Drug/Small Molecule:
alprazolam

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

Links to Unannotated Labels

These links are to labels associated with alprazolam that have not been annotated by PharmGKB.

  1. DailyMed - DrugLabel PA166105066

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all alprazolam variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No Clinical Annotations available No Variant Annotations available
rs776746 12083G>A, 219-237G>A, 321-1G>A, 37303382C>T, 581-237G>A, 689-1G>A, 99270539C>T, CYP3A5*1, CYP3A5*3, CYP3A5*3C, CYP3A5:6986A>G, g.6986A>G, intron 3 splicing defect, rs776746 A>G
C > T
Acceptor
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • TUS-1
  • alprazolam
Trade Names
  • Alplax
  • Alpronax
  • Alviz
  • Bestrol
  • Cassadan
  • Constan
  • D 65MT
  • Esparon
  • Frontal
  • Intensol
  • Niravam
  • Restyl
  • Solanax
  • Tafil
  • Tranax
  • Trankimazin
  • Tranquinal
  • Xanax
  • Xanax XR
  • Xanor
Brand Mixture Names

PharmGKB Accession Id:
PA448333

Description

A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of panic disorders, with or without agoraphobia, and in generalized anxiety disorders. (From AMA Drug Evaluations Annual, 1994, p238)

Source: Drug Bank

Indication

For the management of anxiety disorder or the short-term relief of symptoms of anxiety and for the treatment of panic disorder, with or without agoraphobia.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABA A) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

Source: Drug Bank

Pharmacology

Alprazolam, a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide, clorazepate, and prazepam, alprazolam has a shorter half-life and metabolites with minimal activity. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Avoid taking with grapefruit juice.|Avoid excessive quantities of coffee or tea (Caffeine).|Take with food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Hydroxylated in the liver to alpha-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides.

Source: Drug Bank

Protein Binding

80% (mainly to albumin)

Source: Drug Bank

Absorption

Readily absorbed from the gastrointestinal tract. Bioavailability is 80-90%.

Source: Drug Bank

Half-Life

6.3-26.9 hours

Source: Drug Bank

Toxicity

Oral, mouse: LD 50=1020 mg/kg. Symptoms of overdose include confusion, coma, impaired coordination, sleepiness, and slowed reaction time.

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

Alprazolam and its metabolites are excreted primarily in the urine.

Source: Drug Bank

Chemical Properties

Chemical Formula

C17H13ClN4

Source: Drug Bank

Isomeric SMILES

Cc1nnc2n1-c3ccc(cc3C(=NC2)c4ccccc4)Cl

Source: OpenEye

Canonical SMILES

CC1=NN=C2CN=C(C3=CC=CC=C3)C3=C(C=CC(Cl)=C3)N12

Source: Drug Bank

Average Molecular Weight

308.765

Source: Drug Bank

Monoisotopic Molecular Weight

308.082874143

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
CYP3A4
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
CYP3A5

Drug Targets

Gene Description
GABRA1 (source: Drug Bank)
GABRA2 (source: Drug Bank)
GABRA3 (source: Drug Bank)
GABRA4 (source: Drug Bank)
GABRA5 (source: Drug Bank)
GABRA6 (source: Drug Bank)
GABRB1 (source: Drug Bank)
GABRB2 (source: Drug Bank)
GABRB3 (source: Drug Bank)
GABRD (source: Drug Bank)
GABRE (source: Drug Bank)
GABRG1 (source: Drug Bank)
GABRG2 (source: Drug Bank)
GABRG3 (source: Drug Bank)
GABRP (source: Drug Bank)
GABRQ (source: Drug Bank)
GABRR1 (source: Drug Bank)
GABRR2 (source: Drug Bank)
GABRR3 (source: Drug Bank)
TSPO (source: Drug Bank)

