Land: Vereinigte Staaten
Sprache: Englisch
Quelle: NLM (National Library of Medicine)
TETRABENAZINE (UNII: Z9O08YRN8O) (TETRABENAZINE - UNII:Z9O08YRN8O)
Golden State Medical Supply, Inc.
ORAL
PRESCRIPTION DRUG
Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington's disease. Tetrabenazine tablets are contraindicated in patients: - Who are actively suicidal, or in patients with untreated or inadequately treated depression [see Warnings and Precautions ( 5.1)] . 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)] . With hepatic impairment [see Use in Specific Populations ( 8.6), Clinical Pharmacology ( 12.3)] . - Taking monoamine oxidase inhibitors (MAOIs). Tetrabenazine tablets 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 monoamine oxidase inhibitors (MAOIs). Tetrabenazine tablets 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 tablets [see Drug Interactions ( 7.2)] . Taking reserpine. At least 20 days should elapse after stopping reserpine before starting tetrabenazine tablets [see Drug Interactions ( 7.2)] . - Taking deutetrabenazine or valbenazine [see Drug Interactions ( 7.7)] . 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 tablets 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)].
Tetrabenazine tablets are available in the following strengths and packages: Tetrabenazine tablets 12.5 mg are available for oral administration as white to off-white, round, flat face, bevelled edge, unscored tablets, engraved "T12.5" on one side, "APO" on the other side. They are supplied as follows: Bottles of 112 NDC 51407-480-12 Tetrabenazine tablets 25 mg are available for oral administration as yellow, round, flat face, bevelled edge tablets with functional scoring on one side, engraved "APO" over "T25" on the other side. They are supplied as follows: Bottles of 112 NDC 51407-481-12 Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature].
Abbreviated New Drug Application
Golden State Medical Supply, Inc. ---------- MEDICATION GUIDE Tetrabenazine Tablets (tet”ra ben’ a zeen) Medication Guide available at www1.apotex.com/products/us 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 about tetrabenazine tablets? • Tetrabenazine tablets can cause serious side effects, including: • depression • suicidal thoughts • 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 a 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 Lesen Sie das vollständige Dokument
TETRABENAZINE- TETRABENAZINE TABLET GOLDEN STATE MEDICAL SUPPLY, INC. ---------- HIGHLIGHTS OF PRESCRIBING INFORMATION TETRABENAZINE TABLETS. 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 TABLETS ( 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 TABLETS ARE CONTRAINDICATED IN PATIENTS WHO ARE ACTIVELY SUICIDAL, AND IN PATIENTS WITH UNTREATED OR INADEQUATELY TREATED DEPRESSION ( 4, 5.1) RECENT MAJOR CHANGES Contraindications ( 4) 9/2017 Warnings and Precautions, Tardive Dyskinesia (5.12-removal) 9/2017 INDICATIONS AND USAGE Tetrabenazine tablets are 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) Lesen Sie das vollständige Dokument