Introduction
Xanax XR (extended-release alprazolam) is a benzodiazepine medication primarily used for the management of panic disorder with or without agoraphobia. It is the extended-release formulation of alprazolam, designed to provide sustained therapeutic effects with less frequent dosing compared to the immediate-release formulation.
Mechanism of Action
Alprazolam potentiates the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. It binds to specific sites on the GABA-A receptor complex, enhancing GABA-mediated chloride ion channel opening. This results in increased neuronal membrane hyperpolarization and reduced neuronal excitability, producing anxiolytic, sedative, muscle relaxant, and anticonvulsant effects.
Indications
Xanax XR is FDA-approved for:
- Treatment of panic disorder with or without agoraphobia
- Maintenance therapy after initial stabilization with immediate-release alprazolam
Dosage and Administration
Initial dosage: 0.5-1 mg orally once daily, preferably in the morning Dosage adjustment: May be increased every 3-4 days by no more than 1 mg daily Maximum dosage: 10 mg daily (though typically not exceeding 4 mg daily for most patients) Special populations:- Geriatric patients: Initial dose 0.5 mg once daily
- Hepatic impairment: Reduce dose by 50% or more
- Renal impairment: Use with caution; no specific dosage adjustment recommended
Pharmacokinetics
Absorption: Bioavailability approximately 90%; peak concentration reached 5-11 hours after dosing Distribution: Volume of distribution 0.8-1.3 L/kg; 80% protein-bound Metabolism: Extensive hepatic metabolism via cytochrome P450 3A4 (CYP3A4) to active metabolites including α-hydroxyalprazolam Elimination: Half-life 10.7-15.8 hours; primarily renal excretion (80% as metabolites)Contraindications
- Hypersensitivity to alprazolam, other benzodiazepines, or any component of the formulation
- Acute narrow-angle glaucoma
- Concomitant use with strong CYP3A inhibitors (ketoconazole, itraconazole)
- Myasthenia gravis
- Severe respiratory insufficiency
- Sleep apnea syndrome
- Severe hepatic impairment
Warnings and Precautions
Boxed Warning:- Risk of abuse, misuse, and addiction which can lead to overdose or death
- Physical dependence and withdrawal reactions
- Risks from concomitant use with opioids
- Sedation and impaired coordination: Caution when operating machinery or driving
- Depression and suicidal ideation: Monitor for emergence or worsening of depression
- Paradoxical reactions: Including excitement, stimulation, and acute rage
- Elderly patients: Increased risk of falls and cognitive impairment
- Pregnancy: Potential neonatal withdrawal syndrome and teratogenic effects
- Withdrawal symptoms: Can be life-threatening; taper gradually
Drug Interactions
Major interactions:- CYP3A4 inhibitors (azole antifungals, macrolide antibiotics, protease inhibitors): Increased alprazolam levels
- CYP3A4 inducers (carbamazepine, phenytoin, rifampin): Decreased alprazolam levels
- Opioids: Increased risk of respiratory depression, sedation, and death
- Alcohol: Enhanced CNS depression
- Other CNS depressants: Additive effects
- Oral contraceptives: May decrease alprazolam clearance
- Digoxin: Increased digoxin levels possible
- Imipramine/desipramine: Increased plasma concentrations
Adverse Effects
Common (≥10%):- Somnolence (41%)
- Fatigue (14%)
- Impaired coordination (8-12%)
- Memory impairment (6-12%)
- Depression (6-12%)
- Dizziness, lightheadedness
- Headache
- Cognitive disorder
- Constipation
- Dry mouth
- Weight changes
- Respiratory depression
- Dependence and withdrawal
- Suicidal ideation
- Jaundice
- Seizures (upon withdrawal)
- Hypomania/mania
Monitoring Parameters
- Efficacy: Panic attack frequency and severity, anxiety symptoms
- Safety: Sedation level, coordination, cognitive function
- Psychiatric: Depression, suicidal thoughts, paradoxical reactions
- Addiction potential: Signs of misuse, abuse, or dependence
- Withdrawal symptoms: Especially during dose reduction
- Hepatic function: Periodically in long-term therapy
- Renal function: In patients with renal impairment
Patient Education
- Take exactly as prescribed; do not increase dose without medical supervision
- Swallow tablets whole; do not crush, chew, or break
- Avoid alcohol and other CNS depressants
- Do not abruptly discontinue; taper under medical supervision
- Be aware of potential impairment of mental and physical abilities
- Report any thoughts of self-harm or worsening depression
- Use effective contraception if of reproductive potential
- Store securely to prevent misuse by others
- Keep all medical appointments for monitoring
References
1. Xanax XR [package insert]. New York, NY: Pfizer; 2021. 2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). 3. Baldwin DS, et al. Benzodiazepines: risks and benefits. Int J Psychiatry Clin Pract. 2013;17(2):85-90. 4. Guina J, et al. Benzodiazepines for PTSD: A systematic review and meta-analysis. J Psychiatr Pract. 2015;21(4):281-303. 5. Lader M. Benzodiazepines revisited—will we ever learn? Addiction. 2011;106(12):2086-2109. 6. FDA Drug Safety Communication: FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. September 2020. 7. Schatzberg AF, et al. Manual of Clinical Psychopharmacology. 9th ed. American Psychiatric Publishing; 2019.