Side Effects > Risperdal

Risperdal Side Effects

Generic Name: risperidone

Please note - some side effects for Risperdal may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Risperdal - for the Consumer

Risperdal

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 Risperdal:

Anxiety; constipation; cough; diarrhea; dizziness; drowsiness; dry mouth; fatigue; headache; increased appetite; increased saliva production; lightheadedness; nausea; restlessness; runny nose; stomach pain or upset; trouble sleeping; vomiting; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Risperdal:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal thoughts; confusion; decreased sexual ability; drooling; enlarged breasts; fainting; fast or irregular heartbeat; fever; inability to control urination; increased sweating; missed menstrual period; new or worsening mental or mood changes (eg, aggression, agitation, severe anxiety); nipple discharge; prolonged painful erection; seizures; severe dizziness; stiff or rigid muscles; suicidal thoughts or attempts; symptoms of high blood sugar (eg, increased thirst, hunger, or urination; unusual weakness); tremor; trouble concentrating, speaking, or swallowing; trouble sitting still; trouble walking or standing; uncontrolled muscle movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual bruising; vision changes.

Risperdal Consta

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 Risperdal Consta:

Anxiety; constipation; cough; diarrhea; dizziness; drowsiness; dry mouth; fatigue; headache; increased appetite; increased saliva production; lightheadedness; nausea; restlessness; runny nose; stomach pain or upset; trouble sleeping; vomiting; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Risperdal Consta:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal thoughts; confusion; decreased sexual ability; drooling; enlarged breasts; fainting; fast or irregular heartbeat; fever; inability to control urination; increased sweating; missed menstrual period; new or worsening mental or mood changes (eg, agitation, aggression, severe anxiety); nipple discharge; prolonged painful erection; seizures; severe dizziness; stiff or rigid muscles; suicidal thoughts or attempts; symptoms of high blood sugar (eg, increased thirst, hunger, urination; unusual weakness); tremor; trouble concentrating, speaking, or swallowing; trouble sitting still; trouble walking or standing; uncontrolled muscle movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual bruising; vision changes.

Risperdal M-Tab Orally Disintegrating 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 Risperdal M-Tab Orally Disintegrating Tablets:

Anxiety; constipation; cough; diarrhea; dizziness; drowsiness; dry mouth; fatigue; headache; increased appetite; increased saliva production; lightheadedness; nausea; restlessness; runny nose; stomach pain or upset; trouble sleeping; vomiting; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Risperdal M-Tab Orally Disintegrating Tablets:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal thoughts; confusion; decreased sexual ability; drooling; enlarged breasts; fainting; fast or irregular heartbeat; fever; inability to control urination; increased sweating; missed menstrual period; new or worsening mental or mood changes (eg, aggression, agitation, severe anxiety); nipple discharge; prolonged painful erection; seizures; severe dizziness; stiff or rigid muscles; suicidal thoughts or attempts; symptoms of high blood sugar (eg, increased thirst, hunger, or urination; unusual weakness); tremor; trouble concentrating, speaking, or swallowing; trouble sitting still; trouble walking or standing; uncontrolled muscle movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual bruising; vision changes.

Risperdal Solution

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 Risperdal Solution:

Anxiety; constipation; cough; diarrhea; dizziness; drowsiness; dry mouth; fatigue; headache; increased appetite; increased saliva production; lightheadedness; nausea; restlessness; runny nose; stomach pain or upset; trouble sleeping; vomiting; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur when using Risperdal Solution:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal thoughts; confusion; decreased sexual ability; drooling; enlarged breasts; fainting; fast or irregular heartbeat; fever; inability to control urination; increased sweating; missed menstrual period; new or worsening mental or mood changes (eg, aggression, agitation, severe anxiety); nipple discharge; prolonged painful erection; seizures; severe dizziness; stiff or rigid muscles; suicidal thoughts or attempts; symptoms of high blood sugar (eg, increased thirst, hunger, or urination; unusual weakness); tremor; trouble concentrating, speaking, or swallowing; trouble sitting still; trouble walking or standing; uncontrolled muscle movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual bruising; vision changes.

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Risperdal Side Effects - for the Professional

Risperdal

The following findings are based on the short-term, placebo-controlled, North American, premarketing trials for schizophrenia and acute bipolar mania, and are followed by a description of adverse events and other safety measures in short-term, placebo-controlled trials in pediatric patients treated for irritability associated with autistic disorder. In patients with Bipolar I Disorder, treatment-emergent adverse events are presented separately for risperidone as monotherapy and as adjunctive therapy to mood stabilizers.

Certain portions of the discussion below relating to objective or numeric safety parameters, namely dose-dependent adverse events, vital sign changes, weight gain, laboratory changes, and ECG changes are derived from studies in patients with schizophrenia. However, this information is also generally applicable to bipolar mania and pediatric patients with autistic disorder.

