TETRABENAZINE tablet

Land: Vereinigte Staaten

Sprache: Englisch

Quelle: NLM (National Library of Medicine)

Wirkstoff:

TETRABENAZINE (UNII: Z9O08YRN8O) (TETRABENAZINE - UNII:Z9O08YRN8O)

Verfügbar ab:

Bionpharma Inc.

INN (Internationale Bezeichnung):

Tetrabenazine

Zusammensetzung:

Tetrabenazine 12.5 mg

Verabreichungsweg:

ORAL

Verschreibungstyp:

PRESCRIPTION DRUG

Anwendungsgebiete:

Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington’s disease. Tetrabenazine is contraindicated in patients: - Who are actively suicidal, or in patients with untreated or inadequately treated depression [see Warnings  and Precautions ( 5.1) ] . - With hepatic impairment [see Use in Specific Populations ( 8.6),  Clinical Pharmacology ( 12.3) ] . - Taking monoamine oxidase inhibitors (MAOIs). Tetrabenazine should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI [see Drug Interactions ( 7.3) ] . - Taking reserpine. At least 20 days should elapse after stopping reserpine before starting tetrabenazine [see Drug Interactions ( 7.2) ] . - Taking deutetrabenazine or valbenazine [see Drug Interactions ( 7.7)]. Risk Summary There are no adequate data on the developmental risk associated with the use of tetrabenazine in pregnant women. Administration of tetrabenazine to rats throughout pregnancy and lactation resulted in an increase in stillbirths and postnatal offspring mortality. Administration of a major human metabolite of tetrabenazine to rats during pregnancy or during pregnancy and lactation produced adverse effects on the developing fetus and offspring (increased mortality, decreased growth, and neurobehavioral and reproductive impairment). The adverse developmental effects of tetrabenazine and a major human metabolite of tetrabenazine in rats occurred at clinically relevant doses [see Data] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Tetrabenazine had no clear effects on embryofetal development when administered to pregnant rats throughout the period of organogenesis at oral doses up to 30 mg/kg/day (or 3 times the maximum recommended human dose [MRHD] of 100 mg/day on a mg/m 2 basis). Tetrabenazine had no effects on embryofetal development when administered to pregnant rabbits during the period of organogenesis at oral doses up to 60 mg/kg/day (or 12 times the MRHD on a mg/m 2 basis). When tetrabenazine (5, 15, and 30 mg/kg/day) was orally administered to pregnant rats from the beginning of organogenesis through the lactation period, an increase in stillbirths and offspring postnatal mortality was observed at 15 and 30 mg/kg/day and delayed pup maturation was observed at all doses. A no-effect dose for pre- and postnatal developmental toxicity in rats was not identified. The lowest dose tested (5 mg/kg/day) was less than the MRHD on a mg/m 2 basis. Because rats dosed orally with tetrabenazine do not produce 9-desmethyl-β-DHTBZ, a major human metabolite of tetrabenazine, the metabolite was directly administered to pregnant and lactating rats. Oral administration of 9-desmethyl-β-DHTBZ (8, 15, and 40 mg/kg/day) throughout the period of organogenesis produced increases in embryofetal mortality at 15 and 40 mg/kg/day and reductions in fetal body weights at 40 mg/kg/day, which was also maternally toxic. When 9-desmethyl-β-DHTBZ (8, 15, and 40 mg/kg/day) was orally administered to pregnant rats from the beginning of organogenesis through the lactation period, increases in gestation duration, stillbirths, and offspring postnatal mortality (40 mg/kg/day); decreases in pup weights (40 mg/kg/day); and neurobehavioral (increased activity, learning and memory deficits) and reproductive (decreased litter size) impairment (15 and 40 mg/kg/day) were observed. Maternal toxicity was seen at the highest dose. The no-effect dose for developmental toxicity in rats (8 mg/kg/day) was associated with plasma exposures (AUC) of 9-desmethyl-β-DHTBZ in pregnant rats lower than that in humans at the MRHD. Risk Summary There are no data on the presence of tetrabenazine or its metabolites in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tetrabenazine and any potential adverse effects on the breastfed infant from tetrabenazine or from the underlying maternal condition. Safety and effectiveness in pediatric patients have not been established. The pharmacokinetics of tetrabenazine and its primary metabolites have not been formally studied in geriatric subjects. Because the safety and efficacy of the increased exposure to tetrabenazine and other circulating metabolites are unknown, it is not possible to adjust the dosage of tetrabenazine in hepatic impairment to ensure safe use. The use of tetrabenazine in patients with hepatic impairment is contraindicated [see Contraindications ( 4),  Clinical  Pharmacology ( 12.3) ] . Patients who require doses of tetrabenazine greater than 50 mg per day, should be first tested and genotyped to determine if they are poor (PMs) or extensive metabolizers (EMs) by their ability to express the drug metabolizing enzyme, CYP2D6. The dose of tetrabenazine should then be individualized accordingly to their status as either poor (PMs) or extensive metabolizers (EMs)  [see Dosage and Administration ( 2.2), Warnings and Precautions ( 5. 3),  Clinical Pharmacology ( 12.3) ] . Poor Metabolizers Poor CYP2D6 metabolizers (PMs) will have substantially higher levels of exposure to the primary metabolites (about 3-fold for α-HTBZ and 9-fold for β-HTBZ) compared to EMs. The dosage should, therefore, be adjusted according to a patient’s CYP2D6 metabolizer status by limiting a single dose to a maximum of 25 mg and the recommended daily dose to not exceed a maximum of 50 mg/day in patients who are CYP2D6 PMs [see Dosage and Administration ( 2.2), Warnings and Precautions ( 5.3),  Clinical Pharmacology ( 12.3) ] . Extensive / Intermediate Metabolizers In extensive (EMs) or intermediate metabolizers (IMs), the dosage of tetrabenazine can be titrated to a maximum single dose of 37.5 mg and a recommended maximum daily dose of 100 mg [see Dosage and Administration  ( 2.2 ), Drug Interactions ( 7.1),  Clinical Pharmacology ( 12.3) ] . Tetrabenazine is not a controlled substance. Clinical trials did not reveal patients developed drug seeking behaviors, though these observations were not systematic. Abuse has not been reported from the postmarketing experience in countries where tetrabenazine has been marketed. As with any CNS-active drug, prescribers should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of tetrabenazine misuse or abuse (such as development of tolerance, increasing dose requirements, drug-seeking behavior). Abrupt discontinuation of tetrabenazine from patients did not produce symptoms of withdrawal or a discontinuation syndrome; only symptoms of the original disease were observed to re‑emerge  [see Dosage and  Administration ( 2.4) ] .

