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Cidofovir

Class: Nucleosides and Nucleotides
VA Class: AM800
Chemical Name: (S)-[[2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]phosphonic acid dihydrate
Molecular Formula: C8H14N3O6P•2H2O
CAS Number: 149394-66-1

Medically reviewed by Drugs.com. Last updated on Aug 19, 2019.

Warning

    Nephrotoxicity
  • Major toxicity is renal impairment.1 Acute renal failure resulting in dialysis and/or contributing to death has occurred with as few as 1 or 2 doses of cidofovir.1

  • To reduce risk of nephrotoxicity, IV hydration with 0.9% sodium chloride must be given prior to each cidofovir dose and oral probenecid regimen must be used concomitantly with each cidofovir dose.1 (See Hydration and see Concomitant Probenecid under Dosage and Administration.) Renal function (Scr and urine protein) must be assessed within 48 hours prior to each cidofovir dose and dosage modified as appropriate based on any changes in renal function.1

  • Contraindicated in patients receiving other nephrotoxic drugs.1 (See Interactions.)

    Neutropenia
  • Neutropenia has been observed in association with cidofovir; monitor neutrophil counts closely.1

    Other Warnings
  • The only FDA-labeled indication is treatment of cytomegalovirus (CMV) retinitis in HIV-infected patients.1

  • In animal studies, cidofovir was carcinogenic, teratogenic, and caused hypospermia.1 (See Cautions.)

Introduction

Antiviral; acyclic nucleotide analog (acyclic nucleoside phosphonate); active against herpesviruses and certain other viruses.3 7 10 18 75 76

Uses for Cidofovir

Cytomegalovirus (CMV) Retinitis

Initial treatment (induction therapy) and maintenance therapy (secondary prophylaxis) of CMV retinitis in HIV-infected adults, including those with acquired immunodeficiency syndrome (AIDS).1 21 24 25 31 155 Also used for management of CMV retinitis in HIV-infected adolescents and children.155 156

Safety and efficacy not established for treatment of other CMV infections (e.g., pneumonitis, gastroenteritis), congenital or neonatal CMV disease, or CMV disease in individuals not infected with HIV.1

Like other antivirals, cidofovir is not a cure for CMV retinitis; stabilization or improvement of ocular manifestations may occur, but relapse and/or progression of CMV retinitis possible during or following cidofovir therapy.1 3 17 21 24 25 31

Retinitis is the most common clinical manifestation of CMV end-organ disease in HIV-infected patients;155 ideally should be managed in consultation with an ophthalmologist familiar with diagnosis and treatment of retinal diseases.155 156

Select antiviral regimen for initial treatment of CMV retinitis in HIV-infected individuals based on location and severity of CMV retinal lesions, severity of underlying immunosuppression, concomitant drug therapy, and patient’s ability to adhere to the treatment regimen.155 156 Select antiviral regimen for maintenance therapy based on location of the CMV retinal lesions, vision in contralateral eye, patient's immunologic and virologic status, and patient's response to antiretroviral therapy.155 156

For management of immediate sight-threatening CMV lesions (i.e., within 1.5 mm of the fovea) in HIV-infected adults and adolescents, CDC, NIH, and IDSA state that the preferred regimen is initial treatment (induction therapy) with intravitreal ganciclovir or intravitreal foscarnet (1–4 doses over 7–10 days) in conjunction with oral valganciclovir (twice daily for 14–21 days) followed by maintenance therapy (secondary prophylaxis) with oral valganciclovir (once daily).155 One alternative regimen recommended by these experts for sight-threatening CMV retinitis in HIV-infected adults and adolescents is intravitreal ganciclovir or intravitreal foscarnet (1–4 doses over 7–10 days) in conjunction with IV cidofovir (once weekly for 2 weeks) followed by maintenance therapy (secondary prophylaxis) with IV cidofovir (once every other week).155 Systemic antivirals (without an intravitreal antiviral) usually adequate for management of CMV retinitis in patients with only small peripheral lesions.155

For management of CMV retinitis in HIV-infected pediatric patients, CDC, NIH, IDSA, and others state that IV ganciclovir is drug of choice for initial treatment (induction therapy) and one of several options for maintenance therapy (secondary prophylaxis).156 These experts state that IV cidofovir has not been studied in children with CMV disease, but is a possible alternative for management of CMV retinitis in HIV-infected children when other options cannot be used.156

