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` HIGHLIGHTS OF PRESCRIBING INFORMATION
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` These highlights do not include all the information needed to use
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` VIMPAT® safely and effectively. See full prescribing information for
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` VIMPAT.
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` VIMPAT® (lacosamide) film coated tablet, for oral use, CV
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` VIMPAT® (lacosamide) injection, for intravenous use, CV
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` VIMPAT® (lacosamide) oral solution, CV
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` Initial U.S. Approval: 2008
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` -------------------------RECENT MAJOR CHANGES---------------------
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`Warnings and Precautions (5.3)
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` 11/2018
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` ----------------------------INDICATIONS AND USAGE--------------------------
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` VIMPAT is indicated for the treatment of partial-onset seizures in patients 4
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` years of age and older.
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` As the safety of VIMPAT injection has not been established in pediatric
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` patients, VIMPAT injection is indicated for the treatment of partial-onset
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` seizures only in adult patients (17 years of age and older) (1)
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` ----------------------DOSAGE AND ADMINIS TRATION----------------------
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`• Adults (17 years and older): Initial dosage for monotherapy is 100 mg
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` twice daily; initial dosage for adjunctive therapy is 50 mg twice daily;
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` maximu m recommended dos age for monotherapy and adjunctive therapy is
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` 200 mg twice daily (2.1)
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`• Pediatric Patients 4 Years to less than 17 years: The recommended dosage
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` is based on body weight and is administered orally twice daily (2.1)
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`• Increase dosage based on clinical response and tolerability, no more
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` frequently than once per week (2.1)
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`• Injection: for intravenous and adult use only when oral administration is
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` temporarily not feasible; dosing regimen is the same as oral regimen;
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` administer over 15 to 60 minutes; obtaining ECG before initiation is
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` recommended in certain patients (2.6, 5.3)
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`• Dose adjustment is recommended for severe renal impairment (2.3, 12.3)
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`• Dose adjustment is recommended for mild or moderate hepatic impairment;
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` use in patients with severe hepatic impairment is not recommended (2.4,
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` 12.3)
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` ---------------------DOSAGE FORMS AND STRENGTHS---------------------
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`• 50 mg, 100 mg, 150 mg, 200 mg tablets (3)
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`• 200 mg/20 mL single-dose vial for intravenous use (3)
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`• 10 mg/mL oral solution (3)
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`-------------------------------CONTRAINDICATIONS-----------------------------
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` None (4)
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` -----------------------WARNINGS AND PRECAUTIONS -----------------------
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`• Monitor patients for s uicidal behavior and ideation (5.1)
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`• VIMPAT may cause dizziness and ataxia (5.2)
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`• Cardiac Rhythm and Conduction Abnormalities: Obtaining ECG before
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` beginning and after titration to steady-state maintenance is recommended in
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` patients with underlying proarrhythmic conditions or on concomitant
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` medications that affect cardiac conduction; closely monitor these patients
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` (5.3, 7.2)
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`• VIMPAT may cause syncope (5.4)
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`• VIMPAT should be gradually withdrawn to minimize the potential of
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` increased seizure frequency (5.5)
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`• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/
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` Multi-Organ Hypersensitivity: Discontinue if no alternate etiology (5.6)
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` ------------------------------ADVERS E REACTIONS---------------------------
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`• Adjunctive therapy: Most common adverse reactions in adults (≥10% and
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` greater than placebo) are diplopia, headache, dizziness, nausea (6.1)
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`• Monotherapy: Most common adverse reactions are similar to those seen in
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` adjunctive therapy studies (6.1)
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`• Pediatric patients: Adverse reactions are similar to those seen in adult
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` patients (6.1)
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` To report SUSPECTED ADVERS E REACTIONS, contact UCB, Inc. at
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` 1-844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.g ov/ me dwatc h
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` -----------------------US E IN SPECIFIC POPULATIONS -----------------------
