Risperidone Side Effects

Brand Names: Risperdal, Risperdal Consta, Risperdal M-Tab

Please note - some side effects for Risperidone 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 Risperidone - for the Consumer

Risperidone

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 Risperidone:

Anxiety; appetite changes; constipation; cough; dizziness; drowsiness; dry mouth; fatigue; headache; increased saliva production; indigestion; light-headedness; nausea; pain, swelling, or redness at the injection site; restlessness; runny or stuffy 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 Risperidone:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); abnormal thoughts; confusion; drooling; fainting; fast, slow, or irregular heartbeat; fever, chills, or sore throat; inability to control urination; increased sweating; new or worsening mental or mood changes (eg, agitation, aggression, depression, severe anxiety); 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.

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.

Risperidone 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 Risperidone Orally Disintegrating Tablets:

Anxiety; constipation; cough; diarrhea; dizziness; drowsiness; dry mouth; fatigue; headache; increased appetite; increased saliva production; indigestion; light-headedness; 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 Risperidone Orally Disintegrating Tablets:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; confusion; drooling; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; inability to control urination; increased sweating; new or worsening mental or mood changes (eg, aggression, agitation, depression, severe anxiety); 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.

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.

Risperidone 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 Risperidone Solution:

Anxiety; constipation; cough; diarrhea; dizziness; drowsiness; dry mouth; fatigue; headache; increased appetite; increased saliva production; indigestion; light-headedness; 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 Risperidone Solution:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue, unusual hoarseness); abnormal thoughts; confusion; drooling; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; inability to control urination; increased sweating; new or worsening mental or mood changes (eg, aggression, agitation, depression, severe anxiety); 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.

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.

Risperidone 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 Risperidone Tablets:

Anxiety; constipation; cough; diarrhea; dizziness; drowsiness; dry mouth; fatigue; headache; increased appetite; increased saliva production; indigestion; light-headedness; 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 Risperidone Tablets:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; confusion; drooling; fainting; fast or irregular heartbeat; fever, chills, or persistent sore throat; inability to control urination; increased sweating; new or worsening mental or mood changes (eg, aggression, agitation, depression, severe anxiety); 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.

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.

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Risperidone Side Effects - for the Professional

Risperidone

The following are discussed in more detail in other sections of the labeling:

• Increased mortality in elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1)]
• Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2)]
• Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]
• Tardive dyskinesia [see Warnings and Precautions (5.4)]
• Metabolic changes [see Warnings and Precautions (5.5)]
• Hyperprolactinemia [see Warnings and Precautions (5.6)]
• Orthostatic hypotension [see Warnings and Precautions (5.7)]
• Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions (5.8)]
• Potential for cognitive and motor impairment [see Warnings and Precautions (5.9)]
• Seizures [see Warnings and Precautions (5.10)]
• Dysphagia [see Warnings and Precautions (5.11)]
• Priapism [see Warnings and Precautions (5.12)]
• Thrombotic Thrombocytopenic Purpura (TTP) [see Warnings and Precautions (5.13)]
• Disruption of body temperature regulation [see Warnings and Precautions (5.14)]
• Antiemetic effect [see Warnings and Precautions (5.15)]
• Suicide [see Warnings and Precautions (5.16)]
• Increased sensitivity in patients with Parkinson’s disease or those with dementia with Lewy bodies [see Warnings and Precautions (5.17)]
• Diseases or conditions that could affect metabolism or hemodynamic responses [see Warnings and Precautions (5.17)]

The most common adverse reactions in clinical trials (≥ 10%) were somnolence, increased appetite, fatigue, insomnia, sedation, parkinsonism, akathisia, vomiting, cough, constipation, nasopharyngitis, drooling, rhinorrhea, dry mouth, abdominal pain upper, dizziness, nausea, anxiety, headache, nasal congestion, rhinitis, tremor, and rash.

The most common adverse reactions that were associated with discontinuation from clinical trials (causing discontinuation in > 1% of adults and/or > 2% of pediatrics) were nausea, somnolence, sedation, vomiting, dizziness, and akathisia [see Adverse Reactions (6.5)].

