Vistide

Nucleoside and Nucleotide DNA Polymerase Inhibitor Antivirals

NOTE: To minimize the potential for renal toxicity, patients must receive oral probenecid and hydration with normal saline concurrently with cidofovir.
Probenecid
Adults: 2 g PO given 3 hours prior to each cidofovir infusion, followed by 1 g PO at 2 and 8 hours following the completion of the cidofovir infusion.
Pediatrics: 25 to 40 mg/kg/dose (Max: 2 g/dose) PO given 3 hours prior to each cidofovir infusion, followed by 10 to 20 mg/kg/dose (Max: 1 g/dose) PO at 2 and 8 hours following the completion of the cidofovir infusion.
Hydration
Adults: Infuse 1 L of 0.9% Sodium Chloride Injection over 1 to 2 hours immediately prior to cidofovir infusion. Patients who can tolerate the fluid load should receive a second liter over 1 to 3 hours starting with or after the completion of the cidofovir infusion.
Pediatrics: Infuse 20 mL/kg/hour (Max: 1 L) of 0.9% Sodium Chloride Injection over 1 to 2 hours immediately prior to cidofovir infusion and post infusion. IV hydration may also be given at 3 times the maintenance rate initiated 1 hour before and continued until 1 hour after the completion of cidofovir infusion, followed by hydration at 2 times the maintenance rate for an additional 2 hours.
Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Preparation and administration of cidofovir solutions should follow guidelines established for other potentially mutagenic agents, such as chemotherapy agents, including preparation in a Class II laminar flow biological safety cabinet. Personnel preparing and administering this agent should wear protective surgical gloves and closed front surgical-type gowns with knit cuffs.
Eye/face and respiratory protection may be needed during preparation and administration.

Cidofovir is administered via intravenous infusion. Do not administer intraocularly.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Dilution
Dilute each dose in 100 mL 0.9% Sodium Chloride for injection.
Use diluted solutions of cidofovir within 24 hours of preparation. These solutions may be stored at room temperature or under refrigeration.
 
Intravenous infusion
Infuse over 1 hour.

proteinuria / Delayed / 50.0-88.0
uveitis / Delayed / 11.0-11.0
ocular hypotonia / Delayed / 4.0-4.0
Fanconi syndrome / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
nephrotoxicity / Delayed / Incidence not known
renal tubular necrosis / Delayed / Incidence not known
thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
retinal detachment / Delayed / Incidence not known
corneal opacification / Delayed / Incidence not known
keratitis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
GI bleeding / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
seizures / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
osteonecrosis / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
cardiomyopathy / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
hyperkalemia / Delayed / Incidence not known
laryngeal edema / Rapid / Incidence not known
pneumothorax / Early / Incidence not known
teratogenesis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
new primary malignancy / Delayed / Incidence not known

neutropenia / Delayed / 24.0-43.0
anemia / Delayed / 24.0-24.0
dyspnea / Early / 8.0-23.0
candidiasis / Delayed / 18.0-18.0
iritis / Delayed / 11.0-11.0
phosphaturia / Early / Incidence not known
metabolic acidosis / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
glycosuria / Early / Incidence not known
dysuria / Early / Incidence not known
nephrolithiasis / Delayed / Incidence not known
urinary retention / Early / Incidence not known
urinary incontinence / Early / Incidence not known
hypophosphatemia / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
splenomegaly / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
cataracts / Delayed / Incidence not known
conjunctivitis / Delayed / Incidence not known
amblyopia / Delayed / Incidence not known
dysphagia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
melena / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
fecal incontinence / Early / Incidence not known
colitis / Delayed / Incidence not known
constipation / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
proctitis / Delayed / Incidence not known
cholangitis / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known
furunculosis / Delayed / Incidence not known
hyperacusis / Delayed / Incidence not known
confusion / Early / Incidence not known
hyperesthesia / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known
depression / Delayed / Incidence not known
amnesia / Delayed / Incidence not known
myoclonia / Delayed / Incidence not known
delirium / Early / Incidence not known
ataxia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
migraine / Early / Incidence not known
hallucinations / Early / Incidence not known
hypotonia / Delayed / Incidence not known
bone pain / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known
hypertonia / Delayed / Incidence not known
edema / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
hypertension / Early / Incidence not known
peripheral vasodilation / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypotension / Rapid / Incidence not known
peripheral edema / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
hepatomegaly / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hypercalcemia / Delayed / Incidence not known
hyponatremia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
hyperlipidemia / Delayed / Incidence not known
hypokalemia / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known
hemoptysis / Delayed / Incidence not known
hypoxia / Early / Incidence not known
infertility / Delayed / Incidence not known

