alprazolam (Xanax, Niravam)

Introduction

Tradename: Xanax. DEA-controlled substance: class 4.

Indications

• treatment of anxiety, including generalized anxiety disorder
• short-term management of panic attacks
• treatment of depression, including major depression
• treatment of essential tremor
• NOT for sleeping disorders
• NOT for management of anxieties or stresses of everyday life

Contraindications

• history of addiction
• severe, uncontrolled pain
• narrow-angle glaucoma
• severe respiratory depression
• pre-existing CNS depression Warning:
  • elderly may need assistance with ambulation, especially early in therapy

pregnancy category = d

safety in lactation = -

Dosage

• 0.25-0.5 mg PO TID
• 0.75-4.00 mg/24 hours divided TID
• up to 4 mg/day (anxiety); 10 mg/day (panic attacks)
• may be taken with food
• avoid alcohol ingestion
• re-evaluate for treatment > 4 months duration
• taper when discontinuing after chronic use

Tabs: 0.25, 0.5, 1, 2 mg; Xanax XR (extended release)

Niravam: orally disintegrating tablets

Pharmacokinetics

• rapidly & completely absorbed after oral or sublingual administration
• peak plasma levels in 1-2 hours
• most plasma alprazolam is bound to albumin
• volume of distribution of 0.8 to 1.3 L/kg
• metabolized in the liver by cyt P450 3A4
• major pathway of metabolism is hydroxylation
  • alpha hydroxyalprazolam is the major metabolite
• parent molecule & metabolites excreted in urine
• elimination half-life is 9-16 hours (1 mg dose)
• 1/2 life may be increased up to 20 hours in elderly

elimination via liver

elimination via kidney

1/2life = 11-15 hours

protein binding = 68-74 %

Adverse effects

• common (> 10%)
  • tachycardia, chest pain, drowsiness, fatigue, ataxia, lightheadedness, memory impairment, insomnia, anxiety, depression, headache, rash, decreased libido, dry mouth, constipation, decreased salivation, nausea/vomiting, diarrhea, dysarthria, blurred vision, sweating
• less common (1-10%)
  • syncope, hypotension, confusion, nervousness, dizziness, akasthesia, dermatitis, increased salivation, rigidity, tremor, muscle cramps, tinnitus, nasal congestion, hyperventilation
• other
  • drowsiness
  • dizziness
  • withdrawal: most prone of benzodiazepines to cause seizures during withdrawal
  • agitation
  • anterograde amnesia
  • addiction
  • hiccups

• drug adverse effects of benzodiazepines
• drug adverse effects of psychotropic agents
• drug adverse effects of sedatives

Drug interactions

• disulfiram, nefazodone, fluoxetine, cimetidine & grapefruit juice cause an increase in alprazolam levels
• CNS depressants: in combination increase CNS depression
• antiepileptic agents, rifampin: increase metabolism of alprazolam
• flumazenil (Romazicon): antagonizes affects of benzodiazepines
• any drug that inhibits cyt P450 3A4 may increase levels of alprazolam
• any drug that induces cyt P450 3A4 may diminish levels of alprazolam

• drug interaction(s) of methadone in combination with benzodiazepines
• drug interaction(s) of benzodiazepines with antidepressants
• drug interaction(s) of benzodiazepines with thiazide diuretics
• drug interaction(s) of antipsycotics with benzodiazepines
• drug interaction(s) of antidepressants with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists (except atenolol) with benzodiazepines
• drug interaction(s) of alcoholic beverage with benzodiazepines
• drug interaction(s) of benzodiazepine with opiates

Mechanism of action

• triazolobenzodiazepine that potentiates GABA's inhibitory effects by increasing neuronal permeability to Cl-

More general terms

• benzodiazepine

More specific terms

• alpha-hydroxyalprazolam

Additional terms

• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Component of

• alprazolam/triazolam

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2118
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=178274