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`• Pregnancy: Based on animal data, may cause fetal harm (8.1)
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` See 17 for PATIENT COUNSELING INFORMATION and Medication
` Guide
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` Revised: 1/2019
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` 9 DRUG ABUSE AND DEPENDENCE
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` 9.1 Controlled Substance
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` 9.2 Abuse
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` 9.3 Dependence
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` 10 OVERDOSAGE
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` 11 DESCRIPTION
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` 11.1 VIMPAT Tablets
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` 11.2 VIMPAT Injection
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` 11.3 VIMPAT Oral Solution
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` 12 CLINICAL PHARMACOLOGY
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` 12.1 Mechanism of Action
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` 12.2 Pharmacodynamics
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` 12.3 Pharmacokinetics
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` 13 NONCLINICAL TOXICOLOGY
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` 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
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` 14 CLINICAL STUDIES
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` 14.1 Monotherapy in Patients with Partial-Onset Seizures
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` 14.2 Adjunctive Therapy in Patients with Partial-Onset Seizures
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` 16 HOW SUPPLIED/STORAGE AND HANDLING
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` 16.1 How Supplied
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` 16.2 Storage and Handling
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` 17 PATIENT COUNSELING INFORMATION
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` * Sections or subsections omitted from the full prescribing information are not
` listed
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`Reference ID: 4373796
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` FULL PRESCRIBING INFORMATION: CONTENTS*
` 1 INDICATIONS AND USAGE
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` 2 DOSAGE AND ADMINISTRATION
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` 2.1 Dosage Information
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`2.2 Converting From a Single Antiepileptic (AED) to VIMPAT
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`Monotherapy
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` 2.3 Dosage Information for Patients with Renal Impairment
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` 2.4 Dosage Information for Patients with Hepatic Impairment
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` 2.5 Administration Instructions for VIMPAT Tablets and Oral Solution
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` 2.6 Preparation and Administration Information for VIMPAT Injection for
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` Adult Patients
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` 2.7 Discontinuation of VIMPAT
` 3 DOSAGE FORMS AND STRENGTHS
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` 4 CONTRAINDICATIONS
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` 5 WARNINGS AND PRECAUTIONS
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` 5.1 Suicidal Behavior and Ideation
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` 5.2 Dizziness and Ataxia
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` 5.3 Cardiac Rhythm and Conduction Abnormalities
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` 5.4 Syncope
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` 5.5 Withdrawal of Antiepileptic Drugs (AEDs)
`5.6 Drug Reaction with Eosinophilia and Systemic Symptoms
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`(DRESS)/Multi-Organ Hypersensitivity
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` 5.7 Risks in Patients with Phenylketonuria
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` 6 ADVERS E REACTIONS
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` 6.1 Clinical Trials Experience
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` 6.2 Postmarketing Experience
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` 7 DRUG INTERACTIONS
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` 7.1 Strong CYP3A4 or CYP2C9 Inhibitors
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` 7.2 Concomitant Medications that Affect Cardiac Conduction
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` 8 USE IN SPECIFIC POPULATIONS
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` 8.1 Pregnancy
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` 8.2 Lactation
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` 8.4 Pediatric Use
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` 8.5 Geriatric Use
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` 8.6 Renal Impairment
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` 8.7 Hepatic Impairment
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` FULL PRESCRIBING INFORMATION
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` 1 INDICATIONS AND USAGE
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` VIMPAT is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.
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` As the safety of VIMPAT injection in pediatric patients has not been established, VIMPAT injection is
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` indicated for the treatment of partial-onset seizures only in adult patients (17 years of age and older).
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` 2 DOSAGE AND ADMINISTRATION
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` 2.1 Dosage Information
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` Monotherapy and Adjunctive Therapy
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` The recommended dosage for adults and pediatric patients 4 years to less than 17 years of age is included in
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` Table 1. In pediatric patients 4 years to less than 17 years of age, the recommended dosing regimen is
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` dependent upon body weight and is only recommended to be administered orally. Dosage should be increased
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` based on clinical response and tolerability, no more frequently than once per week. Titration increments should
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` not exceed those shown in Table 1.
