"Feb. 22, 2011 -- The FDA has issued a safety announcement notifying health care professionals that it has updated the pregnancy section of drug labels for the entire class of antipsychotic medications.
Antipsychotic drugs are used to "...
Invega Sustenna Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Invega Sustenna (paliperidone palmitate) is an antipsychotic drug used to treat schizophrenia. Common side effects of Invega Sustenna include drowsiness, dizziness, lightheadedness, weight gain, pain, redness, and swelling at the injection site.
The recommended dosage of Invega Sustenna is 234 mg on the first day of treatment, 156 mg one week later, and 117 mg once a month thereafter. Benztropine, scopolamine, levodopa, bromocriptine, lisinopril, and risperidone may interact with Invega Sustenna. Tell your doctor all medications you take. Do not stop taking Invega Sustenna without first consulting your doctor. Avoid alcohol consumption while taking Invega Sustenna. If you are pregnant only take Invega Sustenna if clearly needed. Talk to your doctor before taking Invega Sustenna if you are breastfeeding.
Our Invega Sustenna (paliperidone palmitate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Patient Information Overview?
A concise overview of the drug for the patient or caregiver from First DataBank.
Invega Sustenna Overview - Patient Information: Side Effects
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor right away if you have any serious side effects, including: difficulty swallowing, restlessness, muscle spasms, signs of infection (such as fever, persistent sore throat).
Get medical help right away if any of these rare but serious side effects occur: fainting, severe dizziness, slow heartbeat, seizures.
Paliperidone may rarely cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor immediately if you develop any unusual/uncontrolled movements (especially of the face, lips, mouth, tongue, arms, or legs).
This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, change in the amount of urine.
This drug may infrequently make your blood sugar level rise, which can cause or worsen diabetes. Tell your doctor immediately if you develop symptoms of high blood sugar such as increased thirst and urination. If you already have diabetes, be sure to check your blood sugar level regularly.
This drug may also cause significant weight gain and a rise in your blood cholesterol (or triglyceride) levels. These effects, along with diabetes, may increase your risk for developing heart disease. Discuss the risks and benefits of treatment with your doctor. (See also Notes section.)
Rarely, this medication may increase your blood level of a certain hormone (prolactin). In females, an increase in prolactin levels may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. In males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.
For males, in the very unlikely event you have a painful or prolonged erection (lasting more than 4 hours), stop using this drug and seek immediate medical attention, or permanent problems could occur.
A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Read the entire patient information overview for Invega Sustenna (Paliperidone Palmitate Extended-Release Injectable Suspension)»
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Invega Sustenna FDA Prescribing Information: Side Effects
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]
- Cerebrovascular adverse reactions, including stroke, in elderly patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS]
- Neuroleptic malignant syndrome [see WARNINGS AND PRECAUTIONS]
- QT prolongation [see WARNINGS AND PRECAUTIONS]
- Tardive dyskinesia [see WARNINGS AND PRECAUTIONS]
- Metabolic changes [see WARNINGS AND PRECAUTIONS]
- Orthostatic hypotension and syncope [see WARNINGS AND PRECAUTIONS]
- Leukopenia, neutropenia, and agranulocytosis [see WARNINGS AND PRECAUTIONS]
- Hyperprolactinemia [See WARNINGS AND PRECAUTIONS]
- Potential for cognitive and motor impairment [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
- Dysphagia [see WARNINGS AND PRECAUTIONS]
- Priapism [see WARNINGS AND PRECAUTIONS]
- Disruption of body temperature regulation [see WARNINGS AND PRECAUTIONS]
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 most common (at least 5% in any INVEGA® SUSTENNA® group) and likely drug-related (adverse events for which the drug rate is at least twice the placebo rate) adverse reactions from the double-blind, placebo-controlled trials were injection site reactions, somnolence/sedation, dizziness, akathisia, and extrapyramidal disorder.
