Renal impairment is the major toxicity of cidofovir. Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with as few as 1 or 2 doses of cidofovir. To reduce possible nephrotoxicity, IV prehydration with normal saline and administration of probenecid must be used with each cidofovir infusion. Renal function (serum creatinine and urine protein) must be monitored within 48 hours prior to each dose of cidofovir and the dose of cidofovir modified for changes in renal function as appropriate. Cidofovir is contraindicated in patients who are receiving other nephrotoxic agents.
Neutropenia has been observed in association with cidofovir treatment. Therefore, neutrophil counts should be monitored during cidofovir therapy.
Cidofovir is indicated only for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS).
In animal studies, cidofovir was carcinogenic, teratogenic and caused hypospermia.
Note: To minimize the likelihood of nephrotoxicity, unless otherwise indicated, premedicate with probenecid 2 g 3 hours prior to the cidofovir dose, then 1 g 2 hours and 8 hours after completion of the infusion. Patients should also receive 1 L of NS IV infused over 1 to 2 hours immediately prior to each cidofovir infusion. If tolerated, a second liter may be administered over 1 to 3 hours at the start of cidofovir infusion or immediately following infusion.
Adenovirus infection (treatment of disseminated, severe, or progressive disease [adjunctive agent] or preemptive therapy in hematopoietic cell transplant recipients ) (off-label use): IV: 5 mg/kg/dose once weekly or 5 mg/kg once weekly for 2 doses then 5 mg/kg once every 2 weeks or 1 mg/kg/dose 3 times weekly; with concomitant probenecid (Ref).
BK virus infection (adjunctive agent) (off-label use):
Hemorrhagic cystitis, hematopoietic cell transplant recipients: Limited data available:
IV: 3 to 5 mg/kg/dose every 1 to 2 weeks with concomitant probenecid or 0.5 to 1.5 mg/kg/dose 1 to 3 times weekly without probenecid (Ref).
Intravesicular: 5 mg/kg/dose (in 60 mL NS) instilled into bladder once weekly; retain for ≥1 hour (Ref).
Viremia or nephropathy, kidney transplant recipients: Limited data available: IV: 0.25 to 1 mg/kg/dose every 1 to 3 weeks without probenecid (Ref).
Cytomegalovirus (eg, treatment of invasive disease including retinitis and preemptive therapy in hematopoietic cell recipients) (alternative agent): IV:
Induction: 5 mg/kg/dose once weekly for 2 consecutive weeks, with concomitant probenecid (Ref).
Maintenance: 5 mg/kg/dose once every 2 weeks with concomitant probenecid (Ref).
Herpes simplex virus infection, acyclovir-resistant (off-label use):
Topical (off-label route): Mucocutaneous infections: Apply cidofovir 1% gel (extemporaneously prepared by a compounding pharmacy) once daily (Ref). Duration of therapy: 5 days; observe for 10 days following treatment; therapy may be repeated if necessary for up to 6 repetitive cycles (Ref). A prolonged duration of 21 to 28 days or longer may be required for patients with HIV (Ref).
Nonvariola orthopoxvirus infection (eg, mpox [monkeypox]) (alternative agent) (off-label use): Note: Reserve use for patients with or at risk for severe disease. Use in combination with tecovirimat; only use as monotherapy in patients who have a contraindication to tecovirimat use (Ref).
IV: Limited data available: 5 mg/kg once weekly for 2 doses, with concomitant probenecid (Ref).
Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.
Preexisting renal impairment: Serum creatinine >1.5 mg/dL, CrCl ≤55 mL/minute, or urine protein ≥100 mg/dL (≥2+ proteinuria): Use is contraindicated.
Changes in renal function during therapy:
Serum creatinine increases by 0.3 to 0.4 mg/dL: Reduce dose to 3 mg/kg.
Serum creatinine increases ≥0.5 mg/dL or development of ≥3+ proteinuria: Discontinue therapy.
