Can a patient with a neurological or psychiatric condition, such as Huntington's disease or tardive dyskinesia, combine a 24 mg and 12 mg capsule of Austedo XR (Deutetrabenazine) to achieve a 36 mg dose?

Combining Austedo XR Capsules to Achieve 36 mg Dose

Yes, you can combine a 24 mg and 12 mg Austedo XR capsule to achieve a 36 mg dose, as the FDA-approved formulation includes both strengths and the drug demonstrates dose-proportional pharmacokinetics across the clinical dosage range. 1

Pharmacokinetic Support for Combination Dosing

The FDA label explicitly states that systemic exposure (Cmax and AUC) for deutetrabenazine and its active metabolites (α-HTBZ and β-HTBZ) increased proportionally to dose following single doses of Austedo XR over the recommended clinical dosage range of 6 mg to 48 mg. 1 This dose-proportional relationship means that combining two capsules to reach 36 mg will produce the same exposure as a single 36 mg capsule would.

• Research confirms linear pharmacokinetics for deutetrabenazine, supporting the validity of combining different capsule strengths to achieve target doses 2
• The active metabolites demonstrate predictable, proportional increases in plasma concentrations across the dose range 3

Available Formulations and Dosing Flexibility

Austedo XR extended-release tablets are available in eight strengths: 6 mg, 12 mg, 18 mg, 24 mg, 30 mg, 36 mg, 42 mg, and 48 mg 1

• While a single 36 mg capsule exists, combining 24 mg + 12 mg is pharmacologically equivalent and acceptable when the 36 mg strength is unavailable 1
• The osmotic delivery system in each capsule functions independently, so taking two capsules simultaneously delivers the combined dose in a controlled manner 1

Important Dosing Considerations

The maximum daily dose of Austedo XR should not exceed 48 mg, and in CYP2D6 poor metabolizers, the daily dose should not exceed 36 mg due to approximately 3-fold increased exposure to active metabolites. 1

• Food has no effect on total (α+β)-HTBZ exposure (AUC), though Cmax increases by approximately 50% with food—this remains lower than tetrabenazine's peak concentrations 3
• Austedo XR can be taken with or without food, providing dosing flexibility 3

Clinical Context

The extended-release formulation allows once-daily dosing due to the longer half-life of deuterated metabolites (3- to 4-fold longer than tetrabenazine) and lower peak-to-trough fluctuations (11-fold lower) 3, 4

• This pharmacokinetic profile improves compliance compared to tetrabenazine's twice-daily dosing requirement 4
• The lower peak concentrations may account for reduced incidence of adverse effects while maintaining efficacy 4