Produktbesonderheiten:

Tetrabenazine tablets are available in the following strengths and packages: The 12.5 mg tetrabenazine tablets are yellowish-buff colored, round-shaped tablets, debossed with “T1” on one side and plain on other side. Bottles of 112:   NDC 69452-117-21. The 25 mg tetrabenazine tablets are yellowish-buff colored, round-shaped tablets, debossed with “T2” on one side and scoreline (functional scoring) on other side. Bottles of 112:   NDC 69452-118-21. Store at 25º C (77º F); excursions permitted between 15º to 30º C (59º to 86º F) [See USP Controlled Room Temperature].

Berechtigungsstatus:

Abbreviated New Drug Application

Gebrauchsinformation

Bionpharma Inc.
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MEDICATION GUIDE
Tetrabenazine (TET-ra-BEN-a-Zeen) Tablets
Read the Medication Guide that comes with tetrabenazine tablets before
you start taking it and each time
you refill the prescription. There may be new information. This
information does not take the place of
talking with your doctor about your medical condition or your
treatment. You should share this
information with your family members and caregivers.
What is the most important information I should know
abouttetrabenazine tablets?
• Tetrabenazine tablets can cause serious side effects, including:
o depression
o suicidal thoughts
o suicidal actions
•
You should not start taking tetrabenazine tablets if you are depressed
(have untreated depression
or depression that is not well controlled by medicine) orhave suicidal
thoughts.
•
Pay close attention to any changes, especially sudden changes, in
mood, behaviors, thoughts or
feelings. This is especially important when tetrabenazine tablets are
started and when the dose is
changed.
Call the doctor right away if you become depressed or have any of the
following symptoms, especially if
they are new, worse, or worry you:
•
feel sad or have crying spells
•
lose interest in seeing your friends or doing things you used to enjoy
•
sleep a lot moreor a lot lessthan usual
•
feel unimportant
•
feel guilty
•
feel hopeless or helpless
•
more irritable, angry or aggressive than usual
•
more or less hungry than usual or notice a big change in your body
weight
•
have trouble paying attention
•
feel tired or sleepy all the time
•
have thoughts about hurting yourself or ending your life
What are tetrabenazine tablets?
Tetrabenazine tablets are medicine that is used to treat the
involuntary movements (chorea) of
Huntington’s disease. Tetrabenazine tablets do not cure the cause of
the involuntary movements, and it
does not treat other symptoms of Huntington’s disease, such as
problems with thinking or emotions.
It is not known whether tetrabenazine tablets are safe and

Fachinformation

TETRABENAZINE- TETRABENAZINE TABLET
BIONPHARMA INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TETRABENAZINE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
TETRABENAZINE TABLETS
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( 5.1)
BALANCE RISKS OF DEPRESSION AND SUICIDALITY WITH THE CLINICAL NEED FOR
CONTROL OF
CHOREA WHEN CONSIDERING THE USE OF TETRABENAZINE( 5.2)
MONITOR PATIENTS FOR THE EMERGENCE OR WORSENING OF DEPRESSION,
SUICIDALITY, OR
UNUSUAL CHANGES IN BEHAVIOR( 5.1)
INFORM PATIENTS, CAREGIVERS AND FAMILIES OF THE RISK OF DEPRESSION AND
SUICIDALITY AND
INSTRUCT TO REPORT BEHAVIORS OF CONCERN PROMPTLY TO THE TREATING
PHYSICIAN( 5.1)
EXERCISE CAUTION WHEN TREATING PATIENTS WITH A HISTORY OF DEPRESSION
OR PRIOR SUICIDE
ATTEMPTS OR IDEATION( 5.1)
TETRABENAZINE IS CONTRAINDICATED IN PATIENTS WHO ARE ACTIVELY
SUICIDAL, AND IN
PATIENTS WITH UNTREATED OR INADEQUATELY TREATED DEPRESSION ( 4, 5.1)
INDICATIONS AND USAGE
Tetrabenazine 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
week’s starting dose is 12.5 mg
daily; 2
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 metabolize