vomiting / Early / 7.0-69.0
nausea / Early / 7.0-69.0
fever / Early / 14.0-58.0
asthenia / Delayed / 43.0-43.0
rash / Early / 30.0-30.0
headache / Early / 30.0-30.0
infection / Delayed / 12.0-28.0
alopecia / Delayed / 27.0-27.0
diarrhea / Early / 26.0-26.0
anorexia / Delayed / 23.0-23.0
chills / Rapid / 22.0-22.0
cough / Delayed / 19.0-19.0
nocturia / Early / Incidence not known
polyuria / Early / Incidence not known
leukocytosis / Delayed / Incidence not known
ocular pain / Early / Incidence not known
miosis / Early / Incidence not known
diplopia / Early / Incidence not known
xerophthalmia / Early / Incidence not known
abdominal pain / Early / Incidence not known
flatulence / Early / Incidence not known
tongue discoloration / Delayed / Incidence not known
weight gain / Delayed / Incidence not known
dental caries / Delayed / Incidence not known
weight loss / Delayed / Incidence not known
dyspepsia / Early / Incidence not known
gingivitis / Delayed / Incidence not known
xerostomia / Early / Incidence not known
dysgeusia / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
sinusitis / Delayed / Incidence not known
rhinitis / Early / Incidence not known
skin discoloration / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
acne vulgaris / Delayed / Incidence not known
seborrhea / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
tinnitus / Delayed / Incidence not known
otalgia / Early / Incidence not known
malaise / Early / Incidence not known
drowsiness / Early / Incidence not known
dizziness / Early / Incidence not known
insomnia / Early / Incidence not known
tremor / Early / Incidence not known
agitation / Early / Incidence not known
libido increase / Delayed / Incidence not known
vertigo / Early / Incidence not known
paresthesias / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
myalgia / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
back pain / Delayed / Incidence not known
syncope / Early / Incidence not known
pallor / Early / Incidence not known
epistaxis / Delayed / Incidence not known
hiccups / Early / Incidence not known
hyperventilation / Early / Incidence not known
hypothermia / Delayed / Incidence not known

Cidofovir therapy is contraindicated in patients with baseline renal disease, renal impairment, or renal failure defined as a serum creatinine concentration greater than 1.5 mg/dL or calculated creatinine clearance 55 mL/min or less and in those who have at least 2+ proteinuria (urine protein 100 mg/dL or greater). Due to dose-dependent nephrotoxicity, renal function, including serum creatinine and urine protein, must be monitored within 48 hours of each dose of cidofovir and the dose of cidofovir modified for changes in renal function as appropriate. Proteinuria may be an early indication of nephrotoxicity. Intravenous normal saline and probenecid therapy must be given concurrently with cidofovir. In clinical trials, very high concentrations of cidofovir were found in the kidneys, and the transport into proximal tubular cells was faster than efflux into the urine, suggesting active tubular secretion. A high concentration of cidofovir in the kidney is believed to be directly related to renal toxicity, but the actual mechanism is unknown. Probenecid is used to antagonize the active tubular secretion of cidofovir in the proximal tubules. Prior foscarnet therapy has been associated with an increased risk of nephrotoxicity; these patients should be closely monitored. Cidofovir use is contraindicated in patients who are receiving agents with nephrotoxic potential. At least 7 days should pass following the administration of agents with nephrotoxic potential prior to the initiation of therapy with cidofovir. These nephrotoxic drugs include amphotericin B, foscarnet, IV pentamidine, IV aminoglycosides, vancomycin, and NSAIDs.

Cidofovir therapy has been associated with neutropenia. Therefore, neutrophil counts should be monitored during cidofovir therapy.

The manufacturer warns of potential male-mediated teratogenicity as cidofovir causes reduced testes weight and hypospermia in animals. These effects may also occur in humans. Men should also be warned about the potential for infertility. Men should practice barrier contraceptive methods during and for 3 months after treatment with cidofovir.

