Invega Hafyera

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 9/8/2021
Invega Hafyera Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Invega Hafyera?

Invega Hafyera (6-month paliperidone palmitate), an every-six-month injection, is an atypical antipsychotic used to treat schizophrenia in adults after they
have been adequately treated with:

A once-a-month paliperidone palmitate extended-release injectable
suspension (e.g., Invega Sustenna) for at least four months or

An every-three-month paliperidone palmitate extended-release injectable
suspension (e.g., Invega Trinza) for at least one three-month cycle

What Are Side Effects of Invega Hafyera?

Side effects of Invega Hafyera include:

  • upper respiratory tract infection,
  • injection site reactions (discomfort, redness, bleeding, hard lump, swelling, and pain),
  • weight gain,
  • headache, and
  • parkinsonism.

Dosage for Invega Hafyera

Invega Hafyera is administered by gluteal injection once every 6 months by a healthcare professional. In initial dose of Invega Hafyera ranges from 1,092 mg to 1,560 mg, depending on the patient’s previous dosage of Invega Sustenna or Invega Trinza.


Invega Hafyera In Children

Safety and effectiveness of Invega Hafyera in patients less than 18 years of age have not been established. Use of Invega Hafyera is not recommended in pediatric patients because of the potential longer duration of an adverse event.

What Drugs, Substances, or Supplements Interact with Invega Hafyera?
 

Invega Hafyera may interact with other medicines such as:

  • centrally acting drugs and alcohol,
  • drugs with potential for inducing orthostatic hypotension,
  • strong inducers of CYP3A4 and P-gp (e.g., carbamazepine, rifampin, or St. John's wort), and
  • levodopa and other dopamine agonists.

Tell your doctor all medications and supplements you use.


Invega Hafyera During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Invega Hafyera; it may cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Invega Hafyera, during pregnancy. Invega Hafyera may pass into breast milk but its effects on nursing infants are unknown. Consult your doctor before breastfeeding.

Additional Information

Our Invega Hafyera (6-month paliperidone palmitate) Extended-Release
Injectable Suspension, for Gluteal Intramuscular Use 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.

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.

SLIDESHOW

Schizophrenia: Symptoms, Types, Causes, Treatment See Slideshow
Invega Hafyera Professional 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]
  • Falls [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]

Clinical Trials Experience

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.

Patient Exposure

The data described in this section is derived from the randomized double-blind active controlled non-inferiority study of INVEGA HAFYERA and 3-month paliperidone palmitate extended-release injectable suspension. During the double-blind phase, 478 patients were randomized to receive 2 injection cycles of INVEGA HAFYERA over a 12-month duration. The mean (SD) duration of exposure was 329.8 (86.97) days in the INVEGA HAFYERA group and 336.4 (80.89) days in the PP3M group during the double-blind phase:

Adverse Reactions In The Double-Blind, Active-Controlled Clinical Trial

Commonly Observed Adverse Reactions

The most common adverse reactions (incidence at least 5% in the double-blind Phase) of the INVEGA HAFYERA clinical trial were, upper respiratory tract infection, injection site reaction, weight increased, headache and parkinsonism.

Discontinuation Of Treatment Due To Adverse Reactions

In the double-blind phase of the INVEGA HAFYERA clinical trial 1.3% of subjects in the INVEGA HAFYERA group and 0.4% of subjects in the 3-month paliperidone palmitate extended-release injectable suspension group discontinued due to adverse reactions.

Adverse Reactions Occurring At An Incidence Of 2% Or More In INVEGA HAFYERA-Treated Patients

Table 7 lists the adverse reactions reported in the INVEGA HAFYERA clinical trial.