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` Table 1: Recommended Dosage for Adults and Pediatric Patients 4 Years and Older*
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` Age and Body
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` Weight
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` Initial Dosage
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` Titration Regimen
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` Maintenance Dosage
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` Adults (17 years and
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` older)
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` Monotherapy:
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` 150 mg to 200 mg twice daily
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` (300 mg to 400 mg per day)
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` Monotherapy:
` 100 mg twice daily
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` (200 mg per day)
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` Increase by 50 mg twice daily
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` (100 mg per day)
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` every week
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` Adjunctive Therapy:
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` 50 mg twice daily
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` (100 mg per day)
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` Alternate Initial
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` Dosage: 200 mg single
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` loading dose, followed
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` 12 hours later by 100 mg
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` twice daily
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` Pediatric patients
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` weighing 50 kg or
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` 50 mg twice daily
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` (100 mg per day)
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` Increase by 50 mg twice daily
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` Pediatric patients
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` weighing 30 kg to less
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` than 50 kg
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` Pediatric patients
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` than 30 kg
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` 1 mg/kg twice daily
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` 1 mg/kg twice daily
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` Increase by 1 mg/kg twice
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` daily (2 mg/kg/day) every
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` Increase by 1 mg/kg twice
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` daily (2 mg/kg/day) every
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` week
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` Adjunctive Therapy:
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` 100 mg to 200 mg twice daily
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` (200 mg to 400 mg per day)
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` Monotherapy:
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` 150 mg to 200 mg twice daily
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` Adjunctive Therapy:
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` 100 mg to 200 mg twice daily
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` 2 mg/kg to 4 mg/kg twice daily
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` 3 mg/kg to 6 mg/kg twice daily
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` (6 mg/kg/day to 12 mg/kg/day)
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` *when not specified, the dosage is the same for monotherapy and adjunctive therapy
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` In adjunctive clinical trials in adult patients, a dosage higher than 200 mg twice daily (400 mg per day) was not
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` more effective and was associated with a substantially higher rate of adverse reactions [see Adverse Reactions
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` (6.1) and Clinical Studies (14.2)].
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` VIMPAT Injection Dosage in Adult Patients (17 years and older)
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` VIMPAT injection may be used for adult patients when oral administration is temporarily not feasible [see
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` Dosage and Administration (2.6) and Warnings and Precautions (5.3)]. VIMPAT injection can be administered
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` intravenously to adult patients with the same dosing regimens described for oral dosing, including the loading
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` dose. The use of VIMPAT injection in pediatric patients has not been studied.
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`The clinical study experience of intravenous VIMPAT is limited to 5 days of consecutive treatment.
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`Loading Dose in Adult Patients (17 Years and Older)
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`VIMPAT and VIMPAT injection may be initiated in adult patients with a single loading dose of 200 mg,
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`followed approximately 12 hours later by 100 mg twice daily (200 mg per day). This maintenance dose regimen
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`Reference ID: 4373796
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` should be continued for one week. VIMPAT can then be titrated as recommended in Table 1. The adult loading
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` dose should be administered with medical supervision because of the increased incidence of CNS adverse
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` reactions [see Adverse Reactions (6.1), Clinical Pharmacology (12.3)].
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` The use of a loading dose in pediatric patients has not been studied.
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` 2.2 Converting From a Single Antiepileptic (AED) to VIMPAT Monotherapy
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` For patients who are already on a single AED and will convert to VIMPAT monotherapy, withdrawal of the
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` concomitant AED should not occur until the therapeutic dosage of VIMPAT is achieved and has been
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` administered for at least 3 days. A gradual withdrawal of the concomitant AED over at least 6 weeks is
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` recommended.
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` 2.3 Dosage Information for Patients with Renal Impairment
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`For patients with mild to moderate renal impairment, no dosage adjustment is necessary.
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`For patients with severe renal impairment [creatinine clearance (CLCR) less than 30 mL/min as estimated by the
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`Cockcroft-Gault equation for adults; CLCR less than 30 mL/min/1.73m2 as estimated by the Schwartz equation
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`for pediatric patients] or end-stage renal disease, a reduction of 25% of the maximum dosage is recommended.
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`In all patients with renal impairment, the dose titration should be performed with caution.
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`Hemodialysis
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`VIMPAT is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment,
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`dosage supplementation of up to 50% should be considered.
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` Concomitant Strong CYP3A4 or CYP2C9 Inhibitors
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` Dose reduction may be necessary in patients with renal impairment who are taking strong inhibitors of CYP3A4
` and CYP2C9 [see Drug Interactions (7.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
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` 2.4 Dosage Information for Patients with Hepatic Impairment
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` For patients with mild or moderate hepatic impairment, a reduction of 25% of the maximum dosage is
`
` recommended. The dose titration should be performed with caution in patients with hepatic impairment.