The manufacturer considers cidofovir to be a potential carcinogen in humans and may cause a new primary malignancy. In animal studies, mammary adenocarcinomas in rats was noted. Women should be warned about the carcinogenic potential of cidofovir and of the limited study of cidofovir in females. Women of childbearing potential should use effective contraception during and for 1 month after treatment with cidofovir. Cidofovir should be used cautiously in children in light of the risk of long-term carcinogenesis and reproductive toxicity.

Vistide

Rx

Antiviral; acyclic phosphonate nucleotide analog; structurally similar to acyclovir; not dependent upon intracellular activation
Used for the treatment of cytomegalovirus (CMV), herpes virus infections, and adenovirus infections
Associated with renal toxicity; use with probenecid and IV hydration to reduce toxicity

5 mg/kg/dose IV once weekly for 2 weeks as an initial therapy. For immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea), give in combination with intravitreal injections of ganciclovir (2 mg/injection) or foscarnet (2.4 mg/injection). Induction therapy should be followed-up with chronic maintenance therapy (secondary prophylaxis). Guidelines suggest cidofovir as second-line induction therapy.

5 mg/kg/dose IV once weekly for 2 weeks as an initial therapy. For immediate sight-threatening lesions (i.e., within 1,500 microns of the fovea), give in combination with intravitreal injections of ganciclovir (2 mg/injection) or foscarnet (2.4 mg/injection). Induction therapy should be followed-up with chronic maintenance therapy (secondary prophylaxis). Guidelines suggest cidofovir as second-line induction therapy.

5 mg/kg/dose IV every other week as an alternative maintenance therapy after treatment of acute infection. Treatment duration depends on the immune status of the patient. For patients who have had a sustained immune response to highly active antiretroviral therapy (i.e., CD4 counts greater than 100 cells/mm3 for 3 to 6 months), have been on CMV treatment for at least 3 to 6 months, and have no active lesions, secondary CMV retinitis prophylaxis may be discontinued after consultation with an ophthalmologist. Maintenance therapy should be restarted if subsequent CD4 counts drop to less than 100 cells/mm3, as relapse occurs most frequently in those patients whose counts decrease to less than 50 cells/mm3 after stopping treatment. However, because relapses may occur at any CD4 count, all patients who have had maintenance CMV therapy discontinued should continue to undergo regular ophthalmologic monitoring (every 3 months) for early detection of CMV relapse (as well as for immune reconstitution uveitis).

5 mg/kg/dose IV every other week as an alternative maintenance therapy after treatment of acute infection. Treatment duration depends on the immune status of the patient. For patients who have had a sustained immune response to highly active antiretroviral therapy (i.e., CD4 counts greater than 100 cells/mm3 for 3 to 6 months), have been on CMV treatment for at least 3 to 6 months, and have no active lesions, secondary CMV retinitis prophylaxis may be discontinued after consultation with an ophthalmologist. Maintenance therapy should be restarted if subsequent CD4 counts drop to less than 100 cells/mm3, as relapse occurs most frequently in those patients whose counts decrease to less than 50 cells/mm3 after stopping treatment. However, because relapses may occur at any CD4 count, all patients who have had maintenance CMV therapy discontinued should continue to undergo regular ophthalmologic monitoring (every 3 months) for early detection of CMV relapse (as well as for immune reconstitution uveitis).

5 mg/kg/dose IV every other week as an alternative maintenance therapy after treatment of acute infection. Discontinuation of secondary prophylaxis may be considered in pediatric patients who have received at least 6 months of highly active antiretroviral therapy with a sustained increase (more than 6 months) in CD4 percentage of at least 15% (pediatric patients younger than 5 years) or CD4 count more than 100 cells/mm3 (children 6 years and older). For retinitis, the decision to discontinue secondary prophylaxis should be made in consultation with an ophthalmologist. Routine follow-up (every 3 to 6 months) with an ophthalmologist is recommended. Restart maintenance therapy if CD4 percentage is less than 15% in pediatric patients younger than 5 years or if CD4 count is less than 100 cells/mm3 in children 6 years and older.

Optimal dosing has not been established and various regimens have been reported based on transplant center-specific protocols. An induction dose of 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by maintenance dose of 5 mg/kg/dose IV every 2 weeks until resolution or viral clearance is commonly used. Other protocols use 5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly until resolution or viral clearance. Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it may be associated with breakthrough CMV and HSV infections and the emergence of antiviral resistance.

