Cidofovir Explained

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.

Cidofovir was approved for medical use in 1996.[1]

Medical use

DNA virus

Its only indication that has received regulatory approval worldwide is cytomegalovirus retinitis. Cidofovir has also shown efficacy in the treatment of aciclovir-resistant HSV infections.[2] Cidofovir has also been investigated as a treatment for progressive multifocal leukoencephalopathy with successful case reports of its use.[3] Despite this, the drug failed to demonstrate any efficacy in controlled studies.[4] Cidofovir might have anti-smallpox efficacy and might be used on a limited basis in the event of a bioterror incident involving smallpox cases.[5] Brincidofovir, a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed.[6] 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.[7] Cidofovir shows anti-BK virus activity in a subgroup of transplant recipients.[8] Cidofovir is being investigated as a complementary intralesional therapy against papillomatosis caused by HPV.[9] [10]

It first received FDA approval on 26 June 1996,[11] TGA approval on 30 April 1998 and EMA approval on 23 April 1997.[12]

It has been used topically to treat warts.[13]

Other

It has been suggested as an antitumour agent, due to its suppression of FGF2.[14] [15] [16]

Administration

Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered with probenecid which decreases side effects to the kidney.[17] Probenecid mitigates nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney.[18] In addition, hydration must be administered to patients receiving cidofovir. 1 liter of normal saline is recommended in conjunction with each dose of cidofovir.[17]

Side effects

The major dose-limiting side effect of cidofovir is nephrotoxicity (i.e., kidney damage).[19] Other common side effects (occurring in >1% of people treated with the drug) include:[20] [19]

Whereas uncommon side effects include: anaemia and elevated liver enzymes and rare side effects include: tachycardia and Fanconi syndrome.[19] Probenecid (a uricosuric drug) and intravenous saline should always be administered with each cidofovir infusion to prevent this nephrotoxicity.[21]

Contraindications

Hypersensitivity to cidofovir or probenecid (as probenecid needs to be given concurrently to avoid nephrotoxicity).[20]

Interactions

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.[20] [22] 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.[22]

Mechanism of action

Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral DNA polymerases.[22] It also inhibits human polymerases, but this action is 8–600 times weaker than its actions on viral DNA polymerases.[22] It also incorporates itself into viral DNA, hence inhibiting viral DNA synthesis during reproduction.[22]

It possesses in vitro activity against the following viruses:[23]

History

Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by Antonín Holý, and developed by Gilead Sciences[24] and is marketed with the brand name Vistide by Gilead in the US, and by Pfizer elsewhere.

Synthesis

Cidofovir can be synthesized from a pyrimidone derivative and a protected derivative of glycidol.[25]

