Austedo

Name: Austedo

How should I take deutetrabenazine?

If you are switching from a similar medicine called tetrabenazine (Xenazine), take your first dose of deutetrabenazine one day after your last dose of tetrabenazine.

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Deutetrabenazine is usually taken 2 times per day with food and a whole glass of water.

Do not crush, chew, or break a deutetrabenazine tablet. Swallow it whole. Tell your doctor if you have trouble swallowing the tablet whole.

Store at room temperature away from moisture, heat, and light.

If you stop taking deutetrabenazine for longer than 1 week, do not start taking it again without your doctor's advice.

Introduction

Deutetrabenazine is a central nervous system agent.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • Concomitant use of strong CYP2D6 inhibitors: Maximum recommended dose of deutetrabenazine is 36 mg per day (18 mg twice daily).1

  • Alcohol or other sedating drugs: May have additive sedation and somnolence.1

Proper Use of Austedo

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should be taken with food.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For chorea:
      • Adults—At first, 6 milligrams (mg) once a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 48 mg per day. If your dose is 12 mg or more per day, take the tablets 2 times a day in equal doses.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you stop taking this medicine for more than 7 days, do not take another dose until you talk to your doctor.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Uses of Austedo

  • It is used to treat disabling involuntary movements in Huntington's chorea.
  • It is used to treat tardive dyskinesia.

What are some other side effects of Austedo?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Feeling sleepy.
  • Feeling tired or weak.
  • Loose stools (diarrhea).
  • Dry mouth.
  • Not able to sleep.
  • Nose or throat irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Warnings and 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.

In a 12-week, double-blind, placebo-controlled trial, suicidal ideation was reported by 2% of patients treated with Austedo, compared to no patients on placebo; no suicide attempts and no completed suicides were reported. Depression was reported by 4% of patients treated with Austedo.

When considering the use of Austedo, the risk of suicidality should be balanced against the need for treatment of chorea. All patients treated with Austedo should be observed for new or worsening depression or suicidality. If depression or suicidality does not resolve, consider discontinuing treatment with Austedo.

Patients, their caregivers, and families should be informed of the risks of depression, worsening depression, and suicidality associated with Austedo, and should be instructed to report behaviors of concern promptly to the treating physician. Patients with Huntington’s disease who express suicidal ideation should be evaluated immediately.

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.

Prescribers should periodically re-evaluate the need for Austedo in their patients by assessing the effect on chorea and possible adverse effects, including sedation/somnolence, depression and suicidality, parkinsonism, akathisia, restlessness, and cognitive decline. It may be difficult to distinguish between adverse reactions and progression of the underlying disease; decreasing the dose or stopping the drug may help the clinician to distinguish between the two possibilities. In some patients, the underlying chorea itself may improve over time, decreasing the need for Austedo.

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 [see Clinical Pharmacology (12.2, 12.3)].

For patients who are CYP2D6 poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary [see Dosage and Administration (2.3, 2.4)]. The use of Austedo in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongations [see Drug Interactions (7.2)].

For patients requiring Austedo doses greater than 24 mg per day who are using Austedo 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.

Austedo should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias. Certain circumstances may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including (1) bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval.

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. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria, rhabdomyolysis, and acute renal failure. The diagnosis of NMS can be complicated; other serious medical illness (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal disorders can present with similar signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.

The management of NMS should include (1) immediate discontinuation of Austedo; (2) intensive symptomatic treatment and medical monitoring; and (3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.

Recurrence of NMS has been reported with resumption of drug therapy. If treatment with Austedo is needed after recovery from NMS, patients should be monitored for signs of recurrence.

Akathisia, Agitation, and Restlessness

Austedo may increase the risk of akathisia, agitation, and restlessness in patients with Huntington’s disease and tardive dyskinesia.

In a 12-week, double-blind, placebo-controlled trial in Huntington’s disease patients, akathisia, agitation, or restlessness was reported by 4% of patients treated with Austedo, compared to 2% of patients on placebo; in patients with tardive dyskinesia, 2% of patients treated with Austedo and 1% of patients on placebo experienced these events.

Patients receiving Austedo should be monitored for signs and symptoms of restlessness and agitation, as these may be indicators of developing akathisia. If a patient develops akathisia during treatment with Austedo, the Austedo dose should be reduced; some patients may require discontinuation of therapy.

