Austedo: Package Insert and Label Information (Page 4 of 5)

14.2 Tardive Dyskinesia

The efficacy of AUSTEDO in the treatment for tardive dyskinesia was established in two 12‑week, randomized, double-blind, placebo-controlled, multi-center trials conducted in 335 adult ambulatory patients with tardive dyskinesia caused by use of dopamine receptor antagonists. Patients had a history of using a dopamine receptor antagonist (antipsychotics, metoclopramide) for at least 3 months (or 1 month in patients 60 years of age and older). Concurrent diagnoses included schizophrenia/schizoaffective disorder (62%) and mood disorder (33%). With respect to concurrent antipsychotic use, 64% of patients were receiving atypical antipsychotics, 12% were receiving typical or combination antipsychotics, and 24% were not receiving antipsychotics.

The Abnormal Involuntary Movement Scale (AIMS) was the primary efficacy measure for the assessment of tardive dyskinesia severity. The AIMS is a 12-item scale; items 1 to 7 assess the severity of involuntary movements across body regions and these items were used in this study. Each of the 7 items was scored on a 0 to 4 scale, rated as: 0=not present; 1=minimal, may be extreme normal (abnormal movements occur infrequently and/or are difficult to detect); 2=mild (abnormal movements occur infrequently and are easy to detect); 3=moderate (abnormal movements occur frequently and are easy to detect) or 4 =severe (abnormal movements occur almost continuously and/or of extreme intensity). The AIMS total score (sum of items 1 to 7) could thus range from 0 to 28, with a decrease in score indicating improvement.

In Study 1, a 12-week, placebo-controlled, fixed-dose trial, adults with tardive dyskinesia were randomized 1:1:1:1 to 12 mg AUSTEDO, 24 mg AUSTEDO, 36 mg AUSTEDO, or placebo. Treatment duration included a 4-week dose escalation period and an 8-week maintenance period followed by a 1-week washout. The dose of AUSTEDO was started at 12 mg per day and increased at weekly intervals in 6 mg/day increments to a dose target of 12 mg, 24 mg or 36 mg per day. The population (n= 222) was 21 to 81 years old (mean 57 years), 48% male, and 79% Caucasian. In Study 1, the AIMS total score for patients receiving AUSTEDO demonstrated statistically significant improvement, from baseline to Week 12, of 3.3 and 3.2 units for the 36 mg and 24 mg arms, respectively, compared with 1.4 units in placebo (Study 1 in Table 5). The improvements on the AIMS total score over the course of the study are displayed in Figure 3. Data did not suggest substantial differences in efficacy across various demographic groups. The treatment response rate distribution, based on magnitude of AIMS total score from baseline to week 12 is displayed in Figure 4.

The mean changes in the AIMS total score by visit are shown in Figure 3.

In Study 2, a 12-week, placebo-controlled, flexible-dose trial, adults with tardive dyskinesia (n=113) received daily doses of placebo or AUSTEDO, starting at 12 mg per day with increases allowed in 6-mg increments at 1-week intervals until satisfactory control of dyskinesia was achieved, until intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached. Treatment duration included a 6-week dose titration period and a 6-week maintenance period followed by a 1-week washout. The population was 25 to 75 years old (mean 55 years), 48% male, and 70% Caucasian. Patients were titrated to an optimal dose over 6 weeks. The average dose of AUSTEDO after treatment was 38.3 mg per day. There was no evidence suggesting substantial differences in efficacy across various demographic groups. In Study 2, AIMS total score for patients receiving AUSTEDO demonstrated statistically significant improvement by 3.0 units from baseline to endpoint (Week 12), compared with 1.6 units in the placebo group with a treatment effect of -1.4 units. Table 5 summarizes the effects of AUSTEDO on tardive dyskinesia based on the AIMS.

Table 5: Improvement in AIMS Total Score in Patients Treated with AUSTEDO in Study 1 and Study 2
Study Treatment Group Primary Efficacy Measure: AIMS Total Score
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Treatment Effect (95% CI)

Study 1

AUSTEDO 36 mg*

(n= 55)

10.1 (3.21)

-3.3 (0.42)

-1.9 (-3.09, -0.79)

AUSTEDO 24 mg

(n= 49)

9.4 (2.93)

-3.2 (0.45)

-1.8 (-3.00, -0.63)

AUSTEDO 12 mg

(n= 60)

9.6 (2.40)

-2.1 (0.42)

-0.7 (-1.84, 0.42)

Placebo (n= 58)

9.5 (2.71)

-1.4 (0.41)

Study 2

AUSTEDO

(12-48 mg/day)*

(n= 56)

9.7 (4.14)

-3.0 (0.45)

-1.4 (-2.6, -0.2)

Placebo (n= 57)

9.6 (3.78)

-1.6 (0.46)

*Dose that was statistically significantly different from placebo after adjusting for multiplicity.