Optimal dosing has not been established and various regimens have been reported based on transplant center-specific protocols. An induction dose of 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by a maintenance dose of 5 mg/kg/dose IV every 2 weeks until resolution or viral clearance is commonly used. Other dosing protocols use 5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly until resolution or viral clearance. Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it may be associated with breakthrough CMV and HSV infections and the emergence of antiviral resistance.

In a placebo-controlled trial, 30 patients were treated with cidofovir 1% gel once daily or placebo. Overall 16 of 19 patients had a complete or partial response to cidofovir (9 complete responses) versus only 2 patients in the placebo group after a median of 43 days of treatment. Guidelines suggest cidofovir as an alternative regimen, but provides no further recommendations.

A review of 20 published reports involving 185 patients with adult onset recurrent respiratory papillomatosis (AORRP) and 85 patients under the age of 12 with juvenile onset recurrent respiratory papillomatosis (JORRP) found intralesional cidofovir to be an effective adjuvant therapy. Cidofovir was administered via intralesional injection at a concentration ranging from 2.5 to 15 mg/mL (mean 7.5 mg/mL). The mean number of injections administered per person was 6 (range 2 to 13 doses). The injection frequency ranged from 2 to 8 weeks, with a mean interval between injections of 26 days. The overall efficacy for AORRP was 74% complete response, 23.8% partial response, 0.6% no response, and 1.6% discontinued therapy. For JORRP, the overall efficacy was 56.5% complete response, 31.8% partial response, and 11.7% no response.

A review of 20 published reports involving 185 patients with adult onset recurrent respiratory papillomatosis (AORRP) and 85 patients under the age of 12 with juvenile onset recurrent respiratory papillomatosis (JORRP) found intralesional cidofovir to be an effective adjuvant therapy. Cidofovir was administered via intralesional injection at a concentration ranging from 2.5 to 15 mg/mL (mean 7.5 mg/mL). The mean number of injections administered per person was 6 (range 2 to 13 doses). The injection frequency ranged from 2 to 8 weeks, with a mean interval between injections of 26 days. The overall efficacy for AORRP was 74% complete response, 23.8% partial response, 0.6% no response, and 1.6% discontinued therapy. For JORRP, the overall efficacy was 56.5% complete response, 31.8% partial response, and 11.7% no response.

In case reports, cidofovir gel 1% to 3% used 1 to 2 times per day has led to successful resolution of this condition. In addition, patients treated with cidofovir for CMV retinitis have reported resolution of molluscum contagiosum.

5 mg/kg/dose IV once weekly for at least 21 to 28 days as an alternative.

5 mg/kg/dose IV once weekly for at least 21 to 28 days as an alternative.

NOTE: Topical formulations of cidofovir are not commercially available and must be extemporaneously compounded using the intravenous formulation.

1% topical gel applied to lesions once daily for at least 21 to 28 days as an alternative.[34362] Alternatively, 1% topical gel applied to lesions 2 to 4 times daily for genital infections.

1% topical gel applied to lesions once daily for at least 21 to 28 days as an alternative.[34362] Alternatively, 1% topical gel applied to lesions 2 to 4 times daily for genital infections.

Contact the CDC for IND protocol enrollment and product availability. 5 mg/kg IV as a one time dose infused over 60 minutes. A second dose 1 week later may be considered if clinically indicated.

5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly for 2 to 4 weeks or until viral clearance and/or immune recovery. 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by 5 mg/kg/dose IV every other week until viral clearance and/or immune recovery has also been reported. Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it is insufficient to treat concomitant CMV infection; if concomitant CMV infection is present, the 5 mg/kg once weekly dose is recommended.

5 mg/kg/dose IV once weekly or 1 mg/kg/dose IV 3 times weekly for 2 to 4 weeks or until viral clearance and/or immune recovery. 5 mg/kg/dose IV once weekly for 2 to 3 weeks, followed by 5 mg/kg/dose IV every other week until viral clearance and/or immune recovery has also been reported. Although the 1 mg/kg 3 times weekly dose may cause less renal toxicity, it is insufficient to treat concomitant CMV infection; if concomitant CMV infection is present, the 5 mg/kg once weekly dose is recommended.