Drug Interactions

Drug Description
amprenavir Increases the effect and toxicity of benzodiazepine (source: Drug Bank)
amprenavir Increases the effect and toxicity of benzodiazepine (source: Drug Bank)
aprepitant Increases the effect and toxicity of benzodiazepine (source: Drug Bank)
carbamazepine Reduces the effect of the benzodiazepine (source: Drug Bank)
carbamazepine Reduces the effect of the benzodiazepine (source: Drug Bank)
cimetidine Increases the effect of the benzodiazepine (source: Drug Bank)
cimetidine Increases the effect of the benzodiazepine (source: Drug Bank)
clarithromycin The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
clarithromycin The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
delavirdine The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
delavirdine The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
digoxin The benzodiazepine increases the effect (source: Drug Bank)
digoxin The benzodiazepine increases the effect (source: Drug Bank)
efavirenz The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
efavirenz The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
erythromycin The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
erythromycin The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
erythromycin The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
ethotoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
fluconazole Increases the effect of the benzodiazepine (source: Drug Bank)
fluconazole Increases the effect of the benzodiazepine (source: Drug Bank)
fosamprenavir Amprenavir increases the effect and toxicity of benzodiazepine (source: Drug Bank)
fosamprenavir Amprenavir increases the effect and toxicity of benzodiazepine (source: Drug Bank)
fosphenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
indinavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
indinavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
itraconazole The imidazole increase the effect of the benzodiazepine (source: Drug Bank)
itraconazole The imidazole increase the effect of the benzodiazepine (source: Drug Bank)
josamycin The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
ketoconazole The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
ketoconazole The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
mephenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
mephenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
nelfinavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
nelfinavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
omeprazole Increases the effect of the benzodiazepine (source: Drug Bank)
omeprazole Increases the effect of the benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
ritonavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
ritonavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
saquinavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
saquinavir The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
telithromycin Increases the effect/toxicity of the benzodiazepine (source: Drug Bank)
telithromycin Increases the effect/toxicity of the benzodiazepine (source: Drug Bank)
voriconazole The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
voriconazole The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam Increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam Increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam Increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam Reduces the effect of the benzodiazepine (source: Drug Bank)
alprazolam Reduces the effect of the benzodiazepine (source: Drug Bank)
alprazolam Increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam Increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam Increased risk of toxicity (source: Drug Bank)
alprazolam Increased risk of toxicity (source: Drug Bank)
alprazolam The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam The benzodiazepine increases the effect of digoxin (source: Drug Bank)
alprazolam The benzodiazepine increases the effect of digoxin (source: Drug Bank)
alprazolam The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam The antiviral agent increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The macrolide increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam Increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam Increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam Amprenavir increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam Amprenavir increases the effect and toxicity of benzodiazepine (source: Drug Bank)
alprazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
alprazolam The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam The protease inhibitor increases the effect of the benzodiazepine (source: Drug Bank)
alprazolam Omeprazole increases the effect of benzodiazepine (source: Drug Bank)
alprazolam Omeprazole increases the effect of benzodiazepine (source: Drug Bank)
alprazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
alprazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
alprazolam Telithromycin increases the effect/toxicity of the benzodiazepine (source: Drug Bank)
alprazolam Telithromycin may reduce clearance of Alprazolam. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Alprazolam if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
alprazolam Tipranavir may decrease the metabolism and clearance of Alprazolam. Consider alternate therapy or monitor for Alprazolam toxic effects if Tipranavir is initiated or dose increased. (source: Drug Bank)
alprazolam The CNS depressants, Triprolidine and Alprazolam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
alprazolam The CNS depressants, Triprolidine and Alprazolam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
alprazolam Voriconazole may increase the serum concentration of alprazolam by decreasing its metabolism. Monitor for alprazolam toxicity if voriconazole is initiated or dose increased. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to alprazolam: 16

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions. PLoS computational biology. 2012. Duke Jon D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenetics and genomics. 2012. Lamba Jatinder, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease. European journal of clinical pharmacology. 2009. Sugahara Hideyo, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects. Science (New York, N.Y.). 2009. Rupprecht Rainer, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prediction of pharmacokinetic drug-drug interactions using human hepatocyte suspension in plasma and cytochrome P450 phenotypic data. II. In vitro-in vivo correlation with ketoconazole. Drug metabolism and disposition: the biological fate of chemicals. 2008. Lu Chuang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite. PloS one. 2008. Agarwal Varsha, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines. Journal of clinical pharmacy and therapeutics. 2007. Fukasawa T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of alprazolam in healthy subjects. Clinical pharmacology and therapeutics. 2006. Park Ji-Young, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The benzodiazepine site of the GABAA receptor: an old target with new potential?. Sleep medicine. 2004. Bateson Alan N. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Mapping of the benzodiazepine recognition site on GABA(A) receptors. Current topics in medicinal chemistry. 2002. Sigel Erwin. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Differential metabolism of alprazolam by liver and brain cytochrome (P4503A) to pharmacologically active metabolite. The pharmacogenomics journal. 2002. Pai H V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. The British journal of psychiatry : the journal of mental science. 2001. Nutt D J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacology & therapeutics. 2000. Hiemke C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The benzodiazepine binding site of GABAA receptors. Trends in pharmacological sciences. 1997. Sigel E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence. Clinical pharmacokinetics. 1997. Sproule B A, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
64980-140-06
DrugBank:
DB00404
ChEBI:
2611
KEGG Compound:
C06817
KEGG Drug:
D00225
PubChem Compound:
2118
PubChem Substance:
176116
46507078
Drugs Product Database (DPD):
2248706
ChemSpider:
2034
Therapeutic Targets Database:
DAP000239
FDA Drug Label at DailyMed:
ea350660-9be8-40b2-98f9-af759a8f7864

Clinical Trials

These are trials that mention alprazolam and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.