Deutetrabenazine: Difference between revisions
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|clinicalStudies====== | |clinicalStudies= | ||
=====Chorea Associated with Huntington’s Disease===== | |||
( | *Double-Blind, Placebo-Controlled Study | ||
*The efficacy of deutetrabenazine as a treatment for chorea associated with Huntington's disease was established primarily in Study 1, a randomized, double-blind, placebo-controlled, multi-center trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. The diagnosis of Huntington’s disease was based on family history, neurological exam, and genetic testing. Treatment duration was 12 weeks, including an 8-week dose titration period and a 4-week maintenance period, followed by a 1-week washout. Patients were not blinded to discontinuation. Deutetrabenazine was started at 6 mg per day and titrated upward, at weekly intervals, in 6 mg increments until satisfactory treatment of chorea was achieved, intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached. The primary efficacy endpoint was the Total Maximal Chorea Score, an item of the Unified Huntington's Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28. | |||
===== | *Of the 90 patients enrolled, 87 patients completed the study. The mean age was 54 (range 23 to 74). Patients were 56% male and 92% Caucasian. The mean dose after titration was 40 mg per day. Table 4 and Figure 1 summarize the effects of deutetrabenazine on chorea based on the Total Maximal Chorea Score. Total Maximal Chorea Scores for patients receiving deutetrabenazine improved by approximately 4.4 units from baseline to the maintenance period (average of Week 9 and Week 12), compared to approximately 1.9 units in the placebo group. The treatment effect of -2.5 units was statistically significant (p<0.0001). The Maintenance Endpoint is the mean of the Total Maximal Chorea Scores for the Week 9 and Week 12 visits. At the Week 13 follow-up visit (1 week after discontinuation of the study medication), the Total Maximal Chorea Scores of patients who had received deutetrabenazine returned to baseline (Figure 1). | ||
[[image:Deutetrabenazineclinicaltrials.png|none|thumb|400px|This image is provided by the National Library of Medicine.]] | |||
( | *Figure 2 shows the distribution of values for the change in Total Maximal Chorea Score in Study 1. Negative values indicate a reduction in chorea and positive numbers indicate an increase in chorea. | ||
*A patient-rated global impression of change assessed how patients rated their overall Huntington’s disease symptoms. Fifty-one percent of patients treated with deutetrabenazine rated their symptoms as “Much Improved” or “Very Much Improved” at the end of treatment, compared to 20% of placebo-treated patients. | |||
=== | *In a physician-rated clinical global impression of change, 42% percent of patients treated with deutetrabenazine rated their symptoms as “Much Improved” or “Very Much Improved” at the end of treatment compared to 13% of placebo-treated patients. | ||
=====Tardive Dyskinesia===== | |||
( | *The efficacy of deutetrabenazine 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 deutetrabenazine, 24 mg deutetrabenazine, 36 mg deutetrabenazine, 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 deutetrabenazine 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 deutetrabenazine 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 deutetrabenazine, 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 deutetrabenazine 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 deutetrabenazine 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 deutetrabenazine on tardive dyskinesia based on the AIMS. | |||
[[image:Deutetrabenazineclinicaltrials1.png|none|thumb|400px|This image is provided by the National Library of Medicine.]] | |||
[[image:Deutetrabenazineclinicaltrials2.png|none|thumb|400px|This image is provided by the National Library of Medicine.]] | |||
[[image:Deutetrabenazineclinicaltrials3.png|none|thumb|400px|This image is provided by the National Library of Medicine.]] | |||
|howSupplied= | |howSupplied= | ||
*Deutetrabenazine tablets are available in the following strengths and packages: | *Deutetrabenazine tablets are available in the following strengths and packages: | ||
Revision as of 14:11, 12 July 2018
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sonya Gelfand
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Black Box Warning
|
WARNING: DEPRESSION AND SUICIDALITY IN PATIENTS WITH HUNTINGTON’S DISEASE
See full prescribing information for complete Boxed Warning.
