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  • Austedo
    / Abic


    Active Ingredient
    Deutetrabenazine 6,9,12 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Extended-Release Tablets

    6 mg ×60

    not in the basket chart

    Extended-Release Tablets

    9 mg ×60

    not in the basket chart

    Extended-Release Capsules

    12 mg ×60

    not in the basket chart

    Dosage

    The dose of Austedo is determined individually for each patient based on reduction of chorea or tardive dyskinesia and tolerability. When first prescribed to patients who are not being switched from tetrabenazine (a related VMAT2 inhibitor), the recommended starting dose is 6 mg administered orally once daily with or without food  for patients with Huntington’s disease and 12 mg per day (6 mg twice daily) for patients with tardive dyskinesia.
    The dose of Austedo may be increased at weekly intervals in increments of 6 mg per day to a maximum recommended daily dosage of 48 mg.
    Administration of total daily dosages of 12 mg or above in two divided doses.
    The drug should be swallowed whole, not chewed, crushed, or broken tablets.
    In patients with risk for QT prolongation, the QT interval should be assessed before and after increasing total Austedo dosage above 24 mg per day.
    Switching Patients from Tetrabenazine (Xenazine) to Austedo
    Discontinue tetrabenazine (Xenazine) and initiate Austedo the following day. The recommended initial dosing regimen of Austedo in patients switching from tetrabenazine (Xenazine) to Austedo:
    Current tetrabenazine daily dosage: 12.5 mg -Initial regimen of Austedo-6 mg.
    Current tetrabenazine daily dosage: 25 mg -Initial regimen of Austedo-6 mg.
    Current tetrabenazine daily dosage: 37.5mg-Initial regimen of Austedo -9mg.
    Current tetrabenazine daily dosage: 50mg-Initial regimen of Austedo -12 mg.
    Current tetrabenazine daily dosage: 62.5- mgInitial regimen of Austedo-15 mg.
    Current tetrabenazine daily dosage: 75mg-Initial regimen of Austedo-18mg.
    Current tetrabenazine daily dosage: 87.5mg-Initial regimen of Austedo-21 mg.
    Current tetrabenazine daily dosage: 100mg-Initial regimen of Austedo-24 mg.
    After patients are switched to Austedo, the dose may be adjusted at weekly intervals.
    See prescribing information for full details.
    Dosage Adjustment with Strong CYP2D6 Inhibitors
    In patients receiving strong CYP2D6 inhibitors (e.g., quinidine, antidepressants such as paroxetine, fluoxetine, and bupropion), the total daily dosage of Austedo should not exceed 36 mg (maximum single dose of 18 mg).
    Dosage Adjustment in Poor CYP2D6 Metabolizers
    In patients who are poor CYP2D6 metabolizers, the total daily dosage of Austedo should not exceed 36 mg (maximum single dose of 18 mg).
    Discontinuation and Interruption of Treatment
    Treatment with Austedo can be discontinued without tapering. Following treatment interruption of greater than one week, Austedo therapy should be re-titrated when resumed. For treatment interruption of less than one week, treatment can be resumed at the previous maintenance dose without titration.
    Pediatric Use
    Austedo is not indicated for children and adolescents under 18 years of age. Safety and effectiveness in pediatric patients have not been established. See prescribing information for full details.
    Geriatric Use
    Clinical studies of Austedo did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. See prescribing information for full details.


    Indications

    Indicated in adults for the treatment of chorea associated with Huntington’s disease.
    Indicated in adults for the treatment tardive dyskinesia.


    Contra-Indications

    Patients with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression.
    Patients with hepatic impairment.
    Patients taking reserpine. At least 20 days should elapse after stopping reserpine before starting Austedo.
    Patients who are  treated with monoamine oxidase inhibitors (MAOIs). Austedo should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI.
    Patients who are  treated with tetrabenazine (Xenazine) or valbenazine.


