Seroquel XR Side Effects

Generic Name: quetiapine,quetiapine fumarate

Please note - some side effects for Seroquel XR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Seroquel XR - for the Consumer

Seroquel XR Sustained-Release Tablets

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Seroquel XR Sustained-Release Tablets:

Constipation; dizziness; drowsiness; dry mouth; increased appetite; joint pain; light-headedness; stomach upset; stuffy nose; tiredness; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Seroquel XR Sustained-Release Tablets:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); confusion; difficult or painful urination; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; hallucinations; increased saliva production or drooling; increased sweating; memory loss; menstrual changes; muscle pain, stiffness, or weakness; new or worsening mental or mood changes (eg, aggressiveness, agitation, anxiety, depression, exaggerated feeling of well-being, hostility, impulsiveness, inability to sit still, irritability, panic attacks, restlessness); numbness, burning, or tingling; persistent, painful erection; red, swollen, blistered, or peeling skin; seizures; severe or prolonged dizziness, light-headedness, or headache; shortness of breath; suicidal thoughts or actions; swelling of the hands, legs, or feet; symptoms of high blood sugar (eg, increased hunger, thirst, or urination; unusual weakness); tremor; trouble concentrating, speaking, or swallowing; trouble sleeping; trouble walking or standing; uncontrolled muscle movements (eg, arm or leg movements, jerking or twisting, twitching of the face or tongue); vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Top

Seroquel XR Side Effects - for the Professional

Seroquel XR

Clinical Studies Experience

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

The information below is derived from a clinical trial database for Seroquel XR consisting of approximately 3400 patients exposed to Seroquel XR for the treatment of Schizophrenia, Bipolar Disorder, and Major Depressive Disorder in placebo-controlled trials. This experience corresponds to approximately 1020.1 patient-years. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, body weights, laboratory analyses and ECG results.

Adverse reactions during exposure were obtained by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized event categories. In the tables and tabulations that follow, standard MedDRA terminology has been used to classify reported adverse reactions.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials

Schizophrenia: There was no difference in the incidence and type of adverse reactions associated with discontinuation (6.4% (61/951) for Seroquel XR vs. 7.5% (24/319) for placebo) in a pool of controlled Schizophrenia trials. There were no adverse reactions leading to discontinuation that occurred at an incidence of ≥ 2% for Seroquel XR in Schizophrenia trials.

Bipolar Disorder:

Mania: In a single clinical trial in patients with bipolar mania, 4.6% (7/151) of patients on Seroquel XR discontinued due to an adverse reaction compared to 8.1% (13/160) on placebo. There were no adverse reactions leading to discontinuation that occurred at an incidence of ≥ 2% for Seroquel XR in the Bipolar Mania trial.

Depression: In a single clinical trial in patients with bipolar depression, 14% (19/137) of patients on Seroquel XR discontinued due to an adverse reaction compared to 4% (5/140) on placebo. Somnolence∗ was the only adverse reaction leading to discontinuation that occurred at an incidence of ≥ 2% in Seroquel XR in the Bipolar Depression trial.

∗ The adverse reaction term “somnolence” includes both “somnolence” and “sedation.”

MDD, Adjunctive Therapy: In adjunctive therapy clinical trials in patients with MDD, 12.1% (76/627) of patients on Seroquel XR discontinued due to adverse reaction compared to 1.9% (6/309) on placebo. Somnolence* was the only adverse reaction leading to discontinuation that occurred at an incidence of ≥ 2% in Seroquel XR in MDD trials.

Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials:

In short-term placebo-controlled studies for schizophrenia the most commonly observed adverse reactions associated with the use of Seroquel XR (incidence of 5% or greater) and observed at a rate on Seroquel XR at least twice that of placebo were somnolence (25%), dry mouth (12%), dizziness (10%), and dyspepsia (5%).

Adverse Reactions Occurring at an Incidence of 1% or More Among Seroquel XR Treated Patients in Short-Term, Placebo-Controlled Trials

Table 11 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy of schizophrenia (up to 6 weeks) in 1% or more in patients treated with Seroquel XR (doses ranging from 300 to 800 mg/day) where the incidence in patients treated with Seroquel XR was greater than the incidence in placebo-treated patients.

Table 11: Treatment-Emergent Adverse Reaction Incidence in 6-Week Placebo-Controlled Clinical Trials for the Treatment of Schizophrenia*

