Usage
Cidofovir is prescribed for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). It is also used for the treatment of acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infections in immunocompromised individuals. Cidofovir is classified as an antiviral agent. It works by inhibiting viral DNA polymerase, thereby suppressing viral replication.
Alternate Names
Cidofovir is also known by its brand name, Vistide.
How It Works
Pharmacodynamics: Cidofovir is actively transported into cells where it is converted to cidofovir diphosphate. Cidofovir diphosphate competitively inhibits viral DNA polymerase, resulting in the termination of viral DNA chain elongation and ultimately suppressing viral replication.
Pharmacokinetics: Cidofovir is administered intravenously and has a long intracellular half-life. It is primarily excreted unchanged in the urine. Probenecid, an inhibitor of renal tubular secretion, is co-administered with cidofovir to decrease renal clearance and enhance antiviral activity. Cidofovir exhibits dose-independent kinetics. Protein binding is low (10% or less).
Mode of Action: Cidofovir acts as a nucleotide analog that inhibits viral DNA polymerase, thus preventing viral DNA synthesis and replication. It is considered a DNA polymerase inhibitor. Cidofovir’s antiviral activity is mediated by its active metabolite, cidofovir diphosphate, directly binding and inhibiting viral DNA polymerase. This terminates DNA chain elongation and subsequently suppresses viral replication.
Elimination Pathways: Cidofovir is primarily eliminated through renal excretion.
Dosage
Standard Dosage
Adults:
Induction: 5 mg/kg body weight, administered as an intravenous infusion over 1 hour, once weekly for 2 consecutive weeks.
Maintenance: 5 mg/kg body weight, administered as an intravenous infusion over 1 hour, once every 2 weeks.
Probenecid is administered orally with each dose of cidofovir: 2 g 3 hours before the cidofovir infusion, followed by 1 g at 2 hours and 1 g at 8 hours after the completion of the cidofovir infusion (total of 4 g probenecid).
Intravenous hydration with normal saline (0.9% NaCl) is essential: At least 1 L infused over 1-2 hours before each cidofovir dose. A second liter may be administered if tolerated, either starting with the cidofovir infusion or immediately following.
Children:
Limited safety and efficacy data are available for pediatric patients. The recommended dose in some contexts is 5 mg/kg IV every other week. This is not FDA-approved and should be considered carefully by a specialist.
Special Cases:
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Elderly Patients: Use with caution due to age-related decline in renal function. Careful monitoring of renal function is necessary.
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Patients with Renal Impairment: Cidofovir is contraindicated in patients with serum creatinine >1.5 mg/dL, creatinine clearance ≤55 mL/min, or urine protein ≥100 mg/dL (≥2+ proteinuria). Dosage reduction or discontinuation may be necessary if renal function declines during treatment.
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Patients with Hepatic Dysfunction: No specific dosage adjustment is provided, but caution should be exercised.
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Patients with Comorbid Conditions: Careful consideration is required for patients with concomitant medical conditions, especially those affecting renal function.
Clinical Use Cases
Cidofovir is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is specific to CMV retinitis in AIDS and acyclovir-resistant mucocutaneous HSV.
Dosage Adjustments
Dosage adjustments may be required based on changes in renal function during treatment. If serum creatinine increases 0.3–0.4 mg/dL above baseline, the maintenance dose should be reduced to 3 mg/kg. If the increase is ≥0.5 mg/dL or proteinuria is ≥3+, cidofovir should be discontinued.
Side Effects
Common Side Effects
Nausea, vomiting, fever, chills, headache, fatigue, proteinuria, decreased intraocular pressure, hair loss.
Rare but Serious Side Effects
Nephrotoxicity (including renal failure), neutropenia, metabolic acidosis, ocular hypotony with uveitis or iritis, decreased visual acuity, hypersensitivity reactions.
Long-Term Effects
Potential long-term effects include infertility and carcinogenicity (based on animal studies).
Adverse Drug Reactions (ADR)
Nephrotoxicity is a clinically significant ADR requiring careful monitoring and dose adjustment. Neutropenia requires monitoring of neutrophil counts. Ocular complications, such as decreased intraocular pressure, uveitis, and iritis, warrant ophthalmologic assessment.
Contraindications
Pre-existing renal impairment (serum creatinine >1.5 mg/dL, creatinine clearance ≤55 mL/min, or urine protein ≥100 mg/dL), concomitant use of other nephrotoxic agents, hypersensitivity to cidofovir or probenecid, direct intraocular injection, and clinically severe hypersensitivity to sulfa-containing drugs are contraindications to cidofovir.
