What is the recommended procedure for switching an adult patient with a history of Huntington's disease or tardive dyskinesia from Austedo (Deutetrabenazine) XR to IR formulation?

Switching from Austedo XR to Austedo IR

When switching from Austedo XR (extended-release) to Austedo IR (immediate-release), use a 1:1 total daily dose conversion and split the daily dose into twice-daily administration with food, implementing the switch the day after discontinuing XR formulation. 1

Conversion Protocol

Dose Conversion Table

• If on Austedo XR 12 mg once daily: Switch to Austedo IR 6 mg twice daily (total 12 mg/day) 1
• If on Austedo XR 24 mg once daily: Switch to Austedo IR 12 mg twice daily (total 24 mg/day) 1
• If on Austedo XR 36 mg once daily: Switch to Austedo IR 18 mg twice daily (total 36 mg/day) 1
• If on Austedo XR 48 mg once daily: Switch to Austedo IR 24 mg twice daily (total 48 mg/day) 1

Implementation Steps

Discontinue Austedo XR and initiate Austedo IR the following day at the equivalent total daily dose divided into two doses. 1 This direct switch approach mirrors the FDA-approved protocol for switching between tetrabenazine and deutetrabenazine formulations. 1

Administer Austedo IR with food in two divided doses per day for total daily dosages of 12 mg or above, whereas Austedo XR can be taken with or without food once daily. 1 This food requirement for IR formulation is critical for optimal absorption and tolerability. 1

Instruct patients to swallow tablets whole without chewing, crushing, or breaking them, as this applies to both formulations. 1

Critical Monitoring During Switch

Pharmacokinetic Considerations

The active metabolites (α-HTBZ and β-HTBZ) have a half-life of approximately 9-10 hours with deutetrabenazine, providing 3-4 fold longer half-lives compared to tetrabenazine. 2, 3 This extended half-life means steady-state concentrations should be maintained during the switch without significant fluctuation. 2

Monitor for changes in symptom control during the first week after switching, as the IR formulation produces higher peak plasma concentrations (Cmax) despite equivalent total exposure (AUC). 2 The XR formulation was specifically designed to reduce peak-to-trough fluctuations by 11-fold compared to IR dosing. 2

Safety Monitoring

Assess for depression, suicidality, and mood changes at baseline and weekly for the first month, as both formulations carry a boxed warning for depression and suicidality in Huntington's disease patients. 1 Both formulations are contraindicated in patients who are suicidal or have untreated/inadequately treated depression. 1

Monitor for akathisia, agitation, restlessness, and parkinsonism during the first 2-4 weeks, as these adverse effects may emerge or worsen with changes in peak drug concentrations. 1

Watch for sedation and somnolence, particularly during the first week, as the IR formulation's higher peak concentrations may transiently increase these effects. 1 Advise patients about potential impairment in driving or operating machinery. 1

Special Population Considerations

CYP2D6 Poor Metabolizers

The maximum recommended daily dose is 36 mg per day (18 mg twice daily of IR formulation) in CYP2D6 poor metabolizers, regardless of formulation. 1 If the patient was on Austedo XR 48 mg daily and is a poor metabolizer, reduce to 36 mg total daily dose (18 mg twice daily) when switching to IR. 1

Patients on Strong CYP2D6 Inhibitors

The maximum recommended dose is 36 mg per day when patients are taking strong CYP2D6 inhibitors (such as paroxetine, fluoxetine, quinidine, or bupropion). 1 Verify concomitant medications before implementing the switch. 1

Common Pitfalls to Avoid

Do not maintain once-daily dosing with IR formulation for total daily doses of 12 mg or above, as the IR formulation requires twice-daily administration to maintain therapeutic levels and minimize peak-related adverse effects. 1

Do not switch patients taking reserpine, MAOIs, tetrabenazine, or valbenazine, as these are absolute contraindications for deutetrabenazine. 1 Reserpine must be discontinued at least 20 days before initiating deutetrabenazine. 1

Avoid switching in patients with hepatic impairment, as both formulations are contraindicated in any degree of hepatic impairment. 1

Do not overlook the food requirement for IR formulation, as administration without food may reduce absorption and efficacy, particularly for doses of 12 mg/day or higher. 1

Monitor QTc interval in patients with cardiac risk factors, though deutetrabenazine does not cause clinically relevant QT prolongation at maximum recommended doses. 4 Unlike tetrabenazine, deutetrabenazine has no significant effect on QT interval. 5