Alternate dosing (Ref):
Note: Given significant risk of nephrotoxicity, avoid use in renal impairment (CrCl ≤55 mL/minute) unless benefit outweighs the risk. Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes. Adjustment based on 5 mg/kg/dose. Induction doses should be given once weekly and maintenance doses every other week.
CrCl ≥1.3 mL/minute/kg: 5 mg/kg/dose with concomitant probenecid.
CrCl 1 to 1.2 mL/minute/kg: 4 mg/kg/dose with concomitant probenecid.
CrCl 0.8 to 0.9 mL/minute/kg: 3 mg/kg/dose with concomitant probenecid.
CrCl 0.7 mL/minute/kg: 2.5 mg/kg/dose with concomitant probenecid.
CrCl 0.5 to 0.6 mL/minute/kg: 2 mg/kg/dose with concomitant probenecid.
CrCl 0.4 mL/minute/kg: 1.5 mg/kg/dose with concomitant probenecid.
CrCl 0.2 to 0.3 mL/minute/kg: 1 mg/kg/dose with concomitant probenecid.
CrCl 0.1 mL/minute/kg: 0.5 mg/kg/dose with concomitant probenecid.
Hemodialysis: Dialyzable (~50%): Administer standard induction or maintenance dose 2 hours before hemodialysis without probenecid.
Peritoneal dialysis: Dialyzable (minimal): 0.5 mg/kg/dose without probenecid.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
(For additional information see "Cidofovir: Pediatric drug information")
Note: Route of administration varies (ie, IV, intravesicular, intralesional, topical); use caution to ensure dosing corresponds to appropriate route. Administration of cidofovir should be accompanied by concomitant oral probenecid and IV normal saline hydration, except in cases where lower doses are used and the site of infection is in the kidney or bladder; various regimens have been reported (Ref).
Adjunctive therapies: Infants, Children, and Adolescents:
Hydration: IV (various regimens reported): 10 to 20 mL/kg of sodium chloride 0.9% (maximum: 1,000 mL) administered for 1 hour before cidofovir infusion and 10 to 20 mL/kg of sodium chloride 0.9% (maximum: 1,000 mL) over 1 hour during cidofovir infusion, followed by 2 hours of maintenance fluids or 5 mL/kg/hour of sodium chloride 0.9% from 3 hours before cidofovir until 3 hours after or increase the maintenance fluid infusion rate to 3 times the maintenance rate for 1 hour before cidofovir infusion and continuing until 1 hour after, then decrease to 2 times the maintenance fluid rate for the subsequent 2 hours.
Probenecid: Oral: 25 to 40 mg/kg/dose (maximum dose: 2,000 mg) administered 3 hours before cidofovir infusion and 10 to 20 mg/kg/dose (maximum dose: 1,000 mg) at 2 to 3 hours and 8 to 9 hours after cidofovir infusion or 1,000 or 1,250 mg/m2/dose administered 3 hours prior to cidofovir, followed by 500 to 1,250 mg/m2/dose 1 to 3 hours and 8 hours after completion.
Adenovirus infection (treatment or preemptive therapy): Limited data available; optimal dose unknown; specific regimens may vary; consult institutional protocols. Note: Typically reserved for patients with disseminated, severe, or progressive disease or as preemptive therapy in hematopoietic cell transplant recipients (Ref).
Infants, Children, and Adolescents: IV: 5 mg/kg/dose once weekly or 5 mg/kg/dose once weekly for 2 doses then 5 mg/kg/dose every 2 weeks or 1 mg/kg/dose 3 times weekly; use with concomitant probenecid and hydration. Treatment duration is patient-specific and depends on various factors, including symptom resolution, immune recovery, and follow-up adenoviral testing (Ref).