The data described in this section are derived from a clinical trial database consisting of 9712 adult and pediatric patients exposed to one or more doses of Risperidone for the treatment of schizophrenia, bipolar mania, autistic disorder, and other psychiatric disorders in pediatrics and elderly patients with dementia. Of these 9712 patients, 2626 were patients who received Risperidone while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with Risperidone varied greatly and included (in overlapping categories) double-blind, fixed- and flexible-dose, placebo- or active-controlled studies and open-label phases of studies, inpatients and outpatients, and short-term (up to 12 weeks) and longer-term (up to 3 years) exposures. Safety was assessed by collecting adverse events and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs.

Adverse events during exposure to study treatment were obtained by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology.

Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of Risperidone (adverse drug reactions) based on the comprehensive assessment of the available adverse event information. A causal association for Risperidone often cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The majority of all adverse reactions were mild to moderate in severity.

Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials - Schizophrenia

Adult Patients With Schizophrenia

Table 4 lists the adverse reactions reported in 1% or more of Risperidone-treated adult patients with schizophrenia in three 4 to 8 week, double-blind, placebo-controlled trials.

Table 4. Adverse Reactions in ≥ 1% of Risperidone-Treated Adult Patients With Schizophrenia in Double-Blind, Placebo-Controlled Trials

* Parkinsonism includes extrapyramidal disorder, musculoskeletal stiffness, parkinsonism, cogwheel rigidity, akinesia, bradykinesia, hypokinesia, masked facies, muscle rigidity, and Parkinson’s disease. Akathisia includes akathisia and restlessness. Dystonia includes dystonia, muscle spasms, muscle contractions involuntary, muscle contracture, oculogyration, tongue paralysis. Tremor includes tremor and parkinsonian rest tremor. Dyskinesia includes dyskinesia, muscle twitching, chorea, and choreoathetosis.
	Percentage of Patients Reporting Event
	Risperidone
System/Organ Class	2 to 8 mg per day	> 8 to 16 mg per day	Placebo
Adverse Reaction	(N = 366)	(N = 198)	(N = 225)
Blood and Lymphatic System Disorders
Anemia	< 1	1	0
Cardiac Disorders
Tachycardia	1	3	0
Ear and Labyrinth Disorders
Ear pain	< 1	1	0
Eye Disorders
Vision blurred	3	1	1
Gastrointestinal Disorders
Nausea	9	4	4
Constipation	8	9	6
Dyspepsia	8	6	5
Vomiting	7	5	7
Dry mouth	4	0	1
Abdominal discomfort	3	1	1
Salivary hypersecretion	2	1	< 1
Diarrhea	2	1	1
Abdominal pain	1	1	0
Abdominal pain upper	1	1	0
Stomach discomfort	1	1	1
General Disorders
Fatigue	3	1	0
Chest pain	2	2	1
Asthenia	2	1	< 1
Immune System Disorders
Hypersensitivity	< 1	1	0
Infections and Infestations
Nasopharyngitis	3	4	3
Upper respiratory tract infection	2	3	1
Sinusitis	1	2	1
Urinary tract infection	1	3	0
Investigations
Weight increased	1	1	0
Blood creatine phosphokinase increased	1	2	< 1
Heart rate increased	< 1	2	0
Metabolism and Nutrition Disorders
Decreased appetite	1	0	< 1
Musculoskeletal and Connective Tissue Disorders
Back pain	4	1	1
Arthralgia	2	3	< 1
Pain in extremity	2	1	1
Joint stiffness	1	1	0
Nervous System Disorders
Parkinsonism*	14	17	8
Akathisia*	10	10	3
Dizziness	7	4	2
Somnolence	7	2	1
Dystonia*	3	4	2
Sedation	3	3	1
Tremor*	2	3	1
Dizziness postural	2	0	0
Dyskinesia*	1	2	2
Syncope	1	1	0
Psychiatric Disorders
Insomnia	32	25	27
Anxiety	16	11	11
Nervousness	1	1	< 1
Renal and Urinary Disorders
Urinary incontinence	1	1	0
Reproductive System and Breast Disorders
Ejaculation failure	< 1	1	0
Respiratory, Thoracic and Mediastinal Disorders
Nasal congestion	4	6	2
Dyspnea	1	2	0
Epistaxis	< 1	2	0
Skin and Subcutaneous Tissue Disorders
Rash	1	4	1
Dry skin	1	3	0
Dandruff	1	1	0
Seborrheic dermatitis	< 1	1	0
Hyperkeratosis	0	1	1
Vascular Disorders
Orthostatic hypotension	2	1	0
Hypotension	1	1	0