Body System/Preferred Term	Placebo	Seroquel XR
	(n=319)	(n=951)
* Reactions for which the Seroquel XR incidence was 1% or more and equal to or less than placebo are not listed in the table, but included the following: headache, insomnia, nausea, vomiting, diarrhea, stomach discomfort, weight increased, diastolic blood pressure decreased, systolic blood pressure decreased, arthralgia, back pain, pain in extremity, extrapyramidal disorder, agitation, psychotic disorder, sleep disorder, nasal congestion, hypertension. † Somnolence combines adverse reaction terms somnolence and sedation. ‡ Extrapyramidal symptoms that were reported for Seroquel XR or placebo include the terms: akathisia, cogwheel rigidity, drooling, dyskinesia dystonia, extrapyramidal disorder, hypertonia, movement disorder, muscle rigidity, oculogyration, parkinsonism, parkinsonian gait, psychomotor hyperactivity, tardive dyskinesia, restlessness and tremor.
Cardiac Disorders
Tachycardia	1%	3%
Eye Disorders
Vision blurred	1%	2%
Gastrointestinal Disorders
Dry Mouth	1%	12%
Constipation	5%	6%
Dyspepsia	2%	5%
Toothache	0%	2%
General Disorders and Administration Site Conditions
Fatigue	2%	3%
Irritability	0%	1%
Pyrexia	0%	1%
Investigations
Heart Rate Increased	1%	4%
Metabolism and Nutrition Disorders
Increased Appetite	0%	2%
Musculoskeletal and Connective Tissue Disorders
Muscle Spasms	1%	2%
Nervous System Disorders
Somnolence†	10%	25%
Dizziness	4%	10%
Tremor	1%	2%
Akathisia	1%	2%
Extrapyramidal Symptoms‡	5%	8%
Psychiatric Disorders
Anxiety	1%	2%
Schizophrenia	1%	2%
Restlessness	1%	2%
Vascular Disorders
Orthostatic Hypotension	5%	7%
Hypotension	1%	3%

In a 3-week, placebo-controlled study in bipolar mania the most commonly observed adverse reactions associated with the use of Seroquel XR (incidence of 5% or greater) and observed at a rate on Seroquel XR at least twice that of placebo were somnolence (50%), dry mouth (34%), dizziness (10%), constipation (10%), weight gain (7%), dysarthria (5%), and nasal congestion (5%).

Table 12 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy of bipolar mania (up to 3 weeks) in 1% or more of patients treated with Seroquel XR (doses ranging from 400 to 800 mg/day) where the incidence in patients treated with Seroquel XR was greater than the incidence in placebo-treated patients.

Table 12: Treatment-Emergent Adverse Reactions in a 3-Week Placebo-Controlled Clinical Trial for the Treatment of Bipolar Mania*

Body System/Preferred Term	PLACEBO	Seroquel XR
	(n=160)	(n=151)
* Reactions for which the Seroquel XR incidence was 1% or more and equal to or less than placebo are not listed in the table, but included the following: headache, peripheral edema, diarrhea, nausea, vomiting, decreased appetite, muscle spasms, musculoskeletal stiffness, myalgia, tremor, akathisia, insomnia, agitation, nightmare, restlessness, erectile dysfunction, pharyngolaryngeal pain, cough, and hypotension. † Extrapyramidal symptoms that were reported for Seroquel XR or placebo include the terms: akathisia, cogwheel rigidity, dystonia, extrapyramidal disorder, restlessness and tremor. ‡ Somnolence combines adverse reaction terms somnolence and sedation.
Cardiac Disorders
Tachycardia	1%	2%
Eye Disorders
Vision blurred	1%	2%
Gastrointestinal Disorders
Dry Mouth	7%	34%
Constipation	3%	10%
Dyspepsia	4%	7%
Toothache	1%	3%
General Disorders and Administration Site Conditions
Fatigue	4%	7%
Sluggishness	1%	2%
Pain	0%	1%
Investigations
Weight Gain	1%	7%
Heart Rate Increased	0%	3%
Injury, Poisoning And Procedural Complications
Contusion	0%	1%
Metabolism And Nutrition Disorders
Increased Appetite	2%	4%
Nervous System Disorders
Extrapyramidal Symptoms†	4%	7%
Somnolence‡	12%	50%
Dizziness	4%	10%
Dysarthria	0%	5%
Lethargy	1%	2%
Postural Dizziness	0%	1%
Musculoskeletal And Connective Tissue Disorders
Back Pain	2%	3%
Arthralgia	0%	1%
Psychiatric Disorders
Abnormal Dreams	0%	3%
Bipolar I Disorder	0%	1%
Respiratory, Thoracic and Mediastinal Disorders
Nasal Congestion	1%	5%
Dry Throat	0%	1%
Vascular Disorders
Orthostatic Hypotension	0%	3%

In the 8-week placebo-controlled bipolar depression study, the most commonly observed adverse reactions associated with the use of Seroquel XR (incidence of 5% or greater) and observed at a rate on Seroquel XR at least twice that of placebo were somnolence (52%), dry mouth (37%), increased appetite (12%), weight gain (7%), dyspepsia (7%), and fatigue (6%).

Table 13: enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during acute therapy of bipolar depression (up to 8 weeks) in 1% or more of patients treated with Seroquel XR 300 mg/day where the incidence in patients treated with Seroquel XR was greater than the incidence in placebo-treated patients.

Table 13: Treatment-Emergent Adverse Reactions in an 8-Week Placebo-Controlled Clinical Trial for the Treatment of Bipolar Depression*