Parkinsonism in Patients with Huntington’s Disease

Austedo may cause parkinsonism in patients with Huntington’s disease.

Because rigidity can develop as part of the underlying disease process in Huntington’s disease, it may be difficult to distinguish between this potential drug-induced adverse reaction and progression of the underlying disease process. Drug-induced parkinsonism has the potential to cause more functional disability than untreated chorea for some patients with Huntington’s disease. If a patient develops parkinsonism during treatment with Austedo, the Austedo dose should be reduced; some patients may require discontinuation of therapy.

Sedation and Somnolence

Sedation is a common dose-limiting adverse reaction of Austedo. In a 12-week, double-blind, placebo-controlled trial examining patients with Huntington’s disease, 11% of Austedo-treated patients reported somnolence compared with 4% of patients on placebo and 9% of Austedo-treated patients reported fatigue compared with 4% of placebo-treated patients.

Patients should not perform activities requiring mental alertness to maintain the safety of themselves or others, such as operating a motor vehicle or operating hazardous machinery, until they are on a maintenance dose of Austedo and know how the drug affects them.

Hyperprolactinemia

Serum prolactin levels were not evaluated in the Austedo development program. Tetrabenazine, a closely related VMAT2 inhibitor, elevates serum prolactin concentrations in humans. Following administration of 25 mg of tetrabenazine to healthy volunteers, peak plasma prolactin levels increased 4- to 5-fold.

Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if Austedo is being considered for a patient with previously detected breast cancer. Although amenorrhea, galactorrhea, gynecomastia, and impotence can be caused by elevated serum prolactin concentrations, the clinical significance of elevated serum prolactin concentrations for most patients is unknown.

Chronic increase in serum prolactin levels (although not evaluated in the Austedo or tetrabenazine development programs) has been associated with low levels of estrogen and increased risk of osteoporosis. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of Austedo.

Binding to Melanin-Containing Tissues

Since deutetrabenazine or its metabolites bind to melanin-containing tissues, it could accumulate in these tissues over time. This raises the possibility that Austedo may cause toxicity in these tissues after extended use. Neither ophthalmologic nor microscopic examination of the eye has been conducted in the chronic toxicity studies in a pigmented species such as dogs. Ophthalmologic monitoring in humans was inadequate to exclude the possibility of injury occurring after long-term exposure.

The clinical relevance of deutetrabenazine’s binding to melanin-containing tissues is unknown. Although there are no specific recommendations for periodic ophthalmologic monitoring, prescribers should be aware of the possibility of long-term ophthalmologic effects [see Clinical Pharmacology (12.2)].

Austedo - Clinical Pharmacology

Mechanism of Action

The precise mechanism by which deutetrabenazine exerts its effects in the treatment of tardive dyskinesia and chorea in patients with Huntington’s disease is unknown but is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. The major circulating metabolites (α-dihydrotetrabenazine [HTBZ] and β-HTBZ) of deutetrabenazine, are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.

Pharmacodynamics

Cardiac Electrophysiology

The effect of a single 12-mg or 24-mg dose of Austedo on the QT interval was studied in a randomized, double-blind, placebo-controlled crossover study in healthy male and female subjects with moxifloxacin as a positive control. At 24 mg, Austedo caused an approximately 4.5 msec mean increase in QTc (90% CI: 2.4, 6.5 msec). Effects at higher exposures to Austedo or its metabolites have not been evaluated.

Melanin Binding

Deutetrabenazine or its metabolites bind to melanin-containing tissues (i.e., eye, skin, fur) in pigmented rats. After a single oral dose of radiolabeled deutetrabenazine, radioactivity was still detected in eye and fur at 35 days following dosing [see Warnings and Precautions (5.9)].

Pharmacokinetics

After oral dosing up to 25 mg, plasma concentrations of deutetrabenazine are generally below the limit of detection because of the extensive hepatic metabolism of deutetrabenazine to the active deuterated dihydro metabolites (HTBZ), α-HTBZ and β-HTBZ. Linear dose dependence of Cmax and AUC was observed for the active metabolites following single or multiple doses of deutetrabenazine (6 mg to 24 mg and 7.5 mg twice daily to 22.5 mg twice daily).

Absorption

Following oral administration of deutetrabenazine, the extent of absorption is at least 80%.

