Cidofovir (cidofovir)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Cidofovir, an acyclic nucleotide analog (acyclic nucleoside phosphonate), is an antiviral agent active against herpesviruses and certain other viruses.
Cidofovir, an acyclic nucleotide analog of cytosine (acyclic nucleoside phosphonate), is an antiviral agent.
Cidofovir is a prodrug and exhibits no antiviral activity until converted intracellularly to the active metabolite, cidofovir diphosphate. Unlike other nucleoside and nucleotide antivirals that require conversion within viral cells to an active metabolite (e.g., acyclovir, ganciclovir), the presence of the phosphonate group in cidofovir is believed to account for the drug's ability to become phosphorylated by cellular (host cell) enzymes to its active intracellular metabolite without initial virus-dependent phosphorylation by viral nucleoside kinases.
Cidofovir is converted intracellularly by pyrimidine nucleoside monophosphate kinase to cidofovir monophosphate, which is further converted to the diphosphate and cidofovir phosphate-choline via other cellular enzymes. Cidofovir diphosphate is a viral DNA polymerase inhibitor and exerts its antiviral effects by interfering with DNA synthesis and inhibiting viral replication. Cidofovir diphosphate stops replication of viral DNA by competitive inhibition of viral DNA polymerase (an enzyme encoded by CMV UL54 gene), incorporation and termination of the growing viral DNA chain, and inactivation of the viral DNA polymerase.
The inhibitory activity of cidofovir diphosphate is highly selective because of its greater affinity for viral DNA polymerases than for human DNA polymerases.
The pharmacokinetics of IV cidofovir have been evaluated in patients with human immunodeficiency virus (HIV) infection when the drug was given with or without a regimen of oral probenecid. In patients with normal renal function, approximately 80-100% of a dose of IV cidofovir (without oral probenecid) was recovered unchanged in urine within 24 hours. Renal clearance of cidofovir (without oral probenecid) is greater than creatinine clearance, indicating that renal tubular secretion contributes to cidofovir elimination.
Following IV administration of cidofovir (with oral probenecid regimen), approximately 70-85% of the dose was excreted unchanged in urine within 24 hours. Renal clearance of cidofovir (with oral probenecid regimen) is consistent with creatinine clearance, indicating that probenecid blocks renal tubular secretion of cidofovir. This effect of probenecid on the pharmacokinetics of cidofovir is used to therapeutic advantage, and a regimen of oral probenecid must be given with each dose of cidofovir.
In vitro studies indicate that cidofovir is less than 6% bound to plasma or serum proteins. In one patient who received a single cidofovir dose of 5 mg/kg by IV infusion over 1 hour (with IV prehydration and concomitant oral probenecid regimen), cidofovir serum concentrations were 8.7 mcg/mL at 15 minutes after completion of the infusion and the drug was undetectable in CSF.
USES: This drug is used with probenecid to treat a certain viral eye infection (retinitis due to cytomegalovirus-CMV) in people with AIDS. It lowers your risk of blindness and other vision problems. Cidofovir belongs to a class of drugs known as antivirals.
It works by stopping the growth of the virus. Cidofovir is not a cure for CMV retinitis, and your disease may still worsen during and after treatment.
Generic name: cidofovir
Pronunciation: (sye-DOH-foh-veer)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Cidofovir
Indications
The following indications are listed for Cidofovir:
- Cmv Retinitis In Aids Patient
Also known as: Cytomegalovirus Retinitis In Aids.
Dosing
Cidofovir is commercially available as the dihydrate; dosage is expressed in terms of anhydrous drug.
Cidofovir is administered by slow IV infusion using a controlled-infusion device (e.g., pump).
Although cidofovir has been administered by intravitreal injection+, a preparation specifically for intravitreal administration is not commercially available in the US and the manufacturer states that direct intraocular injection of the currently available IV preparation of cidofovir (even if diluted) is contraindicated since such administration has been associated with iritis, ocular hypotony, and permanent visual impairment.
Cidofovir has been administered topically+ as a gel or cream for the management of certain mucocutaneous viral infections (e.g., acyclovir-resistant herpes simplex virus (HSV) infections). Although topical preparations of cidofovir are not commercially available in the US, a topical gel containing 1% cidofovir has been prepared extemporaneously using the IV preparation of cidofovir.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Initiation in patients with serum creatinine >1.5 mg/dL, calculated creatinine clearance <=55 mL/minute, or urine protein concentration >=100 mg/dL (equivalent to >=2+ proteinuria).
*Concomitant use with other nephrotoxic drugs. Such agents must be discontinued at least 7 days prior to starting therapy with cidofovir injection.
*Hypersensitivity to cidofovir.
*History of clinically severe hypersensitivity to probenecid or other sulfa-containing drugs.
*Direct intraocular injection of the IV preparation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 15% or more of patients receiving cidofovir (with concomitant probenecid regimen) include nephrotoxicity (proteinuria, elevated serum creatinine), nausea and/or vomiting, fever, neutropenia, asthenia, headache, rash, infection, alopecia, diarrhea, pain, anemia, decreased IOP, anorexia, dyspnea, chills, increased cough, oral moniliasis, and decreased serum bicarbonate.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of cidofovir have not been established in pediatric patients younger than 18 years of age.
Because of the risks of potential long-term carcinogenic and reproductive toxicity, cidofovir should be used with extreme caution in children+ with AIDS. The manufacturer states that the drug should be used in children only after careful evaluation and only when potential benefits outweigh risks.
Some experts state that cidofovir has not been studied in children with CMV disease, but can be considered for the management of CMV retinitis in HIV-infected children+ if other options cannot be used.
There are no adequate and well-controlled studies to date using cidofovir in pregnant women. Cidofovir should be used during pregnancy only if potential benefits justify risks to the fetus.
In animal studies, embryotoxicity (reduced fetal body weights) and maternal toxicity were observed in rats and rabbits receiving IV cidofovir at dosages of 1.5 and 1 mg/kg daily, respectively, during organogenesis. In rabbits receiving IV cidofovir in a dosage of 1 mg/kg daily, maternal toxicity and an increased incidence of fetal external, soft tissue, and skeletal anomalies (meningocele, short snout, and short maxillary bones) were observed.
Women of childbearing potential should be informed that cidofovir is embryotoxic in animals and should be advised to use an effective method of contraception during and for at least 1 month after cidofovir therapy.
Men should be advised to use a reliable method of barrier contraception during and for at least 3 months after cidofovir therapy.
It is not known whether cidofovir is distributed into human milk.
Since there is a potential for adverse effects in nursing infants and because carcinogenicity has been shown in animal studies, cidofovir should not be used in breast-feeding women.
Because of the risk of adverse effects in the infant and the risk of HIV transmission, the manufacturer states that HIV-infected women should not breast-feed infants.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
Dosage of cidofovir for geriatric patients should be selected with caution because of age-related decreases in renal function.
Safety and efficacy of cidofovir have not been evaluated in geriatric patients older than 60 years of age.
Because geriatric patients frequently have reduced glomerular filtration, particular attention should be paid to monitoring renal function prior to and during cidofovir therapy in this age group, and dosage should be modified in response to changes in renal function.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.