See also

Notes and References

  1. Book: Long SS, Prober CG, Fischer M . Principles and Practice of Pediatric Infectious Disease. 2012. Elsevier Health Sciences. 978-1437727029. 1502. en.
  2. Chilukuri S, Rosen T . Management of acyclovir-resistant herpes simplex virus . Dermatologic Clinics . 21 . 2 . 311–320 . April 2003 . 12757254 . 10.1016/S0733-8635(02)00093-1 .
  3. Segarra-Newnham M, Vodolo KM . Use of cidofovir in progressive multifocal leukoencephalopathy . The Annals of Pharmacotherapy . 35 . 6 . 741–744 . June 2001 . 11408993 . 10.1345/aph.10338 . 32026770 .
  4. De Gascun CF, Carr MJ . Human polyomavirus reactivation: disease pathogenesis and treatment approaches . Clinical & Developmental Immunology . 2013 . 373579 . 2013 . 23737811 . 3659475 . 10.1155/2013/373579 . free .
  5. De Clercq E . Cidofovir in the treatment of poxvirus infections . Antiviral Research . 55 . 1 . 1–13 . July 2002 . 12076747 . 10.1016/S0166-3542(02)00008-6 . 9533828 .
  6. Bradbury J . Orally available cidofovir derivative active against smallpox . Lancet . 359 . 9311 . 1041 . March 2002 . 11937193 . 10.1016/S0140-6736(02)08115-1 . 22903225 .
  7. Magee WC, Hostetler KY, Evans DH . Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate . Antimicrobial Agents and Chemotherapy . 49 . 8 . 3153–3162 . August 2005 . 16048917 . 1196213 . 10.1128/AAC.49.8.3153-3162.2005 .
  8. Araya CE, Lew JF, Fennell RS, Neiberger RE, Dharnidharka VR . Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy . Pediatric Transplantation . 10 . 1 . 32–37 . February 2006 . 16499584 . 10.1111/j.1399-3046.2005.00391.x . 24131709 .
  9. Broekema FI, Dikkers FG . Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis . European Archives of Oto-Rhino-Laryngology . 265 . 8 . 871–879 . August 2008 . 18458927 . 2441494 . 10.1007/s00405-008-0658-0 .
  10. Soma MA, Albert DM . Cidofovir: to use or not to use? . Current Opinion in Otolaryngology & Head and Neck Surgery . 16 . 1 . 86–90 . February 2008 . 18197029 . 10.1097/MOO.0b013e3282f43408 . 22895067 .
  11. Web site: Cidofovir Monograph for Professionals . Drugs.com. American Society of Health-System Pharmacists. 5 February 2014.
  12. Web site: Vistide : EPAR – Product Information. European Medicines Agency. Gilead Sciences International Ltd.. 7 November 2013. 5 February 2014. 22 February 2014. https://web.archive.org/web/20140222052403/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000121/WC500052072.pdf. dead.
  13. Fernández-Morano T, del Boz J, González-Carrascosa M, Tortajada B, de Troya M . Topical cidofovir for viral warts in children . Journal of the European Academy of Dermatology and Venereology . 25 . 12 . 1487–1489 . December 2011 . 21261749 . 10.1111/j.1468-3083.2010.03961.x . 32295082 . free .
  14. Kern ER . In vitro activity of potential anti-poxvirus agents . Antiviral Research . 57 . 1–2 . 35–40 . January 2003 . 12615301 . 10.1016/s0166-3542(02)00198-5 . 23136929 . 9628899 .
  15. Andrei G, Snoeck R . Cidofovir Activity against Poxvirus Infections . Viruses . 2 . 12 . 2803–2830 . December 2010 . 21994641 . 10.3390/v2122803 . 3185586 . free .
  16. Web site: Interim Clinical Guidance for the Treatment of Monkeypox. . U.S. Centers for Disease Control and Prevention . 26 May 2022 .
  17. Web site: Details . www.gilead.com . 2019-06-05.
  18. Lacy SA, Hitchcock MJ, Lee WA, Tellier P, Cundy KC . Effect of oral probenecid coadministration on the chronic toxicity and pharmacokinetics of intravenous cidofovir in cynomolgus monkeys . Toxicological Sciences . 44 . 2 . 97–106 . August 1998 . 9742650 . 10.1006/toxs.1998.2481 . free .
  19. Book: Rossi S . 978-0-9805790-9-3 . Australian Medicines Handbook . Adelaide . The Australian Medicines Handbook Unit Trust . 2013 . 2013 .
  20. Web site: Vistide (cidofovir) dosing, indications, interactions, adverse effects, and more. Medscape Reference. WebMD. 4 February 2014.
  21. Web site: Vistide (cidofovir) . . September 2010 . . Dosage and Administration: Dosage . yes.
  22. Web site: Product Information VISTIDE®. TGA eBusiness Services. Gilead Sciences Pty Ltd. 3 September 2013. 5 February 2014.
  23. Safrin S, Cherrington J, Jaffe HS . Clinical uses of cidofovir . Reviews in Medical Virology . 7 . 3 . 145–156 . September 1997 . 10398479 . 10.1002/(SICI)1099-1654(199709)7:3<145::AID-RMV196>3.0.CO;2-0 . 32366514 .
  24. Web site: Press Releases: Gilead . 2007-12-05 . 2013-02-08 . https://web.archive.org/web/20130208114649/http://www.gilead.com/pr_881577 . dead .
  25. Brodfuehrer PR, Howell HG, Sapino Jr C, Vemishetti P . 10.1016/S0040-4039(00)76875-4. A practical synthesis of (S)-HPMPC. 1994 . Tetrahedron Letters. 35. 3243. 20.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cidofovir".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.