BK virus infection; allograft nephropathy in kidney transplant recipients (adjunct to reduction of immune suppression [if appropriate]): Limited data available:
Children and Adolescents: IV: 0.25 to 1 mg/kg/dose every 1 to 3 weeks without probenecid. Pediatric case series report use every 2 to 3 weeks with a most common starting dose of 0.25 mg/kg/dose (Ref).
BK virus infection; hemorrhagic cystitis in hematopoietic cell transplant recipients: Limited data available; optimal dose unknown:
IV: Infants, Children, and Adolescents: 3 to 5 mg/kg/dose every 1 to 2 weeks with concomitant probenecid or 0.5 to 1.5 mg/kg/dose once weekly without probenecid; described treatment duration varies and is dependent on clinical response and/or viral clearance (Ref).
Intravesicular: Children ≥5 years and Adolescents: 5 mg/kg/dose (in 50 to 100 mL of NS) instilled into bladder once weekly; retain for ≥1 hour (Ref).
Cytomegalovirus (CMV) infection; treatment or preemptive therapy in immunocompromised patients (alternative agent):
Infants, Children, and Adolescents: IV: 5 mg/kg/dose once weekly for 2 consecutive weeks followed by 5 mg/kg/dose once every 2 weeks, in combination with probenecid. Duration depends on patient response and degree of immunosuppression (Ref).
Note: In patients who are HIV exposed/infected, continue chronic maintenance therapy/secondary prophylaxis (with ganciclovir, valganciclovir, or foscarnet as appropriate) until patient has been receiving antiretroviral therapy for ≥6 months and achieves age-specific CD4 cell count targets for ≥6 months duration (age <6 years: CD4 percentage ≥15%; age ≥6 years: >100 cells/mm3 (Ref).
Herpes simplex virus infection, mucocutaneous, acyclovir-resistant (alternative agent): Very limited data available:
IV: Children and Adolescents: 5 mg/kg/dose once weekly for 3 weeks, then 5 mg/kg/dose every 1 to 2 weeks if indicated; use in combination with probenecid. Duration dependent on clinical response (Ref).
Topical: Adolescents: Apply cidofovir 1% gel (extemporaneously prepared by a compounding pharmacy) 1 to 4 times daily (Ref). Duration is based on clinical response; prolonged duration of 21 to 28 days or longer may be required for patients with HIV (Ref).
Respiratory papillomatosis, recurrent (adjunctive therapy): Limited data available; treatment protocols variable:
Children and Adolescents: Intralesional: Dosage, volume, and number of injections per treatment variable based on extent of disease and size of airway: Commonly reported as 0.1 to 4 mL per treatment session injected intralesionally using a 5 mg/mL solution every 2 to 6 weeks. Concentrations reported in the literature vary from 2.5 mg/mL to 10 mg/mL; recommended volumes are ≤2 mL for children and ≤4 mL for adolescents; larger volumes have been reported. Maximum dose per session: 3 mg/kg/dose. Longer intervals between doses have also been reported (eg, every 3 to 4 months or as needed) based upon extent and recurrence of disease. Continue therapy until complete response; reported durations variable; a trial of 5 treatments is recommended (Ref).
Altered kidney function: Infants, Children, and Adolescents:
Adenovirus infection: Limited data available; specific protocols vary (Ref). Based on a usual dose of 5 mg/kg/dose once weekly:
CrCl <90 mL/minute/1.73 m2, Scr >1.5 mg/dL, CrCl <0.3 mL/minute/kg, or >2+ proteinuria: IV: Reduce dose to 0.5 to 1 mg/kg/dose 3 times weekly on alternate days for 2 weeks; may then decrease to 0.5 to 1 mg/kg/dose every other week.
Other uses: There are no pediatric-specific recommendations for other uses; based on experience with other indications and in adult patients, dosing adjustment suggested.
