Voriconazole

Last updated
Voriconazole
Voriconazole structure.svg
Voriconazole ball-and-stick model.png
Clinical data
Pronunciation /vɒrɪˈkɒnəzl/ vorr-i-KON-ə-zohl
Trade names Vfend, others
AHFS/Drugs.com Monograph
MedlinePlus a605022
License data
Pregnancy
category
  • AU:B3
Routes of
administration
Intravenous, by mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only) [1]
  • US: ℞-only
  • EU:Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 96% (oral)
Protein binding 58%
Metabolism Liver: CYP2C19 (significant involvement), also CYP2C9, CYP3A4
Metabolites Voriconazole N-oxide (major; minimal antifungal activity)
Elimination half-life Dose-dependent
Excretion Urine (80–83%) [2]
Identifiers
  • (2R,3S)-2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.157.870 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H14F3N5O
Molar mass 349.317 g·mol−1
3D model (JSmol)
  • Fc1cncnc1[C@@H]([C@@](O)(c2ccc(F)cc2F)Cn3ncnc3)C
  • InChI=1S/C16H14F3N5O/c1-10(15-14(19)5-20-7-22-15)16(25,6-24-9-21-8-23-24)12-3-2-11(17)4-13(12)18/h2-5,7-10,25H,6H2,1H3/t10-,16+/m0/s1 Yes check.svgY
  • Key:BCEHBSKCWLPMDN-MGPLVRAMSA-N Yes check.svgY
   (verify)

Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. [3] This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by Scedosporium or Fusarium . [3] It can be taken by mouth or used by injection into a vein. [3]

Contents

Common side effects include vision problems, nausea, abdominal pain, rash, headache, and seeing or hearing things that are not present. [3] Use during pregnancy may result in harm to the baby. [3] It is in the triazole family of medications. [3] It works by affecting fungal metabolism and fungal cell membranes. [3]

Voriconazole was patented in 1990 and approved for medical use in the United States in 2002. [4] [5] It is on the World Health Organization's List of Essential Medicines. [6]

Medical uses

Voriconazole is used to treat invasive aspergillosis and candidiasis and fungal infections caused by Scedosporium and Fusarium species, which may occur in immunocompromised patients, including people undergoing allogeneic bone marrow transplant (BMT), who have hematologic cancers or who undergo organ transplants. [7] [8] [9] [10]

It is also used to prevent fungal infection in people as they undergo BMT. [9] [7]

It is also the recommended treatment for the CNS fungal infections transmitted by epidural injection of contaminated steroids. [11]

It can be taken by mouth or given in a doctor's office or clinic by intravenous infusion. [7]

Contraindications

It is toxic to the fetus; pregnant women should not take it and women taking it should not become pregnant. [2]

People who have hereditary intolerance for galactose, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this drug. It should be used with caution in people with arrhythmias or long QT. [2]

No dose adjustment is necessary for renal impairment or advanced age, but children seem to clear voriconazole faster than adults and drug levels may need monitoring. [12]

Side effects

The labels carry several warnings of the risk of injection site reactions, hypersensitivity reactions; kidney, liver, and pancreas damage; trouble with vision; and adverse effects in skin including damage due to phototoxicity, squamous cell skin cancer, and Stevens–Johnson syndrome; in long-term use there is a warning of the risk of bone fluorosis and periostitis especially in elderly patients. [13] [2] [14] [7]

Additionally, very common adverse effects, occurring in more than 10% of people, include peripheral edema, headaches, trouble breathing, diarrhea, vomiting, abdominal pain, nausea, rashes, and fever. [7]

Common adverse effects, occurring in between 1 and 10% of people, include sinus infections, low numbers of white and red blood cells (agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, and anemia), low blood sugar, reduced amount of potassium and sodium, depression, hallucinations, anxiety, insomnia, agitation, confusion, convulsions, fainting, tremor, weakness, tingling, sleepiness, dizziness, bleeding retina, irregular heart beats, slow or fast heart beats, low blood pressure, inflamed veins, acute respiratory distress syndrome, pulmonary edema, inflamed lips, swollen face, stomach upset, constipation, gingivitis, jaundice, hair loss, flaky skin, itchiness, red skin, back pain, chest pain, and chills. [7]

Interactions

Being metabolized by hepatic cytochrome P450, voriconazole interacts with many drugs. [2] [7] Voriconazole should not be used in conjunction with many drugs (including sirolimus, rifampicin, rifabutin, carbamazepine, quinidine and ergot alkaloids) and dose adjustments and/or monitoring should be done when coadministered with others (including fluconazole, warfarin, ciclosporin, tacrolimus, omeprazole, and phenytoin). Voriconazole may be safely administered with cimetidine, ranitidine, indinavir, macrolide antibiotics, mycophenolate, digoxin and prednisolone. [2]