Body System/Preferred Term	Placebo	Seroquel XR
	(n=140)	(n=137)
* Reactions for which the Seroquel XR incidence was 1% or more and equal to or less than placebo are not listed in the table, but included the following: headache insomnia, nausea, diarrhea, vomiting, nasopharyngitis, upper respiratory tract infection, influenza, pain in extremity, cough and nasal congestion. † Somnolence combines adverse reaction terms somnolence and sedation. ‡ Extrapyramidal symptoms that were reported for Seroquel XR or placebo include the terms: akathisia, dystonia, extrapyramidal disorder, hypertonia, and tremor.
Ear And Labyrinth Disorders
Ear Pain	1%	2%
Gastrointestinal Disorders
Dry Mouth	7%	37%
Constipation	6%	8%
Dyspepsia	1%	7%
Toothache	0%	3%
Abdominal Distension	0%	1%
General Disorders and Administration Site Conditions
Fatigue	2%	6%
Irritability	3%	4%
Immune System Disorders
Seasonal Allergy	1%	2%
Infections And Infestations
Viral Gastroenteritis	1%	4%
Urinary Tract Infection	0%	2%
Sinusitis	1%	2%
Investigations
Weight Gain	1%	7%
Heart Rate Increased	0%	2%
Metabolism and Nutrition Disorder
Increased Appetite	6%	12%
Decreased Appetite	1%	2%
Musculoskeletal And Connective Tissue Disorders
Arthralgia	1%	4%
Back Pain	1%	3%
Muscle Spasms	1%	3%
Myalgia	1%	2%
Neck Pain	0%	2%
Nervous System Disorders
Somnolence†	13%	52%
Extrapyramidal Symptoms‡	1%	4%
Dizziness	11%	13%
Paraesthesia	2%	3%
Disturbance in Attention	1%	2%
Dysarthria	0%	2%
Akathisia	0%	2%
Hypersomnia	0%	2%
Mental Impairment	0%	2%
Migraine	1%	2%
Restless Legs Syndrome	1%	2%
Sinus Headache	1%	2%
Psychiatric Disorders
Abnormal Dreams	0%	3%
Anxiety	1%	2%
Confusional State	0%	2%
Disorientation	0%	2%
Libido Decreased	1%	2%
Renal And Urinary Disorders
Pollakiuria	1%	2%
Respiratory, Thoracic And Mediastinal Disorders
Sinus Congestion	1%	2%
Skin And Subcutaneous Tissue Disorders
Hyperhidrosis	1%	2%
Vascular Disorders
Orthostatic Hypotension	1%	2%

In the 6-week placebo-controlled fixed dose adjunctive therapy clinical trials, for MDD, the most commonly observed adverse reactions associated with the use of Seroquel XR (incidence of 5% or greater and observed at a rate on Seroquel XR and at least twice that of placebo) were somnolence (150 mg: 37%; 300 mg: 43%), dry mouth (150 mg: 27%; 300 mg: 40%), fatigue (150 mg: 14%; 300 mg: 11%), constipation (300 mg only: 11%) and weight increased (300 mg only: 5%).

Table 14 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred during short-term adjunctive therapy of MDD (up to 6 weeks) in 1% or more of patients treated with Seroquel XR (at doses of either 150 mg or 300 mg/day) where the incidence in patients treated with Seroquel XR was greater than the incidence in placebo-treated patients.

Table 14: Treatment-Emergent Adverse Reaction Incidence in Placebo-Controlled Adjunctive Therapy Clinical Trials for the Treatment of MDD by Fixed Dose*

Body System/Preferred Term	Placebo (n=309)	Seroquel XR 150 mg (n=315)	Seroquel XR 300 mg (n=312)
* Reactions for which the Seroquel XR incidence was 1% or more but equal to or less than placebo are not listed in the table, but included the following: headache, insomnia, nausea, disturbance in attention, dysarthria, paraesthesia, tremor, diarrhea, upper abdominal pain, nightmare, nasopharyngitis, sinusitis, decreased appetite, myalgia, arthralgia, pain in extremity, hyperhidrosis, night sweats and nasal congestion. † Somnolence combines adverse event terms somnolence and sedation. ‡ Extrapyramidal symptoms that were reported for Seroquel XR or placebo include the terms: akathisia, cogwheel rigidity, drooling, dyskinesia, extrapyramidal disorder, hypertonia, hypokinesia, psychomotor hyperactivity, restlessness, and tremor.
Ear And Labyrinth Disorders
Vertigo	1%	2%	2%
Eye Disorders
Vision Blurred	1%	2%	1%
Gastrointestinal Disorders
Dry Mouth	8%	27%	40%
Constipation	4%	6%	11%
Nausea	7%	7%	8%
Dyspepsia	2%	2%	3%
Abdominal Distension	0%	0%	1%
Vomiting	1%	3%	1%
General Disorders and Administration Site Conditions
Fatigue	4%	14%	11%
Irritability	3%	4%	2%
Chills	0%	1%	1%
Infections And Infestations
Upper Respiratory Tract Infection	2%	3%	2%
Influenza	0%	2%	1%
Injury, Poisoning And Procedural Complications
Fall	1%	2%	0%
Investigations
Weight Increased	0%	3%	5%
Metabolism And Nutrition Disorders
Increased Appetite	3%	3%	5%
Musculoskeletal And Connective Tissue Disorders
Back pain	1%	3%	3%
Muscle Spasms	1%	2%	1%
Nervous System Disorders
Somnolence†	9%	37%	43%
Dizziness	7%	11%	12%
Extrapyramidal Symptoms‡	4%	4%	6%
Hypersomnia	0%	1%	2%
Dysarthria	0%	1%	1%
Dysgeusia	0%	1%	1%
Lethargy	1%	2%	1%
Akathisia	1%	2%	2%
Psychiatric Disorders
Abnormal Dreams	1%	2%	2%
Anxiety	1%	2%	2%
Restlessness	1%	1%	2%
Libido Decreased	0%	0%	1%
Depression	1%	2%	1%

Adverse Reactions Occurring at an Incidence of 5% or More Among Seroquel XR Treated Patients in Long-Term, Placebo-Controlled Trials

In a longer-term placebo-controlled trial, adult patients with schizophrenia who remained clinically stable on Seroquel XR during open-label treatment for at least 4 months were randomized to placebo (n=103) or to continue on their current Seroquel XR (n=94) for up to 12 months of observation for possible relapse, the adverse reactions reported were generally consistent with those reported in the short-term, placebo-controlled trials. Insomnia (8.5%) and headache (7.4%) were the only adverse events reported by 5% or more patients.