Associated With Discontinuation of Treatment

Schizophrenia

Approximately 9% (244/2607) of Risperdal® (risperidone)-treated patients in Phase 2 and 3 studies discontinued treatment due to an adverse event, compared with about 7% on placebo and 10% on active control drugs. The more common events (≥0.3%) associated with discontinuation and considered to be possibly or probably drug-related included:

Adverse Event	Risperdal®	Placebo
Extrapyramidal symptoms	2.1%	0%
Dizziness	0.7%	0%
Hyperkinesia	0.6%	0%
Somnolence	0.5%	0%
Nausea	0.3%	0%

Suicide attempt was associated with discontinuation in 1.2% of Risperdal®-treated patients compared to 0.6% of placebo patients, but, given the almost 40-fold greater exposure time in Risperdal® compared to placebo patients, it is unlikely that suicide attempt is a Risperdal®-related adverse event. Discontinuation for extrapyramidal symptoms was 0% in placebo patients, but 3.8% in active-control patients in the Phase 2 and 3 trials.

Bipolar Mania In the US placebo-controlled trial with risperidone as monotherapy, approximately 8% (10/134) of Risperdal®-treated patients discontinued treatment due to an adverse event, compared with approximately 6% (7/125) of placebo-treated patients. The adverse events associated with discontinuation and considered to be possibly, probably, or very likely drug-related included paroniria, somnolence, dizziness, extrapyramidal disorder, and muscle contractions involuntary. Each of these events occurred in one Risperdal®-treated patient (0.7%) and in no placebo-treated patients (0%).

In the US placebo-controlled trial with risperidone as adjunctive therapy to mood stabilizers, there was no overall difference in the incidence of discontinuation due to adverse events (4% for Risperdal® vs. 4% for placebo).

Incidence in Controlled Trials

Commonly Observed Adverse Events in Controlled Clinical Trials

Schizophrenia

In two 6- to 8-week placebo-controlled trials, spontaneously-reported, treatment-emergent adverse events with an incidence of 5% or greater in at least one of the Risperdal® groups and at least twice that of placebo were anxiety, somnolence, extrapyramidal symptoms, dizziness, constipation, nausea, dyspepsia, rhinitis, rash, and tachycardia.

Adverse events were also elicited in one of these two trials (i.e., in the fixed-dose trial comparing Risperdal® at doses of 2, 6, 10, and 16 mg/day with placebo) utilizing a checklist for detecting adverse events, a method that is more sensitive than spontaneous reporting. By this method, the following additional common and drug-related adverse events occurred at an incidence of at least 5% and twice the rate of placebo: increased dream activity, increased duration of sleep, accommodation disturbances, reduced salivation, micturition disturbances, diarrhea, weight gain, menorrhagia, diminished sexual desire, erectile dysfunction, ejaculatory dysfunction, and orgastic dysfunction.

Bipolar Mania

In the US placebo-controlled trial with risperidone as monotherapy, the most commonly observed adverse events associated with the use of Risperdal® (incidence of 5% or greater and at least twice that of placebo) were somnolence, dystonia, akathisia, dyspepsia, nausea, parkinsonism, vision abnormal, and saliva increased. In the US placebo-controlled trial with risperidone as adjunctive therapy to mood stabilizers, the most commonly observed adverse events associated with the use of Risperdal® were somnolence, dizziness, parkinsonism, saliva increased, akathisia, abdominal pain, and urinary incontinence.

Adverse Events Occurring at an Incidence of 1% or More Among Risperdal®-Treated Patients - Schizophrenia

The table that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent among Risperdal®-treated patients treated at doses of ≤10 mg/day than among placebo-treated patients in the pooled results of two 6- to 8-week controlled trials. Patients received Risperdal® doses of 2, 6, 10, or 16 mg/day in the dose comparison trial, or up to a maximum dose of 10 mg/day in the titration study. This table shows the percentage of patients in each dose group (≤10 mg/day or 16 mg/day) who spontaneously reported at least one episode of an event at some time during their treatment. Patients given doses of 2, 6, or 10 mg did not differ materially in these rates. Reported adverse events were classified using the World Health Organization preferred terms.

The prescriber should be aware that these figures 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 which prevailed in this clinical trial. 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 non-drug factors to the side effect incidence rate in the population studied.

