DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Seroquel (Quetiapine Fumarate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The information below is derived from a clinical trial database for SEROQUEL consisting of over 3700 patients. This database includes 698 patients exposed to SEROQUEL for the treatment of bipolar depression, 405 patients exposed to SEROQUEL for the treatment of acute bipolar mania (monotherapy and adjunct therapy) and approximately 2600 patients and/or normal subjects exposed to 1 or more doses of SEROQUEL for the treatment of schizophrenia.

Of these approximately 3700 subjects, approximately 3400 (2300 in schizophrenia, 405 in acute bipolar mania, and 698 in bipolar depression) were patients who participated in multiple dose effectiveness trials, and their experience corresponded to approximately 992.6 patient-years. The conditions and duration of treatment with SEROQUEL varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations.

Adverse events 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 events without first grouping similar types of events into a smaller number of standardized event categories.

In the tables and tabulations that follow, standard COSTART terminology has been used to classify reported adverse events for schizophrenia and bipolar mania. MedDRA terminology has been used to classify reported adverse events for bipolar depression.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event 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 Findings Observed in Short-Term, Controlled Trials

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

Bipolar Disorder:

Depression:

Overall, discontinuations due to adverse events were 12.3% for SEROQUEL 300 mg vs 19.0% for SEROQUEL 600 mg and 5.2% for placebo.

Mania:

Overall, discontinuations due to adverse events were 5.7% for SEROQUEL vs. 5.1% for placebo in monotherapy and 3.6% for SEROQUEL vs. 5.9% for placebo in adjunct therapy.

Schizophrenia: Overall, there was little difference in the incidence of discontinuation due to adverse events (4% for SEROQUEL vs. 3% for placebo) in a pool of controlled trials. However, discontinuations due to somnolence and hypotension were considered to be drug related (see PRECAUTIONS):

Adverse Event

SEROQUEL

Placebo

Somnolence

0.8%

0%

Hypotension

0.4%

0%

Adverse Events Occurring at an Incidence of 1% or More Among SEROQUEL Treated Patients in Short-Term, Placebo-Controlled Trials:

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence in the population studied.

Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy of schizophrenia (up to 6 weeks) and bipolar mania (up to 12 weeks) in 1% or more of patients treated with SEROQUEL (doses ranging from 75 to 800 mg/day) where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Table 2Treatment-Emergent Adverse Experience Incidence in 3- to 12-Week Placebo-Controlled Clinical Trials 1 for the Treatment of Schizophrenia and Bipolar Mania (monotherapy)

Body System/ Preferred Term

SEROQUEL (n=719)

Placebo (n=404)

Body as a Whole

Headache

21%

14%

Pain

7%

5%

Asthenia

5%

3%

Abdominal Pain

4%

1%

Back Pain

3%

1%

Fever

2%

1%

Cardiovascular

Tachycardia

6%

4%

Postural Hypotension

4%

1%

Digestive

Dry Mouth

9%

3%

Constipation

8%

3%

Vomiting

6%

5%

Dyspepsia

5%

1%

Gastroenteritis

2%

0%

Gamma Glutamyl Transpeptidase Increased

1%

0%

Metabolic and Nutritional

Weight Gain

5%

1%

SGPT Increased

5%

1%

SGOT Increased

3%

1%

Nervous

Agitation

20%

17%

Somnolence

18%

8%

Dizziness

11%

5%

Anxiety

4%

3%

Respiratory

Pharyngitis

4%

3%

Rhinitis

3%

1%

Skin and Appendages

Rash

4%

2%

Special Senses

Amblyopia

2%

1%

1 Events for which the SEROQUEL incidence was equal to or less than placebo are not listed in the table, but included the following: accidental injury, akathisia, chest pain, cough increased, depression, diarrhea, extrapyramidal syndrome, hostility, hypertension, hypertonia, hypotension, increased appetite, infection, insomnia, leukopenia, malaise, nausea, nervousness, paresthesia, peripheral edema, sweating, tremor, and weight loss.

In these studies, the most commonly observed adverse events associated with the use of SEROQUEL (incidence of 5% or greater) and observed at a rate on SEROQUEL at least twice that of placebo were somnolence (18%), dizziness (11%), dry mouth (9%), constipation (8%), SGPT increased (5%), weight gain (5%), and dyspepsia (5%).

Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during therapy (up to 3-weeks) of acute mania in 5% or more of patients treated with SEROQUEL (doses ranging from 100 to 800 mg/day) used as adjunct therapy to lithium and divalproex where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Table 3 Treatment-Emergent Adverse Experience Incidence in 3-Week Placebo-Controlled Clinical Trials 1 for the Treatment of Bipolar Mania (Adjunct Therapy)

Body System/ Preferred Term

SEROQUEL (n=196)

Placebo (n=203)

Body as a Whole

Headache

17%

13%

Asthenia

10%

4%

Abdominal Pain

7%

3%

Back Pain

5%

3%

Cardiovascular

Postural Hypotension

7%

2%

Digestive

Dry Mouth

19%

3%

Constipation

10%

5%

Metabolic and Nutritional

Weight Gain

6%

3%

Nervous

Somnolence

34%

9%

Dizziness

9%

6%

Tremor

8%

7%

Agitation

6%

4%

Respiratory

Pharyngitis

6%

3%

1 Events for which the SEROQUEL incidence was equal to or less than placebo are not listed in the table, but included the following: akathisia, diarrhea, insomnia, and nausea.

In these studies, the most commonly observed adverse events associated with the use of SEROQUEL (incidence of 5% or greater) and observed at a rate on SEROQUEL at least twice that of placebo were somnolence (34%), dry mouth (19%), asthenia (10%), constipation (10%), abdominal pain (7%), postural hypotension (7%), pharyngitis (6%), and weight gain (6%).

Table 4 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during therapy (up to 8-weeks) of bipolar depression in 5% or more of patients treated with SEROQUEL (doses of 300 and 600 mg/day) where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo treated patients.

Table 4. Treatment-Emergent Adverse Experience Incidence in 8-Week Placebo-Controlled Clinical Trials 1 for the Treatment of Bipolar Depression
Body System/ Preferred TermSEROQUEL (n=698)PLACEBO (n=347)

Gastrointestinal Disorders

Dry Mouth

44%

13%

Constipation

10%

4%

Dyspepsia

7%

4%

Vomiting

5%

4%

General Disorders and Administrative Site Conditions

Fatigue

10%

8%

Metabolism and Nutrition Disorders

Increased Appetite

5%

3%

Nervous System Disorders

Sedation

30%

8%

Somnolence

28%

7%

Dizziness

18%

7%

Lethargy

5%

2%

Respiratory, Thoracic, and Mediastinal Disorders

Nasal Congestion

5%

3%

1 Events for which the SEROQUEL incidence was equal to or less than placebo are not listed in the table, but included the following: nausea, upper respiratory tract infection, and headache.

In these studies, the most commonly observed adverse events associated with the use of SEROQUEL (incidence of 5% or greater) and observed at a rate on SEROQUEL at least twice that of placebo were dry mouth (44%), sedation (30%), somnolence (28%), dizziness (18%), constipation (10%), lethargy (5%), and nasal congestion (5%).

Explorations for interactions on the basis of gender, age, and race did not reveal any clinically meaningful differences in the adverse event occurrence on the basis of these demographic factors.

Dose Dependency of Adverse Events in Short-Term, Placebo-Controlled Trials

Dose-related Adverse Events:

Spontaneously elicited adverse event data from a study of schizophrenia comparing five fixed doses of SEROQUEL (75 mg, 150 mg, 300 mg, 600 mg, and 750 mg/day) to placebo were explored for dose-relatedness of adverse events. Logistic regression analyses revealed a positive dose response (p<0.05) for the following adverse events: dyspepsia, abdominal pain, and weight gain.

Extrapyramidal Symptoms: Data from one 6-week clinical trial of schizophrenia comparing five fixed doses of SEROQUEL (75, 150, 300, 600, 750 mg/day) provided evidence for the lack of treatment-emergent extrapyramidal symptoms (EPS) and dose-relatedness for EPS associated with SEROQUEL treatment. Three methods were used to measure EPS: (1) Simpson-Angus total score (mean change from baseline) which evaluates parkinsonism and akathisia, (2) incidence of spontaneous complaints of EPS (akathisia, akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, neck rigidity, and tremor), and (3) use of anticholinergic medications to treat emergent EPS.