Plasma concentrations of deutetrabenazine are generally below the limit of detection after oral dosing. Peak plasma concentrations (Cmax) of deuterated α-HTBZ and β-HTBZ are reached within 3 to 4 hours after dosing.

Effect of Food

The effects of food on the bioavailability of Austedo were studied in subjects administered a single dose with and without food. Food had no effect on the area under the plasma concentration-time curve (AUC) of α-HTBZ or β-HTBZ, although Cmax was increased by approximately 50% in the presence of food [see Dosage and Administration (2.1)].

Distribution

The median volume of distribution (Vc/F) of the α-HTBZ, and the β-HTBZ metabolites of Austedo are approximately 500 L and 730 L, respectively.

Results of PET-scan studies in humans show that following intravenous injection of 11C-labeled tetrabenazine or α-HTBZ, radioactivity is rapidly distributed to the brain, with the highest binding in the striatum and lowest binding in the cortex.

The in vitro protein binding of tetrabenazine, α-HTBZ, and β-HTBZ was examined in human plasma for concentrations ranging from 50 to 200 ng/mL. Tetrabenazine binding ranged from 82% to 85%, α-HTBZ binding ranged from 60% to 68%, and β-HTBZ binding ranged from 59% to 63%.

Elimination

Austedo is primarily renally eliminated in the form of metabolites.

The half-life of total (α+β)-HTBZ from deutetrabenazine is approximately 9 to 10 hours.

The median clearance values (CL/F) of the α-HTBZ, and the β-HTBZ metabolites of Austedo are approximately 47 L/hour and 70 L/hour, respectively, in the Huntington’s disease patient population.

Metabolism

In vitro experiments in human liver microsomes demonstrate that deutetrabenazine is extensively biotransformed, mainly by carbonyl reductase, to its major active metabolites, α-HTBZ and β-HTBZ, which are subsequently metabolized primarily by CYP2D6, with minor contributions of CYP1A2 and CYP3A4/5, to form several minor metabolites.

Excretion

In a mass balance study in 6 healthy subjects, 75% to 86% of the deutetrabenazine dose was excreted in the urine, and fecal recovery accounted for 8% to 11% of the dose. Urinary excretion of the α-HTBZ and β-HTBZ metabolites from deutetrabenazine each accounted for less than 10% of the administered dose. Sulfate and glucuronide conjugates of the α-HTBZ and β-HTBZ metabolites of deutetrabenazine, as well as products of oxidative metabolism, accounted for the majority of metabolites in the urine.

Specific Populations

Male and Female Patients

There is no apparent effect of gender on the pharmacokinetics of α-HTBZ and β‑HTBZ of deutetrabenazine.

Patients with Renal Impairment

No clinical studies have been conducted to assess the effect of renal impairment on the PK of Austedo.

Patients with Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of deutetrabenazine and its primary metabolites has not been studied. However, in a clinical study conducted to assess the effect of hepatic impairment on the pharmacokinetics of tetrabenazine, a closely related VMAT2 inhibitor, the exposure to α-HTBZ and β-HTBZ was up to 40% greater in patients with hepatic impairment, and the mean tetrabenazine Cmax in patients with hepatic impairment was up to 190-fold higher than in healthy subjects [see Contraindications (4), Use in Specific Populations (8.6)].

Poor CYP2D6 Metabolizers

Although the pharmacokinetics of deutetrabenazine and its metabolites have not been systematically evaluated in patients who do not express the drug metabolizing enzyme CYP2D6, it is likely that the exposure to α-HTBZ and β-HTBZ would be increased similarly to taking strong CYP2D6 inhibitors (approximately 3-fold) [see Dosage and Administration (2.4), Drug Interactions (7.1)].


Drug Interaction Studies

Deutetrabenazine, α-HTBZ, and β-HTBZ have not been evaluated in in vitro studies for induction or inhibition of CYP enzymes or interaction with P-glycoprotein. The results of in vitro studies of tetrabenazine do not suggest that tetrabenazine or its α-HTBZ or β-HTBZ metabolites are likely to result in clinically significant inhibition of CYP2D6, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A. In vitro studies suggest that neither tetrabenazine nor its α-HTBZ or β-HTBZ metabolites are likely to result in clinically significant induction of CYP1A2, CYP3A4, CYP2B6, CYP2C8, CYP2C9, or CYP2C19. Neither tetrabenazine nor its α-HTBZ or β-HTBZ metabolites are likely to be a substrate or inhibitor of P-glycoprotein at clinically relevant concentrations in vivo.