Table 1. Incidence of Treatment-Emergent Adverse Events in 6- to 8-Week Controlled Clinical Trials in Schizophrenia*

	Risperdal®
Body System/ Preferred Term	≤10mg/day (N=324)	16 mg/day (N=77)	Placebo (N=142)
* Events reported by at least 1% of patients treated with Risperdal®≤10 mg/day are included, and are rounded to the nearest %. Comparative rates for Risperdal® 16 mg/day and placebo are provided as well. Events for which the Risperdal® incidence (in both dose groups) was equal to or less than placebo are not listed in the table, but included the following: nervousness, injury, and fungal infection. † Includes tremor, dystonia, hypokinesia, hypertonia, hyperkinesia, oculogyric crisis, ataxia, abnormal gait, involuntary muscle contractions, hyporeflexia, akathisia, and extrapyramidal disorders. Although the incidence of 'extrapyramidal symptoms' does not appear to differ for the '10 mg/day' group and placebo, the data for individual dose groups in fixed dose trials do suggest a dose/response relationship.
Psychiatric
Insomnia	26%	23%	19%
Agitation	22%	26%	20%
Anxiety	12%	20%	9%
Somnolence	3%	8%	1%
Aggressive reaction	1%	3%	1%
Central & peripheral nervous system
Extrapyramidal symptoms†	17%	34%	16%
Headache	14%	12%	12%
Dizziness	4%	7%	1%
Gastrointestinal
Constipation	7%	13%	3%
Nausea	6%	4%	3%
Dyspepsia	5%	10%	4%
Vomiting	5%	7%	4%
Abdominal pain	4%	1%	0%
Saliva increased	2%	0%	1%
Toothache	2%	0%	0%
Respiratory system
Rhinitis	10%	8%	4%
Coughing	3%	3%	1%
Sinusitis	2%	1%	1%
Pharyngitis	2%	3%	0%
Dyspnea	1%	0%	0%
Body as a whole – general
Back pain	2%	0%	1%
Chest pain	2%	3%	1%
Fever	2%	3%	0%
Dermatological
Rash	2%	5%	1%
Dry skin	2%	4%	0%
Seborrhea	1%	0%	0%
Infections
Upper respiratory	3%	3%	1%
Visual
Abnormal vision	2%	1%	1%
Musculo-Skeletal
Arthralgia	2%	3%	0%
Cardiovascular
Tachycardia	3%	5%	0%

Adverse Events Occurring at an Incidence of 2% or More Among Risperdal®-Treated Patients - Bipolar Mania

Tables 2 and 3 display adverse events that occurred at an incidence of 2% or more, and were more frequent among patients treated with flexible doses of Risperdal® (1–6 mg daily as monotherapy and as adjunctive therapy to mood stabilizers, respectively) than among patients treated with placebo. Reported adverse events were classified using the World Health Organization preferred terms.

Table 2. Incidence of Treatment-Emergent Adverse Events in a 3-Week, Placebo-Controlled Trial - Monotherapy in Bipolar Mania*

Body System/ Preferred Term	Risperdal® (N=134)	Placebo (N=125)
* Events reported by at least 2% of patients treated with Risperdal® are included and are rounded to the nearest %. Events reported by at least 2% of patients treated with Risperdal® that were less than the incidence reported by patients treated with placebo are not listed in the table, but included the following: headache, tremor, insomnia, constipation, back pain, upper respiratory tract infection, pharyngitis, and arthralgia.
Central & peripheral nervous system
Dystonia	18%	6%
Akathisia	16%	6%
Dizziness	11%	9%
Parkinsonism	6%	3%
Hypoaesthesia	2%	1%
Psychiatric
Somnolence	28%	7%
Agitation	8%	6%
Manic reaction	8%	6%
Anxiety	4%	2%
Concentration impaired	2%	1%
Gastrointestinal system
Dyspepsia	11%	6%
Nausea	11%	2%
Saliva increased	5%	1%
Mouth dry	3%	2%
Body as a whole – general
Pain	5%	3%
Fatigue	4%	2%
Injury	2%	0%
Respiratory system
Sinusitis	4%	1%
Rhinitis	3%	2%
Coughing	2%	2%
Skin and appendages
Acne	2%	0%
Pruritus	2%	1%
Musculo-Skeletal
Myalgia	5%	2%
Skeletal pain	2%	1%
Metabolic and nutritional
Weight increase	2%	0%
Vision disorders
Vision abnormal	6%	2%
Cardiovascular, general
Hypertension	3%	1%
Hypotension	2%	0%
Heart rate and rhythm
Tachycardia	3%	2%

Table 3. Incidence of Treatment-Emergent Adverse Events in a 3-Week, Placebo-Controlled Trial - Adjunctive Therapy in Bipolar Mania*

