Quetiapine

Quetiapine may cause side effects. Tell your doctor if any of these symptoms or those listed in the SPECIAL PRECAUTIONS section are severe or do not go away:

• dizziness, feeling unsteady, or having trouble keeping your balance
• pain in the joints, back, neck, or ears
• weakness
• dry mouth
• vomiting
• indigestion
• constipation
• gas
• stomach pain or swelling
• increased appetite
• excessive weight gain
• stuffy nose
• headache
• pain
• irritability
• difficulty thinking or concentrating
• difficulty speaking or using language
• loss of coordination
• unusual dreams
• numbness, burning, or tingling in the arms or legs
• missed menstrual periods
• breast enlargement in males
• discharge from the breasts
• decreased sexual desire or ability

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS section, call your doctor immediately or get emergency medical treatment:

• fainting
• falling
• seizures
• changes in vision
• uncontrollable movements of your arms, legs, tongue, face, or lips
• painful erection of the penis that lasts for hours
• fever
• muscle stiffness, pain, or weakness
• excess sweating
• fast or irregular heartbeat
• confusion
• unusual bleeding or bruising
• sore throat, fever, chills, difficult or painful urination and other signs of infection
• hives
• rash
• blisters
• tightening of the neck muscles or the throat
• tongue sticking out
• difficulty breathing or swallowing

Quetiapine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Quetiapine may cause cataracts. You will need to have eye exams to check for cataracts at the beginning of your treatment and every six months during your treatment. Talk to your doctor about the risks of taking quetiapine.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

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Serious side effects have been reported with quetiapine including: Also see “Quetiapine Precautions” section.

• 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 doctor right away if you become severely ill and have some or all of these symptoms:
• Tardive dyskinesia: Tell your healthcare provider about any movements you cannot control in your face, tongue, or other body parts. These may be signs of a serious condition. Tardive dyskinesia may not go away, even if you stop taking quetiapine. Tardive dyskinesia may also start after you stop taking quetiapine.
• Orthostatic hypotension (decreased blood pressure): 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: reported in children and teenagers. Your healthcare provider should check blood pressure in children and adolescents before starting quetiapine and during therapy. Quetiapine is not approved for patients under 18 years of age.
• 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.
• Increases in liver enzymes: Your healthcare provider may do blood tests to check your liver enzyme levels.
• Long lasting and painful erection
• Difficulty swallowing
• high fever
• excessive sweating
• rigid muscles
• confusion
• changes in your breathing, heartbeat, and blood pressure

Common possible side effects with quetiapine include:

• drowsiness
• dry mouth
• constipation
• dizziness
• increased appetite
• upset stomach
• weight gain
• fatigue
• disturbance in speech and language
• stuffy nose

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

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

Before taking 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
• breastfeeding or plans to breastfeed

Tell the healthcare provider about all the medicines that you take or recently have taken including prescription medicines, nonprescription medicines, herbal supplements and vitamins.

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks) largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Quetiapine is not approved for the treatment of patients with dementia-related psychosis.

SUICIDALITY AND ANTIDEPRESSANT DRUGS

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of quetiapine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. 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 in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Quetiapine is not approved for use in pediatric patients.

Some young people have thoughts about suicide when first taking quetiapine. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

Quetiapine is not approved for use in psychotic conditions related to dementia. Quetiapine may increase the risk of death in older adults with dementia-related conditions.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Avoid drinking alcohol. Dangerous side effects could occur.

Quetiapine may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Dizziness or severe drowsiness can cause falls, fractures, or other injuries.

Avoid becoming overheated or dehydrated during exercise and in hot weather. You may be more prone to heat stroke.

Quetiapine can cause a serious heart problem if you use certain medicines at the same time, including antibiotics, antidepressants, heart rhythm medicine, antipsychotic medicines, and medicines to treat cancer, malaria, HIV or AIDS. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with quetiapine.

Taking quetiapine with other drugs that make you sleepy or slow your breathing can cause dangerous or life-threatening side effects. Ask your doctor before taking a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Many drugs can interact with quetiapine. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

• antibiotic or antifungal medicine;

• antiviral medicine to treat hepatitis or HIV/AIDS;

• heart or blood pressure medicine;

• medicine to treat mental illness;

• St. John's wort;

• seizure medicine; or

• tuberculosis medicine.

This list is not complete and many other drugs can interact with quetiapine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

CrCl 10 to 30 mL/minute had 25% lower clearance; plasma concentrations were within the range of concentrations seen in normal subjects.

Obsessive compulsive disorder

Data from a limited number of clinical trials suggest that quetiapine augmentation may be beneficial for the treatment of obsessive compulsive disorder [Dold 2013], [Skapinakis 2007]. Additional data may be necessary to further define the role of quetiapine in this condition.