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` VIMPAT use is not recommended in patients with severe hepatic impairment.
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` Concomitant Strong CYP3A4 and CYP2C9 Inhibitors
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` Dose reduction may be necessary in patients with hepatic impairment who are taking strong inhibitors of
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` CYP3A4 and CYP2C9 [see Drug Interactions (7.1), Use in Specific Populations (8.7), Clinical Pharmacology
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`
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` (12.3)].
`
` 2.5 Administration Instructions for VIMPAT Tablets and Oral Solution
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` VIMPAT may be taken with or without food.
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` VIMPAT Oral Solution
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` A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A
` household teaspoon or tablespoon is not an adequate measuring device.
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` VIMPAT oral solution may also be administered using a nasogastric tube or gastrostomy tube.
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` Discard any unused VIMPAT oral solution remaining after 7 weeks of first opening the bottle.
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` 2.6 Preparation and Administration Information for VIMPAT Injection for Adult Patients
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` Preparation
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` VIMPAT injection can be administered intravenously without further dilution or may be mixed with diluents
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` listed below. The diluted solution should not be stored for more than 4 hours at room temperature.
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` Diluents:
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`Sodium Chloride Injection 0.9% (w/v)
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`Dextrose Injection 5% (w/v)
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`Lactated Ringer's Injection
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` Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
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` administration, whenever solution and container permit. Product with particulate matter or discoloration should
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` not be used.
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`Reference ID: 4373796
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` VIMPAT injection is for single-dose only. Any unused portion of VIMPAT injection should be discarded.
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` Administration
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` The recommended infusion rate is 30 to 60 minutes; however, infusions as rapid as 15 minutes can be
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` administered if required [see Adverse Reactions (6.1), Clinical Pharmacology (12.3)].
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` Intravenous infusion of VIMPAT may cause bradycardia, AV blocks, and ventricular tachyarrhythmia [see
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` Warnings and Precautions (5.3)]. Obtaining an ECG before beginning VIMPAT and after VIMPAT is titrated
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` to steady-state maintenance dose is recommended in patients with underlying proarrhythmic conditions or on
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` concomitant medications that affect cardiac conduction [see Drug Interactions (7.2)].
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` Storage and Stability
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` The diluted solution should not be stored for more than 4 hours at room temperature. Any unused portion of
` VIMPAT injection should be discarded.
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` 2.7 Discontinuation of VIMPAT
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` When discontinuing VIMPAT, a gradual withdrawal over at least 1 week is recommended [see Warnings and
` Precautions (5.5)].
`
`
`
` 3 DOSAGE FORMS AND STRENGTHS
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` VIMPAT Tablets
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`• 50 mg: pink, oval, film-coated, debossed with "SP" on one side and "50" on the other
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`• 100 mg: dark yellow, oval, film-coated, debossed with "SP" on one side and "100" on the other
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`• 150 mg: salmon, oval, film-coated, debossed with "SP" on one side and "150" on the other
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`• 200 mg: blue, oval, film-coated, debossed with "SP" on one side and "200" on the other
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` VIMPAT Injection
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`• 200 mg/20 mL: clear, colorless sterile solution in single-dose vials
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` VIMPAT Oral Solution
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`• 10 mg/mL: clear, colorless to yellow or yellow-brown, strawberry-flavored liquid
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`
` 4 CONTRAINDICATIONS
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` None.
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` 5 WARNINGS AND PRECAUTIONS
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` 5.1 Suicidal Behavior and Ideation
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` Antiepileptic drugs (AEDs), including VIMPAT, increase the risk of suicidal thoughts or behavior in patients
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` taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for
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` the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood
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` or behavior.
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` Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs
` showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk
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` 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these
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` trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or
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` ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated
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` patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530
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` patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated
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` patients, but the number of events is too small to allow any conclusion about drug effect on suicide.
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` The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting
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` treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the
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` analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not
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` be assessed.
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` The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The
` finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests
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` that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100
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` years) in the clinical trials analyzed.
