|
Xenazine ® (tetrabenazine) tablets
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use XENAZINE safely and effectively. See full prescribing information for XENAZINE
Xenazine ® (tetrabenazine) tablets, for oral use
Initial U.S. Approval: 2008
WARNING: DEPRESSION AND SUICIDALITY
See full prescribing information for complete boxed warning.
-
•
-
Increases the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington's disease ( 5.2)
-
•
-
Balance risks of depression and suicidality with the clinical need for control of chorea when considering the use of XENAZINE ( 5.1)
-
•
-
Monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior ( 5.2)
-
•
-
Inform patients, caregivers and families of the risk of depression and suicidality and instruct to report behaviors of concern promptly to the treating physician ( 5.2)
-
•
-
Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation ( 5.2)
-
•
-
XENAZINE is contraindicated in patients who are actively suicidal, and in patients with untreated or inadequately treated depression ( 4, 5.2)
INDICATIONS AND USAGE
XENAZINE is a vesicular monoamine transporter 2 (VMAT) inhibitor indicated for the treatment of chorea associated with Huntington's disease (1)
DOSAGE AND ADMINISTRATION
-
•
-
Individualization of dose with careful weekly titration is required. The 1 st week's starting dose is 12.5 mg daily; 2 nd week, 25 mg (12.5 mg twice daily); then slowly titrate at weekly intervals by 12.5 mg to a tolerated dose that reduces chorea ( 2.1, 2.2)
-
•
-
Doses of 37.5 mg and up to 50 mg per day should be administered in three divided doses per day with a maximum recommended single dose not to exceed 25 mg ( 2.2)
-
•
-
Patients requiring doses above 50 mg per day should be genotyped for the drug metabolizing enzyme CYP2D6 to determine if the patient is a poor metabolizer (PM) or an extensive metabolizer (EM). ( 2.2, 5.3)
-
•
-
Maximum daily dose in PMs: 50 mg with a maximum single dose of 25 mg ( 2.2)
-
•
-
Maximum daily dose in EMs and intermediate metabolizers (IMs): 100 mg with a maximum single dose of 37.5 mg ( 2.2)
-
•
-
If serious adverse reactions occur, titration should be stopped and the dose should be reduced. If the adverse reaction(s) do not resolve, consider withdrawal of XENAZINE ( 2.2)
DOSAGE FORMS AND STRENGTHS
Tablets: 12.5 mg non-scored and 25 mg scored (3)
CONTRAINDICATIONS
-
•
-
Actively suicidal, or who have depression which is untreated or undertreated ( 4, 5.2)
-
•
-
Hepatic impairment ( 4, 8.6, 12.3)
-
•
-
Taking MAOIs or reserpine ( 4, 7.2, 7.3)
WARNINGS AND PRECAUTIONS
-
•
-
Periodically reeva luate the benefit and potential for adverse effects such as worsening mood, cognition, rigidity, and functional capacity ( 5.1)
-
•
-
Do not exceed 50 mg/day and the maximum single dose should not exceed 25 mg if administered in conjunction with a strong CYP2D6 inhibitor (e.g., fluoxetine, paroxetine) ( 5.3, 7.1)
-
•
-
Neuroleptic Malignant Syndrome (NMS): Discontinue if this occurs ( 5.4, 7.6)
-
•
-
Restlessness, agitation, akathisia and parkinsonism: Reduce dose or discontinue if occurs ( 5.5, 5.6)
-
•
-
Dysphagia and aspiration pneumonia: Monitor for dysphagia ( 5.7)
-
•
-
Sedation/Somnolence: May impair patient's ability to drive or operate complex machinery ( 5.8)
-
•
-
QTc prolongation: Not recommended in combination with other drugs that prolong QTc ( 5.9)
-
•
-
Exaggerates extrapyramidal disorders when used with drugs that reduce or antagonize dopamine. Discontinue XENAZINE if this occurs ( 5.12)
ADVERSE REACTIONS
Most common adverse reactions (>10% and at least 5% greater than placebo) were: Sedation/somnolence, fatigue, insomnia, depression, akathisia, anxiety, nausea (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Lundbeck’s XENAZINE Information Center at 1-888-882-6013 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, tetrabenazine may cause fetal harm (8.1)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 6/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
SPL UNCLASSIFIED SECTION
Xenazine® (tetrabenazine) Tablets
1 INDICATIONS AND USAGE
XENAZINE is indicated for the treatment of chorea associated with Huntington's disease.
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Considerations
The chronic daily dose of XENAZINE used to treat chorea associated with Huntington's disease (HD) is determined individually for each patient. When first prescribed, XENAZINE therapy should be titrated slowly over several weeks to identify a dose of XENAZINE that reduces chorea and is tolerated. XENAZINE can be administered without regard to food [see Clinical Pharmacology (12.3)].
2.2 Individualization of Dose
The dose of XENAZINE should be individualized.
Dosing Recommendations Up to 50 mg per day
The starting dose should be 12.5 mg per day given once in the morning. After one week, the dose should be increased to 25 mg per day given as 12.5 mg twice a day. XENAZINE should be titrated up slowly at weekly intervals by 12.5 mg daily, to allow the identification of a tolerated dose that reduces chorea. If a dose of 37.5 to 50 mg per day is needed, it should be given in a three times a day regimen. The maximum recommended single dose is 25 mg. If adverse reactions such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety or sedation occur, titration should be stopped and the dose should be reduced. If the adverse reaction does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants) [see Adverse Reactions (6.1)].
Dosing Recommendations Above 50 mg per day
Patients who require doses of XENAZINE greater than 50 mg per day should be first tested and genotyped to determine if they are poor metabolizers (PMs) or extensive metabolizers (EMs) by their ability to express the drug metabolizing enzyme, CYP2D6. The dose of XENAZINE should then be individualized accordingly to their status as PMs or EMs [see Warnings and Precautions (5.3), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
Extensive and Intermediate CYP2D6 Metabolizers
Genotyped patients who are identified as extensive (EMs) or intermediate metabolizers (IMs) of CYP2D6, who need doses of XENAZINE above 50 mg per day, should be titrated up slowly at weekly intervals by 12.5 mg daily, to allow the identification of a tolerated dose that reduces chorea. Doses above 50 mg per day should be given in a three times a day regimen. The maximum recommended daily dose is 100 mg and the maximum recommended single dose is 37.5 mg. If adverse reactions such as akathisia, parkinsonism, depression, insomnia, anxiety or sedation occur, titration should be stopped and the dose should be reduced. If the adverse reaction does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants) [see Warnings and Precautions (5.3), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
2.3 Dosage Adjustments with CYP2D6 Inhibitors
2.4 Discontinuation of Treatment
Treatment with XENAZINE can be discontinued without tapering. Re-emergence of chorea may occur within 12 to 18 hours after the last dose of XENAZINE [see Drug Abuse and Dependence (9.2)].
| 以下是“全球医药”详细资料 |
|
|
| |
