Isavuconazonium

Identification

Summary

Isavuconazonium is a triazole antifungal used for the treatment of invasive aspergillosis and mucormycosis.

Brand Names
Cresemba
Generic Name
Isavuconazonium
DrugBank Accession Number
DB06636
Background

Isavuconazonium is a second-generation triazole antifungal approved on March 6, 2015 by the FDA and July 2015 by the EMA for the treatment of adults with invasive aspergillosis and invasive mucormycosis, marketed by Astellas under the brand Cresemba.4 It is the prodrug form of isavuconazole, the active moiety, and it is available in oral and parenteral formulations. Due to low solubility in water of isavuconazole on its own, the isovuconazonium formulation is favorable as it has high solubility in water and allows for intravenous administration. This formulation also avoids the use of a cyclodextrin vehicle for solubilization required for intravenous administration of other antifungals such as voriconazole and posaconazole, eliminating concerns of nephrotoxicity associated with cyclodextrin. Isovuconazonium has excellent oral bioavailability, predictable pharmacokinetics, and a good safety profile, making it a reasonable alternative to its few other competitors on the market.1,2,3

On December 08, 2023, the FDA approved the expanded use of isovuconazonium in pediatric patients for the same indications.7

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 717.77
Monoisotopic: 717.241370179
Chemical Formula
C35H35F2N8O5S
Synonyms
  • Isavuconazonium
External IDs
  • BAL-8557
  • BAL8557

Pharmacology

Indication

Isavuconazonium is indicated for the treatment of invasive aspergillosis and mucormycosis in adults and pediatric patients 1 year of age and older in capsule form and adults and pediatric patients 6 years of age and older who weigh 16 kilograms (kg) and greater in injection form.6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofInvasive aspergillosis•••••••••••••••••• ••••••••••••• •••••• •• •• ••••• •• •••••••••
Treatment ofInvasive aspergillosis•••••••••••••••••• ••••••••••••••••••• ••••••• ••• ••••••••
Treatment ofInvasive mucormycosis•••••••••••••••••• ••••••••••••• •••••• •• •• ••••• •• •••••••••
Treatment ofInvasive mucormycosis••••••••••••••••••••••••••• ••••••• ••• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

In patients treated with isavuconazonium for invasive aspergillosis in a controlled trial, there was no significant association between plasma AUC or plasma isavuconazole concentration and efficacy.6

The effect on QTc interval of multiple doses of isavuconazonium capsules was evaluated. Isavuconazonium was administered as 2 capsules (equivalent to 200 mg isavuconazole) three times daily on days 1 and 2 followed by either 2 capsules or 6 capsules (equivalent to 600 mg isavuconazole) once daily for 13 days in a randomized, placebo- and active-controlled (moxifloxacin 400 mg single-dose), four-treatment-arms, parallel study in 160 healthy subjects.6

Isavuconazole resulted in dose-related shortening of the QTc interval. For the 2-capsule dosing regimen, the least squares mean (LSM) difference from placebo was -13.1 msec at 2 hours postdose [90% CI: -17.1, -9.1 msec]. Increasing the dose to 6 capsules resulted in an LSM difference from the placebo of -24.6 msec at 2 hours postdose [90% CI: -28.7, -20.4]. Isavuconazonium was not evaluated in combination with other drugs that reduce the QTc interval, so the additive effects are not known.6

The mechanism of resistance to isavuconazole, like other azole antifungals, is likely due to multiple mechanisms that include substitutions in the target gene CYP51. Changes in sterol profile and elevated efflux pump activity were observed; however, the clinical relevance of these findings is unclear.6

In vitro and animal studies suggest cross-resistance between isavuconazole and other azoles. The relevance of cross-resistance to clinical outcomes has not been fully characterized; however, patients failing prior azole therapy may require alternative antifungal therapy.6

Mechanism of action

Isavuconazonium sulfate is the prodrug of isavuconazole, an azole antifungal. Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, by inhibiting cytochrome P-450-dependent enzyme lanosterol 14-alpha-demethylase (Erg11p). This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weaken the membrane structure and function. Mammalian cell demethylation is less sensitive to isavuconazole inhibition.6

TargetActionsOrganism
ULanosterol 14-alpha demethylaseNot Available
Absorption

In healthy subjects, the pharmacokinetics of isavuconazole following oral administration of isavuconazonium capsules at isavuconazole equivalent doses up to 600 mg per day (6 capsules) are dose-proportional. Following oral administration of isavuconazonium capsules at an isavuconazole equivalent dose of 200 mg in 66 fasted healthy male subjects, a single dose administration of two 186 mg isavuconazonium capsules and five 74.5 mg isavuconazonium capsules exhibited a mean (SD) Cmax and AUC of 3.3 (0.6) mg/L and 112.2 (30.3) mg·hr/L, respectively, and 3.3 (0.6) mg/L and 118.0 (33.1) mg·hr/L, respectively.6