Adverse Reactions that occurred in <5% of patients and were considered drug-related (incidence greater than placebo and consistent with known pharmacology of drug class) in order of decreasing frequency:

heart rate increased, hypotension, weight increased, tremor, akathisia, increased appetite, blurred vision, postural dizziness, pyrexia, dysarthria, dystonia, drooling, syncope, tardive dyskinesia, dysphagia, leukopenia, and rash.

Adverse Reactions in clinical trials with quetiapine and not listed elsewhere in the label:

nightmares, peripheral edema, rhinitis, eosinophilia, hypersensitivity, elevations in gamma-GT levels, and elevations in serum creatine phosphokinase (not associated with NMS).

Extrapyramidal Symptoms (EPS):

Dystonia

Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Four methods were used to measure EPS: (1) Simpson-Angus total score (mean change from baseline) which evaluates Parkinsonism and akathisia, (2) Barnes Akathisia Rating Scale (BARS) Global Assessment Score, (3) incidence of spontaneous complaints of EPS (akathisia, akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, neck rigidity, and tremor), and (4) use of anticholinergic medications to treat emergent EPS.

Adults: In placebo-controlled clinical trials with quetiapine, utilizing doses up to 800 mg per day, the incidence of any adverse reactions potentially related to EPS ranged from 8% to 11% for quetiapine and 4% to 11% for placebo.

In three-arm placebo-controlled clinical trials for the treatment of schizophrenia, utilizing doses between 300 mg and 800 mg of Seroquel XR, the incidence of any adverse reactions potentially related to EPS was 8% for Seroquel XR and 8% for SEROQUEL (without evidence of being dose related), and 5% in the placebo group. In these studies, the incidence of the individual adverse reactions (akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, and muscle rigidity) was generally low and did not exceed 3% for any treatment group.

At the end of treatment, the mean change from baseline in SAS total score and BARS Global Assessment score was similar across the treatment groups. The use of concomitant anticholinergic medications was infrequent and similar across the treatment groups. The incidence of extrapyramidal symptoms was consistent with that seen with the profile of SEROQUEL in schizophrenia patients.

Table 15: Adverse Experiences Associated with Extrapyramidal Symptoms in Placebo-controlled Clinical Trials for Schizophrenia

* Patients with the following terms were counted in this category: nuchal rigidity, hypertonia, dystonia, muscle rigidity, oculogyration † Patients with the following terms were counted in this category: cogwheel rigidity, tremor, drooling, hypokinesia ‡ Patients with the following terms were counted in this category: akathisia, psychomotor agitation § Patients with the following terms were counted in this category: tardive dyskinesia, dyskinesia, choreoathetosis ¶ Patients with the following terms were counted in this category: restlessness; extrapyramidal disorder, movement disorder
Preferred term	Placebo (N=319)		Seroquel XR 300 mg/day (N=91)		Seroquel XR 400 mg/day (N=227)		Seroquel XR 600 mg/day (N=310)		Seroquel XR 800 mg/day (N=323)		All Doses (N=951)
	n	%	n	%	n	%	n	%	n	%	n	%
Dystonic event*	0	0.0	3	3.3	0	0.0	4	1.3	1	0.3	8	0.8
Parkinsonism†	4	1.3	1	1.1	3	1.3	11	3.6	7	2.2	22	2.3
Akathisia‡	4	1.3	0	0.0	3	1.3	7	2.3	7	2.2	17	1.8
Dyskinetic event§	2	0.6	2	2.2	1	0.4	1	0.3	1	0.3	5	0.5
Other extrapyramidal event¶	7	2.2	3	3.3	4	1.8	7	2.3	12	3.7	26	2.7

In a placebo-controlled clinical trial for the treatment of bipolar mania, utilizing the dose range of 400-800 mg/day of Seroquel XR, the incidence of any adverse reactions potentially related to EPS was 6.6% for Seroquel XR and 3.8% in the placebo group. In this study, the incidence of the individual adverse reactions (akathisia, extrapyramidal disorder, tremor, dystonia, restlessness, and cogwheel rigidity) did not exceed 2.0% for any adverse reaction.

Table 16: Adverse Experiences Associated with Extrapyramidal Symptoms in a Placebo-controlled Clinical Trial for Bipolar Mania

* There were no adverse experiences with the preferred term of dyskinetic event. † Patients with the following terms were counted in this category: nuchal rigidity, hypertonia, dystonia, muscle rigidity, oculogyration ‡ Patients with the following terms were counted in this category: cogwheel rigidity, tremor, drooling, hypokinesia § Patients with the following terms were counted in this category: akathisia, psychomotor agitation ¶ Patients with the following terms were counted in this category: restlessness; extrapyramidal disorder, movement disorder
Preferred term*	Placebo (N=160)		Seroquel XR (N=151)
	n	%	n	%
Dystonic event†	0	0.0	1	0.7
Parkinsonism‡	3	1.9	4	2.7
Akathisia§	1	0.6	2	1.3
Other extrapyramidal event¶	2	1.3	3	2.0

In a placebo-controlled clinical trial for the treatment of bipolar depression utilizing 300 mg of Seroquel XR, the incidence of any adverse reactions potentially related to EPS was 4.4% for Seroquel XR and 0.7% in the placebo group. In this study, the incidence of the individual adverse reactions (akathisia, extrapyramidal disorder, tremor, dystonia, hypertonia) did not exceed 1.5% for any individual adverse reaction.