5 mg/kg/dose IV once weekly for 2 weeks, then 5 mg/kg/dose IV every 2 weeks. For people with HIV and severe disease, guidelines recommend considering 5 mg/kg/dose IV once weekly for 2 doses as an adjunct to treatment with tecovirimat. Consult with the CDC or local health department before initiating combination therapy. Additionally, people with HIV not currently taking antiretroviral therapy (ART) should initiate a treatment regimen as soon as possible.

†Indicates off-label use

No dosage adjustment required.

Adult patients (FDA-approved labeling)
CrCl more than 55 mL/minute: No dosage adjustments necessary unless SCr increases from 0.3 to 0.4 above baseline.
CrCl 55 mL/minute or less: Systemic cidofovir therapy is contraindicated; also contraindicated in patients with a SCr more than 1.5 mg/dL or a urine protein of 100 mg/dL or more (equivalent to 2+ proteinuria)
Dosage adjustments based on changes in serum creatinine (SCr):
For increases in SCr of 0.3 to 0.4 mg/dL above baseline: Decrease cidofovir dose to 3 mg/kg/dose IV.
For increases in SCr of 0.5 mg/dL or more above baseline or the development of 3+ proteinuria: Discontinue IV cidofovir.
 
Adult patients (alternative)†
The following dose adjustment has been used in patients receiving an initial dose of 1 mg/kg/dose IV 3 times weekly for adenovirus infection prophylaxis and treatment:
For increases in SCr of 0.3 to 0.4 mg/dL above baseline: Decrease cidofovir dose to 0.5 mg/kg/dose IV 3 times weekly.
 
Pediatric patients†
1 mg/kg/dose IV 3 times weekly for 2 weeks, followed by the same dose every other week has been used for adenovirus infection prophylaxis and treatment in patients with renal dysfunction (serum creatinine more than 1.5 mg/dL, creatinine clearance less than 90 mL/minute/1.73 m2, and 2+ proteinuria).
 
Intermittent hemodialysis or Peritoneal dialysis†
Avoid use.
 
Continuous renal replacement therapy (CRRT)†
Avoid use; if needed, 2 mg/kg/dose IV once weekly.

Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine.
Acetaminophen; Aspirin, ASA; Caffeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Acetaminophen; Aspirin: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Acetaminophen; Aspirin; Diphenhydramine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Acetaminophen; Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Acyclovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as acyclovir, is contraindicated. Acyclovir should be discontinued at least 7 days prior to beginning cidofovir.
Adefovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as adefovir, is contraindicated. Adefovir should be discontinued at least 7 days prior to beginning cidofovir.
Aldesleukin, IL-2: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as cidofovir, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Aliskiren; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Amikacin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Amiloride: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Amiloride; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Aminoglycosides: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Amlodipine; Celecoxib: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Amphotericin B lipid complex (ABLC): (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir.
Amphotericin B liposomal (LAmB): (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir.
Amphotericin B: (Contraindicated) The administration of cidofovir and other potentially nephrotoxic agents, such amphotericin B is contraindicated. Amphotericin B should be discontinued at least 7 days prior to beginning cidofovir.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as cidofovir, as the risk of renal impairment may be increased.
Aspirin, ASA: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Butalbital; Caffeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Caffeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Caffeine; Orphenadrine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Carisoprodol: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Dipyridamole: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Omeprazole: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Aspirin, ASA; Oxycodone: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Atenolol; Chlorthalidone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Azilsartan; Chlorthalidone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Bacitracin: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as bacitracin, is contraindicated. Bacitracin should be discontinued at least 7 days prior to beginning cidofovir.
Benazepril; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Bismuth Subsalicylate: (Major) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents may lead to additive nephrotoxicity. Salicylates should be given with caution to patients taking cidofovir.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents may lead to additive nephrotoxicity. Salicylates should be given with caution to patients taking cidofovir.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Brincidofovir: (Contraindicated) Do not administer brincidofovir with intravenous cidofovir as use of these drugs together is considered duplicate therapy. Brincidofovir is a lipid-linked derivative of cidofovir that is intracellularly converted to cidofovir.
Bumetanide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Bupivacaine; Meloxicam: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir.
Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with cidofovir is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and cidofovir is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Candesartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cidofovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Captopril; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Celecoxib: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Celecoxib; Tramadol: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Chlorothiazide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Chlorthalidone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Chlorthalidone; Clonidine: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Choline Salicylate; Magnesium Salicylate: (Major) Since salicylates cause nephrotoxicity via a similar mechanism as NSAIDs, concurrent use of salicylates and cidofovir should be done with caution. (Major) Since salicylates cause nephrotoxicity, concurrent use of salicylates and cidofovir should be done with caution.
Cisplatin: (Major) Discontinue cisplatin at least 7 days prior to beginning cidofovir. Closely monitor renal function if concomitant use with cisplatin and cidofovir is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins.
Clindamycin: (Contraindicated) Concomitant use of cidofovir and clindamycin is contraindicated due to the increased risk of nephrotoxicity. Clindamycin must be discontinued at least 7 days prior to starting therapy with cidofovir.
Clofarabine: (Contraindicated) The concomitant use of cidofovir and clofarabine is contraindicated due to the potential for additive nephrotoxicity. Discontinue clofarabine 7 days prior to starting cidofovir.
Colistin: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including cidofovir, may increase serum concentrations of either drug.
Cyclosporine: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as cyclosporine is contraindicated. Cyclosporine should be discontinued at least 7 days prior to beginning cidofovir. Monitor renal function and fluid status carefully during cyclosporine usage.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Dichlorphenamide: (Major) Use of dichlorphenamide and adefovir is not recommended because of increased cidofovir exposure and related adverse effects. Monitor closely for signs of drug toxicity if coadministration cannot be avoided. For example, it is important to monitor renal function and for neutropenia for all patients during treatment with cidofovir. Increased cidofovir exposure is possible. Cidofovir is a sensitive OAT1 substrate. Dichlorphenamide inhibits OAT1. Concurrent use may also increase the severity of metabolic acidosis, as both drugs may cause this side effect. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Diclofenac; Misoprostol: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Diflunisal: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Diphenhydramine; Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Diphenhydramine; Naproxen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Diuretics: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Emtricitabine: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions. (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as cidofovir. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and cidofovir are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Enalapril; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Entecavir: (Moderate) Entecavir may affect renal function and should be used cautiously in combination with other drugs that may also affect renal function, including cidofovir.
Eprosartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Ethacrynic Acid: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Etodolac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Fenoprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Flurbiprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Foscarnet: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as foscarnet, is contraindicated. Foscarnet should be discontinued at least 7 days prior to beginning cidofovir.
Fosinopril; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Furosemide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Ganciclovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as ganciclovir, is contraindicated. Ganciclovir should be discontinued at least 7 days prior to beginning cidofovir.