	Risperdal® + Mood Stabilizer	Placebo + Mood Stabilizer
Body System/ Preferred Term	(N=52)	(N=51)
* Events reported by at least 2% of patients treated with Risperdal® are included and are rounded to the nearest %. Events reported by at least 2% of patients treated with Risperdal® that were less than the incidence reported by patients treated with placebo are not listed in the table, but included the following: dyspepsia, nausea, vomiting, headache, tremor, insomnia, chest pain, fatigue, pain, skeletal pain, hypertension, and vision abnormal.
Gastrointestinal system
Saliva increased	10%	0%
Diarrhea	8%	4%
Abdominal pain	6%	0%
Constipation	6%	4%
Mouth dry	6%	4%
Tooth ache	4%	0%
Tooth disorder	4%	0%
Central & peripheral nervous system
Dizziness	14%	2%
Parkinsonism	14%	4%
Akathisia	8%	0%
Dystonia	6%	4%
Psychiatric
Somnolence	25%	12%
Anxiety	6%	4%
Confusion	4%	0%
Respiratory system
Rhinitis	8%	4%
Pharyngitis	6%	4%
Coughing	4%	0%
Body as a whole - general
Asthenia	4%	2%
Urinary system
Urinary incontinence	6%	2%
Heart rate and rhythm
Tachycardia	4%	2%
Metabolic and nutritional
Weight increase	4%	2%
Skin and appendages
Rash	4%	2%

Dose Dependency of Adverse Events

Extrapyramidal Symptoms

Data from two fixed-dose trials provided evidence of dose-relatedness for extrapyramidal symptoms associated with risperidone treatment.

Two methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 4 fixed doses of risperidone (2, 6, 10, and 16 mg/day), including (1) a parkinsonism score (mean change from baseline) from the Extrapyramidal Symptom Rating Scale, and (2) incidence of spontaneous complaints of EPS:

Dose Groups	Placebo	Ris 2	Ris 6	Ris 10	Ris 16
Parkinsonism	1.2	0.9	1.8	2.4	2.6
EPS Incidence	13%	13%	16%	20%	31%

Similar methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 5 fixed doses of risperidone (1, 4, 8, 12, and 16 mg/day):

Dose Groups	Ris 1	Ris 4	Ris 8	Ris 12	Ris 16
Parkinsonism	0.6	1.7	2.4	2.9	4.1
EPS Incidence	7%	12%	18%	18%	21%

Other Adverse Events

Adverse event data elicited by a checklist for side effects from a large study comparing 5 fixed doses of Risperdal® (1, 4, 8, 12, and 16 mg/day) were explored for dose-relatedness of adverse events. A Cochran-Armitage Test for trend in these data revealed a positive trend (p<0.05) for the following adverse events: sleepiness, increased duration of sleep, accommodation disturbances, orthostatic dizziness, palpitations, weight gain, erectile dysfunction, ejaculatory dysfunction, orgastic dysfunction, asthenia/lassitude/increased fatigability, and increased pigmentation.

Vital Sign Changes

Risperdal® is associated with orthostatic hypotension and tachycardia.

Weight Changes

The proportions of Risperdal® and placebo-treated patients meeting a weight gain criterion of ≥ 7% of body weight were compared in a pool of 6- to 8-week, placebo-controlled trials, revealing a statistically significantly greater incidence of weight gain for Risperdal® (18%) compared to placebo (9%).

Laboratory Changes

A between-group comparison for 6- to 8-week placebo-controlled trials revealed no statistically significant Risperdal®/placebo differences in the proportions of patients experiencing potentially important changes in routine serum chemistry, hematology, or urinalysis parameters. Similarly, there were no Risperdal®/placebo differences in the incidence of discontinuations for changes in serum chemistry, hematology, or urinalysis. However, Risperdal® administration was associated with increases in serum prolactin.

ECG Changes

Between-group comparisons for pooled placebo-controlled trials revealed no statistically significant differences between risperidone and placebo in mean changes from baseline in ECG parameters, including QT, QTc, and PR intervals, and heart rate. When all Risperdal® doses were pooled from randomized controlled trials in several indications, there was a mean increase in heart rate of 1 beat per minute compared to no change for placebo patients. In short-term schizophrenia trials, higher doses of risperidone (8–16 mg/day) were associated with a higher mean increase in heart rate compared to placebo (4–6 beats per minute).

Adverse Events and Other Safety Measures in Pediatric Patients With Autistic Disorder

In the two 8-week, placebo-controlled trials in pediatric patients treated for irritability associated with autistic disorder (n=156), two patients (one treated with Risperdal® and one treated with placebo) discontinued treatment due to an adverse event.

In addition to spontaneous reporting, in one of the studies, adverse events were also elicited from a checklist for detecting selected events, a method that is more sensitive than spontaneous reporting.

The most common adverse events with Risperdal® that occurred at an incidence equal to or greater than 5% and at a rate of at least twice that of placebo are shown in Table 4.

Table 4 Incidence of Treatment-Emergent Adverse Events in Two 8-Week, Placebo-Controlled Trials in Pediatric Patients with Autistic Disorder

Body System Preferred Term	Risperdal® (n=76)	Placebo (n=80)
Psychiatric
Somnolence	67%	23%
Appetite increased	49%	19%
Confusion	5%	0%
Gastrointestinal
Saliva increased	22%	6%
Constipation	21%	8%
Dry mouth	13%	6%
Body as a whole-general
Fatigue	42%	13%
Central & peripheral nervous system
Tremor	12%	1%
Dystonia	12%	6%
Dizziness	9%	3%
Automatism	7%	1%
Dyskinesia	7%	0%
Parkinsonism	8%	0%
Respiratory
Upper respiratory tract infection	34%	15%
Metabolic and nutritional
Weight increase	5%	0%
Heart rate and rhythm
Tachycardia	7%	0%

Weight increase was reported more frequently with Risperdal® than with placebo. The average weight increase over 8 weeks was 2.6 kg in patients treated with Risperdal® compared with 0.9 kg in patients treated with placebo.