SEROQUEL

Dose Groups

Placebo

75 mg

150 mg

300 mg

600

mg

750

mg

Parkinsonism

-0.6

-1.0

-1.2

-1.6

-1.8

-1.8

EPS incidence

16%

6%

6%

4%

8%

6%

Anticholinergic medications

14%

11%

10%

8%

12%

11%

In six additional placebo-controlled clinical trials (3 in acute mania and 3 in schizophrenia) using variable doses of SEROQUEL, there were no differences between the SEROQUEL and placebo treatment groups in the incidence of EPS, as assessed by Simpson-Angus total scores, spontaneous complaints of EPS and the use of concomitant anticholinergic medications to treat EPS.

In two placebo-controlled clinical trials for the treatment of bipolar depression using 300 mg and 600 mg of SEROQUEL, the incidence of adverse events potentially related to EPS was 12% in both dose groups and 6% in the placebo group. In these studies, the incidence of the individual adverse events (eg, akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, muscle contractions involuntary, psychomotor hyperactivity and muscle rigidity) were generally low and did not exceed 4% in any treatment group.

The 3 treatment groups were similar in mean change in SAS total score and BARS Global Assessment score at the end of treatment. The use of concomitant anticholinergic medications was infrequent and similar across the three treatment groups.

Vital Signs and Laboratory Studies

Vital Sign Changes: SEROQUEL is associated with orthostatic hypotension (see PRECAUTIONS).

Weight Gain: In schizophrenia trials the proportions of patients meeting a weight gain criterion of ≥7% of body weight were compared in a pool of four 3- to 6-week placebo-controlled clinical trials, revealing a statistically significantly greater incidence of weight gain for SEROQUEL (23%) compared to placebo (6%). In mania monotherapy trials the proportions of patients meeting the same weight gain criterion were 21% compared to 7% for placebo and in mania adjunct therapy trials the proportion of patients meeting the same weight criterion were 13% compared to 4% for placebo. In bipolar depression trials, the proportions of patients meeting the same weight gain criterion were 8% compared to 2% for placebo.

Laboratory Changes: An assessment of the premarketing experience for SEROQUEL suggested that it is associated with asymptomatic increases in SGPT and increases in both total cholesterol and triglycerides (see PRECAUTIONS).

In placebo controlled monotherapy clinical trials involving 3368 patients on SEROQUEL 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 SEROQUEL, compared to 0.1% (2/1349) in patients treated with placebo. (See PRECAUTIONS: Leukopenia, neutropenia and agranulocytosis)

In post-marketing clinical trials, elevations in total cholesterol (predominantly LDL cholesterol) have been observed.

Hyperglycemia In 2 long-term placebo-controlled clinical trials, mean exposure 213 days for SEROQUEL (646 patients) and 152 days for placebo (680 patients), the exposure-adjusted rate of any increased blood glucose level (≥ 126 mg/dl) for patients more than 8 hours since a meal was 18.0 per 100 patient years for SEROQUEL (10.7% of patients) and 9.5 for placebo per 100 patient years (4.6% of patients).

In short-term (12 weeks duration or less) placebo-controlled clinical trials (3342 patients treated with SEROQUEL and 1490 treated with placebo), the percent of patients who had a fasting blood glucose ≥ 126 mg/dl or a non fasting blood glucose ≥ 200 mg/dl was 3.5% for quetiapine and 2.1% for placebo.

In a 24 week trial (active-controlled, 115 patients treated with SEROQUEL) designed to evaluate glycemic status with oral glucose tolerance testing of all patients, at week 24 the incidence of a treatment-emergent post-glucose challenge glucose level ≥ 200 mg/dl was 1.7% and the incidence of a fasting treatment-emergent post-glucose challenge glucose level ≥ 126 mg/dl was 2.6%.

