Clinical data | |
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Trade names | Vistide |
AHFS/Drugs.com | Monograph |
Pregnancy category |
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Routes of administration | Intravenous |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | complete |
Protein binding | <6% |
Elimination half-life | 2.6 hours (active metabolites: 15–65 hours) |
Excretion | renal The above pharmacokinetic parameters are measured for cidofovir used in conjunction with probenecid. [3] |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
NIAID ChemDB | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.166.433 |
Chemical and physical data | |
Formula | C8H14N3O6P |
Molar mass | 279.189 g·mol−1 |
3D model (JSmol) | |
Specific rotation | -97.3 |
Melting point | 260 °C (500 °F) |
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Cidofovir, brand name Vistide, is a topical or injectable antiviral medication primarily used as a treatment for cytomegalovirus (CMV) retinitis (an infection of the retina of the eye) in people with AIDS. [4] [5]
Cidofovir was approved for medical use in 1996. [6]
Its only indication that has received regulatory approval worldwide is cytomegalovirus retinitis. [4] [5] Cidofovir has also shown efficacy in the treatment of aciclovir-resistant HSV infections. [7] Cidofovir has also been investigated as a treatment for progressive multifocal leukoencephalopathy with successful case reports of its use. [8] Despite this, the drug failed to demonstrate any efficacy in controlled studies. [9] Cidofovir might have anti-smallpox efficacy and might be used on a limited basis in the event of a bioterror incident involving smallpox cases. [10] Brincidofovir, a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed. [11] It has inhibitory effects on varicella-zoster virus replication in vitro although no clinical trials have been done to date, likely due to the abundance of safer alternatives such as aciclovir. [12] Cidofovir shows anti-BK virus activity in a subgroup of transplant recipients. [13] Cidofovir is being investigated as a complementary intralesional therapy against papillomatosis caused by HPV. [14] [15]
It first received FDA approval on 26 June 1996, [16] TGA approval on 30 April 1998 [5] and EMA approval on 23 April 1997. [17]
It has been suggested as an antitumour agent, due to its suppression of FGF2. [19] [20] [21]
Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered with probenecid which decreases side effects to the kidney. [22] Probenecid mitigates nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney. [23] In addition, hydration must be administered to patients receiving cidofovir. 1 liter of normal saline is recommended in conjunction with each dose of cidofovir. [22]
The major dose-limiting side effect of cidofovir is nephrotoxicity (i.e., kidney damage). [24] Other common side effects (occurring in >1% of people treated with the drug) include: [4] [24]
Whereas uncommon side effects include: anaemia and elevated liver enzymes and rare side effects include: tachycardia and Fanconi syndrome. [24] Probenecid (a uricosuric drug) and intravenous saline should always be administered with each cidofovir infusion to prevent this nephrotoxicity. [25]
Hypersensitivity to cidofovir or probenecid (as probenecid needs to be given concurrently to avoid nephrotoxicity). [4]
It is known to interact with nephrotoxic agents (e.g. amphotericin B, foscarnet, IV aminoglycosides, IV pentamide, vancomycin, tacrolimus, non-steroid anti-inflammatory drugs, etc.) to increase their nephrotoxic potential. [4] [5] As it must be given concurrently with probenecid it is advised that drugs that are known to interact with probenecid (e.g. drugs that probenecid interferes with the renal tubular secretion of, such as paracetamol, aciclovir, aminosalicylic acid, etc.) are also withheld. [5]
Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral DNA polymerases. [5] It also inhibits human polymerases, but this action is 8–600 times weaker than its actions on viral DNA polymerases. [5] It also incorporates itself into viral DNA, hence inhibiting viral DNA synthesis during reproduction. [5]
It possesses in vitro activity against the following viruses: [26]
Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by Antonín Holý, and developed by Gilead Sciences [27] and is marketed with the brand name Vistide by Gilead in the US, and by Pfizer elsewhere.
Cidofovir can be synthesized from a pyrimidone derivative and a protected derivative of glycidol. [28]
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.
Aciclovir, also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following transplant and severe complications of Epstein–Barr virus infection. It can be taken by mouth, applied as a cream, or injected.
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Orthopoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and mpox. The most widely known member of the genus is Variola virus, which causes smallpox. It was eradicated globally by 1977, through the use of Vaccinia virus as a vaccine. The most recently described species is the Alaskapox virus, first isolated in 2015.
Foscarnet (phosphonomethanoic acid), known by its brand name Foscavir, is an antiviral medication which is primarily used to treat viral infections involving the Herpesviridae family. It is classified as a pyrophosphate analog DNA polymerase inhibitor. Foscarnet is the conjugate base of a chemical compound with the formula HO2CPO3H2 (Trisodium phosphonoformate).
Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012, for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014, the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015, the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.
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Brincidofovir, sold under the brand name Tembexa, is an antiviral drug used to treat smallpox. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.
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