Based on the American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder and the World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Obsessive-Compulsive Disorder, antipsychotics given as augmentation in treatment-resistant obsessive compulsive disorder are effective and recommended in the management of this condition in patients who have a partial response to initial treatment; however, evidence supporting quetiapine is limited.

Delirium in the critically ill patient

Data from a limited number of patients in a prospective, randomized, double-blind, placebo-controlled study suggest that quetiapine may be beneficial in critically ill patients with delirium [Devlin 2010]. Additional data may be necessary to further define the role of quetiapine for this condition.

Delusional parasitosis

Data from a limited number of patients studied in case reports suggest that quetiapine may be beneficial for the treatment of delusional parasitosis [Freudenmann 2008], [Milia 2008]. Additional data may be necessary to further define the role of quetiapine in this condition.

Generalized anxiety disorder

Data from double-blind, randomized, placebo-controlled trials support the use of extended release quetiapine as monotherapy in the treatment of generalized anxiety disorder [Bandelow 2010], [Katzman 2011], [Khan 2011], [Merideth 2012], [Mezhebovsky 2013], [Stein 2011]. Additional data may be necessary to further define the role of quetiapine in this population.

Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the treatment of anxiety, obsessive-compulsive, and post-traumatic stress disorders, quetiapine is effective and recommended in the management of generalized anxiety disorder.

Post-traumatic stress disorder

Data from a limited number of patients in open-label clinical trials suggest that mono- or adjunctive therapy with quetiapine may be beneficial for the treatment of post-traumatic stress disorder in patients who have had an inadequate response with antidepressants [Ahearn 2006], [Hamner 2003], [Kozaric-Kovacic 2007]. Additional data may be necessary to further define the role of quetiapine in this condition.

Based on the American Psychiatric Association (APA) practice guidelines for the Treatment of Patients with Posttraumatic Stress Disorder and the World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Post-Traumatic Stress Disorder, therapy with quetiapine is suggested as a treatment option for patients when concomitant psychotic symptoms are present or when first-line approaches have been ineffective in controlling symptoms; however, evidence supporting use is greater for other antipsychotic agents including risperidone and olanzapine.

Psychosis/agitation associated with dementia

Data from a randomized, double-blind, placebo-controlled study supports the use of quetiapine in the treatment of psychosis/agitation in dementia [Zhong 2007]; data from a limited number of patients in open-label trials also suggest quetiapine may be beneficial in the treatment of psychosis/agitation in Alzheimer dementia [Fujikawa 2004], [McManus 1999], [Scharre 2002]. Additional trials may be necessary to further define the role of quetiapine in this condition.

Based on the American Psychiatric Association (APA) practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia, antipsychotics, such as quetiapine, may be considered for the treatment of agitation and psychosis in certain patients; however, evidence for efficacy is modest and use should be limited to patients whose symptoms are dangerous, severe, or cause significant patient distress due to safety risks associated with antipsychotic use. Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the Biological Treatment of Alzheimer Disease and Other Dementias, drug treatment with quetiapine for behavioral and psychological aspects (including hyperactivity and psychosis) is recommended at low doses and for short durations, as a last option after addressing causative factors and using psychosocial interventions.

Psychosis in Parkinson disease

Data from a limited number of patients in two randomized, blinded-rater trials suggest that quetiapine may be beneficial in the treatment of psychosis in patients with Parkinson disease [Merims 2006], [Morgante 2004]. Additional trials may be necessary to further define the role of quetiapine in this condition.

Based on the American Academy of Neurology guidelines for the treatment of condition depression, psychosis, and dementia in Parkinson disease, quetiapine given for psychosis in Parkinson disease may be effective and can be considered in the management of this condition.

Administer extended release tablet without food or with a light meal (≤300 calories).

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Monitor therapy

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Amifampridine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Bilastine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: QUEtiapine may increase serum concentrations of the active metabolite(s) of CarBAMazepine. CarBAMazepine may decrease the serum concentration of QUEtiapine. Management: Quetiapine dose increases to as much as 5 times the regular dose may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7 to 14 days of discontinuing carbamazepine. Consider therapy modification

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Clarithromycin: May enhance the QTc-prolonging effect of QUEtiapine. Clarithromycin may increase the serum concentration of QUEtiapine. Avoid combination

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7-14 days of discontinuing the inducer. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce the quetiapine dose to one sixth of the regular dose following strong CYP3A4 inhibitor initiation. In patients receiving strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and up-titrate as needed. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Monitor therapy

Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Hydroxychloroquine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Indapamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Consider therapy modification

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methadone: May enhance the QTc-prolonging effect of QUEtiapine. QUEtiapine may increase the serum concentration of Methadone. Avoid combination