After oral administration of isavuconazonium in healthy volunteers, the active moiety, isavuconazole, generally reaches maximum plasma concentrations (Cmax) 2 hours to 3 hours after single and multiple dosing. The absolute bioavailability of isavuconazole following oral administration of isavuconazonium is 98%. No significant concentrations of the prodrug or inactive cleavage product were seen in plasma after oral administration.6

Following intravenous administration of isavuconazonium, maximal plasma concentrations of the prodrug and inactive cleavage product were detectable during infusion and declined rapidly following the end of administration. The prodrug was below the level of detection by 1.25 hours after the start of a one-hour infusion. The total exposure of the prodrug based on AUC was less than 1% that of isavuconazole. The inactive cleavage product was quantifiable in some subjects up to 8 hours after the start of infusion. The total exposure of inactive cleavage product based on AUC was approximately 1.3% that of isavuconazole. Isavuconazonium given orally as an intravenous solution administered via nasogastric (NG) tube provides systemic isavuconazole exposure that is similar to the oral capsule.6

Coadministration of isavuconazonium equivalent to isavuconazole 400 mg oral dose with a high-fat meal reduced isavuconazole Cmax by 9% and increased AUC by 9%. isavuconazonium can be taken with or without food.6

Volume of distribution

Isavuconazole is extensively distributed with a mean steady-state volume of distribution (Vss) of approximately 450 L.6

Protein binding

Isavuconazole is highly protein bound (greater than 99%), predominantly to albumin.6

Metabolism

In in vitro studies, isavuconazonium sulfate is rapidly hydrolyzed in blood to isavuconazole by esterases, predominantly by butylcholinesterase. Isavuconazole is a substrate of cytochrome P450 enzymes 3A4 and 3A5.6

Following single doses of [cyano 14C] isavuconazonium and [pyridinylmethyl 14C] isavuconazonium in humans, in addition to the active moiety (isavuconazole) and the inactive cleavage product, several minor metabolites were identified. Except for the active moiety isavuconazole, no individual metabolite was observed with an AUC greater than 10% of drug-related material.6

In vivo studies indicate that CYP3A4, CYP3A5, and subsequently uridine diphosphate-glucuronosyltransferases (UGT) are involved in the metabolism of isavuconazole.6

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Route of elimination

Following oral administration of radio-labeled isavuconazonium sulfate to healthy volunteers, a mean of 46.1% of the total radioactive dose was recovered in the feces and 45.5% was recovered in the urine.6

Renal excretion of isavuconazole itself was less than 1% of the dose administered.6

The inactive cleavage product is primarily eliminated by metabolism and subsequent renal excretion of the metabolites. Renal elimination of intact cleavage product was less than 1% of the total dose administered. Following intravenous administration of radio-labeled cleavage product, 95% of the total radioactive dose was excreted in the urine.6

Half-life

Based on a population pharmacokinetics analysis of healthy subjects and patients, the mean plasma half-life of isavuconazole was 130 hours.6

Clearance

In healthy subjects, the clearance of isavuconazole was estimated to be from 2.4 to 4.1 L/h.3 Chinese subjects were found to have on average a 40% lower clearance compared to Western subjects (1.6 L/hr for Chinese subjects as compared to 2.6 L/hr for Western subjects).6

Adverse Effects
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Toxicity

Based on findings from animal studies, isavuconazonium may cause fetal harm when administered to a pregnant woman. There are no available human data on the use of isavuconazonium in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, perinatal mortality was increased in the offspring of pregnant rats dosed orally with isavuconazonium sulfate at approximately 0.5 times the clinical exposure during pregnancy through the weaning period. In animal studies when isavuconazonium chloride was administered by oral gavage to pregnant rats and rabbits during organogenesis at exposures corresponding to less than the human maintenance dose increases in the incidences of multiple skeletal abnormalities, including rudimentary cervical ribs and fused zygomatic arches were observed.6

During clinical studies, total daily isavuconazonium doses higher than the recommended dose regimen were associated with an increased rate of adverse reactions. At supratherapeutic doses (three times the recommended maintenance dose) evaluated in a thorough QT study, there were proportionally more treatment-emergent adverse reactions than in the therapeutic dose group (maintenance dose) for the following: headache, dizziness, paresthesia, somnolence, disturbance in attention, dysgeusia, dry mouth, diarrhea, oral hypoesthesia, vomiting, hot flush, anxiety, restlessness, palpitations, tachycardia, photophobia and arthralgia. Adverse reactions leading to discontinuation of the study drug occurred in 7 of 39 (17.9%) subjects in the supratherapeutic dose group.6