|
Overview
Deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor that is FDA approved for the treatment of chorea associated with Huntington’s disease, and tardive dyskinesia. There is a Black Box Warning for this drug as shown here. Common adverse reactions include somnolence, diarrhea, dry mouth, fatigue, nasopharyngitis, and insomnia.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition 1
- Dosing Information
- (Dosage)
Condition 2
- Dosing Information
- (Dosage)
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Non–Guideline-Supported Use
Condition 1
- Dosing Information
- (Dosage)
Condition 2
- Dosing Information
- (Dosage)
Condition 3
- Dosing Information
- (Dosage)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition 1
- Dosing Information
- (Dosage)
Condition 2
- Dosing Information
- (Dosage)
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Non–Guideline-Supported Use
Condition 1
- Dosing Information
- (Dosage)
Condition 2
- Dosing Information
- (Dosage)
Condition 3
- Dosing Information
- (Dosage)
Contraindications
CONTRAINDICATIONS
Warnings
|
WARNING: DEPRESSION AND SUICIDALITY IN PATIENTS WITH HUNTINGTON’S DISEASE
See full prescribing information for complete Boxed Warning.
|
Conidition 1
(Description)
Conidition 2
(Description)
Conidition 3
(Description)
Adverse Reactions
Clinical Trials Experience
Central Nervous System
- (list/description of adverse reactions)
Cardiovascular
- (list/description of adverse reactions)
Respiratory
- (list/description of adverse reactions)
Gastrointestinal
- (list/description of adverse reactions)
Hypersensitive Reactions
- (list/description of adverse reactions)
Miscellaneous
- (list/description of adverse reactions)
Condition 2
Central Nervous System
- (list/description of adverse reactions)
Cardiovascular
- (list/description of adverse reactions)
Respiratory
- (list/description of adverse reactions)
Gastrointestinal
- (list/description of adverse reactions)
Hypersensitive Reactions
- (list/description of adverse reactions)
Miscellaneous
- (list/description of adverse reactions)
Postmarketing Experience
(Description)
Drug Interactions
- Drug 1
- Drug 2
- Drug 3
- Drug 4
- Drug 5
Drug 1
(Description)
Drug 2
(Description)
Drug 3
(Description)
Drug 4
(Description)
Drug 5
(Description)
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
(Description)
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Deutetrabenazine in women who are pregnant.
Labor and Delivery
(Description)
Nursing Mothers
(Description)g
Pediatric Use
(Description)
Geriatic Use
(Description)
Gender
(Description)
Race
(Description)
Renal Impairment
(Description)
Hepatic Impairment
(Description)
Females of Reproductive Potential and Males
(Description)
Immunocompromised Patients
(Description)
Others
(Description)
Administration and Monitoring
Administration
(Oral/Intravenous/etc)
Monitoring
Condition 1
(Description regarding monitoring, from Warnings section)
Condition 2
(Description regarding monitoring, from Warnings section)
Condition 3
(Description regarding monitoring, from Warnings section)
IV Compatibility
There is limited information regarding the compatibility of Deutetrabenazine and IV administrations.
Overdosage
Acute Overdose
Signs and Symptoms
(Description)
Management
(Description)
Chronic Overdose
Signs and Symptoms
(Description)
Management
(Description)
Pharmacology
Deutetrabenazine
| |
| Systematic (IUPAC) name | |
| ? | |
| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | ? |
| Chemical data | |
| Formula | ? |
| Mol. mass | ? |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Mechanism of Action
(Description)
Structure
(Description with picture)
Pharmacodynamics
(Description)
Pharmacokinetics
(Description)
Nonclinical Toxicology
(Description)
Clinical Studies
Chorea Associated with Huntington’s Disease
- Double-Blind, Placebo-Controlled Study
- The efficacy of deutetrabenazine as a treatment for chorea associated with Huntington's disease was established primarily in Study 1, a randomized, double-blind, placebo-controlled, multi-center trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. The diagnosis of Huntington’s disease was based on family history, neurological exam, and genetic testing. Treatment duration was 12 weeks, including an 8-week dose titration period and a 4-week maintenance period, followed by a 1-week washout. Patients were not blinded to discontinuation. Deutetrabenazine was started at 6 mg per day and titrated upward, at weekly intervals, in 6 mg increments until satisfactory treatment of chorea was achieved, intolerable side effects occurred, or until a maximal dose of 48 mg per day was reached. The primary efficacy endpoint was the Total Maximal Chorea Score, an item of the Unified Huntington's Disease Rating Scale (UHDRS). On this scale, chorea is rated from 0 to 4 (with 0 representing no chorea) for 7 different parts of the body. The total score ranges from 0 to 28.