LS Mean = Least-squares mean; SD = Standard deviation; SE = Standard error; CI = 2-sided 95% confidence interval

Figure 3: Least Square Means of Change in AIMS Total Score from Baseline for AUSTEDO Compared to Placebo (Study 1)

figure-03.jpg
(click image for full-size original)

SE = Standard error

Figure 4: Percent of Patients with Specified Magnitude of AIMS Total Score Improvement at the End of Week 12 (Study 1)

figure-04.jpg
(click image for full-size original)

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

AUSTEDO tablets are available in the following strengths and packages:

6 mg: round, purple-coated tablets, with “SD” over “6” printed in black ink on one side.

Bottles of 60 tablets: NDC 68546-170-60.

9 mg: round, blue-coated tablets, with “SD” over “9” printed in black ink on one side.

Bottles of 60 tablets: NDC 68546-171-60.

12 mg: round, beige-coated tablets, with “SD” over “12” printed in black ink on one side.

Bottles of 60 tablets: NDC 68546-172-60.

16.2 Storage

Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Protect from light and moisture.

17 PATIENT COUNSELING INFORMATION

Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide).

Administration Instructions

Advise patients to take AUSTEDO with food. AUSTEDO tablets should be swallowed whole and not chewed, crushed, or broken [see Dosage and Administration (2.1)].

Risk of Depression and Suicide in Patients with Huntington’s Disease

Advise patients, their caregivers, and families that AUSTEDO may increase the risk of depression, worsening depression, and suicidality, and to immediately report any symptoms to a healthcare provider [see Contraindications (4), Warnings and Precautions (5.2)].

Prolongation of the QTc Interval

Inform patients to consult their physician immediately if they feel faint, lose consciousness, or have heart palpitations [see Warnings and Precautions (5.3)]. Advise patients to inform physicians that they are taking AUSTEDO before any new drug is taken.

Parkinsonism

Inform patients that AUSTEDO may cause Parkinson-like symptoms, which could be severe. Advise patients to consult their healthcare provider if they experience slight shaking, body stiffness, trouble moving, trouble keeping their balance, or falls [see Warnings and Precautions (5.6)].

Risk of Sedation and Somnolence

Advise patients that AUSTEDO may cause sedation and somnolence and may impair the ability to perform tasks that require complex motor and mental skills. Until they learn how they respond to a stable dose of AUSTEDO, patients should be careful doing activities that require them to be alert, such as driving a car or operating machinery [see Warnings and Precautions (5.7)].

Interaction with Alcohol or Other Sedating Drugs

Advise patients that alcohol or other drugs that cause sleepiness will worsen somnolence [see Drug Interactions (7.5)].

Concomitant Medications

Advise patients to notify their physician of all medications they are taking and to consult with their healthcare provider before starting any new medications because of a potential for interactions [see Contraindications (4) and Drug Interactions (7.1, 7.4)].

Manufactured for:
Teva Neuroscience, Inc. Parsippany, NJ 07054

© 2022 Teva Neuroscience, Inc.

AUS-008

U.S. Patent Nos: 8,524,733; 9,233,959; 9,296,739; 9,550,780; 9,814,708; 10,959,996

XENAZINE® is a trademark of Valeant Pharmaceuticals Luxembourg S.A.R.L.

MEDICATION GUIDE

MEDICATION GUIDE AUSTEDO® (aw-STED-oh) (deutetrabenazine) tablets, for oral use

What is the most important information I should know about AUSTEDO?

  • AUSTEDO can cause serious side effects in people with Huntington’s disease, including:
    • depression
    • suicidal thoughts
    • suicidal actions
  • Do not start taking AUSTEDO if you have Huntington’s disease and are depressed (have untreated depression or depression that is not well controlled by medicine) or have suicidal thoughts.
  • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is especially important when AUSTEDO is started and when the dose is changed.

Call your healthcare provider 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 more or a lot less than usual
  • feel unimportant
  • feel guilty
  • feel hopeless or helpless
  • feel more irritable, angry, or aggressive than usual
  • feel 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 is AUSTEDO?

AUSTEDO is a prescription medicine that is used to treat:

  • the involuntary movements (chorea) of Huntington’s disease. AUSTEDO does 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.
  • movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia).

It is not known if AUSTEDO is safe and effective in children.

Who should not take AUSTEDO?

Do not take AUSTEDO if you:

  • have Huntington’s disease and are depressed or have thoughts of suicide. See “What is the most important information I should know about AUSTEDO?”
  • have liver problems.
  • are taking a monoamine oxidase inhibitor (MAOI) medicine. Do not take an MAOI within 14 days after you stop taking AUSTEDO. Do not start AUSTEDO if you stopped taking an MAOI in the last 14 days. Ask your healthcare provider or pharmacist if you are not sure.
  • are taking reserpine. Do not take medicines that contain reserpine (such as Serpalan and Renese-R) with AUSTEDO. If your healthcare provider plans to switch you from taking reserpine to AUSTEDO, you must wait at least 20 days after your last dose of reserpine before you start taking AUSTEDO.
  • are taking tetrabenazine (Xenazine). If your healthcare provider plans to switch you from tetrabenazine (Xenazine) to AUSTEDO, take your first dose of AUSTEDO on the day after your last dose of tetrabenazine (Xenazine).
  • are taking valbenazine (Ingrezza).

