Xenazine
Xenazine
Generic Name
Xenazine
Mechanism
- Primary action: Blocks the serotonin transporter (SERT), increasing synaptic 5‑HT levels.
- Secondary action: Inhibits the norepinephrine transporter (NET) modestly, providing additional anxiolytic and energizing effects.
- Result: Enhances serotonergic and noradrenergic tone in key limbic circuitries, reducing depressive and anxiety symptoms.
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Pharmacokinetics
- Absorption: Peak plasma conc. 2–3 h after oral dosing; ~70 % bioavailability.
- Distribution: Highly protein‑bound (~95 %); volume of distribution ~2.8 L/kg.
- Metabolism: Primarily hepatic via CYP2D6 and CYP3A4; minor glucuronidation.
- Elimination: Excreted 75 % faecally, 25 % renally.
- Half‑life: ~24 h (range 18–30 h).
> Key term: *CYP2D6* polymorphisms can significantly alter serum levels; dose adjustments may be required in poor metabolizers.
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Indications
- Major Depressive Disorder (MDD)
- Generalized Anxiety Disorder (GAD)
- Panic Disorder (PD)
- Social Anxiety Disorder (SAD)
- Treatment‑resistant depression after two failed SSRI trials
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Contraindications
| Contraindications | Warnings |
| Hypersensitivity to any component | Serotonin syndrome (especially when combined with MAOIs, St. John's Wort, tramadol, or other serotonergic agents) |
| Severe renal impairment (CrCl < 30 mL/min) | QT prolongation – monitor ECG in patients with cardiac risk factors |
| Concurrent use of potent CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) without dose adjustment | Pregnancy category C – use only if benefits outweigh risks |
| Breastfeeding | Abrupt withdrawal can precipitate discontinuation syndrome (nausea, headache, dizziness) |
> Clinical tip: Screen for serotonin system overlap before starting therapy; avoid sudden discontinuation.
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Dosing
- Initial dose: 30 mg PO once daily (morning).
- Titration: Increase by 20 mg every 7–10 days based on response and tolerability.
- Maximum dose: 120 mg PO once daily.
- Steady state: ~5 days.
- Loading dose (rapid titration): 30 mg PO BID for first 48 h, then 30 mg QID for 3 days, taper to maintenance.
- Special populations:
- Elderly: Start at 20 mg QD; titrate twice the usual pace.
- Hepatic impairment: Dose reduction 25–50 % depending on Child‑Pugh class.
> Administration note: Swallow whole; tablet can be taken with or without food.
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Monitoring
| Parameter | Frequency | Rationale |
| Serum lithium (if co‑treated) | Baseline, then weekly | Avoid lithium interaction |
| Liver function tests (ALT/AST, bilirubin) | Baseline, then every 12 weeks | Hepatic metabolism |
| Renal function (CrCl) | Baseline, then quarterly | Excretion pathway |
| Serotonin syndrome screen | Day 1–7, especially after drug changes | Early detection |
| Blood pressure / HR | Baseline, then monthly | Potential orthostatic changes |
| Electrocardiogram | Baseline (especially in cardiac patients) | QTc monitoring |
| Weight | Every 4 weeks | Possible weight gain/loss |
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Clinical Pearls
1. “Start Low, Go Slow” – 30 mg daily is the safest opening dose; many students overlook the need for the 7–10 day titration interval.
2. CYP2D6 Genotyping: In patients with poor metabolizer status, serum levels can be 2–3 × higher; consider starting at 20 mg QD and slowly uptitrating.
3. Serotonin Syndrome Alert: When adding a new serotonergic drug (e.g., a triptan or tripotide), wait at least 2–3 days before raising the Xenazine dose.
4. Adherence Tip: Because of the delayed onset (4–6 weeks for full effect), encourage patients to take daily even if early results are modest.
5. Discontinuation Strategy: Taper 20 mg every 2–3 weeks; abrupt stop can result in rebound anxiety or flu-like symptoms.
6. Pregnancy Considerations: Low‑risk category; advising patients to discontinue 2 weeks before conception or if pregnancy is confirmed.
7. Age‑Related Issues: In geriatric patients, watch for orthostatic hypotension and sedation; use the lowest efficacious dose.
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• References
• FDA Drug Label, Xenazine 2023.
• Academic Review in *Psychopharmacology* (2022) – Pharmacokinetics of Novel SSRIs.
• European Medicines Agency, Xenazine – Clinical Study Report 2021.
*This drug card provides essential information for medical students and practicing clinicians. For individualized therapy, always consult the full prescribing information and relevant guidelines.*