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` Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
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`Reference ID: 4373796
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` Table 2:
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` Indication
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` Risk by Indication for Antiepileptic Drugs in the Pooled Analysis
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` Risk
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` Placebo Patients Drug Patients
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` Relative Risk:
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` with Events Per
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` Incidence of
` Difference:
` with Events
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` Additional Drug
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` Per 1000 Patients 1000 Patients
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` Events in Drug
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` Patients/Incidence in Patients with
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` Events Per 1000
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` Placebo Patients
` Patients
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` 2.4
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` 2.9
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` 0.9
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` 1.9
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` Epilepsy
`
` Psychiatric
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` Other
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` Total
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` 1.0
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` 5.7
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` 1.0
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` 2.4
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` 3.4
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` 8.5
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` 1.8
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` 4.3
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` 3.5
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` 1.5
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` 1.9
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` 1.8
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` The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials
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` for psychiatric or other conditions, but the absolute risk differences were similar.
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` Anyone considering prescribing VIMPAT or any other AED must balance this risk with the risk of untreated
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` illness. Epilepsy and many other illnesses for which antiepileptics are prescribed are themselves associated with
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` morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and
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` behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms
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` in any given patient may be related to the illness being treated.
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` 5.2 Dizziness and Ataxia
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` VIMPAT may cause dizziness and ataxia. In adult patients with partial-onset seizures taking 1 to 3 concomitant
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` AEDs, dizziness was experienced by 25% of patients randomized to the recommended doses (200 to 400
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` mg/day) of VIMPAT (compared with 8% of placebo patients) and was the adverse event most frequently
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` leading to discontinuation (3%). Ataxia was experienced by 6% of patients randomized to the recommended
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` doses (200 to 400 mg/day) of VIMPAT (compared to 2% of placebo patients). The onset of dizziness and ataxia
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` was most commonly observed during titration. There was a substantial increase in these adverse events at doses
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` higher than 400 mg/day [see Adverse Reactions (6.1)]. Dizziness and ataxia were also observed in pediatric
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` clinical trials.
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` 5.3 Cardiac Rhythm and Conduction Abnormalities
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` PR Interval Prolongation, Atrioventricular Block, and Ventricular Tachyarrhythmia
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` Dose-dependent prolongations in PR interval with VIMPAT have been observed in clinical studies in adult
` patients and in healthy volunteers [see Clinical Pharmacology (12.2)]. In adjunctive clinical trials in adult
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` patients with partial-onset seizures, asymptomatic first-degree atrioventricular (AV) block was observed as an
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` adverse reaction in 0.4% (4/944) of patients randomized to receive VIMPAT and 0% (0/364) of patients
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` randomized to receive placebo. One case of profound bradycardia was observed in a patient during a 15-minute
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` infusion of 150 mg VIMPAT.When VIMPAT is given with other drugs that prolong the PR interval, further PR
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` prolongation is possible.
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` In the postmarketing setting, there have been reports of cardiac arrhythmias in patients treated with VIMPAT,
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` including bradycardia, AV block, and ventricular tachyarrhythmia, which have rarely resulted in asystole,
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` cardiac arrest, and death. Most, although not all, cases have occurred in patients with underlying proarrhythmic
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` conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval.
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` These events have occurred with both oral and intravenous routes of administration and at prescribed doses as
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` well as in the setting of overdose [see Overdosage (10)].
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` Vimpat should be used with caution in patients with underlying proarrhythmic conditions such as known
`
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` cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick
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` sinus syndrome without pacemaker), severe cardiac disease (such as myocardial ischemia or heart failure, or
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` structural heart disease), and cardiac sodium channelopathies (e.g., Brugada Syndrome). VIMPAT should also
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` be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium
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` channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that
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` prolong the PR interval [see Drug Interactions (7.2)]. In such patients, obtaining an ECG before beginning
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` VIMPAT, and after VIMPAT is titrated to steady-state maintenance dose, is recommended. In addition, these
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` patients should be closely monitored if they are administered VIMPAT through the intravenous route [see
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` Adverse Reactions (6.1), Drug Interactions (7.2)].
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` Atrial Fibrillation and Atrial Flutter
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` In the short-term investigational trials of VIMPAT in adult patients with partial-onset seizures there were no
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` cases of atrial fibrillation or flutter. Both atrial fibrillation and atrial flutter have been reported in open label
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` partial-onset seizure trials and in postmarketing experience. In adult patients with diabetic neuropathy, for
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` which VIMPAT is not indicated, 0.5% of patients treated with VIMPAT experienced an adverse reaction of
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`
`Reference ID: 4373796
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` atrial fibrillation or atrial flutter, compared to 0% of placebo-treated patients. VIMPAT administration may
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` predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy
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` and/or cardiovascular disease.