Table 17: Adverse Experiences Associated with Extrapyramidal Symptoms in a Placebo-controlled Clinical Trial for Bipolar Depression

* There were no adverse experiences with the preferred term of dyskinetic event. † Patients with the following terms were counted in this category: nuchal rigidity, hypertonia, dystonia, muscle rigidity, oculogyration ‡ Patients with the following terms were counted in this category: cogwheel rigidity, tremor, drooling, hypokinesia § Patients with the following terms were counted in this category: akathisia, psychomotor agitation ¶ Patients with the following terms were counted in this category: restlessness; extrapyramidal disorder, movement disorder
Preferred term*	Placebo (N=140)		Seroquel XR (N=137)
	n	%	n	%
Dystonic event†	0	0.0	2	1.5
Parkinsonism‡	1	0.7	1	0.7
Akathisia§	0	0.0	2	1.5
Other extrapyramidal event¶	0	0.0	1	0.7

In two placebo-controlled short-term adjunctive therapy clinical trials for the treatment of MDD utilizing between 150 mg and 300 mg of Seroquel XR, the incidence of any adverse reactions potentially related to EPS was 5.1% for Seroquel XR and 4.2% for the placebo group.

Table 18 shows the percentage of patients experiencing adverse reactions potentially associated with EPS in adjunct clinical trials for MDD by dose:

Table 18: Adverse Reactions Potentially Associated with EPS in MDD Trials by Dose, Adjunctive Therapy Clinical Trials (6 weeks duration)

* Patients with the following terms were counted in this category: nuchal rigidity, hypertonia, dystonia, muscle rigidity, oculogyration † Patients with the following terms were counted in this category: cogwheel rigidity, tremor, drooling, hypokinesia ‡ Patients with the following terms were counted in this category: akathisia, psychomotor agitation § Patients with the following terms were counted in this category: tardive dyskinesia, dyskinesia, choreoathetosis ¶ Patients with the following terms were counted in this category: restlessness; extrapyramidal disorder, movement disorder
Preferred term	Placebo (N=309)		Seroquel XR 150 mg/day (N=315)		Seroquel XR 300 mg/day (N=312)		All Doses (N=627)
	n	%	n	%	n	%	n	%
Dystonic event*	0	0.0	1	0.3	0	0.0	1	0.2
Parkinsonism†	5	1.6	3	1.0	4	1.3	7	1.1
Akathisia‡	3	1.0	5	1.6	8	2.6	13	2.1
Dyskinetic event§	0	0.0	0	0.0	1	0.3	1	0.2
Other extrapyramidal event¶	5	1.6	5	1.6	7	2.2	12	1.9

Children and Adolescents: Safety and effectiveness of Seroquel XR have not been established in pediatric patients and Seroquel XR is not approved for patients under the age of 18 years. In a short-term placebo-controlled monotherapy trial in adolescent patients with schizophrenia (6-week duration), the aggregated incidence of extrapyramidal symptoms was 12.9% for SEROQUEL and 5.3% for placebo, though the incidence of the individual adverse events (eg, akathisia, tremor, extrapyramidal disorder, hypokinesia, restlessness, psychomotor hyperactivity, muscle rigidity, dyskinesia) did not exceed 4.1% in any treatment group. In a short-term placebo-controlled monotherapy trial in children and adolescent patients with bipolar mania (3-week duration), the aggregated incidence of extrapyramidal symptoms was 3.6% for SEROQUEL and 1.1% for placebo.

Table 19 below presents a listing of patients with adverse experiences potentially associated with EPS in the short-term placebo-controlled monotherapy trial in adolescent patients with schizophrenia (6-week duration).

Table 19 Adverse experiences potentially associated with EPS in the short-term placebo-controlled monotherapy trial in adolescent patients with schizophrenia (6-week duration).

* Patients with the following terms were counted in this category: nuchal rigidity, hypertonia, dystonia, muscle rigidity † Patients with the following terms were counted in this category: cogwheel rigidity, tremor ‡ Patients with the following terms were counted in this category: akathisia § Patients with the following terms were counted in this category: tardive dyskinesia, dyskinesia, choreoathetosis ¶ Patients with the following terms were counted in this category: restlessness; extrapyramidal disorder
Preferred term	Placebo (N=75)		SEROQUEL 400 mg/day (N=73)		SEROQUEL 800 mg/day (N=74)		All SEROQUEL (N=147)
	n	:%	n	%	n	%	n	%
Dystonic event*	0	0.0	2	2.7	0	0.0	2	1.4
Parkinsonism†	2	2.7	4	5.5	4	5.4	8	5.4
Akathisia‡	3	4.0	3	4.1	4	5.4	7	4.8
Dyskinetic event§	0	0.0	2	2.7	0	0.0	2	1.4
Other extrapyramidal event¶	0	0.0	2	2.7	2	2.7	4	2.7