Hemodialysis: High flux hemodialysis removes ~50% to 75% based on adult data (Ref). In pediatric solid organ transplant recipients with adenovirus, it has been recommended to administer dose ≥1 hour after and/or ≥4 hours before hemodialysis to allow for intracellular cidofovir distribution (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Endocrine & metabolic: Decreased serum bicarbonate
Hematologic & oncologic: Neutropenia
Ophthalmic: Hypotony of eye (can be severe: Intraocular pressure of 0 to 1 mm Hg), iritis, uveitis
Renal: Decreased creatinine clearance, increased serum creatinine, nephrotoxicity
1% to 10%:
Endocrine & metabolic: Fanconi syndrome
Gastrointestinal: Nausea, vomiting
Respiratory: Dyspnea, pneumonia
Frequency not defined:
Renal: Acute kidney injury
Endocrine & metabolic: Metabolic acidosis
Hepatic: Hepatic insufficiency
Hypersensitivity to cidofovir or any component of the formulation; history of clinically severe hypersensitivity to probenecid or other sulfa-containing medications; serum creatinine >1.5 mg/dL; CrCl ≤55 mL/minute; urine protein ≥100 mg/dL (≥2+ proteinuria); use with or within 7 days of nephrotoxic agents; direct intraocular injection
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Carcinogenic/teratogenic: [US Boxed Warning]: Possibly carcinogenic and teratogenic based on animal data. May cause hypospermia.
• Metabolic acidosis: Monitor for signs of metabolic acidosis; decreased sodium bicarbonate with proximal tubule injury and renal wasting syndrome (including Fanconi syndrome), as well as metabolic acidosis with hepatic impairment and pancreatitis (including some fatal cases) have been reported.
• Nephrotoxicity: [US Boxed Warning]: Acute renal failure resulting in dialysis and/or contributing to death has occurred with as few as 1 or 2 doses of cidofovir. Renal function (serum creatinine and urine protein) must be monitored within 48 hours prior to each dose of cidofovir and the dose of cidofovir modified as appropriate. Administration must be accompanied by oral probenecid and intravenous saline prehydration.
• Neutropenia: [US Boxed Warning]: Neutropenia has been reported; monitor neutrophil counts during therapy.
• Ocular complications: Decreased intraocular pressure, sometimes associated with decreased visual acuity, uveitis, or iritis may occur; monitor intraocular pressure for and signs of iritis/uveitis during therapy. If uveitis or iritis occurs, consider treatment with topical corticosteroids with or without topical cycloplegic agents.
• Renal impairment: Contraindicated in patients with a baseline serum creatinine >1.5 mg/dL, CrCl ≤55 mL/minute, or urine protein ≥100 mg/dL (≥2+ proteinuria); dosage adjustment or discontinuation of therapy may be required for changes in renal function during treatment.
• Administration: For intravenous use only, not for direct intraocular injection; iritis, ocular hypotony, and permanent impairment of vision may occur.
• Appropriate use: [US Boxed Warning]: Indicated only for CMV retinitis treatment in patients with AIDS.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Generic: 75 mg/mL (5 mL)
Solution (Cidofovir Intravenous)
75 mg/mL (per mL): $177.60 - $237.29
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Generic: 75 mg/mL (5 mL)
IV: For IV infusion only. Infuse over 1 hour. Administer with concomitant probenecid. Hydrate with 1 L of NS IV over 1 to 2 hours immediately prior to cidofovir infusion. If tolerated, a second liter may be administered over a 1- to 3-hour period at the start of or immediately following cidofovir infusion.
Topical: Off-label route: An extemporaneously prepared gel may be prepared by a compounding pharmacy and applied topically for mucocutaneous infections (Ref).
Intravesicular: Off-label route: Instill into bladder via Foley catheter over 15 minutes. If indwelling catheter is in place, clamp catheter for at least 1 hour after instillation. Remove Foley catheter after drug administration for patients who do not require indwelling catheter (Ref).
IV: Administer by IV infusion over 1 hour.