ECG Changes: Between group comparisons for pooled placebo-controlled trials revealed no statistically significant SEROQUEL/placebo differences in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc, and PR intervals. However, the proportions of patients meeting the criteria for tachycardia were compared in four 3- to 6-week placebo-controlled clinical trials for the treatment of schizophrenia revealing a 1% (4/399) incidence for SEROQUEL compared to 0.6% (1/156) incidence for placebo. In acute (monotherapy) bipolar mania trials the proportions of patients meeting the criteria for tachycardia was 0.5% (1/192) for SEROQUEL compared to 0% (0/178) incidence for placebo. In acute bipolar mania (adjunct) trials the proportions of patients meeting the same criteria was 0.6% (1/166) for SEROQUEL compared to 0% (0/171) incidence for placebo. In bipolar depression trials, no patients had heart rate increases to > 120 beats per minute. 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. This slight tendency to tachycardia may be related to SEROQUEL's potential for inducing orthostatic changes (see PRECAUTIONS).

Other Adverse Events Observed During the Pre-Marketing Evaluation of SEROQUEL

Following is a list of COSTART terms that reflect treatment-emergent adverse events as defined in the introduction to the ADVERSE REACTIONS section reported by patients treated with SEROQUEL at multiple doses ≥75 mg/day during any phase of a trial within the premarketing database of approximately 2200 patients treated for schizophrenia. All reported events are included except those already listed in Table 2 or elsewhere in labeling, those events for which a drug cause was remote, and those event terms which were so general as to be uninformative. It is important to emphasize that, although the events reported occurred during treatment with SEROQUEL, they were not necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

Nervous System: Frequent: hypertonia, dysarthria; Infrequent: abnormal dreams, dyskinesia, thinking abnormal, tardive dyskinesia, vertigo, involuntary movements, confusion, amnesia, psychosis, hallucinations, hyperkinesia, libido increased*, urinary retention, incoordination, paranoid reaction, abnormal gait, myoclonus, delusions, manic reaction, apathy, ataxia, depersonalization, stupor, bruxism, catatonic reaction, hemiplegia; Rare: aphasia, buccoglossal syndrome, choreoathetosis, delirium, emotional lability, euphoria, libido decreased*, neuralgia, stuttering, subdural hematoma.

Body as a Whole: Frequent : flu syndrome; Infrequent : neck pain, pelvic pain*, suicide attempt, malaise, photosensitivity reaction, chills, face edema, moniliasis; Rare: abdomen enlarged.

Digestive System: Frequent : anorexia; Infrequent: increased salivation, increased appetite, gamma glutamyl transpeptidase increased, gingivitis, dysphagia, flatulence, gastroenteritis, gastritis, hemorrhoids, stomatitis, thirst, tooth caries, fecal incontinence, gastroesophageal reflux, gum hemorrhage, mouth ulceration, rectal hemorrhage, tongue edema; Rare: glossitis, hematemesis, intestinal obstruction, melena, pancreatitis.

Cardiovascular System: Frequent : palpitation; Infrequent : vasodilatation, QT interval prolonged, migraine, bradycardia, cerebral ischemia, irregular pulse, T wave abnormality, bundle branch block, cerebrovascular accident, deep thrombophlebitis, T wave inversion; Rare: angina pectoris, atrial fibrillation, AV block first degree, congestive heart failure, ST elevated, thrombophlebitis, T wave flattening, ST abnormality, increased QRS duration.

Respiratory System: Frequent : pharyngitis, rhinitis, cough increased, dyspnea; Infrequent : pneumonia, epistaxis, asthma; Rare: hiccup, hyperventilation.

Metabolic and Nutritional System: Frequent : peripheral edema; Infrequent : weight loss, alkaline phosphatase increased, hyperlipemia, alcohol intolerance, dehydration, hyperglycemia, creatinine increased, hypoglycemia; Rare: glycosuria, gout, hand edema, hypokalemia, water intoxication.

Skin and Appendages System: Frequent : sweating; Infrequent : pruritus, acne, eczema, contact dermatitis, maculopapular rash, seborrhea, skin ulcer; Rare: exfoliative dermatitis, psoriasis, skin discoloration.

Urogenital System: Infrequent : dysmenorrhea*, vaginitis* , urinary incontinence, metrorrhagia*, impotence*, dysuria, vaginal moniliasis*, abnormal ejaculation*, cystitis, urinary frequency, amenorrhea*, female lactation*, leukorrhea*, vaginal hemorrhage*, vulvovaginitis* orchitis*; Rare: gynecomastia*, nocturia, polyuria, acute kidney failure.