Table 20 below presents a listing of patients with Adverse Experiences potentially associated with EPS in a short-term placebo-controlled monotherapy trial in children and adolescent patients with bipolar mania (3-week duration)

Table 20: Adverse experiences potentially associated with EPS in a short-term placebo-controlled monotherapy trial in children and adolescent patients with bipolar mania (3-week duration)

* There were no adverse experiences with the preferred term of dystonic or dyskinetic events. † Patients with the following terms were counted in this category: cogwheel rigidity, tremor ‡ Patients with the following terms were counted in this category: akathisia § Patients with the following terms were counted in this category: restlessness; extrapyramidal disorder
Preferred term*	Placebo (N=90)		SEROQUEL 400 mg/day (N=95)		SEROQUEL 600 mg/day (N=98)		All SEROQUEL (N=193)
	n	%	n	%	n	%	n	%
Parkinsonism†	1	1.1	2	2.1	1	1.0	3	1.6
Akathisia‡	0	0.0	1	1.0	1	1.0	2	1.0
Other extrapyramidal event§	0	0.0	1	1.1	1	1.0	2	1.0

Children and Adolescents: Safety and effectiveness of Seroquel XR have not been established in pediatric patients and Seroquel XR is not approved for patients under the age of 18 years. In acute placebo-controlled trials in children and adolescent patients with schizophrenia (6-week duration) or bipolar mania (3-week duration), the incidence of increased appetite was 7.6% for SEROQUEL compared to 2.4% for placebo. In a 26-week open-label study that enrolled patients from the above two pediatric trials, the incidence of increased appetite was 7% for SEROQUEL.

Vital Signs and Laboratory Values

Hyperglycemia, hyperlipidemia, weight gain, orthostatic hypotension and changes in thyroid hormone levels have been reported with quetiapine. Increases in blood pressure have also been reported with quetiapine in children and adolescents [see Warnings and Precautions (5.4, 5.5, 5.6, 5.8, 5.9 and 5.14)].

Laboratory Changes:

Neutrophil Counts

In three-arm Seroquel XR placebo-controlled monotherapy clinical trials, among patients with a baseline neutrophil count ≥ 1.5 x 109/L, the incidence of at least one occurrence of neutrophil count <1.5 x 109/L was 1.5% in patients treated with Seroquel XR and 1.5% for SEROQUEL, compared to 0.8% in placebo-treated patients.

In placebo-controlled monotherapy clinical trials involving 3368 patients on quetiapine fumarate and 1515 on placebo, the incidence of at least one occurrence of neutrophil count <1.0 x 109/L among patients with a normal baseline neutrophil count and at least one available follow up laboratory measurement was 0.3% (10/2967) in patients treated with quetiapine, compared to 0.1% (2/1349) in patients treated with placebo. Patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue Seroquel XR at the first sign of a decline in WBC in absence of other causative factors [see Warnings and Precautions (5.10)].

Decreased Hemoglobin

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

ECG Changes:

2.5% of Seroquel XR patients, and 2.3% of placebo patients, had tachycardia (>120 bpm) at any time during the trials. Seroquel XR was associated with a mean increase in heart rate, assessed by ECG, of 6.3 beats per minute compared to a mean increase of 0.4 beats per minute for placebo. This is consistent with the rates for SEROQUEL. The incidence of adverse reactions of tachycardia was 1.9% for Seroquel XR compared to 0.5% for placebo. SEROQUEL use was associated with a mean increase in heart rate, assessed by ECG, of 7 beats per minute compared to a mean increase of 1 beat per minute among placebo patients. The slight tendency for tachycardia may be related to quetiapine’s potential for inducing orthostatic changes [see Warnings and Precautions (5.8)].

Children and Adolescents: Safety and effectiveness of Seroquel XR have not been established in pediatric patients. In the acute (6-week) schizophrenia trial in adolescents, potentially clinically significant increases in heart rate (> 110 bpm) occurred in 5.2% of patients receiving SEROQUEL 400 mg and 8.5% of patients receiving SEROQUEL 800 mg compared to 0% of patients receiving placebo. Mean increases in heart rate were 3.8 bpm and 11.2 bpm for SEROQUEL 400 mg and 800 mg groups, respectively, compared to a decrease of 3.3 bpm in the placebo group [see Warnings and Precautions (5.8)].

In the acute (3-week) bipolar mania trial in children and adolescents, potentially clinically significant increases in heart rate (> 110 bpm) occurred in 1.1% of patients receiving SEROQUEL 400 mg and 2.4% of patients receiving SEROQUEL 600 mg compared to 0% of patients receiving placebo. Mean increases in heart rate were 12.8 bpm and 13.4 bpm for SEROQUEL 400 mg and 600 mg groups, respectively, compared to a decrease of 1.7 bpm in the placebo group [see Warnings and Precautions (5.8)].

Post Marketing Experience

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

Adverse reactions reported since market introduction which were temporally related to SEROQUEL therapy include anaphylactic reaction and galactorrhea.

Other adverse reactions reported since market introduction, which were temporally related to SEROQUEL therapy, but not necessarily causally related, include the following: agranulocytosis, cardiomyopathy, hyponatremia, myocarditis, rhabdomyolysis, syndrome of inappropriate antidiuretic hormone secretion (SIADH), Stevens-Johnson syndrome (SJS), and decreased platelets.