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` 5.4 Syncope
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` In the short-term controlled trials of VIMPAT in adult patients with partial-onset seizures with no significant
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` system illnesses, there was no increase in syncope compared to placebo. In the short-term controlled trials in
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` adult patients with diabetic neuropathy, for which VIMPAT is not indicated, 1.2% of patients who were treated
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` with VIMPAT reported an adverse reaction of syncope or loss of consciousness, compared with 0% of placebo-
`
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` treated patients with diabetic neuropathy. Most of the cases of syncope were observed in patients receiving
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` doses above 400 mg/day. The cause of syncope was not determined in most cases. However, several were
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` associated with either changes in orthostatic blood pressure, atrial flutter/fibrillation (and associated
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` tachycardia), or bradycardia. Cases of syncope have also been observed in open-label clinical partial-onset
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` seizure studies in adult and pediatric patients. These cases were associated with a history of risk factors for
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` cardiac disease and the use of drugs that slow AV conduction.
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` 5.5 Withdrawal of Antiepileptic Drugs (AEDs)
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` As with all AEDs, VIMPAT should be withdrawn gradually (over a minimum of 1 week) to minimize the
`
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` potential of increased seizure frequency in patients with seizure disorders.
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`
`
` 5.6 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity
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` Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi -organ
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` hypersensitivity, has been reported in patients taking antiepileptic drugs, including VIMPAT. Some of these
`
` events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash,
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`
` lymphadenopathy and/or facial swelling, in association with other organ system involvement, such as hepatitis,
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` nephritis, hematologic abnormalities, myocarditis, or myositis, sometimes resembling an acute viral infection.
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` Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here
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` may be involved. It is important to note that early manifestations of hypersensitivity (e.g., fever,
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` lymphadenopathy) may be present even though rash is not evident. If such signs or symptoms are present, the
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` patient should be evaluated immediately. VIMPAT should be discontinued if an alternative etiology for the
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` signs or symptoms cannot be established.
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`
` 5.7 Risks in Patients with Phenylketonuria
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`
` Phenylalanine can be harmful in patients with phenylketonuria (PKU). VIMPAT oral solution contains
`
`
` aspartame, a source of phenylalanine. A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains
`
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`
` 0.32 mg of phenylalanine. Before prescribing VIMPAT oral solution to a patient with PKU, consider the
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`
` combined daily amount of phenylalanine from all sources, including VIMPAT oral solution.
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`
`
` 6 ADVERSE REACTIONS
`
`
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`
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`
`
` The following serious adverse reactions are described below and elsewhere in the labeling:
`
`• Suicidal Behavior and Ideation [see Warnings and Precautions (5.1)]
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`
`
`
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`• Dizziness and Ataxia [see Warnings and Precautions (5.2)]
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`
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`• Cardiac Rhythm and Conduction Abnormalities [see Warnings and Precautions (5.3)]
`
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`
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`• Syncope [see Warnings and Precautions (5.4)]
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`• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
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` Reactions [see Warnings and Precautions (5.6)]
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` 6.1 Clinical Trials Experience
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` Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the
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` clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not
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` reflect the rates observed in practice.
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` VIMPAT Tablet and Oral Solution
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` In the premarketing development of adjunctive therapy for partial-onset seizures, 1327 adult patients received
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` 852 for longer than 12 months. The monotherapy development program included 425 adult patients, 310 of
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` whom were treated for longer than 6 months, and 254 for longer than 12 months.
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` Monotherapy Historical-Control Trial (Study 1)
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` In the monotherapy trial, 16% of patients randomized to receive VIMPAT at the recommended doses of 300
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` and 400 mg/day discontinued from the trial as a result of an adverse reaction. The adverse reaction most
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` commonly (≥1% on VIMPAT) leading to discontinuation was dizziness.
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`Reference ID: 4373796
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` Adverse reactions that occurred in this study were generally similar to those that occurred in adjunctive
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` placebo-controlled studies. One adverse reaction, insomnia