Special Senses: Infrequent : conjunctivitis, abnormal vision, dry eyes, tinnitus, taste perversion, blepharitis, eye pain; Rare: abnormality of accommodation, deafness, glaucoma.

Musculoskeletal System: Infrequent : pathological fracture, myasthenia, twitching, arthralgia, arthritis, leg cramps, bone pain.

Hemic and Lymphatic System: Frequent: leukopenia; Infrequent: leukocytosis, anemia, ecchymosis, eosinophilia, hypochromic anemia; lymphadenopathy, cyanosis; Rare: hemolysis, thrombocytopenia.

Endocrine System: Infrequent : hypothyroidism, diabetes mellitus; Rare : hyperthyroidism.

*adjusted for gender

Post Marketing Experience:

Adverse events reported since market introduction which were temporally related to SEROQUEL therapy include: anaphylactic reaction and restless legs.

Other adverse events 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), and Stevens Johnson syndrome (SJS).



REPORTS OF SUSPECTED SEROQUEL SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Seroquel. The information is not vetted and should not be considered as verified clinical evidence.

Possible Seroquel side effects / adverse reactions in 30 year old male

Reported by a individual with unspecified qualification from United States on 2011-10-03

Patient: 30 year old male weighing 81.6 kg (179.5 pounds)

Reactions: Upper Limb Fracture, Incorrect Dose Administered

Suspect drug(s):
Seroquel
    Dosage: three tablets
    Administration route: Oral

Seroquel
    Dosage: one tablets
    Administration route: Oral



Possible Seroquel side effects / adverse reactions in 63 year old female

Reported by a pharmacist from Germany on 2011-10-03

Patient: 63 year old female weighing 85.0 kg (187.0 pounds)

Reactions: Herpes Ophthalmic

Suspect drug(s):
Mirtazapine
    Administration route: Oral

Seroquel
    Administration route: Oral

Valproic Acid
    Administration route: Oral

Venlafaxine HCL
    Administration route: Oral



Possible Seroquel side effects / adverse reactions in 57 year old female

Reported by a individual with unspecified qualification from United States on 2011-10-03

Patient: 57 year old female weighing 98.9 kg (217.6 pounds)

Reactions: Drug Dose Omission, Tachyphrenia, Diabetes Mellitus, Impaired Work Ability, Abnormal Behaviour, Mental Status Changes, Suicidal Ideation, Anxiety, Activities of Daily Living Impaired, Obesity, Insomnia, Blood Cholesterol Increased, Depression, Asthenia, Myocardial Infarction

Suspect drug(s):
Seroquel
    Dosage: 200 mg/400 mg
    Administration route: Oral
    Indication: Psychotic Disorder
    Start date: 2004-01-01

Seroquel
    Administration route: Oral

Seroquel
    Dosage: 200 mg tk 1 t po bid and two ts po qhs utd
    Administration route: Oral
    Start date: 2006-06-30

Seroquel
    Dosage: 200 mg/400 mg
    Administration route: Oral
    Indication: Depression
    Start date: 2004-01-01

Seroquel
    Dosage: 200 mg tk 1 t po bid and two ts po qhs utd
    Administration route: Oral
    Start date: 2006-06-30

Seroquel
    Dosage: 200 mg tk 1 t po bid and two ts po qhs utd
    Administration route: Oral
    Start date: 2006-06-30

Seroquel
    Dosage: 200 mg tk 1 t po bid and two ts po qhs utd
    Administration route: Oral
    Start date: 2006-06-30

Seroquel
    Administration route: Oral

Seroquel
    Dosage: 200 mg/400 mg
    Administration route: Oral
    Indication: Bipolar Disorder
    Start date: 2004-01-01

Seroquel
    Administration route: Oral

Seroquel
    Dosage: 200 mg/400 mg
    Administration route: Oral
    Indication: Mania
    Start date: 2004-01-01

Seroquel
    Administration route: Oral

Other drugs received by patient: Haldol; Xanax; Ibuprofen; Hydroxyzine; Methadone HCL; Abilify; Celexa; Lipitor; Xanax; Celexa



See index of all Seroquel side effect reports >>

Drug label data at the top of this Page last updated: 2007-10-16

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2012