XENAZINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XENAZINE (XENAZINE).
Deutetrabenazine selectively and reversibly inhibits vesicular monoamine transporter 2 (VMAT2), thereby reducing dopamine and monoamine storage and release in presynaptic neurons.
| Metabolism | Metabolized primarily by CYP2D6 to active metabolites, with minor contributions from CYP1A2 and CYP3A4. |
| Excretion | Primarily renal (75-85% as metabolites, <2% unchanged); minimal biliary/fecal elimination. |
| Half-life | 7-16 hours (mean 9-12 hours); requires twice-daily dosing for steady-state control of chorea. |
| Protein binding | 60-65% bound to serum proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | 10-15 L/kg; extensive tissue distribution with high CNS penetration. |
| Bioavailability | Oral: approximately 66-75% (due to first-pass metabolism). |
| Onset of Action | Oral: 2-4 weeks for initial clinical effect (chorea reduction); full effect may require 6-8 weeks. |
| Duration of Action | 12-24 hours (dosing interval-dependent); sustained reduction in chorea with regular twice-daily administration. |
| Molecular Weight | 417.6 |
12.5 mg orally twice daily initially; titrate slowly by 12.5 mg every 3-5 days up to 50 mg twice daily (total daily dose 100 mg). Maximum recommended total daily dose: 100 mg.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines for renal impairment; use with caution, monitor for adverse effects. Not recommended in severe renal impairment (CrCl <30 mL/min) due to risk of accumulation. |
| Liver impairment | Contraindicated in Child-Pugh class C (severe hepatic impairment); in Child-Pugh class B, initiate at 6.25 mg twice daily, maximum 37.5 mg total daily dose. No adjustment for Child-Pugh A. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. In clinical trials (off-label), weight-based dosing not defined; use not recommended. |
| Geriatric use | No specific dose adjustment; start at low end of dosing range (12.5 mg twice daily), titrate slowly due to increased sensitivity to anticholinergic and sedative effects. Monitor for QT prolongation. |
| 1st trimester | Contraindicated: risk of fetal harm based on animal data and potential for extrapyramidal symptoms. |
| 2nd trimester | Contraindicated: avoid use unless no safer alternative; may cause fetal extrapyramidal effects. |
| 3rd trimester | Contraindicated: risk of neonatal extrapyramidal symptoms and withdrawal; use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for XENAZINE (XENAZINE).
| Placental transfer | Crosses placenta in animals; human data limited but expected due to low molecular weight. |
| Breastfeeding | Present in breast milk; infant exposure may cause sedation, hypotonia, and feeding difficulties. Decision to breastfeed should consider importance of drug to mother and potential risks to infant. |
■ FDA Black Box Warning
May increase the risk of depression, suicidal thoughts, and behavior in patients with Huntington's disease. Balance risks with clinical need.
| Serious Effects |
Hypersensitivity to tetrabenazine or any componentHepatic impairmentCurrent or history of suicidal ideation or depressionConcurrent use with MAOIs or reserpineProlonged QT interval or concomitant QT-prolonging drugs
| Precautions | Suicidality and depression, QT prolongation, Akathisia, agitation, and restlessness, Parkinsonism, Sedation and somnolence, Hyperprolactinemia, Neuroleptic malignant syndrome (NMS) |
| Food/Dietary | Take with food to minimize gastrointestinal upset. Avoid alcohol as it may increase CNS depression and risk of hepatic injury. No specific food restrictions; maintain adequate hydration to prevent urinary retention. |
Loading safety data…
| Lactation Rating |
| L4 - Possibly Hazardous |
| Teratogenic Risk | Pregnancy category C. In animal studies, tetrabenazine (the active ingredient) has shown developmental toxicity including reduced fetal weight and increased skeletal variations at doses similar to human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. First trimester: potential teratogenicity; second and third trimesters: possible fetal effects from maternal dopamine depletion. |
| Fetal Monitoring | Monitor for maternal extrapyramidal symptoms, sedation, depression, suicidality, and QT prolongation. In pregnancy, assess fetal growth via ultrasound. Newborns exposed in utero should be monitored for extrapyramidal signs, sedation, and withdrawal symptoms. |
| Fertility Effects | In animal studies, tetrabenazine caused decreased fertility in males (reduced sperm count and motility) and females (prolonged estrous cycles) at clinically relevant doses. Human fertility effects unknown. |
| Clinical Pearls | Xenazine (tetrabenazine) is a VMAT2 inhibitor used for chorea in Huntington disease. Monitor for depression, suicidality, and extrapyramidal symptoms. Do not use with MAOIs or reserpine. Titrate slowly; maximum dose 100 mg/day. QT prolongation risk; obtain baseline ECG and monitor electrolytes. Avoid in hepatic impairment. |
| Patient Advice | Take with food to reduce nausea. · Do not stop abruptly; taper to avoid withdrawal. · Report mood changes, suicidal thoughts, or involuntary movements. · Avoid alcohol and driving until you know how the drug affects you. · Notify your doctor if you are pregnant, breastfeeding, or plan to become pregnant. |