The data described in this section are derived from a clinical trial database consisting of a total of 3817 subjects with schizophrenia who received at least one dose of INVEGA® SUSTENNA® in the recommended dose range of 39 mg to 234 mg and a total of 510 subjects with schizophrenia who received placebo. Among the 3817 INVEGA® SUSTENNA® -treated subjects, 1293 received INVEGA® SUSTENNA® in four fixed-dose, double-blind, placebo-controlled trials (one 9-week and three 13-week studies), 849 received INVEGA® SUSTENNA® in the maintenance trial (of whom 205 continued to receive INVEGA® SUSTENNA® during the double-blind placebo-controlled phase of this study), and 1675 received INVEGA® SUSTENNA® in five non-placebo controlled trials (three noninferiority active-comparator trials, one long-term open-label pharmacokinetic and safety study, and an injection site [deltoidgluteal] cross-over trial). One of the 13-week studies included a 234 mg INVEGA® SUSTENNA® initiation dose followed by treatment with either 39 mg, 156 mg, or 234 mg every 4 weeks.
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.
The majority of all adverse reactions were mild to moderate in severity.
Clinical Trials Experience
Commonly Reported Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials
Table 5 lists the adverse reactions reported in 2% or more of INVEGA® SUSTENNA® -treated subjects and at a greater proportion than in the placebo group with schizophrenia in the four fixed-dose, double-blind, placebo-controlled trials.
Table 5: Incidence of Treatment Emergent Adverse
Reactions in ≥ 2% of INVEGA® SUSTENNA® -Treated Subjects (and greater
than Placebo) with Schizophrenia in Four Fixed-Dose, Double-Blind, Placebo-
|System Organ Class Adverse Event||Placeboa
|Total percentage of subjects with adverse event||70||75||68||69||63||60||63|
|Abdominal discomfort/abdominal pain upper||2||2||4||4||1||2||4|
|General disorders and administration site conditions|
|Injection site reactions||2||0||4||6||9||7||10|
|Infections and infestations|
|Upper respiratory tract infection||2||2||2||2||1||2||4|
|Urinary tract infection||1||0||1||< 1||1||1||2|
|Musculoskeletal and connective tissue disorders|
|Musculoskeletal stiffness||1||1||< 1||< 1||1||1||2|
|Pain in extremity||1||0||2||2||2||3||0|
|Nervous system disorders|
|Respiratory, thoracic and mediastinal disorders|
|Percentages are rounded to whole numbers. Table includes
adverse events that were reported in 2% or more of subjects in any of the
INVEGA® SUSTENNA® dose groups and which occurred at greater incidence than in
the placebo group.
a Placebo group is pooled from all studies and included either deltoid or gluteal injection depending on study design.
b Initial deltoid injection of 234 mg followed by either 39 mg, 156 mg, or 234 mg every 4 weeks by deltoid or gluteal injection. Other dose groups (39 mg, 78 mg, and 156 mg) are from studies involving only gluteal injection. [See Clinical Studies]
Adverse events for which the INVEGA® SUSTENNA® incidence was equal to or less than placebo are not listed in the table, but included the following: dyspepsia, psychotic disorder, schizophrenia, and tremor. The following terms were combined: somnolence/sedation, breast tenderness/breast pain, abdominal discomfort/abdominal pain upper/stomach discomfort, and tachycardia/sinus tachycardia/heart rate increased. All injection site reaction-related adverse events were collapsed and are grouped under “Injection site reactions”.
Other Adverse Reactions Observed During the Clinical Trial Evaluation of INVEGA® SUSTENNA®
The following additional adverse reactions occurred in INVEGA® SUSTENNA® -treated subjects in the above four fixed-dose, double-blind, placebo-controlled trials, in the double-blind phase of the maintenance trial, or in INVEGA® SUSTENNA® -treated subjects with schizophrenia who participated in other clinical trials, and were not reported in Table 5 or in other sections of labeling above. They were determined to be adverse reactions based upon reasons to suspect causality such as timing of onset or termination with respect to drug use, plausibility in light of the drug's known pharmacology, occurrence at a frequency above that expected in the treated population or occurrence of an event typical of drug-induced adverse reactions.