There was a higher incidence of adverse events reflecting extrapyramidal symptoms (EPS) in the Risperdal® group (27.6%) compared with the placebo group (10.0%). In addition, between-group comparison of the severity of EPS were assessed objectively by the following rating instruments: the Simpson-Angus Rating Scale (SARS) and the Abnormal Involuntary Movement Scale (AIMS) in one study, and the Extrapyramidal Symptom Rating Scale (ESRS) in the other study. The mean changes between baseline and endpoint in the total ESRS score were –0.3 in the Risperdal® group and –0.4 in the placebo group. The median change from baseline to endpoint was 0 in both treatment groups for each EPS rating scale.

Somnolence was the most frequent adverse event, and was reported at a higher incidence in the Risperdal® group compared with the placebo group. The vast majority of cases (96%) were either mild or moderate in severity. These events were most often of early onset with peak incidence occurring during the first 2 weeks of treatment, and median duration was 16 days. Patients experiencing persistent somnolence may benefit from a change in dosing regimen.

Other Events Observed During the Premarketing Evaluation of Risperdal®

During its premarketing assessment, multiple doses of Risperdal® were administered to 2607 adult patients with schizophrenia and 1923 pediatric patients in Phase 2 and 3 studies. The conditions and duration of exposure to Risperdal® varied greatly, and included (in overlapping categories) open-label and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies, and short-term or longer-term exposure. In most studies, untoward events associated with this exposure were obtained by spontaneous report 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 untoward events into a smaller number of standardized event categories. In two large studies, adverse events were also elicited utilizing the UKU (direct questioning) side effect rating scale, and these events were not further categorized using standard terminology. (Note: These events are marked with an asterisk in the listings that follow.)

In the listings that follow, spontaneously reported adverse events were classified using World Health Organization (WHO) preferred terms. The frequencies presented, therefore, represent the proportion of the 2607 adult or 1923 pediatric patients exposed to multiple doses of Risperdal® who experienced an event of the type cited on at least one occasion while receiving Risperdal®. All reported events are included, except those already listed in Table 1, 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 Risperdal®, they were not necessarily caused by it. Serious adverse reactions experienced by the pediatric population were similar to those seen in the adult population.

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.

Psychiatric Disorders

Frequent: increased dream activity1, diminished sexual desire1, nervousness. Infrequent: impaired concentration, depression, apathy, catatonic reaction, euphoria, increased libido, amnesia. Rare: emotional lability, nightmares, delirium, withdrawal syndrome, yawning.

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1

Incidence based on elicited reports.

Central and Peripheral Nervous System Disorders

Frequent: increased sleep duration1. Infrequent: dysarthria, vertigo, stupor, paraesthesia, confusion. Rare: aphasia, cholinergic syndrome, hypoesthesia, tongue paralysis, leg cramps, torticollis, hypotonia, coma, migraine, hyperreflexia, choreoathetosis.

Gastrointestinal Disorders

Frequent: anorexia, reduced salivation1. Infrequent: flatulence, diarrhea, increased appetite, stomatitis, melena, dysphagia, hemorrhoids, gastritis. Rare: fecal incontinence, eructation, gastroesophageal reflux, gastroenteritis, esophagitis, tongue discoloration, cholelithiasis, tongue edema, diverticulitis, gingivitis, discolored feces, GI hemorrhage, hematemesis.

Body as a Whole/General Disorders

Frequent: fatigue. Infrequent: edema, rigors, malaise, influenza-like symptoms. Rare: pallor, enlarged abdomen, allergic reaction, ascites, sarcoidosis, flushing.

Respiratory System Disorders

Infrequent: hyperventilation, bronchospasm, pneumonia, stridor. Rare : asthma, increased sputum, aspiration.

Skin and Appendage Disorders

Frequent: increased pigmentation1, photosensitivity1 Infrequent: increased sweating, acne, decreased sweating, alopecia, hyperkeratosis, pruritus, skin exfoliation. Rare: bullous eruption, skin ulceration, aggravated psoriasis, furunculosis, verruca, dermatitis lichenoid, hypertrichosis, genital pruritus, urticaria.

Cardiovascular Disorders

Infrequent: palpitation, hypertension, hypotension, AV block, myocardial infarction. Rare: ventricular tachycardia, angina pectoris, premature atrial contractions, T wave inversions, ventricular extrasystoles, ST depression, myocarditis.