Isavuconazole is not removed by hemodialysis. There is no specific antidote for isavuconazole. Treatment should be supportive with appropriate monitoring.6

In a 2-year rat carcinogenicity study and a 2-year mouse carcinogenicity study, dose-related increases in hepatocellular adenomas and/or carcinomas were observed in male and female B6C3F1/Crl mice and male, but not female Han Wistar rats at doses as low as 0.1 times the exposure seen in humans administered the maintenance dose. Hepatic hemangiomas were increased in female mice at 300 mg/kg, at an exposure similar to the maintenance dose. Hepatoblastoma was increased in male mice at 100 mg/kg, about 0.4 times the systemic exposures based on AUC comparisons. Thyroid follicular cell adenomas were observed in male and female rats at doses as low as 60 mg/kg in male rats (about 0.2 times the human clinical maintenance dose). The relevance of rat thyroid tumors to human carcinogenic risk remains unclear.6

A significant increase in the incidence of skin fibromas was seen in male rats at 300 mg/kg, exposures 0.8 times the human exposure at the human clinical maintenance dose. Uterine adenocarcinomas were observed in female rats at 200 mg/kg, at systemic exposures similar to the human exposure at the human clinical maintenance dose.6

No mutagenic or clastogenic effects were detected in the in vitro bacterial reverse mutation assay and the in vivo bone marrow micronucleus assay in rats.6

Oral administration of isavuconazonium sulfate did not affect fertility in male or female rats treated at doses up to 90 mg/kg/day (approximately 0.3 times the systemic exposure at the human clinical maintenance dose).6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Isavuconazonium.
AbametapirThe serum concentration of Isavuconazonium can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Isavuconazonium can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Isavuconazonium.
AbirateroneThe metabolism of Isavuconazonium can be decreased when combined with Abiraterone.
Food Interactions
  • Avoid grapefruit products. Grapefruit is a moderate to strong inhibitor of CYP3A4. Strong CYP3A4 inhibitors are contraindicated with isavuconazonium.
  • Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of isavuconazonium and may reduce its serum concentration. Co-administration of isavuconazonium with St. John's Wort is contraindicated.
  • Take with or without food. The bioavailability of isavuconazonium is not significantly impacted by food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Isavuconazonium sulfate31Q44514JV946075-13-4LWXUIUUOMSMZKJ-KLFWAVJMSA-M
Active Moieties
NameKindUNIICASInChI Key
Isavuconazoleprodrug60UTO373KE241479-67-4DDFOUSQFMYRUQK-RCDICMHDSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CresembaCapsule100 mgOralAvir Pharma Inc2019-05-02Not applicableCanada flag
CresembaCapsule186 mg/1OralAstellas Pharma US, Inc.2015-03-062017-01-31US flag
CresembaCapsule40 mg/1OralAstellas Pharma US, Inc.2022-11-22Not applicableUS flag
CresembaInjection, powder, lyophilized, for solution40 mg/1mLIntravenousAstellas Pharma US, Inc.2015-03-06Not applicableUS flag
CresembaPowder, for solution200 mg / vialIntravenousAvir Pharma Inc2019-05-31Not applicableCanada flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid esters
Alternative Parents
Phenylpropanes / Benzonitriles / Fluorobenzenes / 2,4-disubstituted thiazoles / Imidolactams / Pyridines and derivatives / Aryl fluorides / Triazoles / Heteroaromatic compounds / Carbamate esters
show 14 more
Substituents
1,2,4-triazole / 2,4-disubstituted 1,3-thiazole / Alcohol / Alpha-amino acid ester / Amine / Aromatic alcohol / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle
show 32 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organic cation (CHEBI:85978)
Affected organisms
  • Candida albicans and other yeasts
  • Aspergillis, Candida and other fungi

