Drug/Small Molecule:
posaconazole

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 gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



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.

? = Mouse-over for quick help

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?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • posaconazole
Trade Names
  • Noxafil
Brand Mixture Names

PharmGKB Accession Id:
PA151958574

Description

Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients.

Source: Drug Bank

Indication

For prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised as a result of procedures such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or due to hematologic malignancies with prolonged neutropenia from chemotherapy. Also for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole. Posaconazole is used as an alternative treatment for invasive aspergillosis, Fusarium infections, and zygomycosis in patients who are intolerant of, or whose disease is refractory to, other antifungals.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

As a triazole antifungal agent, posaconazole exerts its antifungal activity through blockage of the cytochrome P-450 dependent enzyme, sterol 14alpha-demethylase, in fungi by binding to the heme cofactor located on the enzyme. This leads to the inhibition of the synthesis of ergosterol, a key component of the fungal cell membrane, and accumulation of methylated sterol precursors. This results in inhibition of fungal cell growth and ultimately, cell death.

Source: Drug Bank

Pharmacology

Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Posaconazole primarily circulates as the parent compound in plasma. Of the circulating metabolites, the majority are glucuronide conjugates formed via UDP glucuronidation (phase 2 enzymes). Posaconazole does not have any major circulating oxidative (CYP450 mediated) metabolites. The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose.

Source: Drug Bank

Protein Binding

Posaconazole is highly protein bound (>98%), predominantly to albumin.

Source: Drug Bank

Absorption

Posaconazole is absorbed with a median Tmax of approximately 3 to 5 hours.

Source: Drug Bank

Half-Life

Posaconazole is eliminated with a mean half-life (t½) of 35 hours (range 20 to 66 hours).

Source: Drug Bank

Toxicity

During the clinical trials, some patients received posaconazole up to 1600 mg/day with no adverse events noted that were different from the lower doses. In addition, accidental overdose was noted in one patient who took 1200 mg BID for 3 days. No related adverse events were noted by the investigator.

Source: Drug Bank

Route of Elimination

The excreted metabolites in urine and feces account for ~17% of the administered radiolabeled dose.

Source: Drug Bank

Volume of Distribution

  • 1774 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C37H42F2N8O4

Source: Drug Bank

Isomeric SMILES

CC[C@@H]([C@H](C)O)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OC[C@@H]5C[C@](OC5)(CN6C=NC=N6)C7=C(C=C(C=C7)F)F

Source: Drug Bank

CC[C@@H]([C@H](C)O)N1N=CN(C1=O)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCC2CO[C@](CN3C=NC=N3)(C2)C2=C(F)C=C(F)C=C2)C=C1

Source: Drug Bank

Canonical SMILES

CC[C@@H]([C@H]

Source: Drug Bank

Average Molecular Weight

700.7774

Source: Drug Bank

Monoisotopic Molecular Weight

700.329708282

Source: Drug Bank

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.

Drug Targets

Gene Description
CYP51A1 (source: Drug Bank)

Drug Interactions

Drug Description
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Posaconazole may increase the serum concentration of bromazepam by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of bromazepam if posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Significant decrease of posaconazole levels (source: Drug Bank)
posaconazole Significant decrease of posaconazole levels (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Increased level of cyclosporine (source: Drug Bank)
posaconazole Increased level of cyclosporine (source: Drug Bank)
posaconazole Posaconazole may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Modifications of drug levels for both agents (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Modifications of drug levels for both agents (source: Drug Bank)
posaconazole Modifications of drug levels for both agents (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Modification of drug levels for both agents (source: Drug Bank)
posaconazole Modification of drug levels for both agents (source: Drug Bank)
posaconazole The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconzole may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity. (source: Drug Bank)
posaconazole Posaconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen. (source: Drug Bank)
posaconazole Posaconazole may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen. (source: Drug Bank)
posaconazole Posaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Posaconazole is initiated, discontinued, or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Posaconazole is initiated, discontinued, or dose changed. (source: Drug Bank)
posaconazole Posaconazole may increase the plasma concentration of Telithromycin. Consider alternate therapy or monitor therapeutic/adverse effects. (source: Drug Bank)
posaconazole Posaconazole may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided. (source: Drug Bank)
posaconazole The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole Contraindicated co-administration (source: Drug Bank)
posaconazole The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Tipranavir may increase the serum concentration of Posaconazole. Posaconazole may increase the serum concentration of Tipranavir. (source: Drug Bank)
posaconazole Posaconazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity. (source: Drug Bank)
posaconazole Posaconazole may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity. (source: Drug Bank)
posaconazole Posaconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. (source: Drug Bank)
posaconazole The CYP3A4 inhibitor, Posaconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole The CYP3A4 inhibitor, Posaconazole, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole The strong CYP3A4 inhibitor, Posaconazole, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil. (source: Drug Bank)
posaconazole Posaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Posaconazole is initiated, discontinued, or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if posaconazole is initiated, discontinued or dose changed. (source: Drug Bank)
No related diseases are available

Publications related to posaconazole: 3

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The enzymatic basis of drug-drug interactions with systemic triazole antifungals. Clinical pharmacokinetics. 2008. Nivoix Yasmine, 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
Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. The New England journal of medicine. 2007. Ullmann Andrew 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
Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. The New England journal of medicine. 2007. Cornely Oliver A, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0085-1328-01
DrugBank:
DB01263
KEGG Drug:
D02555
PubChem Compound:
147912
PubChem Substance:
17396726
46508639
ChemSpider:
130409
Therapeutic Targets Database:
DAP001101
FDA Drug Label at DailyMed:
b073b082-7b57-4423-8c06-4fd4263d6f84

Clinical Trials

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

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

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