Search
alprazolam (Xanax, Niravam)
Tradename: Xanax. DEA-controlled substance: class 4.
Indications:
1) treatment of anxiety, including generalized anxiety disorder
2) short-term management of panic attacks
3) treatment of depression, including major depression
4) treatment of essential tremor
4) NOT for sleeping disorders
5) NOT for management of anxieties or stresses of everyday life
Contraindications:
1) history of addiction
2) severe, uncontrolled pain
3) narrow-angle glaucoma
4) severe respiratory depression
5) pre-existing CNS depression Warning:
- elderly may need assistance with ambulation, especially early in therapy
Dosage:
1) 0.25-0.5 mg PO TID [1]
2) 0.75-4.00 mg/24 hours divided TID [2]
3) up to 4 mg/day (anxiety); 10 mg/day (panic attacks)
4) may be taken with food
5) avoid alcohol ingestion
6) re-evaluate for treatment > 4 months duration
7) taper when discontinuing after chronic use
Tabs: 0.25, 0.5, 1, 2 mg; Xanax XR (extended release)
Niravam: orally disintegrating tablets
Pharmacokinetics:
1) rapidly & completely absorbed after oral or sublingual administration
2) peak plasma levels in 1-2 hours
3) most plasma alprazolam is bound to albumin
4) volume of distribution of 0.8 to 1.3 L/kg
5) metabolized in the liver by cyt P450 3A4
6) major pathway of metabolism is hydroxylation
- alpha hydroxyalprazolam is the major metabolite
7) parent molecule & metabolites excreted in urine
8) elimination half-life is 9-16 hours (1 mg dose)
9) 1/2 life may be increased up to 20 hours in elderly
Adverse effects:
1) common (> 10%) [4]
- 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
2) less common (1-10%) [4]
- syncope, hypotension, confusion, nervousness, dizziness, akasthesia, dermatitis, increased salivation, rigidity, tremor, muscle cramps, tinnitus, nasal congestion, hyperventilation
3) other [3]
- drowsiness
- dizziness
- withdrawal: most prone of benzodiazepines to cause seizures during withdrawal
- agitation
- anterograde amnesia
- addiction
- hiccups
Drug interactions:
1) disulfiram, nefazodone, fluoxetine, cimetidine & grapefruit juice cause an increase in alprazolam levels
2) CNS depressants: in combination increase CNS depression
3) antiepileptic agents, rifampin: increase metabolism of alprazolam
4) flumazenil (Romazicon): antagonizes affects of benzodiazepines
5) any drug that inhibits cyt P450 3A4 may increase levels of alprazolam
6) any drug that induces cyt P450 3A4 may diminish levels of alprazolam
Mechanism of action:
- triazolobenzodiazepine that potentiates GABA's inhibitory effects by increasing neuronal permeability to Cl-
Interactions
drug interactions
drug adverse effects (more general classes)
Related
cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
Specific
alpha-hydroxyalprazolam
General
benzodiazepine
Properties
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 11-15 HOURS
therapeutic-range 10-50 NG/ML
toxic-range >75 NG/ML
protein-binding 68-74%
pregnancy-category D
safety in lactation -
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
- Manual of Medical Therapeutics, 28th ed, Ewald &
McKenzie (eds), Little, Brown & Co, Boston, 1995,
pg 7
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed.,
W.B. Saunders, 1995
- Prescriber's Letter 13(3): 2006
Cytochrome P450 drug interactions
Detail-Document#: 220233
(subscription needed) http://www.prescribersletter.com
- Wikipedia: Alprazolam
http://en.wikipedia.org/wiki/Alprazolam
- Greenblatt DJ and Wight CE
Clinical pharmakinetics of alprazolam, Therapeutic implications.
Clin Pharmacokinet. 1993 Jun;24(6):453-71.
PMID: 8513649
Component-of
alprazolam/triazolam