    Special Precautions

    Depression and Suicidality in Patients with Huntington’s Disease: Patients with Huntington’s disease are at increased risk for depression, and suicidal ideation or behaviors (suicidality). Austedo may increase the risk for suicidality in patients with Huntington’s disease.
    Clinical Worsening and Adverse Events in Patients with Huntington’s Disease: Huntington’s disease is a progressive disorder characterized by changes in mood, cognition, chorea, rigidity, and functional capacity over time. VMAT2 inhibitors, including Austedo, may cause a worsening in mood, cognition, rigidity, and functional capacity.
    QTc Prolongation: Tetrabenazine, a closely related VMAT2 inhibitor, causes an increase (about 8 msec) in the corrected QT (QTc) interval. A clinically relevant QT prolongation may occur in some patients treated with Austedo who are CYP2D6 poor metabolizers or are co-administered a strong CYP2D6 inhibitor. For patients who are CYP2D6 poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary.
    Neuroleptic Malignant Syndrome (NMS)
    A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission.
    While NMS has not been observed in patients receiving Austedo, it has been observed in patients receiving tetrabenazine (a closely related VMAT2 inhibitor). Clinicians should be alerted to the signs and symptoms associated with NMS.
    Akathisia, Agitation, and Restlessness: Austedo may increase the risk of akathisia, agitation, and restlessness in patients with
    Huntington’s disease and tardive dyskinesia.
    Parkinsonism: Austedo may cause parkinsonism in patients with Huntington’s disease or tardive dyskinesia.
    Parkinsonism has also been observed with other VMAT2 inhibitors.
    Because rigidity can develop as part of the underlying disease process in Huntington’s disease, it may be difficult to distinguish between potential drug-induced parkinsonism and progression of underlying Huntington’s disease. Drug-induced parkinsonism has the potential to cause more functional disability than untreated chorea for some patients with Huntington’s disease.
    Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of Austedo.
    Hyperprolactinemia: Serum prolactin levels were not evaluated in the Austedo development program. Tetrabenazine, a closely related VMAT2 inhibitor, elevates serum prolactin concentrations in humans.
    Binding to Melanin-Containing Tissues: Since deutetrabenazine or its metabolites bind to melanin-containing tissues, it could accumulate in these tissues over time.
    Excipients with known effect: The 6 mg tablets contain FD&C red #40 lake, which may cause allergic reactions. The 12 mg tablets contain FD&C yellow #6 lake, which may cause allergic reactions.
    See prescribing information for full details.


    Side Effects

    Somnolence, diarrhea, dry mouth, and fatigue. See prescribing information for full details.

     


    Drug interactions

    Strong CYP2D6 Inhibitors:

    A reduction in Austedo dose may be necessary when adding a strong CYP2D6 inhibitor in patients maintained on a stable dose of Austedo. Concomitant use of strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, bupropion) has been shown to increase the systemic exposure to the active dihydro-metabolites of deutetrabenazine by approximately 3- fold. The daily dose of Austedo should not exceed 36 mg per day, and the maximum single dose of Austedo should not exceed 18 mg in patients taking strong CYP2D6 inhibitors.
    Drugs that Cause QTc Prolongation: Tetrabenazine, a closely related VMAT2 inhibitor, may cause an increase in the corrected QT (QTc) interval. Clinically relevant QT prolongation may also occur with Austedo. For patients requiring Austedo doses above 24 mg per day, who are using Austedo in combination with other drugs known to prolong QTc, assess the QTc interval before and after increasing the dose of Austedo or other medications that are known to prolong QTc. Drugs known to prolong QTc include antipsychotic medications (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), Class 1A (e.g., quinidine, procainamide), and Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.
    Reserpine: Reserpine binds irreversibly to VMAT2 and the duration of its effect is several days. Prescribers should wait for chorea or dyskinesia to reemerge before administering Austedo to help reduce the risk of overdosage and major depletion of serotonin and norepinephrine in the central nervous system. At least 20 days should elapse after stopping reserpine before starting Austedo. Austedo and reserpine should not be used concomitantly.
    Monoamine Oxidase Inhibitors (MAOIs)
    Austedo is contraindicated in patients taking MAOIs. Austedo should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI.
    Neuroleptic Drugs: The risk of parkinsonism, NMS, and akathisia may be increased by concomitant use of Austedo and dopamine antagonists or antipsychotics.
    Alcohol or Other Sedating Drugs: Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.
    Concomitant Tetrabenazine or Valbenazine: Austedo is contraindicated in patients currently taking tetrabenazine or valbenazine. AUSTEDO may be initiated the day following discontinuation of tetrabenazine.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: There are no adequate data on the developmental risk associated with the use of Austedo in pregnant women.
    See prescribing information for full details.
    Lactation: There are no data on the presence of deutetrabenazine or its metabolites in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. See prescribing information for full details.


    Overdose

    Overdoses ranging from 100 mg to 1 g have been reported in the literature with tetrabenazine, a closely related VMAT2 inhibitor. The following adverse reactions occurred with overdosing: acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor.
    Treatment should consist of those general measures employed in the management of overdosage with any central nervous system-active drug. General supportive and symptomatic measures are recommended. Cardiac rhythm and vital signs should be monitored. In managing overdosage, the possibility of multiple drug involvement should always be considered.


    Manufacturer
    Teva Pharmaceutical Industries Ltd, Israel
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