Vision Disorders

Infrequent: abnormal accommodation, xerophthalmia. Rare: diplopia, eye pain, blepharitis, photopsia, photophobia, abnormal lacrimation.

Metabolic and Nutritional Disorders

Infrequent: hyponatremia, weight increase, creatine phosphokinase increase, thirst, weight decrease, diabetes mellitus. Rare: decreased serum iron, cachexia, dehydration, hypokalemia, hypoproteinemia, hyperphosphatemia, hypertriglyceridemia, hyperuricemia, hypoglycemia.

Urinary System Disorders

Frequent: polyuria/polydipsia1. Infrequent: urinary incontinence, hematuria, dysuria. Rare: urinary retention, cystitis, renal insufficiency.

Musculo-Skeletal System Disorders

Infrequent: myalgia. Rare: arthrosis, synostosis, bursitis, arthritis, skeletal pain.

Reproductive Disorders, Female

Frequent: menorrhagia1, orgastic dysfunction1, dry vagina1 Infrequent: nonpuerperal lactation, amenorrhea, female breast pain, leukorrhea, mastitis, dysmenorrhea, female perineal pain, intermenstrual bleeding, vaginal hemorrhage.

Liver and Biliary System Disorders

Infrequent: increased SGOT, increased SGPT. Rare: hepatic failure, cholestatic hepatitis, cholecystitis, cholelithiasis, hepatitis, hepatocellular damage.

Platelet, Bleeding, and Clotting Disorders

Infrequent: epistaxis, purpura. Rare: hemorrhage, superficial phlebitis, thrombophlebitis, thrombocytopenia.

Hearing and Vestibular Disorders

Rare: tinnitus, hyperacusis, decreased hearing.

Red Blood Cell Disorders

Infrequent: anemia, hypochromic anemia. Rare: normocytic anemia.

Reproductive Disorders, Male

Frequent: erectile dysfunction1 Infrequent: ejaculation failure.

White Cell and Resistance Disorders

Infrequent: granulocytopenia Rare: leukocytosis, lymphadenopathy, leucopenia, Pelger-Huet anomaly.

Endocrine Disorders

Rare: gynecomastia, male breast pain, antidiuretic hormone disorder.

Special Senses

Rare: bitter taste.

Postintroduction Reports

Adverse events reported since market introduction which were temporally (but not necessarily causally) related to Risperdal® therapy, include the following: anaphylactic reaction, angioedema, apnea, atrial fibrillation, cerebrovascular disorder, including cerebrovascular accident, diabetes mellitus aggravated, including diabetic ketoacidosis, hyperglycemia, intestinal obstruction, jaundice, mania, pancreatitis, Parkinson's disease aggravated, pituitary adenomas, pulmonary embolism, precocious puberty, and QT prolongation. There have been rare reports of sudden death and/or cardiopulmonary arrest in patients receiving Risperdal®. A causal relationship with Risperdal® has not been established. It is important to note that sudden and unexpected death may occur in psychotic patients whether they remain untreated or whether they are treated with other antipsychotic drugs.

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Side Effects by Body System

Nervous system

Nervous system side effects have frequently included insomnia (26%), dystonia (18%), akathisia (16%), extrapyramidal symptoms (17%), headache (14%), dizziness (11%), parkinsonism (6%), asthenia (4%), somnolence (3%), and hypoesthesia (2%). Increased dream activity, nervousness, impaired concentration, increased sleep duration, dysarthria, vertigo, stupor, paraesthesia, confusion, and amnesia have also been reported. Delirium, withdrawal syndrome, yawning, aphasia, cholinergic syndrome, hypoesthesia, tongue paralysis, leg cramps, torticollis, hypotonia, coma, migraine, hyperreflexia, choreoathetosis, seizures, neuroleptic malignant syndrome, tardive dyskinesia, and sleep- related eating disorder (SRED) have been reported rarely.

Extrapyramidal symptoms may be less frequently associated with risperidone than most other available antipsychotics. Treatment of extrapyramidal effects, in addition to general supportive measures, may include judicious use of one or more of the following: benztropine, trihexyphenidyl, biperiden, or diphenhydramine.

Sedation may occur, particularly at higher doses. Blurred vision, vertigo, impaired concentration, increased appetite and decreased appetite have also been reported.

At least three cases of tardive dyskinesia have also been reported with risperidone use with one case accompanied by risperidone induced parkinsonism. Tardive dyskinesia involves involuntary, dyskinetic, repetitive movements. Tardive dyskinesia may be irreversible and is related to both the duration of therapy and the total amount of drug consumed. Frequent discontinuation and resumption of therapy may predispose patients to the development of tardive dyskinesia.