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylphenidate: May enhance the adverse/toxic effect of Antipsychotic Agents. Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Mizolastine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: May diminish the therapeutic effect of Antipsychotic Agents. Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Probucol: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Promazine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Ritonavir: May increase the serum concentration of QUEtiapine. Management: The ritonavir Canadian labeling states this combination should not be used. U.S. labeling recommends using an alternative when possible; if the combination must be used, quetiapine dose reductions are needed. Consider therapy modification

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

St John's Wort: QUEtiapine may enhance the serotonergic effect of St John's Wort. This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of QUEtiapine. Management: Quetiapine dose increases to as much as 5 times the regular dose may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7-14 days of discontinuing the inducer. Monitor closely. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Teneligliptin: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Vinflunine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Xipamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse events were observed in animal reproduction studies. Quetiapine crosses the placenta and can be detected in cord blood (Newport 2007). Congenital malformations have not been observed in humans (based on limited data). Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization. Quetiapine may cause hyperprolactinemia, which may decrease reproductive function in both males and females.

Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers 2009). The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy is limited and routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to a typical antipsychotic that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008).

Healthcare providers are encouraged to enroll women 18-45 years of age exposed to quetiapine during pregnancy in the Atypical Antipsychotics Pregnancy Registry (1-866-961-2388 or http://www.womensmentalhealth.org/pregnancyregistry).

MANIA Associated with Bipolar Disorder:

-Immediate-release (IR) tablets:
Day 1: Twice daily dosing totaling 100 mg/day orally
Day 2: Twice daily dosing totaling 200 mg/day orally
Day 3: Twice daily dosing totaling 300 mg/day orally
Day 4: Twice daily dosing totaling 400 mg/day orally
-Further dose adjustments should be in increments of no greater than 200 mg/day
Recommended dose: 400 to 800 mg per day in divided doses
Maximum dose: 800 mg/day

-Extended-release (XR) tablets:
Day 1: 300 mg orally once a day
Day 2: 600 mg orally once a day
Recommended dose: 400 to 800 mg/day
Maximum dose: 800 mg/day

DEPRESSIVE Episodes Associated with Bipolar Disorder:

-Immediate-release (IR) tablets:
Day 1: 50 mg orally once a day at bedtime
Day 2: 100 mg orally once a day at bedtime
Day 3: 200 mg orally once a day at bedtime
Day 4: 300 mg orally once a day at bedtime
Recommended dose: 300 mg/day
Maximum dose: 300 mg/day

-Extended-release (XR) tablets:
Day 1: 50 mg orally once a day
Day 2: 100 mg orally once a day
Day 3: 200 mg orally once a day
Day 4: 300 mg orally once a day
Recommended dose: 300 mg/day
Maximum dose: 300 mg/day

MAINTENANCE TREATMENT:
-As adjunct to lithium or divalproex: 400 to 800 mg orally/day (IR should be dosed twice a day; XR once a day)
-Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Comments:
-After initial dose titration, adjustments can be made upwards or downwards depending on clinical response and tolerability.
-When restarting this drug in patients who have been off therapy for more than 1 week, the initial dosing schedule should be followed; for patients who have been off this drug for less than 1 week, the maintenance dose may be reinitiated.

Uses:
-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;
-For the acute treatment of depressive episodes associated with bipolar disorder;
-For the maintenance treatment of bipolar 1 disorder as an adjunct to lithium or divalproex.

Extended-release (XR) tablets:
-Initial dose: 50 mg orally once a day
-Dose increases should be made in increments of 50 mg/day depending on clinical response and tolerability
Recommended dose: 150 mg to 300 mg orally once a day
Maximum dose: 300 mg/day

Comments:
-Consider slower dose titration and careful monitoring during the initial dosing period; lower target doses may be appropriate in elderly patients, especially those who are debilitated or have a predisposition to hypotensive reactions.
-When restarting this drug in patients who have been off therapy for more than 1 week, the initial dosing schedule should be followed.
-Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Use: As adjunctive therapy to antidepressants for the treatment of major depressive disorder.

No adjustment recommended

US BOXED WARNINGS: 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.
-This drug is not approved for use in patients with dementia-related psychosis.
SUICIDAL THOUGHTS AND BEHAVIORS:
-Antidepressants may increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. There was no increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24 and there was a reduction in risk with antidepressant use in patients aged 65 and older.
-Patients of all ages who are started on antidepressant therapy should be monitored for suicidal thoughts and behaviors; families and caregivers should be advised of the need for vigilance.

Safety and efficacy for the treatment of schizophrenia have not been established in patients younger than 13 years; safety and efficacy in the maintenance treatment of schizophrenia has not been established in patients less than 18 years.

Safety and efficacy for the treatment of bipolar mania have not been established in patients younger than 10 years; safety and effectiveness in patients with bipolar depression or for the maintenance treatment of bipolar disorder has not been established in patients less than 18 years.

