Dosing & Adverse Events

Reaching your patient's maintenance dose is the key factor to the clinical success of Xenazine.²

Start Low, Go Slow¹

The dose of Xenazine should be individualized by starting low and going slow by 12.5 mg increments weekly until a patient experiences clinical effect or an intolerable AE occurs.

• Xenazine should be re-titrated after any treatment interruption lasting longer than 5 days or due to a change in the patient's medical condition or concomitant medications.¹
• Treatment of Xenazine can be discontinued without tapering. Reemergence of chorea may occur within 12 to 18 hours after the last dose of Xenazine.¹

• To initiate treatment with Xenazine in patients on a stable dose of a strong CYP2D6 inhibitor (such as fluoexetine, paroexetine, or quinidine), follow the dosing recommendation for poor CYP2D6 metabolizers.¹
• Caution should be used when adding therapy with a strong CYP2D6 inhibitor to patients already receiving a stable dose of Xenazine; the daily dose of Xenazine should be halved.¹
• Patients taking neuroleptic drugs were excluded from the Xenazine pivotal studies. Adverse reactions associated with Xenazine, such as QTc prolongation, neuroleptic malignant syndrome (NMS), and extrapyramidal disorders, may be exaggerated by concomitant use of dopamine antagonists.¹
• 91% of patients in the HSG Trial experienced AEs during the titration phase, and 35% experienced onset of 1 or more new AEs during the maintenance phase.¹
• Certain AEs may be dose dependent and may resolve or lessen with dose adjustment.³
  • If AEs such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety, or intolerable sedation occur, titration should be stopped and the dose should be reduced.¹
• If AE does not resolve, consideration should be given to withdrawal of Xenazine treatment or initiation of other specific treatment (e.g., antidepressants).¹
• For patients taking a total daily dose of < 50 mg, the maximum recommended single dose of Xenazine is 25 mg.¹
• Doses above 100 mg/day are not recommended for any patient.

The Majority of AEs Occurred During the Titration Phase²

Common AEs from the HSG Trial reported during the titration (weeks 0 to 9) and maintenance (weeks 9 to 12) phases.

Xenazine Treatment-Emergent AEs¹

• At the conclusion of the trial (week 12) when patients were at their maintenance dose, there was no significant difference in adverse events between Xenazine and placebo patients with regard to specific adverse events that had not been reported at baseline.³
  • 9% of Xenazine patients and 3% of placebo patients did not complete the study.³
• The most common concomitant medications at HSG study entry included antidepressants (60%) and benzodiazepines (17%).³
• Dose titration was discontinued or dosage of Xenazine was reduced because of 1 or more AEs in 28 of 54 (52%) patients randomized. The AEs most commonly reported were sedation (15), akathisia (7), parkinsonism (4), depression (3), anxiety (2), fatigue (1), and diarrhea (1). Some patients had more than 1 AE and are therefore counted more than once.¹

Sources:

• Xenazine [package insert]. Deerfield, IL: Lundbeck Inc; 2009.
• Data on file, Lundbeck Inc.
• Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006; 66(3):366-372.