Drug Interactions
Cidofovir interacts with other nephrotoxic drugs, potentially increasing the risk of nephrotoxicity. Probenecid is co-administered to decrease cidofovir’s renal clearance, but can also alter the pharmacokinetics of other drugs. Concomitant use with zidovudine may require a zidovudine dose reduction. Interactions with other antiviral medications, certain antibiotics, and immunosuppressants should be carefully evaluated. Medications that are renally cleared may accumulate in the presence of cidofovir.
Pregnancy and Breastfeeding
Cidofovir is classified as Pregnancy Category C by the US FDA and D by the Australian TGA. It should be avoided during pregnancy unless the benefits clearly outweigh the risks. Effective contraception is recommended during treatment and for at least 30 days after the last dose for females and 90 days after the last dose for males. Cidofovir is not recommended during breastfeeding. It is unknown if it is excreted in human milk, but potential serious adverse reactions in the infant are a concern.
Drug Profile Summary
- Mechanism of Action: Inhibits viral DNA polymerase.
- Side Effects: Nephrotoxicity, neutropenia, ocular hypotony, proteinuria, nausea, vomiting.
- Contraindications: Renal impairment, concomitant nephrotoxic drugs, hypersensitivity to cidofovir or probenecid.
- Drug Interactions: Probenecid, other nephrotoxic agents, zidovudine.
- Pregnancy & Breastfeeding: Avoid during pregnancy unless benefits outweigh risks; not recommended while breastfeeding.
- Dosage: 5 mg/kg IV once weekly for 2 weeks (induction), then 5 mg/kg IV every 2 weeks (maintenance). Adjust dosage for renal impairment.
- Monitoring Parameters: Renal function (serum creatinine, urine protein), neutrophil count, intraocular pressure, visual acuity.
Popular Combinations
Cidofovir is typically administered in combination with probenecid and intravenous saline hydration. It’s not typically combined with other antiviral agents in a regimen for CMV retinitis.
Precautions
Assess renal function before and during treatment. Monitor for neutropenia. Administer with probenecid and IV saline hydration. Pregnant women should use effective contraception, and breastfeeding is not recommended. Caution should be exercised in elderly patients due to age-related decrease in renal function.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cidofovir?
A: Adults: Induction: 5 mg/kg IV over 1 hour once weekly for 2 weeks. Maintenance: 5 mg/kg IV over 1 hour every 2 weeks. Children: Safety and efficacy not established in children. There is no FDA-approved pediatric regimen. A limited evidence based dose of 5 mg/kg IV every other week can be considered in some situations. Renal impairment necessitates dosage adjustments or contraindicates use.
Q2: What are the major side effects of Cidofovir?
A: Nephrotoxicity is the primary dose-limiting side effect. Other side effects include neutropenia, proteinuria, ocular complications (decreased intraocular pressure, uveitis), nausea, and vomiting.
Q3: What is the mechanism of action of Cidofovir?
A: Cidofovir inhibits viral DNA polymerase, thus blocking viral DNA synthesis and replication.
Q4: What are the contraindications for Cidofovir use?
A: Renal impairment, concomitant use of nephrotoxic agents, hypersensitivity to cidofovir or probenecid, direct intraocular injection, and clinically severe hypersensitivity to sulfa-containing drugs.
Q5: Can Cidofovir be used during pregnancy or breastfeeding?
A: Cidofovir should be avoided during pregnancy unless the benefits clearly outweigh the risks (Pregnancy Category C). It is not recommended for use during breastfeeding.
Q6: What is the role of Probenecid in Cidofovir therapy?
A: Probenecid is co-administered with cidofovir to reduce renal clearance of cidofovir, thereby increasing its serum levels and enhancing antiviral activity.
Q7: How is Cidofovir administered?
A: Cidofovir is administered as an intravenous infusion over 1 hour, along with mandatory IV hydration.
Q8: What monitoring is required during Cidofovir treatment?
A: Renal function (serum creatinine, urine protein), complete blood count (with differential) for neutropenia, intraocular pressure, and visual acuity should be monitored before each dose.
Q9: Why is hydration important during Cidofovir administration?
A: Pre-hydration with intravenous saline is essential to reduce the risk of nephrotoxicity.
Q10: Is there a potential for drug interactions with Cidofovir?
A: Yes, cidofovir has a potential for drug interactions, especially with other nephrotoxic drugs, probenecid, and zidovudine. It is crucial to review a patient’s complete medication list for potential interactions before initiating therapy.