In post-marketing clinical trials, elevations in total cholesterol (predominantly LDL cholesterol), dyspnea, palpitations, somnambulism (and other related events) and hypothermia have been reported.

Top

Side Effects by Body System - for Healthcare Professionals

Nervous system

Lower (worse) baseline scores predicted greater cognitive improvement. Change In cognitive performance was weakly related to change in symptom scores.

Nervous system side effects have included agitation (20%), somnolence (18%), dizziness (11%), tremor (8%), and anxiety (4%). Hypertonia, dysarthria, abnormal dreams, dyskinesia, abnormal thinking, tardive dyskinesia, vertigo, involuntary movements, confusion, amnesia, hyperkinesia, increased libido, incoordination, abnormal gait, myoclonus, apathy, ataxia, stupor, bruxism, hemiplegia, aphasia, buccoglossal syndrome, choreoathetosis, delirium, decreased libido, neuralgia, stuttering, akathisia, dystonia, parkinsonism, and subdural hematoma have also been reported; however, causality has not been established. Two cases of neuroleptic malignant syndrome that may possibly have been related to quetiapine use have also been reported. One case of quetiapine associated restless leg syndrome has been reported.

Nervous system side effects specifically associated with the extended-release tablets have included sedation (13%), somnolence (12%), and dizziness (10%).

Quetiapine has been associated with improvement on cognitive test performance in patients in the early stages of schizophrenia.

Gastrointestinal

Gastrointestinal side effects have included dry mouth (9%), constipation (8%), vomiting (6%), dyspepsia (5%), gastroenteritis (2%), and increased gamma glutamyl transpeptidase level (1%). Anorexia, increased salivation, increased appetite, gingivitis, dysphagia, flatulence, gastroenteritis, gastritis, hemorrhoids, stomatitis, thirst, tooth caries, fecal incontinence, gastroesophageal reflux, gum hemorrhage, mouth ulceration, rectal hemorrhage tongue edema, glossitis, hematemesis, intestinal obstruction, melena, and pancreatitis have also been reported; however, causality has not been established.

Gastrointestinal side effects specifically associated with the extended-release tablets have included dry mouth (12%), constipation (6%), and dyspepsia (5%).

Cardiovascular

Cardiovascular side effects have included tachycardia (6%), postural hypotension (4%), and palpitation. Vasodilatation, QT interval prolongation, bradycardia, cerebral ischemia, irregular pulse, T wave abnormality, bundle branch block, cerebrovascular accident, venous thromboembolism, T wave inversion, anginal pectoris, atrial fibrillation, first degree atrioventricular (AV) block, congestive heart failure, elevated ST, thrombophlebitis, T wave flattening, ST abnormality, cardiomyopathy (including fatal cardiomyopathy), myocarditis, and increased QRS duration have also been reported.

Cardiovascular side effects specifically associated with the extended-release tablets have included orthostatic hypotension (7%).

Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents, including quetiapine, for the treatment of behavioral disorders in the elderly patient with dementia showed a risk of death 1.6 to 1.7 times greater in the drug treated patient than in the placebo treated patient. The average length of duration for the trials was 10 weeks with the cause of death in the majority of cases, though not all, reported as either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Similar results (i.e., increased risk of mortality with atypical antipsychotics) were reported in another meta-analysis involving elderly dementia patients that consisted of 15 randomized, placebo-controlled trials (n=3353) of 10 to 12 weeks in duration. Quetiapine is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.

An increased risk of mortality, possibly due to heart failure or sudden death, has been reported with the use of atypical antipsychotic agents in the treatment of behavioral disorders in the elderly patient with dementia.

The results of a large retrospective cohort study appear to indicate that atypical antipsychotic agents (i.e., risperidone, olanzapine, clozapine, quetiapine) increase the risk of venous thromboembolism in elderly patients; however, these events seem to be rare.

Endocrine

A study of U.S. military veterans with schizophrenia has reported that patients on quetiapine had 3.34 times as many cases of diabetes when compared to patients taking decades old drugs for psychosis including haloperidol, thioridazine, and others.

Additional studies have confirmed that patients receiving atypical antipsychotics (i.e., clozapine, risperidone, olanzapine, quetiapine, ziprasidone) are at an increased risk of developing hyperglycemia and/or diabetes mellitus.

Treatment with quetiapine has been shown to cause significant decreases in total serum thyroxine (T4) and triiodothyronine (T3) levels and a significant increase in thyroid-stimulating hormone (TSH) levels after 6 weeks of therapy.

Endocrine side effects have included hypothyroidism, diabetes mellitus, and hyperthyroidism. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) has also been associated with quetiapine use.

Metabolic

Treatment with quetiapine has been associated with moderate weight gain. Most of the weight gain (greater than 60%) appears to occur within the first 12 weeks of therapy with modest changes occurring after 6 months. In one study, the mean weight gain after 1 and 2 years of treatment with quetiapine was 3.19 kg (7 lbs) and 5.16 kg (11 lbs), respectively. The weight gain reported with quetiapine does not appear to be dose-related.

Metabolic side effects have included weight gain, increased SGPT, and increased SGOT in 5% of patients. Weight loss, hyperglycemia, and hypoglycemia have been reported infrequently. In postmarketing clinical trials, elevations in total cholesterol (predominantly LDL cholesterol) have been observed.