The deutetrabenazine metabolites, 2-methylpropanoic acid of β-HTBZ (M1) and monohydroxy tetrabenazine (M4), have been evaluated in a panel of in vitro drug-drug interaction studies; the results indicate that M1/M4 are not expected to cause clinically relevant drug interactions.

CYP2D6 Inhibitors

In vitro studies indicate that the α-HTBZ and β-HTBZ metabolites of deutetrabenazine are substrates for CYP2D6. The effect of CYP2D6 inhibition on the pharmacokinetics of deutetrabenazine and its metabolites was studied in 24 healthy subjects following a single 22.5 mg dose of deutetrabenazine given after 8 days of administration of the strong CYP2D6 inhibitor paroxetine 20 mg daily. In the presence of paroxetine, systemic exposure (AUCinf) of α-HTBZ was 1.9-fold higher and β-HTBZ was 6.5-fold higher, resulting in approximately 3-fold increase in AUCinf for total (α+β)-HTBZ. Paroxetine decreased the clearance of α-HTBZ and β-HTBZ metabolites of Austedo with corresponding increases in mean half-life of approximately 1.5-fold and 2.7-fold, respectively. In the presence of paroxetine, Cmax of α-HTBZ and β-HTBZ were 1.2-fold and 2.2-fold higher, respectively.

The effect of moderate or weak CYP2D6 inhibitors such as duloxetine, terbinafine, amiodarone, or sertraline on the exposure of deutetrabenazine and its metabolites has not been evaluated.

Digoxin

Austedo was not evaluated for interaction with digoxin. Digoxin is a substrate for P-glycoprotein. A study in healthy subjects showed that tetrabenazine (25 mg twice daily for 3 days) did not affect the bioavailability of digoxin, suggesting that at this dose, tetrabenazine does not affect P‑glycoprotein in the intestinal tract. In vitro studies also do not suggest that tetrabenazine or its metabolites are P-glycoprotein inhibitors.

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: o depression o suicidal thoughts o 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. o If you are at risk of QT prolongation, your healthcare provider should check your heart before and after increasing your Austedo dose above 24 mg a day. • 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: o high fever o stiff muscles o problems thinking o very fast or uneven heartbeat o increased sweating • Restlessness. You may get a condition where you feel a strong urge to move. This is called akathisia. • Parkinsonism in people with Huntington’s disease. Symptoms of parkinsonism include: slight shaking, body stiffness, trouble moving, or keeping your balance.

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

• sleepiness (sedation) • tiredness • diarrhea • 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.

Distributed by:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

AUSMG-002

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: August 2017

What other drugs will affect Austedo?

Austedo can cause a serious heart problem, especially if you use certain medicines at the same time, such as antibiotics, antifungal medicine, antidepressants, anti-malaria medicine, asthma inhalers, antipsychotic medicine, cancer medicine, certain HIV/AIDS medicine, heart or blood pressure medicine, or medicine to prevent vomiting.

Taking Austedo with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking a sleeping pill, narcotic medication, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with this medicine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Deutetrabenazine Pregnancy Warnings

Animal studies have revealed this drug had no clear adverse effects on embryo-fetal development at doses up to 6 times the maximum recommended human dose (MRHD) when it was administered during organogenesis. Findings in animals also showed oral administration of this drug resulted in estrous cycle disruption at all doses tested; the lowest dose tested was similar to the MRHD on a body surface area basis. The effects of this drug on animals during pregnancy and lactation have not been assessed. There are no controlled data in human pregnancy. Closely related VMAT2 inhibitor tetrabenazine caused increased stillbirths, postnatal offspring mortality, and delayed offspring maturation when administered to animals throughout pregnancy and lactation. Additionally, oral administration of tetrabenazine to animals resulted in disrupted estrous cyclicity in females at doses greater than 5 mg/kg/day; however, there were no effects on mating and fertility indices or sperm parameters in males. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

Safety has not been established; the manufacturer makes no recommendation regarding use during pregnancy. US FDA pregnancy category: Not Assigned

Deutetrabenazine Breastfeeding Warnings

Safety has not been established; benefit should outweigh risk. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in the nursing infant and on milk production are unknown.

(web3)