Ear and labyrinth disorders: vertigo
Eye disorders: eye movement disorder, eye rolling, oculogyric crisis, vision blurred
Gastrointestinal disorders: salivary hypersecretion
Immune system disorders: hypersensitivity
Investigations: electrocardiogram abnormal
Metabolism and nutrition disorders: decreased appetite, hyperinsulinemia, increased appetite
Nervous system disorders: bradykinesia, cerebrovascular accident, convulsion, dizziness postural, drooling, dysarthria, dyskinesia, dystonia, hypertonia, lethargy, oromandibular dystonia, parkinsonism, psychomotor hyperactivity, syncope
Psychiatric disorders: restlessness
Reproductive system and breast disorders: amenorrhea, breast discharge, erectile dysfunction, galactorrhea, gynecomastia, menstrual disorder, menstruation delayed, menstruation irregular, sexual dysfunction
Discontinuations Due to Adverse Events
The percentages of subjects who discontinued due to adverse events in the four fixed-dose, double-blind, placebo-controlled trials were 5.0% and 7.8% in INVEGA® SUSTENNA® - and placebo-treated subjects, respectively.
Dose-Related Adverse Reactions
Based on the pooled data from the four fixed-dose, double-blind, placebo-controlled trials, among the adverse reactions that occurred at ≥ 2% incidence in the subjects treated with INVEGA® SUSTENNA® , only akathisia increased with dose. Hyperprolactinemia also exhibited a dose relationship, but did not occur at ≥ 2% incidence in INVEGA® SUSTENNA® -treated subjects from the four fixed-dose studies.
An examination of population subgroups in the double-blind placebo-controlled trials did not reveal any evidence of differences in safety on the basis of age, gender, or race alone; however, there were few subjects ≥ 65 years of age.
Extrapyramidal Symptoms (EPS)
Pooled data from the two double-blind, placebo-controlled, 13-week, fixed-dose trials provided information regarding treatment-emergent EPS. Several methods were used to measure EPS: (1) the Simpson-Angus global score (mean change from baseline or score at the end of trial) which broadly evaluates Parkinsonism, (2) the Barnes Akathisia Rating Scale global clinical rating score (mean change from baseline or score at the end of trial) which evaluates akathisia, (3) use of anticholinergic medications to treat emergent EPS, (4) the Abnormal Involuntary Movement Scale scores (mean change from baseline or scores at the end of trial) (Table 6), and (5) incidence of spontaneous reports of EPS (Table 7).
Table 6: Treatment-Emergent Extrapyramidal Symptoms
(EPS) Assessed by Incidence of Rating Scales and Use of Anticholinergic
|Scale||Percentage of Subjects|
|Use of Anticholinergic Medicationsd||12||10||12||11|
|a For Parkinsonism, percent of subjects with Simpson-Angus
Total score > 0.3 at endpoint (Total score defined as total sum of items
score divided by the number of items)
b For Akathisia, percent of subjects with Barnes Akathisia Rating Scale global score ≥ 2 at endpoint
c For Dyskinesia, percent of subjects with a score ≥ 3 on any of the first 7 items or a score ≥ 2 on two or more of any of the first 7 items of the Abnormal Involuntary Movement Scale at endpoint
d Percent of subjects who received anticholinergic medications to treat emergent EPS
Table 7: Treatment-Emergent Extrapyramidal Symptoms
(EPS)-Related Adverse Events by MedDRA Preferred Term
|EPS Group||Percentage of Subjects|
|Overall percentage of subjects with EPS-related adverse events||10||12||11||11|
|Parkinsonism group includes: Extrapyramidal disorder,
hypertonia, musculoskeletal stiffness, parkinsonism, drooling, masked facies,
muscle tightness, hypokinesia
Hyperkinesia group includes: Akathisia, restless legs syndrome, restlessness
Dyskinesia group includes: Dyskinesia, choreoathetosis, muscle twitching, myoclonus, tardive dyskinesia
Dystonia group includes: Dystonia, muscle spasms
The results across all phases of the maintenance trial exhibited comparable findings. In the 9-week, fixed-dose, double-blind, placebo-controlled trial, the proportions of Parkinsonism and akathisia assessed by incidence of rating scales were higher in the INVEGA® SUSTENNA® 156 mg group (18% and 11%, respectively) than in the INVEGA® SUSTENNA® 78 mg group (9% and 5%, respectively) and placebo group (7% and 4%, respectively).
