healthcare provider may do blood tests to check your prolactin levels.
• sleepiness, drowsiness, feeling tired, difficulty thinking and doing normal activities
• increased body temperature
• difficulty swallowing
• trouble sleeping or trouble staying asleep (insomnia), nausea, or vomiting if you suddenly stop taking quetiapine tablets. These symptoms usually get better 1 week after you start having them.

The most common side effects of quetiapine tablets include:

In Adults:

• dry mouth
• dizziness
• weakness
• abdominal pain
• constipation
• sore throat
• difficulty moving

In Children and Adolescents:

• nausea
• dry mouth
• weight gain
• increased appetite
• vomiting
• rapid heart beat

These are not all the possible side effects of quetiapine tablets. For more information, ask your healthcare provider or pharmacist.

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

You may also report side effects to Lupin Pharmaceuticals, Inc. at 1-800-399-2561.

How should I store quetiapine tablets?

• Store quetiapine tablets at room temperature, between 68°F to 77°F (20°C to 25°C).
• Keep quetiapine tablets and all medicines out of the reach of children.

General information about the safe and effective use of quetiapine tablets.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use quetiapine tablets for a condition for which it was not prescribed. Do not give quetiapine tablets to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about quetiapine tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about quetiapine tablets that is written for health professionals.

For more information, go to www.lupinpharmaceuticals.com, or call 1-800-399-2561.

What are the ingredients in quetiapine tablets?

Active ingredient: quetiapine fumarate

Inactive ingredients: dibasic calcium phosphate dihydrate, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium starch glycolate and titanium dioxide. The 25 mg tablets contain iron oxide red and iron oxide black; and the 100 mg and 400 mg tablets contain only iron oxide yellow.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:      

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States.

MADE IN INDIA.

Rev: April 2017                                                                                               ID#: 251262

Quetiapine Tablets USP, 25 mg

Rx only

NDC 68180-445-01

Container Label: Bottle of 100 Tablets

Quetiapine Tablets USP, 50 mg

Rx only

NDC 68180-446-01

Container Label: Bottle of 100 Tablets

Quetiapine Tablets USP, 100 mg

Rx only

NDC 68180-447-01

Container Label: Bottle of 100 Tablets

Quetiapine Tablets USP, 200 mg

Rx only

NDC 68180-448-01

Container Label: Bottle of 100 Tablets

Quetiapine Tablets USP, 300 mg

Rx only

NDC 68180-449-01

Container Label: Bottle of 100 Tablets

Quetiapine Tablets USP, 400 mg

Rx only

NDC 68180-450-01

Container Label: Bottle of 100 Tablets