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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XENAZINE (XENAZINE).
| Breastfeeding | M/P ratio unknown. Tetrabenazine and its active metabolites are excreted in animal milk. No human data available. Due to potential for serious adverse reactions in nursing infants, including sedation, extrapyramidal symptoms, and dopamine depletion, breastfeeding is not recommended during therapy. |
| 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. |
■ 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 |
["Concurrent use with reserpine","Use within 20 days of discontinuing monoamine oxidase inhibitors (MAOIs)","Suicidal ideation/behavior (due to black box warning)","Hepatic impairment"]
| Precautions | ["Suicidality and depression","QT prolongation","Akathisia, agitation, and restlessness","Parkinsonism","Sedation and somnolence","Hyperprolactinemia","Neuroleptic malignant syndrome (NMS)"] |
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| 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. |