Pharmacology

Pharmacokinetics

Voriconazole is well absorbed orally with a bioavailability of 96%, allowing patients to be switched between intravenous and oral administration.[ citation needed ]

History

Pfizer brought the drug to market as Vfend. A generic version of the tablet form of voriconazole was introduced in the US in 2011 after Pfizer and Mylan settled litigation under the Hatch-Waxman Act; a generic version of the injectable form was introduced in 2012. In Europe patent protection expired in 2011 and pediatric administrative exclusivity expired in Europe in 2016. [15]

Society and culture

Brand names

As of July 2017, the medication is marketed under the following names worldwide: Cantex, Pinup, Vedilozin, Vfend, Vodask, Volric, Voramol, Voriconazol, Voriconazole, Voriconazolum, Voricostad, Vorikonazol, Voritek, Voriz, Vornal, and Vosicaz. [16]

Related Research Articles

<span class="mw-page-title-main">Candidiasis</span> Fungal infection due to any type of Candida

Candidiasis is a fungal infection due to any species of the genus Candida. When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers, among other symptoms.

<span class="mw-page-title-main">Itraconazole</span> Medication used to treat fungal infections

Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth or intravenously.

<span class="mw-page-title-main">Nystatin</span> Antifungal medication

Nystatin, sold under the brand name Mycostatin among others, is an antifungal medication. It is used to treat Candida infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin.

<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

<span class="mw-page-title-main">Fungal infection</span> Disease caused by fungi to animals or humans

Fungal infection, also known as mycosis, is a disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common tinea of the skin, such as tinea of the body, groin, hands, feet and beard, and yeast infections such as pityriasis versicolor. Subcutaneous types include eumycetoma and chromoblastomycosis, which generally affect tissues in and beneath the skin. Systemic fungal infections are more serious and include cryptococcosis, histoplasmosis, pneumocystis pneumonia, aspergillosis and mucormycosis. Signs and symptoms range widely. There is usually a rash with superficial infection. Fungal infection within the skin or under the skin may present with a lump and skin changes. Pneumonia-like symptoms or meningitis may occur with a deeper or systemic infection.

<span class="mw-page-title-main">Caspofungin</span> Antifungal medication

Caspofungin is a lipopeptide antifungal drug from Merck & Co., Inc.. It is a member of a class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall.

<span class="mw-page-title-main">Fungemia</span> Internal, blood-borne infection by fungi, including yeasts.

Fungemia is the presence of fungi or yeast in the blood. The most common type, also known as candidemia, candedemia, or systemic candidiasis, is caused by Candida species. Candidemia is also among the most common bloodstream infections of any kind. Infections by other fungi, including Saccharomyces, Aspergillus and Cryptococcus, are also called fungemia. It is most commonly seen in immunosuppressed or immunocompromised patients with severe neutropenia, cancer patients, or in patients with intravenous catheters. It has been suggested that otherwise immunocompetent patients taking infliximab may also be at a higher risk.

<span class="mw-page-title-main">Anidulafungin</span> Antifungal medication

Anidulafungin (INN) is a semisynthetic echinocandin used as an antifungal drug. It was previously known as LY303366. It may also have application in treating invasive Aspergillus infection when used in combination with voriconazole. It is a member of the class of antifungal drugs known as the echinocandins; its mechanism of action is by inhibition of (1→3)-β-D-glucan synthase, an enzyme important to the synthesis of the fungal cell wall.

<span class="mw-page-title-main">Dicloxacillin</span> Chemical compound

Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

<span class="mw-page-title-main">Posaconazole</span> Pharmaceutical drug

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<span class="mw-page-title-main">Aspergillosis</span> Medical condition

Aspergillosis is a fungal infection of usually the lungs, caused by the genus Aspergillus, a common mould that is breathed in frequently from the air, but does not usually affect most people. It generally occurs in people with lung diseases such as asthma, cystic fibrosis or tuberculosis, or COVID-19 or those who are immunocompromized such as those who have had a stem cell or organ transplant or those who take medications such as steroids and some cancer treatments which suppress the immune system. Rarely, it can affect skin.

<span class="mw-page-title-main">Echinocandin</span> Group of chemical compounds

Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.

<span class="mw-page-title-main">Clotrimazole</span> Chemical compound

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References

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  9. 1 2 Omrani AS, Almaghrabi RS (December 2017). "Complications of hematopoietic stem transplantation: Fungal infections". Hematology/Oncology and Stem Cell Therapy. 10 (4): 239–244. doi: 10.1016/j.hemonc.2017.05.013 . PMID   28636889.
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  11. "Interim Treatment Guidance for Central Nervous System and Parameningeal Infections Associated with Injection of Contaminated Steroid Products". Centers for Disease Control and Prevention. Retrieved 6 November 2016.
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Further reading