Its only indication that has received regulatory approval worldwide iscytomegalovirus retinitis.[3][4] Cidofovir has also shown efficacy in the treatment ofaciclovir-resistantHSV infections.[6] Cidofovir has also been investigated as a treatment forprogressive multifocal leukoencephalopathy with successful case reports of its use.[7] Despite this, the drug failed to demonstrate any efficacy in controlled studies.[8] Cidofovir might have anti-smallpox efficacy and might be used on a limited basis in the event of abioterror incident involving smallpox cases.[9]Brincidofovir, a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed.[10] It has inhibitory effects on varicella-zoster virus replicationin vitro although no clinical trials have been done to date, likely due to the abundance of safer alternatives such asaciclovir.[11] Cidofovir shows anti-BK virus activity in a subgroup of transplant recipients.[12] Cidofovir is being investigated as a complementary intralesional therapy againstpapillomatosis caused byHPV.[13][14]
It first receivedFDA approval on 26 June 1996,[15]TGA approval on 30 April 1998[4] andEMA approval on 23 April 1997.[16]
Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered withprobenecid which decreases side effects to the kidney.[21] Probenecid mitigates nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney.[22] In addition, hydration must be administered to patients receiving cidofovir. 1 liter of normal saline is recommended in conjunction with each dose of cidofovir.[21]
The major dose-limiting side effect of cidofovir is nephrotoxicity (i.e., kidney damage).[23] Other common side effects (occurring in >1% of people treated with the drug) include:[3][23]
Whereas uncommon side effects include:anaemia and elevated liver enzymes and rare side effects include:tachycardia andFanconi syndrome.[23]Probenecid (a uricosuric drug) and intravenous saline should always be administered with each cidofovir infusion to prevent this nephrotoxicity.[24]
It is known to interact with nephrotoxic agents (e.g.amphotericin B,foscarnet, IVaminoglycosides, IV pentamide,vancomycin,tacrolimus, non-steroid anti-inflammatory drugs, etc.) to increase their nephrotoxic potential.[3][4] 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.[4]
Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viralDNA polymerases.[4] It also inhibits human polymerases, but this action is 8–600 times weaker than its actions on viral DNA polymerases.[4] It also incorporates itself into viral DNA, hence inhibiting viral DNA synthesis during reproduction.[4]
It possessesin vitro activity against the following viruses:[25]
Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, byAntonín Holý, and developed byGilead Sciences[27] and is marketed with the brand nameVistide by Gilead in the US, and byPfizer elsewhere.
^Cundy, Kenneth C. "Clinical Pharmacokinetics of the Antiviral Nucleotide Analogues Cidofovir and Adefovir." Clinical Pharmacokinetics 36.2 (1999): 127–143.
^Araya CE, Lew JF, Fennell RS, Neiberger RE, Dharnidharka VR (February 2006). "Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy".Pediatric Transplantation.10 (1):32–37.doi:10.1111/j.1399-3046.2005.00391.x.PMID16499584.S2CID24131709.
^"Vistide: EPAR – Product Information"(PDF).European Medicines Agency. Gilead Sciences International Ltd. 7 November 2013. Archived fromthe original(PDF) on 22 February 2014. Retrieved5 February 2014.
^Brodfuehrer PR, Howell HG, Sapino Jr C, Vemishetti P (1994). "A practical synthesis of (S)-HPMPC".Tetrahedron Letters.35 (20): 3243.doi:10.1016/S0040-4039(00)76875-4.