Table 7: Incidences of Adverse Reactions 2% or More of INVEGA HAFYERA-Treated Patients for the Double-Blind Phase of the Randomized Double-blind Active Controlled Trial in Patients with Schizophrenia

System Organ Class Double Blind
PP3M1
(N=224) %
INVEGA HAFYERA
(N=478) %
Adverse Reaction
Gastrointestinal disorders
Diarrhea* 1 2
General disorders and administration site conditions
Injection site reaction* 5 11
Infections and infestations
Upper respiratory tract infection* 13 12
Urinary tract infection 1 3
Metabolism and nutrition disorders
Weight increased 8 9
Musculoskeletal and connective tissue disorders
Back pain* 1 3
Musculoskeletal pain* 1 3
Nervous system disorders
Akathisia* 4 4
Headache 5 7
Extrapyramidal symptoms* 5 7
Psychiatric disorders
Psychosis* 3 3
Anxiety 0 3
Insomnia* 2 3
1 PP3M - Every-three-month paliperidone palmitate extended-release injectable suspension
* The following terms were combined:
Diarrhea includes: Diarrhea, Diarrhea infectious.
Injection site reaction: includes Injection site reaction, Injection site discomfort, Injection site erythema, Injection site hemorrhage, Injection site induration, Injection site nodule, Injection site oedema, Injection site pain, Injection site swelling.
Weight increased includes: Weight increased, Body mass index increased, Obesity, Waist circumference increased.
Upper respiratory tract infection includes: Upper respiratory tract infection, Nasopharyngitis, Pharyngitis, Rhinitis, Viral pharyngitis, Viral upper respiratory tract infection.
Back pain includes: Back pain, Neck pain, Spinal pain.
Musculoskeletal pain includes: Musculoskeletal pain, Musculoskeletal chest pain, Myalgia, Pain in extremity.
Akathisia includes: Akathisia, Restless legs syndrome, Restlessness.
Extrapyramidal symptoms includes: blepharospasms, bradykinesia, drooling, dyskinesia, dystonia, hypokinesia, musculoskeletal stiffness, muscle rigidity, muscle spasms, oculogyric crisis, Parkinsonism, Parkinsonism rest tremor, reduced facial expression, tardive dyskinesia.
Insomnia includes: Insomnia, Initial insomnia, Middle insomnia.
Psychosis includes: acute psychosis, delusion, delusion of reference, hallucination (auditory), psychotic disorder, psychotic symptom, and schizophrenia.

Demographic Differences

An examination of population subgroups in the INVEGA HAFYERA trial did not reveal any evidence of differences in safety on the basis of age, gender, or race alone.

Extrapyramidal Symptoms (EPS)

Data from the randomized double-blind active controlled study provided information regarding EPS. Several methods were used to measure EPS: (1) the Simpson-Angus Rating Scale Global Score which broadly evaluates parkinsonism, (2) the Barnes Akathisia Rating Scale Global Clinical Rating Score which evaluates akathisia, (3) the Abnormal Involuntary Movement Scale scores which evaluates dyskinesia, and (4) use of anticholinergic medications to treat EPS (Table 8) and (5) incidence of spontaneous reports of EPS (Table 9).

Table 8: Extrapyramidal Symptoms (EPS) Assessed by Rating Scales Incidence and Use of Anticholinergic Medication During the Double-blind Phase

PP3M1
(N=224) %
INVEGA HAFYERA
(N=478) %
Use of Anticholinergic Medication(a) 13 15
Parkinsonism(b) 6 7
Akathisia(c) 3 3
1 PP3M - Every-three-month paliperidone palmitate extended-release injectable suspension
(a) Use of Anti-EPS Medication During the Double-blind Phase
(b) Percent of subjects with Simpson-Angus Scale Global Score >0.3(Global Score defined as total sum of items score divided by the number of items).
(c) Percent of subjects with Barnes Akathisia Rating Scale Global Clinical Rating Score ≥2
(d) Percent of subjects with a score ≥3 on any of the first seven items or a score ≥2 on two or more of any of the first seven items of the Abnormal Involuntary Movement Scale
Note: Percentages are calculated based on number of subjects in the DB Safety analysis set per treatment group.

Table 9: Extrapyramidal Symptoms (EPS)-Related Events by MedDRA Preferred Term

EPS Group Double-blind Phase
PP3M1
(N=224)%
INVEGA HAFYERA
(N=478)%
Overall percentage of subjects with EPS-related adverse events 9 10
Parkinsonism 4 5
Hyperkinesia 4 4
Tremor 0 <1
Dyskinesia 1 2
Dystonia 1 1
1 PP3M - Every-three-month paliperidone palmitate extended-release injectable suspension
Parkinsonism group includes: Bradykinesia, drooling, hypokinesia, muscle rigidity, musculoskeletal stiffness, parkinsonism, parkinsonian rest tremor, reduced facial expression
Hyperkinesia group includes: Akathisia, restlessness, restless legs syndrome
Dyskinesia group includes: Dyskinesia, muscle twitching, tardive dyskinesia
Dystonia group includes: Blepharospasm, dystonia, muscle spasms, oculogyric crisis

Dystonia

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.