Dermatologic

Dermatologic side effects have included rash (4%) and sweating. Pruritus, acne, eczema, contact dermatitis, maculopapular rash, seborrhea, skin ulcer, exfoliative dermatitis, psoriasis, and skin discoloration have also been reported; however, causality has not been established. A rare case of erythema multiforme minor, that resolved following discontinuation of quetiapine, has been reported.

Respiratory

Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents, including quetiapine, for the treatment of behavioral disorders in the elderly patient with dementia showed a risk of death 1.6 to 1.7 times greater in the drug treated patient than in the placebo treated patient. The average length of duration for the trials was 10 weeks with the cause of death in the majority of cases, though not all, reported as either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Quetiapine is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.

An increased risk of mortality, possibly due to an infection, such as pneumonia, has been reported with the use of atypical antipsychotic agents in the treatment of behavioral disorders in the elderly patient with dementia.

A case of acute respiratory failure has been reported in a patient with COPD following a single oral dose of 50 mg.

Respiratory side effects have included pharyngitis (6%) and rhinitis (3%). Increased cough, dyspnea, pneumonia, epistaxis, asthma, hiccup, and hyperventilation have also been reported; however, causality has not been established. A single case of hyperventilation and respiratory alkalosis has been reported. One case of acute respiratory failure has been reported.

Other

Other side effects have included headache (21%), pain (7%), asthenia (5%), abdominal pain (4%), back pain (3%), fever (2%), and ear pain (1%). Flu syndrome, neck pain, pelvic pain, suicide attempt, malaise, photosensitivity reaction, chills, face edema, moniliasis, enlarged abdomen, migraine, peripheral edema, increased alkaline phosphatase level, hyperlipemia, alcohol intolerance, dehydration, increased creatinine, glycosuria, gout, hand edema, hypokalemia, tinnitus, deafness, and water intoxication have also been reported; however, causality has not been established. Postmarketing reports have included galactorrhea, agranulocytosis, hyponatremia, Stevens-Johnson syndrome, decreased platelets, somnambulism (and other related events) and hypothermia, however, causality has not been established.

Hematologic

Hematologic side effects have included leukopenia, leukocytosis, anemia, ecchymosis, eosinophilia, hypochromic anemia, lymphadenopathy, cyanosis, hemolysis, and thrombocytopenia; however, causality has not been established. A single case of thrombotic thrombocytopenic purpura has been reported. Decreases in hemoglobin to 13 g/dl or less in males and 12 g/dl or less in females have been reported.

Ocular

Ocular side effects have included amblyopia (2%). Conjunctivitis, abnormal vision, dry eyes, blepharitis, eye pain, abnormality of accommodation, and glaucoma have also been reported; however, causality has not been established. One case of cataracts has been reported. One case of photopsia has been reported.

One case of photopsia associated with high-dose quetiapine (1000 mg daily) has been reported. Symptoms resolved following a reduction in dose (900 mg daily).

Genitourinary

A 48 year old female with no prior history of urinary retention presented to the emergency room unable to void several months after initiating treatment with quetiapine. The patient self prescribed an increase in dosage from 900 mg/day to 1800 mg/day several weeks prior to this incident. Ten days prior to the visit to the emergency department she increased dosage again to 2400 mg/day. The urinary retention resolved within 48 hours of decreasing dosage back to the prescribed 900 mg/day. Urinary hesitancy developed again two months later after the patient again increased her dosage to 1800 mg/day without medical advice. The condition again resolved following a return to a dosage of 900 mg/day.

Genitourinary side effects have included dysmenorrhea, vaginitis, urinary incontinence, metrorrhagia, impotence, dysuria, vaginal moniliasis, abnormal ejaculation, cystitis, urinary frequency, amenorrhea, female lactation, leukorrhea, vaginal hemorrhage, vulvovaginitis, orchitis, gynecomastia, nocturia, and polyuria; however, causality has not been established. Rare cases of priapism have been reported with quetiapine use.

Musculoskeletal

Two cases of rhabdomyolysis have been reported. One case occurred as a result of a quetiapine overdose and the second occurred after 14 days of quetiapine therapy (25 mg/day). In the second case, elevated serum creatinine kinase and liver enzyme levels gradually returned to normal following discontinuation of quetiapine.

Musculoskeletal side effects have included pathological fracture, myasthenia, twitching, arthralgia, arthritis, leg cramps, and bone pain; however, causality has not been established. Rare cases of rhabdomyolysis have been reported.

Psychiatric

Psychiatric side effects have included psychosis, hallucinations, paranoid reactions, delusions, manic reaction, depersonalization, catatonic reaction, emotional lability, suicide attempt, and euphoria.

Renal

Renal side effects have included acute kidney failure; however, causality has not been established.

Hepatic

A 30 year old patient experienced acute symptoms of cholestasis after 8 years of risperidone therapy. Once the drug was discontinued, the symptoms resolved completely. Eleven months later, quetiapine was introduced and the patient once again developed acute symptoms of cholestasis which later resolved after quetiapine discontinuation.

Hepatic side effects including at least one case of delayed onset cholestasis have been reported.

Hypersensitivity

Hypersensitivity side effects including anaphylactic reaction have been reported.

Top

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.