Consult WARNINGS section for additional precautions.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Weakness, lack of energy, headache, dry mouth, constipation, weight gain, changes in cholesterol and triglyceride levels.
• Drowsiness or dizziness that may affect your ability to drive or operate machinery or perform hazardous tasks. Alcohol may enhance these effects.
• Other common side effects include chills, cold sweats, confusion, and agitation.
• Some people, such as seniors, the frail, and those with a predisposition to low blood pressure may be more sensitive to the effects of quetiapine. A slower rate of dose titration and lower target dosages may be needed.
• A drop in blood pressure on standing, particularly during the initial dose titration period. To counteract this effect, the dosage of quetiapine may need to be reduced then titrated back up slowly. May not be suitable for people with known cardiovascular disease (history of a heart attack, angina, heart failure, or arrhythmia), stroke or people at risk of dehydration. May increase blood pressure in adolescents.
• May not be suitable for people with diabetes or may precipitate diabetes especially in those with pre-existing risk factors (such as obesity and lack of physical activity).
• People with liver disease or taking other medications that may interact with quetiapine may need a dosage adjustment. Only one-sixth of the quetiapine dose is needed when taken with drugs that are CYP3A4 inhibitors (for example, ketoconazole, ritonavir, or nefazodone). A dosage increase of up to fivefold is recommended when quetiapine is taken with CYP3A4 inducers (such as phenytoin, carbamazepine, rifampin, or St John's wort).
• The use of antipsychotics in elderly patients with dementia has been associated with an increased risk of death, mostly due to cardiovascular or infectious causes. Quetiapine is not FDA-approved for use in elderly patients with dementia.
• May not be suitable for some people including those with cataracts, heart disease, high cholesterol, thyroid dysfunction, abnormal blood counts, high prolactin levels, or liver disease.
• Antipsychotics such as quetiapine have been associated with a serious syndrome called Neuroleptic Malignant Syndrome; symptoms include high body temperature, muscle rigidity, and mental disturbances. Seek urgent medical advice if these symptoms develop.
• As with other antipsychotics and antidepressants, quetiapine may increase the risk of suicidal thoughts or behavior, particularly in adolescents.
• May cause a discontinuation syndrome if abruptly stopped; symptoms include nausea, insomnia, headache, diarrhea, vomiting, irritability, and dizziness. Gradual withdrawal is advised.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

• Immediate-release tablets can be administered either with or without food. Administer extended release tablets without food or alternatively, following a light meal (less than 300 calories). Swallow extended-release tablets whole, do not crush or chew.
• Most people are started on a lower dosage which is gradually increased to reduce the risk of side effects such as drowsiness and low blood pressure.
• Get up slowly when going from a lying down or sitting position to standing.
• Can be given once daily, or divided into three doses per day depending on response and tolerability.
• Talk to your doctor if you experience any changes in your mood or you develop anxiety, panic attacks, insomnia, get easily agitated, or have thoughts of suicide.
• Seek urgent medical advice if you develop a high temperature, muscle rigidity or confusion.
• Do not drive or operate machinery or perform hazardous tasks if quetiapine makes you sleepy or impairs your mental functioning.
• Your doctor may need to monitor your blood sugar levels before quetiapine initiation and periodically thereafter as occasionally quetiapine can precipitate diabetes in some people. Talk to your doctor if you feel excessively thirsty or are urinating more than normal.
• Your doctor may also need to monitor your lipid levels on quetiapine initiation and periodically thereafter as quetiapine may increase LDL-cholesterol and triglyceride levels.
• Quetiapine may make you gain weight. Ensure you eat healthy foods and keep up your physical activity levels as recommended by your doctor.
• Antipsychotic agents, such as quetiapine, have been associated with a disruption in the ability to regulate body temperature. If you are taking quetiapine, avoid strenuous exercise, exposure to extreme heat, or dehydration.
• Be careful when going from a sitting or lying down position to a standing position as quetiapine may make you feel dizzy or light headed, which may increase your risk of falling.
• Do not take any other medication, including over-the-counter medication, without asking a doctor or pharmacist first if it is alright to take with quetiapine.
• Do not stop taking this medicine suddenly. If you feel you are not gaining any benefit from this drug, or the side effects are intolerable, talk with your doctor about slowly discontinuing it.

Based on milk samples from a mother who received quetiapine 200 mg daily throughout pregnancy and postpartum, it is estimated that an exclusively breastfed infant would receive 0.09% to 0.43% of a weight-adjusted maternal dose. Limited long-term follow-up of infants exposed to this drug during breastfeeding have shown generally normal development. However, due to the potential for serious adverse reactions in nursing infants and a lack of robust data, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Use is not recommended; a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes Comments: If this drug is used, monitor infants for drowsiness and developmental milestones.