Pain Assessment And Local Injection Site Reactions

Investigator Ratings Of Injection Site

Induration, redness and swelling were observed in 13% in the INVEGA HAFYERA group and 9% in the PP3M group during the double-blind Phase. Investigator evaluation of tenderness was higher for subjects in the INVEGA HAFYERA group versus the 3-month paliperidone palmitate extended-release injectable suspension group (31% vs. 19%) during the double-blind Phase. Active INVEGA HAFYERA medication was given at double-blind baseline and Month 6, while placebo medication was given at the other injection times.

Subject Ratings Of Injection Site Pain

The average score for the subject's evaluation of injection pain on a scale of 0 to 100 was approximately 16 at the open-label Phase end point and approximately 5 in both groups at the double-blind Phase end point.

Other Adverse Reactions Observed During The Clinical Trial Evaluation Of INVEGA HAFYERA

The following additional adverse reactions were identified in the randomized double-blind active controlled study. The following list does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications.

Blood and lymphatic system disorders: anemia

Cardiac disorders: bradycardia, tachycardia

Ear and labyrinth disorders: vertigo

Gastrointestinal disorders: constipation, nausea, vomiting

General disorders and administration site conditions: fatigue

Hepatobiliary disorders: transaminases increased

Infections and infestations: cystitis, respiratory tract infection, tonsillitis

Metabolism and nutritional disorders: decreased appetite, increased appetite, weight decreased

Psychiatric disorders: depression

Reproductive system and breast disorders: breast pain, menstrual disorder

Skin and subcutaneous tissue disorders: rash

Vascular disorders: hypertension

Additional Adverse Reactions Reported In Clinical Trials With The 1-Month And 3-Month Paliperidone Palmitate Extended-Release Injectable Suspension

The following is a list of additional adverse reactions that have been reported in clinical trials with the 1-month and 3-month paliperidone palmitate extended-release injectable suspensions that are not listed elsewhere:

Cardiac disorders: atrioventricular block first degree, bundle branch block, palpitations, postural orthostatic tachycardia syndrome

Eye disorders: eye movement disorder, eye rolling, oculogyric crisis, vision blurred

Gastrointestinal disorders: abdominal discomfort/abdominal pain upper, diarrhea, dry mouth, toothache

General disorders and administration site conditions: asthenia, chest discomfort

Immune system disorders: hypersensitivity

Investigations: electrocardiogram abnormal

Metabolism and nutrition disorders: hyperinsulinemia

Musculoskeletal and connective tissue disorders: myalgia, pain in extremity, joint stiffness, muscle spasms, muscle twitching, nuchal rigidity

Nervous system disorders: bradykinesia, cerebrovascular accident, convulsion, dizziness, dizziness postural, dysarthria, hypertonia, lethargy, oromandibular dystonia, psychomotor hyperactivity, syncope

Psychiatric disorders: agitation, nightmare

Reproductive system and breast disorders: breast discharge, erectile dysfunction, gynecomastia, sexual dysfunction

Respiratory, thoracic and mediastinal disorders: cough

Skin and subcutaneous tissue disorders: drug eruption, eczema, pruritus, pruritus generalized, urticaria

Vascular disorders: hypotension, orthostatic hypotension

Additional 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

Gastrointestinal disorders: abdominal pain, constipation, flatulence, small intestinal obstruction

General disorders and administration site conditions: edema, edema peripheral

Immune system disorders: anaphylactic reaction

Musculoskeletal and connective tissue disorders: arthralgia, torticollis, trismus

Nervous system disorders: grand mal convulsion, parkinsonian gait, transient ischemic attack

Psychiatric disorders: sleep disorder

Reproductive system and breast disorders: breast engorgement, breast tenderness, retrograde ejaculation

Respiratory, thoracic and mediastinal disorders: nasal congestion, pharyngolaryngeal pain, pneumonia aspiration

Skin and subcutaneous tissue disorders: rash papular

Vascular disorders: ischemia

Postmarketing Experience

The following adverse reactions have been identified during post-approval 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, catatonia, ileus, somnambulism, swollen tongue, thrombotic thrombocytopenic purpura, urinary incontinence, and urinary retention.