Chemical Identifiers

UNII
VH2L779W8Q
CAS number
742049-41-8
InChI Key
RSWOJTICKMKTER-QXLBVTBOSA-N
InChI
InChI=1S/C35H35F2N8O5S/c1-22(33-42-30(18-51-33)25-9-7-24(15-38)8-10-25)35(48,28-14-27(36)11-12-29(28)37)19-45-21-44(20-41-45)23(2)50-34(47)43(4)32-26(6-5-13-40-32)17-49-31(46)16-39-3/h5-14,18,20-23,39,48H,16-17,19H2,1-4H3/q+1/t22-,23?,35+/m0/s1
IUPAC Name
1-[(2R,3R)-3-[4-(4-cyanophenyl)-1,3-thiazol-2-yl]-2-(2,5-difluorophenyl)-2-hydroxybutyl]-4-[1-({methyl[3-({[2-(methylamino)acetyl]oxy}methyl)pyridin-2-yl]carbamoyl}oxy)ethyl]-1H-1,2,4-triazol-4-ium
SMILES
[H]C(C)(OC(=O)N(C)C1=C(COC(=O)CNC)C=CC=N1)[N+]1=CN(C[C@](O)(C2=C(F)C=CC(F)=C2)[C@@]([H])(C)C2=NC(=CS2)C2=CC=C(C=C2)C#N)N=C1

References

General References
  1. Rybak JM, Marx KR, Nishimoto AT, Rogers PD: Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent. Pharmacotherapy. 2015 Nov;35(11):1037-51. doi: 10.1002/phar.1652. Epub 2015 Nov 2. [Article]
  2. Miceli MH, Kauffman CA: Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent. Clin Infect Dis. 2015 Nov 15;61(10):1558-65. doi: 10.1093/cid/civ571. Epub 2015 Jul 15. [Article]
  3. Desai A, Kovanda L, Kowalski D, Lu Q, Townsend R, Bonate PL: Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5483-91. doi: 10.1128/AAC.02819-15. Print 2016 Sep. [Article]
  4. Wilson DT, Dimondi VP, Johnson SW, Jones TM, Drew RH: Role of isavuconazole in the treatment of invasive fungal infections. Ther Clin Risk Manag. 2016 Aug 3;12:1197-206. doi: 10.2147/TCRM.S90335. eCollection 2016. [Article]
  5. FDA Approved Drug Products: Cresemba (isavuconazonium sulfate) [Link]
  6. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
  7. FDA Approves Expanded Use of CRESEMBA® (isavuconazonium sulfate) in Children with Invasive Aspergillosis and Invasive Mucormycosis [Link]
KEGG Drug
D10643
PubChem Compound
6918606
PubChem Substance
310264875
ChemSpider
5293801
RxNav
1608322
ChEBI
85978
ChEMBL
CHEMBL1183349
Wikipedia
Isavuconazonium
FDA label
Download (851 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral100 mg/1
CapsuleOral100 mg
CapsuleOral186 mg/1
CapsuleOral186.3 Mg
CapsuleOral40 mg/1
Injection, powder, for solutionIntravenous200 MG
Injection, powder, lyophilized, for solutionIntravenous40 mg/1mL
Powder, for solutionIntravenous200 mg / vial
Capsule, coatedOral186.3 mg
Injection, powder, lyophilized, for solutionIntravenous200 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7459561No2008-12-022020-10-31US flag
US6812238Yes2004-11-022026-05-01US flag
US10206879Yes2019-02-192028-03-14US flag
US10603280Yes2020-03-312028-03-14US flag
US10812238No2020-10-202025-10-31US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00516 mg/mLALOGPS
logP1.73ALOGPS
logP0.52Chemaxon
logS-5.2ALOGPS
pKa (Strongest Acidic)12.57Chemaxon
pKa (Strongest Basic)6.45Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count9Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area159.37 Å2Chemaxon
Rotatable Bond Count15Chemaxon
Refractivity193.86 m3·mol-1Chemaxon
Polarizability71.63 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-248.12622
predicted
DeepCCS 1.0 (2019)
[M+H]+249.95111
predicted
DeepCCS 1.0 (2019)
[M+Na]+255.55693
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Not Available
Pharmacological action
Unknown
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity).
Gene Name
ERG11
Uniprot ID
P50859
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
61304.95 Da

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Inducer
Curator comments
Isavuconazonium is a prodrug to Isavuconazole which is the actual CYP3A4 substrate, but it will therefore still participate in CYP3A4 drug interactions when taken.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Rybak JM, Marx KR, Nishimoto AT, Rogers PD: Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent. Pharmacotherapy. 2015 Nov;35(11):1037-51. doi: 10.1002/phar.1652. Epub 2015 Nov 2. [Article]
  2. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Curator comments
This is butylcholinesterase
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Miceli MH, Kauffman CA: Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent. Clin Infect Dis. 2015 Nov 15;61(10):1558-65. doi: 10.1093/cid/civ571. Epub 2015 Jul 15. [Article]
  2. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. FDA Approved Drug Products: CRESEMBA® (isavuconazonium sulfate) capsules/injection, for oral/intravenous use [Link]

Drug created at March 19, 2008 16:42 / Updated at March 18, 2024 16:48