Gentamicin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cidofovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Hydrochlorothiazide, HCTZ; Methyldopa: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Hydrochlorothiazide, HCTZ; Moexipril: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Hydrocodone; Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Ibuprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Ibuprofen; Famotidine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Ibuprofen; Oxycodone: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Ibuprofen; Pseudoephedrine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like cidofovir. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
Indapamide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Indomethacin: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and cidofovir due to the risk of glomerulonephritis and nephrotoxicity.
Irbesartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Ketoprofen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Ketorolac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Lamivudine, 3TC; Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Lisinopril; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Losartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Magnesium Salicylate: (Major) Since salicylates cause nephrotoxicity, concurrent use of salicylates and cidofovir should be done with caution.
Mannitol: (Major) Avoid use of mannitol and cidofovir, if possible. Concomitant administration of nephrotoxic drugs, such as cidofovir, increases the risk of renal failure after administration of mannitol.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and cidofovir as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); cidofovir is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Meclofenamate Sodium: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Mefenamic Acid: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Meloxicam: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Methenamine; Sodium Salicylate: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Methotrexate: (Major) Avoid concomitant use of methotrexate with cidofovir due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Cidofovir and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with cidofovir may result in decreased renal function as well as increased methotrexate plasma concentrations.
Methyclothiazide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Metolazone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Metoprolol; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Nabumetone: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Naproxen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Naproxen; Esomeprazole: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Naproxen; Pseudoephedrine: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Nitisinone: (Moderate) Monitor for increased cidofovir-related adverse effects if coadministered with nitisinone. Increased cidofovir exposure is possible. Nitisinone inhibits OAT1. Cidofovir is an OAT1 substrate.
Nonsteroidal antiinflammatory drugs: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Olmesartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with cidofovir due to the risk of increased oxaliplatin-related adverse reactions. Cidofovir is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
Oxaprozin: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Pamidronate: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as pamidronate, is contraindicated. Pamidronate should be discontinued at least 7 days prior to beginning cidofovir.
Paromomycin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Pentamidine: (Contraindicated) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, including cidofovir. The combination use of IV pentamidine and cidofovir is contraindicated. Pentamidine should be discontinued at least 7 days prior to beginning cidofovir.
Piroxicam: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Plazomicin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Probenecid: (Minor) Probenecid impairs the tubular secretion of cidofovir. While cidofovir serum concentrations are higher as a result of the effects of probenecid, probenecid is recommended for use in combination with cidofovir to offset cidofovir-induced nephrotoxicity.
Probenecid; Colchicine: (Minor) Probenecid impairs the tubular secretion of cidofovir. While cidofovir serum concentrations are higher as a result of the effects of probenecid, probenecid is recommended for use in combination with cidofovir to offset cidofovir-induced nephrotoxicity.
Propranolol; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Protease inhibitors: (Moderate) Additive adverse effects may be seen when cidofovir is given with other agents that cause neutropenia. Patients receiving anti-retroviral protease inhibitors in combination with cidofovir may have an increased risk of iritis or uveitis.
Quinapril; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Salsalate: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs), such as salsalate, is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Spironolactone: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Spironolactone; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Streptomycin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Sulindac: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Sumatriptan; Naproxen: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Tacrolimus: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as tacrolimus is contraindicated. Tacrolimus should be discontinued at least 7 days prior to beginning cidofovir.
Talimogene Laherparepvec: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Telavancin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic drugs such as telavancin is contraindicated. Discontinue telavancin at least 7 days prior to beginning cidofovir.
Telmisartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as cidofovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent, such as cidofovir. If concurrent use is necessary, closely monitor for changes in renal function. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse events. Renal impairment, which may include acute renal failure and hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate.
Tobramycin: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Tolmetin: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Torsemide: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Triamterene: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Triamterene; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Valacyclovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as valacyclovir, is contraindicated. Valacyclovir should be discontinued at least 7 days prior to beginning cidofovir.
Valdecoxib: (Contraindicated) The concomitant administration of cidofovir and nonsteroidal antiinflammatory drugs (NSAIDs) is contraindicated due to the potential for increased nephrotoxicity. NSAIDs should be discontinued 7 days prior to beginning cidofovir.
Valsartan; Hydrochlorothiazide, HCTZ: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Vancomycin: (Contraindicated) The administration of cidofovir other potentially nephrotoxic agents, such as IV vancomycin, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
Voclosporin: (Contraindicated) Concomitant use of cidofovir and voclosporin is contraindicated due to the increased risk of nephrotoxicity. Voclosporin must be discontinued at least 7 days prior to starting therapy with cidofovir.
Zidovudine, ZDV: (Major) Concomitant use of probenecid with zidovudine may produce substantially higher serum concentrations of zidovudine. Because cidofovir must be given concomitantly with probenecid, the manufacturer of cidofovir recommends that on the days of concomitant cidofovir and probenecid therapy, zidovudine should either be discontinued temporarily or the zidovudine dosage should be reduced by 50%. Limited data suggest that probenecid may inhibit glucuronidation and/or reduce renal excretion of zidovudine.
Zoledronic Acid: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as zoledronic acid, is contraindicated. Zoledronic acid should be discontinued at least 7 days prior to beginning cidofovir.

