Xanax XR
Xanax XR
Generic Name
Xanax XR
Mechanism
- Benzodiazepine binding to the GABA‑A receptor complex
- Enhances chloride influx → neuronal hyperpolarization
- Increases the frequency of inhibitory postsynaptic potentials, yielding anxiolytic, sedative, muscle‑relaxant, and anticonvulsant effects.
- Extended‑release formulation provides a rapid initial rise (immediate‑release core) followed by a slow, controlled release (extended layer) to maintain steady plasma concentrations.
Pharmacokinetics
- Absorption: Rapid oral uptake; peak plasma concentration (Cmax) ~10–30 min for immediate‑release core, ±24 h for the extended component.
- Distribution: High protein binding (~86 %); crosses the blood‑brain barrier.
- Metabolism: Primarily via CYP3A4 and CYP2D6 to inactive metabolites; hepatic metabolism requires caution in hepatic impairment.
- Half‑life: 11–16 h (immediate) vs 18–36 h (extended) due to sustained release.
- Excretion: Renal (≈30 %) and biliary routes.
Indications
- Generalized Anxiety Disorder (GAD) – adult and pediatric ≥12 yrs, when long‑acting control is desired.
- Panic Disorder – as maintenance therapy after acute loading.
- Short‑term bridge during tapering of other anxiolytics or sedatives.
Contraindications
- Absolute Contraindications
- Severe respiratory insufficiency, acute narrow‑angle glaucoma.
- Concomitant use with alcohol, opioids, or other CNS depressants.
- Relative Contraindications
- Pregnancy (Category D); use only if benefits outweigh risks.
- Pediatric <12 yrs – data limited.
- Elderly and debilitated patients: increased sensitivity → higher risk of sedation, falls, cognitive impairment.
- Warnings
- Dependence, tolerance, and withdrawal: taper slowly.
- Paradoxical reactions (agitation, disinhibition).
Dosing
| Age | Initial Loading Dose | Maintenance Dose | Titration | Maximum |
| Adults | 0.5 mg PO once daily (XR) | 2–3 mg/day (divided) | 0.5 mg increments q2–4 weeks | 6 mg/day |
| Elderly | 0.25 mg PXR | 1–2 mg/day | Slower titration | 3 mg/day |
| Children ≥12 yrs | 0.25 mg/day | 0.5–1 mg/day | 0.25 mg increments q2 weeks | 1.5 mg/day |
• Take with food to reduce GI discomfort.
• Do not crush/swallow XR capsules; they must remain intact for graded release.
Adverse Effects
- *Common*: somnolence, dizziness, headache, dry mouth, impaired coordination.
- *Serious*: respiratory depression (with concurrent CNS depressants), paradoxical agitation, memory impairment, hepatotoxicity (rare).
- *Abuse Potential*: high; monitor for euphoric use or non‑therapeutic escalation.
Monitoring
- Clinical: anxiety score (HAM-A), sedation level, withdrawal signs.
- Laboratory: liver function tests at baseline, then every 3 months if chronic use.
- Safety: periodic review of concomitant CNS depressants; screen for substance misuse.
- Compliance: pill count, patient diary.
Clinical Pearls
- Rapid‑Release Core vs Extended Layer – The XR capsule releases a small immediate dose that flattens the therapeutic curve, avoiding the pronounced peak‑trough variability seen with standard tablets.
- Avoid “Jolting” the Release – Never break, chew, or split the capsule; this destroys the controlled‑release matrix leading to supratherapeutic peaks.
- Use During Withdrawal – When tapering from high‑dose benzodiazepines, XR can provide a smooth decline, but the long half‑life may prolong withdrawal; use with a taper schedule.
- Drug‑Drug Interaction Check – CYP3A4 inhibitors (e.g., ketoconazole) can elevate plasma levels by >50 %; consider dose reduction.
- Age‑Specific Caution – In the elderly, a single 0.25‑mg dose may suffice initially; monitor for falls and delirium.
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• References (for deeper review)
1. *Goodman & Gilman’s The Pharmacological Basis of Therapeutics*, 13th ed.
2. FDA label for Xanax® Extended‑Release, 2024.
3. UpToDate®: Alprazolam.
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