Pediatric Patients With Schizophrenia 

Table 5 lists the adverse reactions reported in 5% or more of Risperidone-treated pediatric patients with schizophrenia in a 6 week double-blind, placebo-controlled trial.

Table 5. Adverse Reactions in ≥ 5% of Risperidone-Treated Pediatric Patients With Schizophrenia in a Double-Blind Trial

* Parkinsonism includes extrapyramidal disorder, muscle rigidity, musculoskeletal stiffness, and hypokinesia. Akathisia includes akathisia and restlessness. Dystonia includes dystonia and oculogyration.
	Percentage of Patients Reporting Event
	Risperidone
System/Organ Class	1 to 3 mg per day	4 to 6 mg per day	Placebo
Adverse Reaction	(N = 55)	(N = 51)	(N = 54)
Gastrointestinal Disorders
Salivary hypersecretion	0	10	2
Nervous System Disorders
Parkinsonism*	16	28	11
Sedation	13	8	2
Somnolence	11	4	2
Tremor	11	10	6
Akathisia*	9	10	4
Dizziness	7	14	2
Dystonia*	2	6	0
Psychiatric Disorders
Anxiety	7	6	0

Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials - Bipolar Mania

Adult Patients With Bipolar Mania

Table 6 lists the adverse reactions reported in 1% or more of Risperidone-treated adult patients with bipolar mania in four 3 week, double-blind, placebo-controlled monotherapy trials.

Table 6. Adverse Reactions in ≥ 1% of Risperidone-Treated Adult Patients With Bipolar Mania in Double-Blind, Placebo-Controlled Monotherapy Trials

* Parkinsonism includes extrapyramidal disorder, parkinsonism, musculoskeletal stiffness, hypokinesia, muscle rigidity, muscle tightness, bradykinesia, cogwheel rigidity. Akathisia includes akathisia and restlessness. Tremor includes tremor and parkinsonian rest tremor. Dystonia includes dystonia, muscle spasms, oculogyration, torticollis. Dyskinesia includes muscle twitching and dyskinesia.
	Percentage of Patients Reporting Event
	Risperidone	Placebo
System/Organ Class	1 to 6 mg per day	(N = 424)
Adverse Reaction	(N = 448)
Cardiac Disorders
Tachycardia	1	< 1
Eye Disorders
Vision blurred	2	1
Gastrointestinal Disorders
Nausea	5	2
Diarrhea	3	2
Salivary hypersecretion	3	1
Dyspepsia	2	2
Stomach discomfort	2	< 1
General Disorders
Fatigue	2	1
Asthenia	1	1
Pyrexia	1	1
Infections and Infestations
Nasopharyngitis	1	1
Investigations
Aspartate aminotransferase increased	1	< 1
Nervous System Disorders
Parkinsonism*	25	9
Akathisia*	9	3
Tremor*	6	3
Dizziness	6	5
Sedation	6	2
Somnolence	5	2
Dystonia*	5	1
Lethargy	2	1
Dyskinesia*	1	< 1
Reproductive System and Breast Disorders
Galactorrhea	1	0
Skin and Subcutaneous Tissue Disorders
Acne	1	0

Table 7 lists the adverse reactions reported in 2% or more of Risperidone-treated adult patients with bipolar mania in two 3 week, double-blind, placebo-controlled adjuvant therapy trials.

