ZIPRASIDONE MESYLATE

ZIPRASIDONE MESYLATE- ziprasidone mesylate injection, powder, lyophilized, for solution
HF Acquisition Co LLC, DBA HealthFirst

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use ZIPRASIDONE MESYLATE FOR INJECTION safely and effectively. See full prescribing information for ZIPRASIDONE MESYLATE FOR INJECTION.
ZIPRASIDONE MESYLATE for injection for intramuscular use Initial U.S. Approval: 2001

RECENT MAJOR CHANGES

BOXED WARNING 11/2018
Dosage and Administration (2.4) Removed 11/2018
Warnings and Precautions ( 5.1, 5.2) 11/2018

INDICATIONS AND USAGE

Ziprasidone mesylate for injection is an atypical antipsychotic. In choosing among treatments, prescribers should be aware of the capacity of ziprasidone mesylate for injection to prolong the QT interval and may consider the use of other drugs first ( 5.3)
Ziprasidone mesylate for injection as an intramuscular injection is indicated for the:
• Acute treatment of agitation in schizophrenic patients.

DOSAGE AND ADMINISTRATION

Acute treatment of agitation associated with schizophrenia (intramuscular administration): 10 mg — 20 mg up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every 2 hours. Doses of 20 mg may be administered every 4 hours. ( 2.3)

DOSAGE FORMS AND STRENGTHS

• Intramuscular injection: 20 mg/mL single-use vials (3)

CONTRAINDICATIONS

• Do not use in patients with a known history of QT prolongation (4.1)

• Do not use in patients with recent acute myocardial infarction ( 4.1)

• Do not use in patients with uncompensated heart failure ( 4.1)

• Do not use in combination with other drugs that have demonstrated QT prolongation ( 4.1)

• Do not use in patients with known hypersensitivity to ziprasidone ( 4.2)

WARNINGS AND PRECAUTIONS

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). ( 5.2)
QT Interval Prolongation: Ziprasidone mesylate for injection use should be avoided in patients with bradycardia, hypokalemia or hypomagnesemia, congenital prolongation of the QT interval, or in combination with other drugs that have demonstrated QT prolongation. ( 5.3)
Neuroleptic Malignant Syndrome (NMS): Potentially fatal symptom complex has been reported with antipsychotic drugs. Manage with immediate discontinuation of drug and close monitoring. ( 5.4)
Severe Cutaneous Adverse Reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson syndrome has been reported with ziprasidone exposure. DRESS and other Severe Cutaneous Adverse Reactions (SCAR) are sometimes fatal. Discontinue ziprasidone mesylate for injection if DRESS or SCAR are suspected.( 5.5)
Tardive Dyskinesia: May develop acutely or chronically. ( 5.6)
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. ( 5.7)
Hyperglycemia and Diabetes Mellitus (DM): Monitor all patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients with DM risk factors should undergo blood glucose testing before and during treatment. ( 5.7)
Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. ( 5.7)
Weight Gain: Weight gain has been reported. Monitor weight gain. ( 5.7)
Rash: Discontinue in patients who develop a rash without an identified cause. ( 5.8)
Orthostatic Hypotension: Use with caution in patients with known cardiovascular or cerebrovascular disease. (5.9)
Leukopenia, Neutropenia, and Agranulocytosis has been reported with antipsychotics. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue ziprasidone mesylate for injection at the first sign of a decline in WBC in the absence of other causative factors. ( 5.11)
Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold. ( 5.12)
Potential for Cognitive and Motor impairment: Patients should use caution when operating machinery. ( 5.13)
Suicide: Closely supervise high-risk patients. (5.18)

ADVERSE REACTIONS

Commonly observed adverse reactions (incidence ≥5% and at least twice the incidence for placebo) were:

• Schizophrenia: Somnolence, respiratory tract infection. ( 6.1)

• Manic and Mixed Episodes Associated with Bipolar Disorder: Somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting. ( 6.1)

• Intramuscular administration (≥5% and at least twice the lowest intramuscular ziprasidone group): Headache, nausea, somnolence. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma at 864-879-9994 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

• Ziprasidone should not be used in combination with other drugs that have demonstrated QT prolongation. ( 4.1, 7.3)

• The full prescribing information contains additional drug interactions. ( 7).

USE IN SPECIFIC POPULATIONS

Pregnancy: Ziprasidone should be used during pregnancy only if the potential benefit justifies the potential risk. ( 8.1)
Nursing Mothers: Breast feeding is not recommended. ( 8.3)
Pediatric Use: Safety and effectiveness for pediatric patients has not been established. ( 8.4)
Renal Impairment: Intramuscular ziprasidone should be administered with caution to patients with impaired renal function as the cyclodextrin excipient is cleared by renal filtration. ( 8.6)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 1/2020

TABLE OF CONTENTS

FULL PRESCRIBING INFORMATION: CONTENTS*
BOXED WARNING
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.3 Acute Treatment of Agitation in Schizophrenia
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
4.1 QT Prolongation
4.2 Hypersensitivity
5 WARNINGS AND PRECAUTIONS
5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis
5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis
5.3 QT Prolongation and Risk of Sudden Death
5.4 Neuroleptic Malignant Syndrome (NMS)
5.5 Severe Cutaneous Adverse Reactions
5.6 Tardive Dyskinesia
5.7 Metabolic Changes
5.8 Rash
5.9 Orthostatic Hypotension
5.10 Falls
5.11 Leukopenia, Neutropenia, and Agranulocytosis
5.12 Seizures
5.13 Dysphagia
5.14 Hyperprolactinemia
5.15 Potential for Cognitive and Motor Impairment
5.16 Priapism
5.17 Body Temperature Regulation
5.18 Suicide
5.19 Patients with concomitant illnesses
5.20 Laboratory Tests
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Metabolic Pathway
7.2 In Vitro Studies
7.3 Pharmacodynamic Interactions
7.4 Pharmacokinetic Interactions
7.5 Lithium
7.6 Oral Contraceptives
7.7 Dextromethorphan
7.8 Valproate
7.9 Other Concomitant Drug Therapy
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
8.8 Age and Gender Effects
8.9 Smoking
9 DRUG ABUSE AND DEPENDENCE
9.3 Dependence
10 OVERDOSAGE
10.1 Human Experience
10.2 Management of Overdosage
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.3 Acute Treatment of Agitation in Schizophrenia
16HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION

* Sections or subsections omitted from the full prescribing information are not listed.