At least fourteen cases of neuroleptic malignant syndrome have been reported with risperidone use. Fever, altered consciousness, autonomic dysfunction and muscle rigidity are the hallmarks of the neuroleptic malignant syndrome. The neuroleptic malignant syndrome is associated with a case fatality rate of about 20%. Immediate discontinuation of neuroleptic therapy, consideration of dantrolene administration as well as intensive monitoring and supportive care are indicated. Nine of the 13 cases reported were between 15 and 43 years old. One of the cases had a delayed onset and another case resulted in death.

One study has reported that in patients who were given risperidone, there was a positive correlation between improvement in psychopathology and improvement in cognitive test of explicit memory and alertness.

Cardiovascular

Cardiovascular side effects have frequently included tachycardia, hypertension, and hypotension. Palpitation, AV block, and myocardial infarction have also been reported. Ventricular tachycardia, angina pectoris, premature atrial contractions, T wave inversions, ventricular extrasystoles, syncope, edema, ST depression, myocarditis, venous thromboembolism, and bradycardia have been reported rarely. Prolongation of the QT interval has been reported in some patients. One fatal cardiac event following initiation of risperidone therapy has been reported.

Cerebrovascular events (e.g., stroke and transient ischemic attack), including fatalities, have rarely been reported and then primarily in elderly patients with dementia- related psychosis.

An increased risk of mortality, possibly due to heart failure or sudden death, has been reported with the use of atypical antipsychotic agents, including risperidone, in the treatment of behavioral disorders in the elderly patient with dementia. However, it should be noted that conflicting data exist regarding an increased risk of mortality and use of risperidone in elderly dementia patients.

During postmarketing surveillance, retinal artery occlusion in the presence of abnormal arteriovenous anastomosis has been reported following injection of long-acting risperidone.

Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents, including risperidone, 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. Risperidone is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia. However, in contrast, the results of another meta-analysis of 6 randomized, double-blind, placebo-controlled, clinical trials (n=1721) found a nonsignificant increase in overall mortality in elderly dementia patients treated with risperidone.

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.

Based on data from four placebo controlled trials conducted in elderly patients (n=1230), cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in elderly patients with dementia- related psychosis. In placebo controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with risperidone compared to patients treated with placebo. Risperidone has not been shown to be safe or effective in the treatment of patients with dementia- related psychosis. Additional information on these and other clinical trials conducted in elderly patients can be obtained by calling 1-800- JANSSEN (800-526-7736). However, the association between the use of atypical antipsychotics (i.e., risperidone, olanzapine) and the risk of cerebrovascular events appears to be somewhat controversial. The results of a case-control study found no increased risk of cerebrovascular events in elderly patients treated with atypical antipsychotics.

Endocrine

Hyperprolactinemia in some patients may cause sexual dysfunction (i.e., decreased libido, impaired performance), gynecomastia, reduced fertility, galactorrhea, menstrual irregularities (i.e., amenorrhea, oligomenorrhea), and osteoporosis. In addition, as many as one-third of human breast cancers may be prolactin-dependent in vitro. Treatment of risperidone- induced hyperprolactinemia may include use of bromocriptine, amantadine, or cabergoline as well as discontinuation of therapy.

A study of U.S. military veterans with schizophrenia has reported that patients on risperidone had 1.49 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.

Endocrine side effects have included hyperprolactinemia, diabetes, and antidiuretic hormone disorder. Compared with other antipsychotic drugs, risperidone is associated with a greater elevation in prolactin levels.

Genitourinary

A case of priapism lasting approximately 36- hours in duration was reported in a 32- year- old male approximately 8 weeks after initiation of risperidone for the treatment of schizophrenia and 2 weeks after an increase in daily dosage to 5 mg. Risperidone was discontinued immediately. The patient reported, after this event, that he had been experiencing prolonged erections since initiation of risperidone therapy, a phenomenon commonly reported with priapism. However, the patient did not report these events to his clinicians until after this event.

Approximately 18 cases of risperidone- associated priapism have been reported, including a patient who developed priapism while being switched from the oral to the intramuscular formulation. Risperidone- induced priapism is believed to be caused by alpha-adrenergic blockade.

Genitourinary side effects have frequently included urinary incontinence, polyuria, and polydipsia. Hematuria and dysuria have also been reported. Urinary retention, gynecomastia, and cystitis have been reported rarely. Menorrhagia, galactorrhea, orgastic dysfunction, dry vagina, nonpuerperal lactation, amenorrhea, breast pain, leukorrhea, mastitis, dysmenorrhea, perineal pain, intermenstrual bleeding, and vaginal hemorrhage have been reported in females. Erectile dysfunction, ejaculation failure, breast pain, and priapism have been reported in males. Hyperprolactinemia caused by risperidone may impair reproductive function in both male and female patients. Hyperprolactinemia causes a reduction in the pituitary secretion of gonadotropin which, in turn, impairs gonadal steroidogenesis.