Table 7. Adverse Reactions in ≥ 2% of Risperidone-Treated Adult Patients With Bipolar Mania in Double-Blind, Placebo-Controlled Adjuvant Therapy Trials

* Parkinsonism includes extrapyramidal disorder, hypokinesia and bradykinesia. Akathisia includes hyperkinesia and akathisia.
	Percentage of Patients Reporting Event
System/Organ Class	Risperidone + Mood Stabilizer	Placebo + Mood Stabilizer
Adverse Reaction	(N = 127)	(N = 126)
Cardiac Disorders
Palpitations	2	0
Gastrointestinal Disorders
Dyspepsia	9	8
Nausea	6	4
Diarrhea	6	4
Dry mouth	4	4
Vomiting	4	6
Constipation	3	3
Salivary hypersecretion	2	0
General Disorders
Chest pain	2	1
Fatigue	2	2
Infections and Infestations
Nasopharyngitis	2	3
Urinary tract infection	2	1
Investigations
Weight increased	2	2
Nervous System Disorders
Parkinsonism*	14	4
Headache	14	15
Akathisia*	8	0
Dizziness	7	2
Sedation	6	3
Tremor	6	2
Somnolence	3	1
Lethargy	2	1
Psychiatric Disorders
Insomnia	4	8
Anxiety	3	2
Respiratory, Thoracic and Mediastinal Disorders
Pharyngolaryngeal pain	5	2
Cough	2	0

Pediatric Patients With Bipolar Mania 

Table 8 lists the adverse reactions reported in 5% or more of Risperidone-treated pediatric patients with bipolar mania in a 3 week, double-blind, placebo-controlled trial.

Table 8. Adverse Reactions in ≥ 5% of Risperidone-Treated Pediatric Patients With Bipolar Mania in Double-Blind, Placebo-Controlled Trials

* Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, bradykinesia, and nuchal rigidity. Dystonia includes dystonia, laryngospasm, and muscle spasms. Akathisia includes restlessness and akathisia.
	Percentage of Patients Reporting Event
	Risperidone
System/Organ Class	0.5 to 2.5 mg per day	3 to 6 mg per day	Placebo
Adverse Reaction	(N = 50)	(N = 61)	(N = 58)
Eye Disorders
Vision blurred	4	7	0
Gastrointestinal Disorders
Abdominal pain upper	16	13	5
Nausea	16	13	7
Vomiting	10	10	5
Diarrhea	8	7	2
Dyspepsia	10	3	2
Stomach discomfort	6	0	2
General Disorders
Fatigue	18	30	3
Metabolism and Nutrition Disorders
Increased appetite	4	7	2
Nervous System Disorders
Somnolence	22	30	12
Sedation	20	23	7
Dizziness	16	13	5
Parkinsonism*	6	12	3
Dystonia*	6	5	0
Akathisia*	0	8	2
Psychiatric Disorders
Anxiety	0	8	3
Respiratory, Thoracic and Mediastinal Disorders
Pharyngolaryngeal pain	10	3	5
Skin and Subcutaneous Tissue Disorders
Rash	0	7	2

Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials - Autistic Disorder

Table 9 lists the adverse reactions reported in 5% or more of Risperidone-treated pediatric patients treated for irritability associated with autistic disorder in two 8 week, double-blind, placebo-controlled trials.

Table 9. Adverse Reactions in ≥ 5% of Risperidone-Treated Pediatric Patients Treated for Irritability Associated With Autistic Disorder in Double-Blind, Placebo-Controlled Trials

* Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, muscle rigidity, cogwheel rigidity, and muscle tightness.
	Percentage of Patients Reporting Event
System/Organ Class	Risperidone	Placebo
Adverse Reaction	0.5 to 4.0 mg per day	(N = 80)
	(N = 76)
Cardiac Disorders
Tachycardia	5	0
Gastrointestinal Disorders
Vomiting	25	21
Constipation	21	8
Dry mouth	15	6
Salivary hypersecretion	9	0
Nausea	8	6
General Disorders
Fatigue	42	13
Feeling abnormal	5	0
Infections and Infestations
Nasopharyngitis	21	10
Rhinitis	13	10
Upper respiratory tract infection	8	3
Investigations
Weight increased	5	0
Metabolism and Nutrition Disorders
Increased appetite	47	19
Nervous System Disorders
Somnolence	49	18
Sedation	29	3
Drooling	16	5
Tremor	12	1
Parkinsonism*	11	1
Dizziness	9	3
Dyskinesia	7	3
Lethargy	5	3
Respiratory, Thoracic and Mediastinal Disorders
Cough	24	18
Rhinorrhea	16	13
Nasal congestion	13	5
Skin and Subcutaneous Tissue Disorders
Rash	11	8

In another study with patients treated for irritability associated with autistic disorder, headache (6%), epistaxis (6%) and pyrexia (6%) were also observed in Risperidone-treated pediatric subjects.

Other Adverse Reactions Observed During the Clinical Trial Evaluation of Risperidone

The following adverse reactions occurred in < 1% of the adult patients and in < 5% of the pediatric patients treated with Risperidone in the above double-blind, placebo-controlled clinical trial data sets. In addition, the following also includes adverse reactions reported in Risperidone-treated patients who participated in other studies, including double-blind, active-controlled and open-label studies in schizophrenia and bipolar mania studies in pediatric patients with psychiatric disorders other than schizophrenia, bipolar mania, or autistic disorder, and studies in elderly patients with dementia.

Blood and Lymphatic System Disorders: granulocytopenia, neutropenia

Cardiac Disorders: sinus bradycardia, sinus tachycardia, atrioventricular block first degree, bundle branch block left, bundle branch block right, atrioventricular block

Ear and Labyrinth Disorders: tinnitus

Endocrine Disorders: hyperprolactinemia

Eye Disorders: ocular hyperemia, eye discharge, conjunctivitis, eye rolling, eyelid edema, eye swelling, eyelid margin crusting, dry eye, lacrimation increased, photophobia, glaucoma, visual acuity reduced

Gastrointestinal Disorders: dysphagia, fecaloma, fecal incontinence, gastritis, lip swelling, cheilitis, aptyalism

General Disorders: edema peripheral, thirst, gait disturbance, influenza-like illness, pitting edema, edema, chills, sluggishness, malaise, chest discomfort, face edema, discomfort, generalized edema, drug withdrawal syndrome, peripheral coldness

Immune System Disorders: drug hypersensitivity

Infections and Infestations: pneumonia, influenza, ear infection, viral infection, pharyngitis, tonsillitis, bronchitis, eye infection, localized infection, cystitis, cellulitis, otitis media, onychomycosis, acarodermatitis, bronchopneumonia, respiratory tract infection, tracheobronchitis, otitis media chronic

Investigations: body temperature increased, blood prolactin increased, alanine aminotransferase increased, electrocardiogram abnormal, eosinophil count increased, white blood cell count decreased, blood glucose increased, hemoglobin decreased, hematocrit decreased, body temperature decreased, blood pressure decreased, transaminases increased

Metabolism and Nutrition Disorders: polydipsia, anorexia

Musculoskeletal and Connective Tissue Disorders: joint swelling, musculoskeletal chest pain, posture abnormal, myalgia, neck pain, muscular weakness, rhabdomyolysis

Nervous System Disorders: balance disorder, disturbance in attention, dysarthria, unresponsive to stimuli, depressed level of consciousness, movement disorder, hypersomnia, transient ischemic attack, coordination abnormal, cerebrovascular accident, speech disorder, loss of consciousness, hypoesthesia, tardive dyskinesia, cerebral ischemia, cerebrovascular disorder, neuroleptic malignant syndrome, diabetic coma, head titubation

Psychiatric Disorders: agitation, blunted affect, confusional state, middle insomnia, sleep disorder, listlessness, libido decreased, anorgasmia