- Of the 90 patients enrolled, 87 patients completed the study. The mean age was 54 (range 23 to 74). Patients were 56% male and 92% Caucasian. The mean dose after titration was 40 mg per day. Table 4 and Figure 1 summarize the effects of deutetrabenazine on chorea based on the Total Maximal Chorea Score. Total Maximal Chorea Scores for patients receiving deutetrabenazine improved by approximately 4.4 units from baseline to the maintenance period (average of Week 9 and Week 12), compared to approximately 1.9 units in the placebo group. The treatment effect of -2.5 units was statistically significant (p<0.0001). The Maintenance Endpoint is the mean of the Total Maximal Chorea Scores for the Week 9 and Week 12 visits. At the Week 13 follow-up visit (1 week after discontinuation of the study medication), the Total Maximal Chorea Scores of patients who had received deutetrabenazine returned to baseline (Figure 1).
- Figure 2 shows the distribution of values for the change in Total Maximal Chorea Score in Study 1. Negative values indicate a reduction in chorea and positive numbers indicate an increase in chorea.
- A patient-rated global impression of change assessed how patients rated their overall Huntington’s disease symptoms. Fifty-one percent of patients treated with deutetrabenazine rated their symptoms as “Much Improved” or “Very Much Improved” at the end of treatment, compared to 20% of placebo-treated patients.
- In a physician-rated clinical global impression of change, 42% percent of patients treated with deutetrabenazine rated their symptoms as “Much Improved” or “Very Much Improved” at the end of treatment compared to 13% of placebo-treated patients.
Tardive Dyskinesia
- The efficacy of deutetrabenazine 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 deutetrabenazine, 24 mg deutetrabenazine, 36 mg deutetrabenazine, 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 deutetrabenazine 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 deutetrabenazine 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 deutetrabenazine, 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 deutetrabenazine 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 deutetrabenazine 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 deutetrabenazine on tardive dyskinesia based on the AIMS.
How Supplied
- Deutetrabenazine 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.
Storage
- Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Protect from light and moisture.
Images
Drug Images
{{#ask: Page Name::Deutetrabenazine |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Deutetrabenazine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
- Advise the patient or caregiver to read the FDA-approved patient labeling.
Administration Instructions
- Advise patients to take deutetrabenazine with food. Deutetrabenazine tablets should be swallowed whole and not chewed, crushed, or broken.
Risk of Depression and Suicide in Patients with Huntington’s Disease
- Advise patients, their caregivers, and families that deutetrabenazine may increase the risk of depression, worsening depression, and suicidality, and to immediately report any symptoms to a healthcare provider.
Prolongation of the QTc Interval
- Inform patients to consult their physician immediately if they feel faint, lose consciousness, or have heart palpitations. Advise patients to inform physicians that they are taking deutetrabenazine before any new drug is taken.
Risk of Sedation and Somnolence
- Advise patients that deutetrabenazine 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 deutetrabenazine, patients should be careful doing activities that require them to be alert, such as driving a car or operating machinery.
Interaction with Alcohol or Other Sedating Drugs
- Advise patients that alcohol or other drugs that cause sleepiness will worsen somnolence.
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.
Precautions with Alcohol
Alcohol-Deutetrabenazine interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
- Austedo
Look-Alike Drug Names
There is limited information regarding Deutetrabenazine Look-Alike Drug Names in the drug label.
Drug Shortage Status
Drug Shortage
Price
References
The contents of this FDA label are provided by the National Library of Medicine.