In the 13-week study involving 234 mg initiation dosing, the incidence of any treatmentemergent EPS-related adverse events was similar to that of the placebo group (8%), but exhibited a dose-related pattern with 6%, 10%, and 11% in the INVEGA® SUSTENNA® 234/39 mg, 234/156 mg, and 234/234 mg groups, respectively. Hyperkinesia was the most frequent category of EPS-related adverse events in this study, and was reported at a similar rate between the placebo (4.9%) and INVEGA® SUSTENNA® 234/156 mg (4.8%) and 234/234 mg (5.5%) groups, but at a lower rate in the 234/39 mg group (1.3%).
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.
Laboratory Test Abnormalities
In the pooled data from the two double-blind, placebo-controlled, 13-week, fixed-dose trials, a between-group comparison revealed no medically important differences between INVEGA® SUSTENNA® and placebo in the proportions of subjects experiencing potentially clinically significant changes in routine serum chemistry, hematology, or urinalysis parameters. Similarly, there were no differences between INVEGA® SUSTENNA® and placebo in the incidence of discontinuations due to changes in hematology, urinalysis, or serum chemistry, including mean changes from baseline in fasting glucose, insulin, c-peptide, triglyceride, HDL, LDL, and total cholesterol measurements. However, INVEGA® SUSTENNA® was associated with increases in serum prolactin [see WARNINGS AND PRECAUTIONS]. The results from the 13-week study involving 234 mg initiation dosing, the 9-week, fixed-dose, double-blind, placebo-controlled trial, and the double-blind phase of the maintenance trial exhibited comparable findings.
Pain Assessment and Local Injection Site Reactions
In the pooled data from the two 13-week, fixed-dose, double-blind, placebo-controlled trials, the mean intensity of injection pain reported by subjects using a visual analog scale (0 = no pain to 100 = unbearably painful) decreased in all treatment groups from the first to the last injection (placebo: 10.9 to 9.8; 39 mg: 10.3 to 7.7; 78 mg: 10.0 to 9.2; 156 mg: 11.1 to 8.8). The results from both the 9-week, fixed-dose, double-blind, placebo-controlled trial and the double-blind phase of the maintenance trial exhibited comparable findings.
In the 13-week study involving 234 mg initiation dosing, occurrences of induration, redness, or swelling, as assessed by blinded study personnel, were infrequent, generally mild, decreased over time, and similar in incidence between the INVEGA® SUSTENNA® and placebo groups. Investigator ratings of injection pain were similar for the placebo and INVEGA® SUSTENNA® groups. Investigator evaluations of the injection site after the first injection for redness, swelling, induration, and pain were rated as absent for 69-100% of subjects in both the INVEGA® SUSTENNA® and placebo groups. At Day 92, investigators rated absence of redness, swelling, induration, and pain in 95-100% of subjects in both the INVEGA® SUSTENNA® and placebo groups.
Adverse Reactions Reported In Clinical Trials With Oral Paliperidone
The following is a list of additional adverse reactions that have been reported in clinical trials with oral paliperidone:
Cardiac disorders: bundle branch block left, sinus arrhythmia
Psychiatric disorders: sleep disorder
Reproductive system and breast disorders: breast engorgement, breast tenderness/breast pain, retrograde ejaculation
Skin and subcutaneous tissue disorders: rash papular
The following adverse reactions have been identified during postapproval use of paliperidone; because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: angioedema, ileus, swollen tongue, thrombotic thrombocytopenic purpura, urinary incontinence, and urinary retention.
Very rarely, cases of anaphylactic reaction after injection with INVEGA® SUSTENNA® have been reported during postmarketing experience in patients who have previously tolerated oral risperidone or oral paliperidone.
Adverse Reactions Reported With Risperidone
Paliperidone is the major active metabolite of risperidone. Adverse reactions reported with oral risperidone and risperidone long-acting injection can be found in the ADVERSE REACTIONS sections of the package inserts for those products.
Read the entire FDA prescribing information for Invega Sustenna (Paliperidone Palmitate Extended-Release Injectable Suspension) »
Additional Invega Sustenna Information
- Invega Sustenna Drug Interactions Center: paliperidone palmitate im
- Invega Sustenna Side Effects Center
- Invega Sustenna Overview including Precautions
- Invega Sustenna FDA Approved Prescribing Information including Dosage
Invega Sustenna - User Reviews
Invega Sustenna User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get tips on therapy and treatment.