Cidofovir/Vistide Intravenous Inj Sol: 1mL, 75mg

5 mg/kg/week IV.

5 mg/kg/week IV.

Safety and efficacy have not been established; however, doses up to 5 mg/kg/week IV have been used off-label.

Safety and efficacy have not been established; however, doses up to 5 mg/kg/week IV have been used off-label.

Safety and efficacy have not been established; however, doses up to 5 mg/kg/week IV have been used off-label.

Safety and efficacy have not been established.

Cidofovir has antiviral activity against a wide variety of DNA viruses, including cytomegalovirus (CMV) and herpesviruses. In infected cells, cidofovir inhibits viral DNA polymerase, which is responsible for replication of new viral RNA and DNA. Cidofovir is taken up intracellularly via active transport or fluid-phase endocytosis to exert its antiviral effects. Intracellularly, cidofovir is metabolized to its active diphosphate form. Cidofovir competes with deoxycytosinetriphospate (dCTP) for incorporation into viral DNA. Cidofovir is much more selective for viral DNA polymerase versus human DNA polymerase. Once two consecutive molecules of cidofovir are incorporated into the viral DNA chain, DNA production is halted. Incorporation of one cidofovir molecule slows DNA production by 31%. Viral DNA polymerase is unable to remove cidofovir diphosphate once it has been incorporated into viral DNA. The prolonged activity of cidofovir may be due to its ability to stop DNA production and the fact that viral DNA polymerase is unable to remove cidofovir diphosphate once incorporated. The mechanism of action of cidofovir in human papillomavirus (HPV) differs from CMV, since HPV utilizes host cell DNA polymerase versus viral polymerase. HPV-infected cells treated with cidofovir show cell cycle arrest in the S-phase indicating decreased DNA production. Cidofovir has also been shown to induce DNA fragmentation and Caspase-3 protease activity, which is important in the induction of apoptosis in HVP-positive cells. Cidofovir also has activity against cervical cancer cells infected with HPV. Cidofovir also inhibits ribonucleotide reductase; although, the clinical significance of this is not known.
 
It has also been postulated that cidofovir can accumulate in healthy cells, establishing a reservoir of drug. If the cell is invaded by a susceptible virus, cidofovir can inhibit the infection by reducing the production of new viral DNA. There are insufficient data at this time to assess the frequency and significance of resistance to cidofovir therapy following treatment in humans. Resistance to cidofovir, and cross-resistance between cidofovir, ganciclovir, and foscarnet has been observed in vitro.

Cidofovir is administered as an intravenous injection.
 
Intracellularly, cidofovir is metabolized via pyrimidine nucleoside monophosphate kinase to cidofovir monophosphate and is then metabolized to the diphosphate analog. The diphosphate analog is further metabolized to cidofovir monophosphate-choline. The mean elimination half-lives of the monophosphate, diphosphate, and choline metabolites are 6, 17, and > 48 hours, respectively. The choline metabolite may serve as an intracellular reservoir of cidofovir diphosphate, the active form. Cellular protection from infection with herpes simplex virus and CMV has been documented in vitro for up to 7 days following treatment with cidofovir.
 
Renal clearance is significantly higher than baseline creatinine clearance, suggesting that tubular secretion plays a large role in the clearance of cidofovir. At therapeutic doses of cidofovir, probenecid reduces tubular secretion so that the clearance of cidofovir is closer in magnitude to creatinine clearance. However, there is no significant change in cidofovir half-life. The administration of probenecid also results in an increase in cidofovir maximum concentration as compared to cidofovir alone.

Due to low bioavailability (5—22%), cidofovir is not administered orally.

Following intravenous administration, cidofovir distributes in total body water. Serum concentrations are proportional to dose and decline biexponentially. The plasma elimination half-life is 2.6 hours (+/- 1.2 hours).

Although there are no adequate and well-controlled studies in pregnant women, cidofovir was embryotoxic and teratogenic in animal studies. Cidofovir was embryotoxic (reduced fetal body weights) in rats at 1.5 mg/kg/day and in rabbits at 1 mg/kg/day, doses which were also maternally toxic, following daily intravenous dosing during the period of organogenesis. The no-observable-effect levels for embryotoxicity in rats (0.5 mg/kg/day) and in rabbits (0.25 mg/kg/day) were approximately 0.04 and 0.05 times the clinical dose (5 mg/kg every other week) based on AUC, respectively. An increased incidence of fetal external, soft tissue, and skeletal anomalies (meningocele, short snout, and short maxillary bones) occurred in rabbits at the high dose (1 mg/kg/day) which was also maternally toxic. Cidofovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known if cidofovir is excreted in human milk; however, use during breast-feeding is not recommended because of its potential for carcinogenic and other adverse effects in the infant. Additionally, cidofovir may be used to treat infections in patients with HIV and the Centers for Disease Control and Prevention (CDC) recommends that in the US, HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a drug administered to the mother, health care providers are encouraged to report the adverse effect to the FDA.