Gastrointestinal

Gastrointestinal side effects have frequently included constipation, nausea, dyspepsia, vomiting, abdominal pain, tooth ache, tooth disorder, dry mouth, and hypersalivation. Anorexia, hyposalivation, flatulence, diarrhea, increased appetite, stomatitis, melena, dysphagia, hemorrhoids, and gastritis have also been reported. Fecal incontinence, eructation, gastroesophageal reflux, gastroenteritis, esophagitis, tongue discoloration, cholelithiasis, tongue edema, diverticulitis, gingivitis, discolored feces, gastrointestinal hemorrhage, bitter taste, and hematemesis have also been reported.

Hepatic

Hepatic side effects have included mild reversible elevations in liver function tests, including SGOT and SGPT. Hepatic failure, cholestatic hepatitis, cholecystitis, cholelithiasis, hepatitis, and hepatocellular damage have been reported rarely.

At least one case of rapid onset risperidone induced hepatotoxicity has been reported.

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.

Psychiatric

Psychiatric side effects have frequently included agitation, anxiety, manic reaction, and aggressive reaction. Diminished sexual desire, depression, apathy, catatonic reaction, euphoria, and increased libido have also been reported. Emotional lability, nightmares, and obsessive-compulsive symptoms have been reported rarely.

Ocular

Ocular side effects were looked at in one study on the adverse effects of risperidone on eye movement. The study reported a prolonged latency and decreased peak velocity and accuracy of saccadic eye movements that was detectable four weeks after treatment initiation.

Ocular side effects have frequently included abnormal vision. Abnormal accommodation and xerophthalmia have also been reported. Diplopia, eye pain, blepharitis, photopsia, photophobia, and abnormal lacrimation have been reported rarely. A case of periorbital edema has also been reported.

Metabolic

Hyperglycemia has been reported in some cases to be extreme and associated with ketoacidosis or hyperosmolar coma and death.

Treatment with risperidone has been associated with moderate weight gain (mean 2.1 kg). Risperidone- associated weight gain appears to be more pronounced in the young, males, non- white race, and those with a lower body mass index.

Metabolic side effects have frequently included weight gain. Hyponatremia, creatine phosphokinase increase, thirst, weight decrease, and hyperglycemia have also been reported. Decreased serum iron, cachexia, dehydration, hypokalemia, hypoproteinemia, hyperphosphatemia, hypertriglyceridemia, hyperuricemia, and hypoglycemia have been reported rarely.

Respiratory

Respiratory side effects have frequently included rhinitis, coughing, sinusitis, pharyngitis, upper respiratory infection, and dyspnea. Hyperventilation, bronchospasm, pneumonia, and stridor have also been reported. Asthma, increased sputum, and aspiration have been reported rarely. A case of respiratory dyskinesia has also been reported.

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

Collective data gathered from 17 placebo-controlled clinical studies (n=5106) involving the use of atypical antipsychotic agents, including risperidone, 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. Risperidone is not approved by the FDA for use in the treatment of behavioral disorders in elderly patients with dementia.

A case of respiratory dyskinesia characterized by involuntary movements of the respiratory musculature, irregular respiration, grunting, and hyperventilation was reported in a patient following discontinuation of risperidone. Symptoms resolved after restarting risperidone and subsequently, were less severe with a more gradual withdrawal of risperidone.

Other

Other side effects have frequently included back pain, chest pain, fever, pain, fatigue, and injury. Edema, rigors, malaise, and influenza-like symptoms have also been reported. Pallor, enlarged abdomen, ascites, sarcoidosis, flushing, tinnitus, hyperacusis, decreased hearing, and nose bleeds have been reported rarely.

Dermatologic

Dermatologic side effects have frequently included rash, dry skin, seborrhea, acne, pruritus, increased pigmentation, and photosensitivity. Increased sweating, acne, decreased sweating, alopecia, hyperkeratosis, and skin exfoliation have also been reported. Bullous eruption, skin ulceration, aggravated psoriasis, furunculosis, verruca, dermatitis lichenoid, hypertrichosis, genital pruritus, and urticaria have been reported rarely.

Musculoskeletal

Musculoskeletal side effects have frequently included arthralgia, myalgia, and skeletal pain. Arthrosis, synostosis, bursitis, arthritis, and skeletal pain have been reported rarely. Decreased bone density may occur in both male and female patients as a result of risperidone- induced prolonged hyperprolactinemia. A case of Pisa syndrome has also been reported.

Renal

Renal side effects have rarely included renal insufficiency.

Hypersensitivity

Hypersensitivity side effects have rarely included allergic reaction.

Hematologic

Hematologic side effects have rarely included epistaxis, purpura, hemorrhage, superficial phlebitis, thrombophlebitis, thrombocytopenia, anemia, hypochromic anemia, normocytic anemia, leukocytosis, lymphadenopathy, leukopenia, and Pelger-Huet anomaly.

Immunologic

Immunologic side effects have included one case of risperidone- induced erythema multiforme minor and a case of immunoallergic hepatitis.

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