Renal and Urinary Disorders: enuresis, dysuria, pollakiuria

Reproductive System and Breast Disorders: menstruation irregular, amenorrhea, gynecomastia, vaginal discharge, menstrual disorder, erectile dysfunction, retrograde ejaculation, ejaculation disorder, sexual dysfunction, breast enlargement

Respiratory, Thoracic, and Mediastinal Disorders: wheezing, pneumonia aspiration, sinus congestion, dysphonia, productive cough, pulmonary congestion, respiratory tract congestion, rales, respiratory disorder, hyperventilation, nasal edema

Skin and Subcutaneous Tissue Disorders: erythema, skin discoloration, skin lesion, pruritus, skin disorder, rash erythematous, rash papular, rash generalized, rash maculopapular

Vascular Disorders: flushing

Additional Adverse Reactions Reported With Risperidone Injection

The following is a list of additional adverse reactions that have been reported during the premarketing evaluation of Risperidone injection, regardless of frequency of occurrence:

Cardiac Disorders: bradycardia

Ear and Labyrinth Disorders: vertigo

Eye Disorders: blepharospasm

Gastrointestinal Disorders: toothache, tongue spasm

General Disorders and Administration Site Conditions: pain

Infections and Infestations: lower respiratory tract infection, infection, gastroenteritis, subcutaneous abscess

Injury and Poisoning: fall

Investigations: weight decreased, gamma-glutamyltransferase increased, hepatic enzyme increased

Musculoskeletal, Connective Tissue, and Bone Disorders: buttock pain

Nervous System Disorders: convulsion, paresthesia

Psychiatric Disorders: depression

Skin and Subcutaneous Tissue Disorders: eczema

Vascular Disorders: hypertension

Discontinuations Due to Adverse Reactions

Schizophrenia - Adults

Approximately 7% (39/564) of Risperidone-treated patients in double-blind, placebo-controlled trials discontinued treatment due to an adverse event, compared with 4% (10/225) who were receiving placebo. The adverse reactions associated with discontinuation in 2 or more Risperidone-treated patients were:

Table 10. Adverse Reactions Associated With Discontinuation in 2 or More Risperidone-Treated Adult Patients in Schizophrenia Trials

	Risperidone
	2 to 8 mg/day	> 8 to 16 mg/day	Placebo
Adverse Reaction	(N = 366)	(N = 198)	(N = 225)
Dizziness	1.4%	1.0%	0%
Nausea	1.4%	0%	0%
Vomiting	0.8%	0%	0%
Parkinsonism	0.8%	0%	0%
Somnolence	0.8%	0%	0%
Dystonia	0.5%	0%	0%
Agitation	0.5%	0%	0%
Abdominal pain	0.5%	0%	0%
Orthostatic hypotension	0.3%	0.5%	0%
Akathisia	0.3%	2.0%	0%

Discontinuation for extrapyramidal symptoms (including Parkinsonism, akathisia, dystonia, and tardive dyskinesia) was 1% in placebo-treated patients, and 3.4% in active control-treated patients in a double-blind, placebo- and active-controlled trial.

Schizophrenia - Pediatrics

Approximately 7% (7/106), of Risperidone-treated patients discontinued treatment due to an adverse event in a double-blind, placebo-controlled trial, compared with 4% (2/54) placebo-treated patients. The adverse reactions associated with discontinuation for at least one Risperidone-treated patient were dizziness (2%), somnolence (1%), sedation (1%), lethargy (1%), anxiety (1%), balance disorder (1%), hypotension (1%), and palpitation (1%).