Intralesional (recurrent respiratory papillomatosis): Administer in appropriate setting by experienced surgeon, typically following surgical intervention/lesion debulking. Volume and number of injections per treatment variable, based on extent of disease and size of airway; recommended volumes are ≤2 mL for children and ≤4 mL for adolescents; larger volumes have been reported (Ref).
Intravesicular (hemorrhagic cystitis): Instill into bladder via Foley catheter slowly (eg, over 15 minutes). If indwelling catheter is in place, clamp catheter for ≥1 hour after instillation. For patients who do not require indwelling catheter, Foley catheter can be removed after drug administration (Ref).
Topical (mucocutaneous herpes simplex virus): Apply topically to affected area (Ref).
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) for preparation. Double gloving, a gown, and (if dosage form allows) CSTDs are required during administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
Cytomegalovirus retinitis: Treatment of cytomegalovirus (CMV) retinitis in patients with AIDS.
Limitations of use: Safety and efficacy have not been established for treatment of other CMV infections (eg, pneumonitis, gastroenteritis), congenital or neonatal CMV disease, or CMV disease in non-HIV infected individuals.
Adenovirus infection; BK virus infection; Cytomegalovirus, preemptive therapy in hematopoietic cell recipients; Herpes simplex virus infection, acyclovir-resistant; Nonvariola orthopoxvirus infection (eg, mpox [monkeypox])
Substrate of OAT1/3; Inhibits MRP2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Tenofovir Products: Cidofovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Risk C: Monitor therapy
In animal studies, cidofovir caused hypospermia.
Patients who could become pregnant should use effective contraception during therapy and for 1 month after the last cidofovir dose. Males should use a barrier contraceptive during therapy and for 3 months following the last dose of cidofovir.
Cidofovir was teratogenic in animal reproduction studies.
The indications for treating CMV retinitis during pregnancy are the same as in nonpregnant HIV infected woman; however, systemic therapy should be avoided during the first trimester when possible. When therapy is needed to treat maternal infection, use of cidofovir is not recommended (HHS [Adult OI 2021]). Cidofovir is not recommended as an alternative therapy to treat patients with mpox (monkeypox) during the first trimester (CDC 2022).
It is not known if cidofovir is present in breast milk.
Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended. In addition, HIV-infected mothers are discouraged from breastfeeding to decrease the potential transmission of HIV. Cidofovir is not recommended as an alternative therapy to treat lactating patients with mpox (monkeypox) (CDC 2022).
Serum creatinine and urine protein (at baseline and within 48 hours of each dose), WBC with differential (prior to each dose); intraocular pressure and visual acuity, signs and symptoms of uveitis/iritis; metabolic acidosis.
Cidofovir is converted to cidofovir diphosphate (the active intracellular metabolite); cidofovir diphosphate suppresses CMV replication by selective inhibition of viral DNA synthesis. Incorporation of cidofovir diphosphate into growing viral DNA chain results in viral DNA synthesis rate reduction.
The following pharmacokinetic data are based on a combination of cidofovir administered with probenecid unless otherwise specified:
Distribution: Does not cross significantly into cerebrospinal fluid.
Children ≥2 years and Adolescents ≤14 years: 0.591 L/kg (with probenecid) (Caruso Brown 2015).
Adults: 0.41 L/kg (with probenecid); 0.537 L/kg (without probenecid).
Protein binding: <6%.
Metabolism: Minimal; phosphorylation occurs intracellularly to the active metabolite cidofovir diphosphate.
Half-life elimination, plasma: Mean range: 2.4 to 3.2 hours (Cundy 1995; Lalezari 1995); intracellular elimination half-lives of metabolites are longer (range: 24 to 87 hours) (Lea 1996).
Excretion: Urine (70% to 85% as unchanged drug).
Renal clearance without probenecid: 150±26.9 mL/minute/1.73 m2.
Renal clearance with probenecid: 98.6±27.9 mL/minute/1.73 m2.
Altered kidney function: Clearance decreases proportionally with CrCl.
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