Cases of anaphylactic reaction after injection with the 1-month paliperidone palmitate extended-release suspension have been reported during postmarketing experience in patients who have previously tolerated oral risperidone or oral paliperidone.

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 (6) section of the Prescribing Information for those products.

DRUG INTERACTIONS

Drugs Having Clinically Important Interactions With INVEGA HAFYERA

Because paliperidone palmitate is hydrolyzed to paliperidone, results from studies with oral paliperidone should be taken into consideration when assessing drug-drug interaction potential. In addition, consider the 6-month dosing interval and the half-life of INVEGA HAFYERA [see CLINICAL PHARMACOLOGY].

Table 10 presents clinically significant drug interactions with INVEGA HAFYERA.

Table 10: Clinically Important Drug Interactions with INVEGA HAFYERA

Centrally acting Drugs and Alcohol
Clinical Rationale
Clinical Recommendation
Given the primary CNS effects of paliperidone, concomitant use of centrally acting drugs and alcohol may modulate the CNS effects of INVEGA HAFYERA.
INVEGA HAFYERA should be used with caution with other centrally acting drugs and alcohol.
Drugs with Potential for Inducing Orthostatic Hypotension
Clinical Rationale
Clinical Recommendation
Because INVEGA HAFYERA has the potential for inducing orthostatic hypotension, an additive effect may occur when INVEGA HAFYERA is administered with other therapeutic agents that have this potential [see WARNINGS AND PRECAUTIONS].
Monitor orthostatic vital signs in patients who are vulnerable to hypotension [see WARNINGS AND PRECAUTIONS].
Strong Inducers of CYP3A4 and P-gp
Clinical Rationale
Clinical Recommendation Examples
The concomitant use of INVEGA HAFYERA and strong inducers of CYP3A4 and Pgp may decrease the exposure of paliperidone [see CLINICAL PHARMACOLOGY].
Avoid using CYP3A4 and/or P-gp inducers with INVEGA HAFYERA during the 6-month dosing interval, if possible. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended-release tablets [see DOSAGE AND ADMINISTRATION].
carbamazepine, rifampin, or St. John’s Wort
Levodopa and Other Dopamine Agonists
Clinical Rationale
Clinical Recommendation
Paliperidone may antagonize the effect of levodopa and other dopamine agonists.
Monitor and manage patient as clinically appropriate.

Drugs Having No Clinically Important Interactions With INVEGA HAFYERA

Based on pharmacokinetic studies with oral paliperidone, no dosage adjustment of INVEGA HAFYERA is required when administered concomitantly with valproate [see CLINICAL PHARMACOLOGY]. Additionally, no dosage adjustment is necessary for valproate when co-administered with INVEGA HAFYERA [see CLINICAL PHARMACOLOGY].

Pharmacokinetic interaction between lithium and INVEGA HAFYERA is unlikely.

Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P450 isozymes. In vitro studies indicate that CYP2D6 and CYP3A4 may be involved in paliperidone metabolism; however, there is no evidence in vivo that inhibitors of these enzymes significantly affect the metabolism of paliperidone. Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, and CYP2C19; an interaction with inhibitors or inducers of these isozymes is unlikely [see CLINICAL PHARMACOLOGY].

Drug Abuse And Dependence

Controlled Substance

INVEGA HAFYERA contains paliperidone, which is not a controlled substance.

Abuse

Paliperidone has not been systematically studied in animals or humans for its potential for abuse.

Dependence

Paliperidone has not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

Read the entire FDA prescribing information for Invega Hafyera (6-month Paliperidone Palmitate)

QUESTION

Schizophrenia is the most disabling mental illness. See Answer

© Invega Hafyera Patient Information is supplied by Cerner Multum, Inc. and Invega Hafyera Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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