Bipolar Mania - Adults

In double-blind, placebo-controlled trials with Risperidone as monotherapy, approximately 6% (25/448) of Risperidone-treated patients discontinued treatment due to an adverse event, compared with approximately 5% (19/424) of placebo-treated patients. The adverse reactions associated with discontinuation in Risperidone-treated patients were:

Table 11. Adverse Reactions Associated With Discontinuation in 2 or More Risperidone-Treated Adult Patients in Bipolar Mania Clinical Trials

	Risperidone
	1 to 6 mg/day	Placebo
Adverse Reaction	(N = 448)	(N = 424)
Parkinsonism	0.4%	0%
Lethargy	0.2%	0%
Dizziness	0.2%	0%
Alanine aminotransferase increased	0.2%	0.2%
Aspartate aminotransferase increased	0.2%	0.2%

Bipolar Mania - Pediatrics

In a double-blind, placebo-controlled trial 12% (13/111) of Risperidone-treated patients discontinued due to an adverse event, compared with 7% (4/58) of placebo-treated patients. The adverse reactions associated with discontinuation in more than one Risperidone-treated pediatric patient were nausea (3%), somnolence (2%), sedation (2%), and vomiting (2%).

Autistic Disorder - Pediatrics

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

Dose Dependency of Adverse Reactions in Clinical Trials

Extrapyramidal Symptoms

Data from two fixed-dose trials in adults with schizophrenia 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	Risperidone2 mg	Risperidone6 mg	Risperidone 10 mg	Risperidone 16 mg
Parkinsonism	1.2	0.9	1.8	2.4	2.6
EPS Incidence	13%	17%	21%	21%	35%

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	Risperidone 1 mg	Risperidone4 mg	Risperidone8 mg	Risperidone 12 mg	Risperidone 16 mg
Parkinsonism	0.6	1.7	2.4	2.9	4.1
EPS Incidence	7%	12%	17%	18%	20%

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.

Other Adverse Reactions

Adverse event data elicited by a checklist for side effects from a large study comparing 5 fixed doses of Risperidone (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 reactions: somnolence, vision abnormal, dizziness, palpitations, weight increase, erectile dysfunction, ejaculation disorder, sexual function abnormal, fatigue, and skin discoloration.

Changes in ECG

Between-group comparisons for pooled placebo-controlled trials in adults 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 Risperidone 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 to 16 mg/day) were associated with a higher mean increase in heart rate compared to placebo (4 to 6 beats per minute). In pooled placebo-controlled acute mania trials in adults, there were small decreases in mean heart rate, similar among all treatment groups.

In the two placebo-controlled trials in children and adolescents with autistic disorder (aged 5 to 16 years) mean changes in heart rate were an increase of 8.4 beats per minute in the Risperidone  groups and 6.5 beats per minute in the placebo group. There were no other notable ECG changes.

In a placebo-controlled acute mania trial in children and adolescents (aged 10 to 17 years), there were no significant changes in ECG parameters, other than the effect of Risperidone to transiently increase pulse rate (< 6 beats per minute). In two controlled schizophrenia trials in adolescents (aged 13 to 17 years), there were no clinically meaningful changes in ECG parameters including corrected QT intervals between treatment groups or within treatment groups over time.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Risperidone; because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency: agranulocytosis, alopecia, anaphylactic reaction, angioedema, atrial fibrillation, blood cholesterol increased, blood triglycerides increased, diabetes mellitus, diabetic ketoacidosis in patients with impaired glucose metabolism, drug withdrawal syndrome neonatal, dysgeusia, hypoglycemia, hypothermia, inappropriate antidiuretic hormone secretion, intestinal obstruction, jaundice, mania, pancreatitis, priapism, QT prolongation, sleep apnea syndrome, thrombocytopenia, urinary retention, and water intoxication.

Other adverse events reported since market introduction, which were temporally related to Risperidone but not necessarily causally related, include the following: pituitary adenoma, pulmonary embolism, precocious puberty, cardiopulmonary arrest, and sudden death.

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Side Effects by Body System - for Healthcare Professionals

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. Head titubation and dysgeusia have also been reported.

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

The results of the large scale clinical trial noted that treatment related changes in glucose tolerance were largely explained by changes in insulin sensitivity.

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. A large scale clinical trial at clinically relevant doses has reported significant reductions in glucose tolerance during treatment with risperidone.

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.

Postmarketing experience has included sleep apnea syndrome.

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. Postmarketing experience has included hypothermia and pyrexia.

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 Huët anomaly. Neutropenia has also been reported

Immunologic

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

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