erzofri

For patients naïve to oral or injectable paliperidone, or oral or injectable risperidone, establish tolerability with oral paliperidone or oral risperidone prior to initiating treatment with ERZOFRI. ( 2.1 ) Each injection must be administered by a healthcare professional. ( 2.1 ) Initiate ERZOFRI by intramuscular injection in the deltoid muscle. Following the initial dose, monthly doses can be administered in either the gluteal or deltoid muscle. Do not administer by any other route. ( 2.1 ) Dosage recommendations: Indication Initial Dose (deltoid) Day 1 Monthly Dosage Administered 4 weeks after the first injection. (deltoid or gluteal) Maximum Monthly Dosage Schizophrenia ( 2.1 ) 351 mg 39 mg to 234 mg Recommended monthly dosage for treatment of schizophrenia is 117 mg. Some patients may benefit from lower or higher monthly doses within the additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg). 234 mg Schizoaffective disorder ( 2.1 ) 351 mg 78 mg to 234 mg Adjust dose based on tolerability and/or efficacy using available strengths. The 39 mg strength was not studied in the long-term schizoaffective disorder study. 234 mg Missed dose: Refer to the Full Prescribing Information. ( 2.2 ) Mild renal impairment: Administer 234 mg on treatment Day 1 in the deltoid muscle. Follow with the recommended monthly maintenance dose of 78 mg, administered in the deltoid or…

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 reactions, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2) ] Neuroleptic malignant syndrome [see Warnings and Precautions (5.3) ] QT prolongation [see Warnings and Precautions (5.4) ] Tardive dyskinesia [see Warnings and Precautions (5.5) ] Metabolic changes [see Warnings and Precautions (5.6) ] Orthostatic hypotension and syncope [see Warnings and Precautions (5.7) ] Falls [see Warnings and Precautions (5.8) ] Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions (5.9) ] Hyperprolactinemia [see Warnings and Precautions (5.10) ] Potential for cognitive and motor impairment [see Warnings and Precautions (5.11) ] Seizures [see Warnings and Precautions (5.12) ] Dysphagia [see Warnings and Precautions (5.13) ] Priapism [see Warnings and Precautions (5.14) ] Disruption of body temperature regulation [see Warnings and Precautions (5.15) ] The most common adverse reactions (incidence ≥ 5% and occurring at least twice as often as placebo) were injection site reactions, somnolence/sedation, dizziness, akathisia, and extrapyramidal disorder. ( 6 ) To report SUSPECTED ADVERSE…

ERZOFRI is contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the ERZOFRI formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone [see Adverse Reactions (6.1 , 6.2) ] . Known hypersensitivity to paliperidone, risperidone, or to any excipients in ERZOFRI. ( 4 )

Human Experience While experience with paliperidone overdose is limited, among the few cases of overdose reported in premarketing trials with oral paliperidone, the highest estimated ingestion was 405 mg. Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and QT prolongation. Torsades de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose with oral paliperidone. Paliperidone is the major active metabolite of risperidone. Refer to the OVERDOSAGE section of the risperidone prescribing information for overdose experience with risperidone. Management of Overdosage There is no specific antidote to paliperidone. Provide supportive care, including close medical supervision and monitoring. Treatment should consist of general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdosage. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use supportive and symptomatic measures. Consider the pharmacokinetic profile of ERZOFRI and the half-life of paliperidone when assessing treatment needs and recovery. Consider contacting…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Drugs that may cause orthostatic hypotension: An additive effect may occur when co-administered with ERZOFRI. ( 7.1 ) Strong CYP3A4 and P-glycoprotein (P-gp) inducers : Avoid using a strong inducer of CYP3A4 and/or P-gp during a dosing interval for ERZOFRI. If concomitant use is necessary, consider using paliperidone extended-release tablets. ( 2.5 , 7.1 , 12.3 ) 7.1 Drugs Having Clinically Important Interactions with ERZOFRI Because paliperidone palmitate is hydrolyzed to paliperidone [see Clinical Pharmacology (12.3) ] , results from studies with oral paliperidone should be taken into consideration when assessing drug-drug interaction potential. Table 12 presents clinically significant drug interactions with ERZOFRI. Table 12: Clinically Important Drug Interactions with ERZOFRI Centrally Acting Drugs and Alcohol Clinical Rationale: Given the primary CNS effects of paliperidone, concomitant use of centrally acting drugs and alcohol may modulate the CNS effects of ERZOFRI. Clinical Recommendation: ERZOFRI should be used with caution in combination with other centrally acting drugs and alcohol [see Adverse Reactions (6.1 , 6.2) ] . Drugs with Potential for Inducing Orthostatic Hypotension Clinical Rationale: Because ERZOFRI has the potential for inducing orthostatic hypotension, an additive effect may occur when ERZOFRI is administered with other therapeutic agents that have this potential [see Warnings and Precautions (5.7) ] . Clinical Recommendation: Monitor orthostatic vital signs in patients who are vulnerable to hypotension [see Warnings and Precautions (5.7) ] . Strong Inducers of CYP3A4 and P-gp Clinical Rationale: The concomitant use of paliperidone and strong inducers of CYP3A4 and P-gp may decrease the exposure of paliperidone [see Clinical Pharmacology (12.3) ] . Clinical Recommendation: Avoid using CYP3A4 and/or P-gp inducers with ERZOFRI during the 1-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 (2.5) ] . Levodopa and Other Dopamine Agonists Clinical Rationale: Paliperidone may antagonize the effect of levodopa and other dopamine agonists. Clinical Recommendation: Monitor and manage patient as clinically appropriate. 7.2 Drugs Having No Clinically Important Interactions with ERZOFRI Based on pharmacokinetic studies with oral paliperidone, no dosage adjustment of ERZOFRI is required when administered with valproate [see Clinical Pharmacology (12.3) ]. Additionally, no dosage adjustment is necessary for valproate when co-administered with ERZOFRI [See Clinical Pharmacology (12.3) ]. Pharmacokinetic interaction between lithium and ERZOFRI is also 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 (12.3) ]