|Main uses||CMV retinitis, herpes simplex virus, monkeypox|
|Side effects||Kidney problems, nausea, fever, low white blood cells, headache, rash, hair loss, diarrhea, heart burn|
|Typical dose||5 mg/kg|
|Elimination half-life||2.6 hours (active metabolites: 15-65 hours)|
|Excretion||Kidney The above pharmacokinetics are with probenecid.|
|Chemical and physical data|
|Molar mass||279.189 g·mol−1|
|3D model (JSmol)|
|Melting point||260 °C (500 °F)|
Cidofovir, sold under the brand name Vistide, is an antiviral used to treat cytomegalovirus (CMV) retinitis in people with HIV/AIDS. Is also used for herpes simplex virus that is resistant to acyclovir, monkeypox, and certain complications of smallpox vaccination. It is generally given by injection into a vein.
Common side effects include kidney problems, nausea, fever, low white blood cells, headache, rash, hair loss, diarrhea, and heart burn. Other side effects may include pancreatitis, male infertility, and hearing loss. It is given with intravenous fluids and probenecid to decrease the risk of kidney problems. There are concerns that use in pregnancy may harm the baby. It works by blocking the DNA polymerase of the 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. Cidofovir has also been investigated as a treatment for progressive multifocal leukoencephalopathy with successful case reports of its use. Despite this, the drug failed to demonstrate any efficacy in controlled studies. Cidofovir might have anti-smallpox efficacy and might be used on a limited basis in the event of a bioterror incident involving smallpox cases. Brincidofovir, a cidofovir derivative with much higher activity against smallpox that can be taken orally has been developed. 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. Cidofovir shows anti-BK virus activity in a subgroup of transplant recipients. Cidofovir is being investigated as a complementary intralesional therapy against papillomatosis caused by HPV.
For CMV retinitis it is given at a dose of 5 mg/kg once per week for two weeks and than 5 mg every two weeks.
Cidofovir is only available as an intravenous formulation. Cidofovir is to be administered with probenecid which decreases side effects to the kidney. Probenecid mitigates nephrotoxicity by inhibiting organic anion transport of the proximal tubule epithelial cells of the kidney. In addition, hydration such as 1 liter of normal saline is recommended in conjunction with each dose.
Whereas uncommon side effects include: anaemia and elevated liver enzymes and rare side effects include: tachycardia and Fanconi syndrome. Probenecid (a uricosuric drug) and intravenous saline should always be administered with each cidofovir infusion to prevent this nephrotoxicity.
Hypersensitivity to cidofovir or probenecid (as probenecid needs to be given concurrently to avoid nephrotoxicity).
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. 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.
Mechanism of action
Its active metabolite, cidofovir diphosphate, inhibits viral replication by selectively inhibiting viral DNA polymerases. It also inhibits human polymerases but this action is 8-600 times weaker than its actions on viral DNA polymerases. It also incorporates itself into viral DNA hence inhibiting viral DNA synthesis during reproduction.
It possesses in vitro activity against the following viruses:
- Human herpesviruses
- Human poxviruses (including the smallpox virus)
- Human papillomavirus
Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by Antonín Holý, and developed by Gilead Sciences and is marketed with the brand name "Vistide" by Gilead in the USA, and by Pfizer elsewhere.
- Brincidofovir, a prodrug of cidofovir that can be taken by mouth
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