Before taking AUSTEDO, tell your healthcare provider about all of your medical conditions, including if you:

  • have emotional or mental problems (for example, depression, nervousness, anxiety, anger, agitation, psychosis, previous suicidal thoughts or suicide attempts).
  • have liver disease.
  • have an irregular heart rhythm or heartbeat (QT prolongation, cardiac arrhythmia) or a heart problem called congenital long QT syndrome.
  • have low levels of potassium or magnesium in your blood (hypokalemia or hypomagnesemia).
  • have breast cancer or a history of breast cancer.
  • are pregnant or plan to become pregnant. It is not known if AUSTEDO can harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if AUSTEDO passes into breast milk.

Tell your healthcare provider about all of the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking AUSTEDO with certain other medicines may cause side effects. Do not start any new medicines while taking AUSTEDO without talking to your healthcare provider first.

How should I take AUSTEDO?

  • Take AUSTEDO exactly as your healthcare provider tells you to take it.
  • Take AUSTEDO by mouth and with food.
  • Swallow AUSTEDO tablets whole with water. Do not chew, crush, or break AUSTEDO tablets before swallowing. If you cannot swallow AUSTEDO tablets whole, tell your healthcare provider. You may need a different medicine.
  • If your dose of AUSTEDO is 12 mg or more each day, take AUSTEDO tablets 2 times a day in equal doses with food.
  • Your healthcare provider will increase your dose of AUSTEDO each week for several weeks, until you and your healthcare provider find the right dose for you.
  • Tell your healthcare provider if you stop taking AUSTEDO for more than 1 week. Do not take another dose until you talk to your healthcare provider.

What should I avoid while taking AUSTEDO?

Sleepiness (sedation) is a common side effect of AUSTEDO. While taking AUSTEDO, do not drive a car or operate dangerous machinery until you know how AUSTEDO affects you. Drinking alcohol and taking other drugs that may also cause sleepiness while you are taking AUSTEDO may increase any sleepiness caused by AUSTEDO.

What are the possible side effects of AUSTEDO?

AUSTEDO can cause serious side effects, including:

  • Depression and suicidal thoughts or actions in people with Huntington’s disease. See “What is the most important information I should know about AUSTEDO?”
  • Irregular heartbeat (QT prolongation). AUSTEDO increases your chance of having certain changes in the electrical activity in your heart. These changes can lead to a dangerous abnormal heartbeat. Taking AUSTEDO with certain medicines may increase this chance.
  • Neuroleptic Malignant Syndrome (NMS). Call your healthcare provider right away and go to the nearest emergency room if you develop these signs and symptoms that do not have another obvious cause:
    • high fever
    • problems thinking
    • increased sweating
    • stiff muscles
    • very fast or uneven heartbeat
  • Restlessness. You may get a condition where you feel a strong urge to move. This is called akathisia.
  • Parkinsonism. Symptoms of parkinsonism include: slight shaking, body stiffness, trouble moving, trouble keeping your balance, or falls.

The most common side effects of AUSTEDO in people with Huntington’s disease include:

  • sleepiness (sedation)
  • diarrhea
  • tiredness
  • dry mouth

The most common side effects of AUSTEDO in people with tardive dyskinesia include:

  • inflammation of the nose and throat (nasopharyngitis)
  • problems sleeping (insomnia)

These are not all the possible side effects of AUSTEDO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store AUSTEDO?

  • Store AUSTEDO tablets at room temperature, between 68°F to 77°F (20°C to 25°C).
  • Keep the bottle tightly closed to protect AUSTEDO from light and moisture.

Keep AUSTEDO tablets and all medications out of reach of children.

General information about the safe and effective use of AUSTEDO.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use AUSTEDO for a condition for which it was not prescribed. Do not give AUSTEDO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about AUSTEDO that is written for health professionals.

What are the ingredients in AUSTEDO?

Active ingredient: deutetrabenazine

Inactive ingredients: ammonium hydroxide, black iron oxide, n‑butyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, polyethylene oxide, polysorbate 80, polyvinyl alcohol, povidone, propylene glycol, shellac, talc, titanium dioxide, and FD&C blue #2 lake. The 6 mg tablets also contain FD&C red #40 lake. The 12 mg tablets also contain FD&C yellow #6 lake.

Manufactured for:Teva Neuroscience, Inc. Parsippany, NJ 07054

© 2022 Teva Neuroscience, Inc.

AUSMG-007

For more information, go to www.AUSTEDO.com or call 1-888-483-8279.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: May 2022

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