Because of risk of relapse, chronic maintenance therapy (secondary prophylaxis) of CMV retinitis usually continued until immune reconstitution occurs as a result of effective antiretroviral therapy.155 156 CDC, NIH, and IDSA state that discontinuance of maintenance therapy of CMV retinitis can be considered in HIV-infected adults and adolescents if CMV lesions have been treated for ≥3–6 months and are inactive and there has been a sustained (i.e., 3–6 months) increase in CD4+ T-cell count to >100/mm3 in response to antiretroviral therapy.155 Although safety of discontinuing maintenance therapy of CMV retinitis in HIV-infected pediatric patients not well studied, discontinuance of such therapy can be considered in those receiving antiretroviral therapy who have a sustained (i.e., >6 months) increase in CD4+ T-cell percentage to >15% (children <6 years of age) or increase in CD4+ T-cell count to >100/mm3 (children ≥6 years of age).156

If maintenance therapy of CMV retinitis discontinued, continue regular ophthalmologic monitoring (optimally every 3–6 months) for early detection of CMV relapse or immune reconstitution uveitis.155 156 If CD4+ T-cell count decreases to <100/mm3 (adults, adolescents, children ≥6 years of age) or CD4+ T-cell percentage decreases to <15% (children <6 years of age), reinitiate CMV retinitis maintenance therapy.155 156

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Management of mucocutaneous infections caused by acyclovir-resistant HSV types 1 and 2 (HSV-1 and HSV-2) in immunocompromised individuals, including HIV-infected patients.39 40 42 75 155 156

Drugs of choice for management of orolabial lesions or initial or recurrent genital lesions caused by HSV are valacyclovir, famciclovir, and acyclovir.155 156 344

For management of mucocutaneous lesions caused by acyclovir-resistant HSV in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend IV foscarnet as drug of choice and state that IV cidofovir is a potential alternative.155 For HIV-infected children, these experts recommend IV foscarnet as drug of choice for acyclovir-resistant HSV infections and state that IV cidofovir is recommended for infections caused by HSV resistant to acyclovir and foscarnet.156

Has been used topically for management of mucocutaneous HSV infections, including genital herpes, caused by acyclovir-resistant strains.43 75 78 155 156 344

Adenovirus Infections

Has been used for treatment of adenovirus infections in immunocompromised patients (e.g., allogeneic hematopoietic stem cell transplant recipients, solid organ transplant recipients).75 Safety and efficacy not established and data are limited.75

Varicella-Zoster Virus (VZV) Infections

Has been recommended as a possible alternative for management of VZV infections.155

Preferred antivirals for management of acute, localized herpes zoster (shingles) in HIV-infected adults and adolescents are acyclovir, famciclovir, and valacyclovir.155 For management of proven or suspected acyclovir-resistant VZV infections in HIV-infected adults or adolescents, CDC, NIH, and IDSA recommend IV foscarnet and state that IV cidofovir is a possible alternative.155

Although optimal regimens for management of progressive outer retinal necrosis caused by VZV not identified, CDC, NIH, and IDSA recommend that such infections in HIV-infected adults and adolescents be treated with at least one IV antiviral (acyclovir, ganciclovir, foscarnet, cidofovir) used in conjunction with at least one intravitreal antiviral (ganciclovir or foscarnet).155 Prognosis for visual preservation in patients with progressive outer retinal necrosis caused by VZV is poor;155 such infections should be managed in consultation with an ophthalmologist.155

Smallpox

Alternative for treatment of certain serious complications of smallpox vaccination, including eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and aberrant vaccinia infection caused by inadvertent autoinoculation (if severe because of large numbers of lesions, toxicity, or pain).63 70 Safety and efficacy not determined and possible benefits not known.63

Vaccinia immune globulin IV (VIGIV) considered first-line treatment for serious complications of smallpox vaccination.63 70

If VIGIV alone is inadequate or if VIGIV not readily available, may consider use of certain antivirals (e.g., cidofovir, tecovirimat, brincidofovir) for treatment of complications of smallpox vaccination after consultation with CDC.70

Contact state or local health department or CDC Emergency Operations Center at 770-488-7100 for assistance with diagnosis and management of suspected complications of smallpox vaccination.70

Suggested as a possible alternative for treatment of smallpox.49 50 51 Although cidofovir is active in vitro against poxviruses, including variola virus (causative agent of smallpox), and has in vivo activity in mice against cowpox and vaccinia virus,53 54 55 59 60 64 possible role, if any, for treatment of smallpox not determined.49 50 51

Monkeypox

Although efficacy not established for treatment of human monkeypox,71 cidofovir is active in vitro against monkeypox and has in vivo activity against the virus in animal models.53 66 67 68 71 75

Monkeypox virus is an orthopoxvirus closely related to the causative agent of smallpox.50 71 Although no specific treatments are available for human monkeypox infection, CDC states that monkeypox outbreaks can be controlled through use of smallpox vaccine, VIGIV, and certain antivirals (e.g., cidofovir, tecovirimat, brincidofovir).71

If an outbreak of monkeypox occurs in the US, CDC will establish updated guidelines for use of smallpox vaccine, VIGIV, or antivirals for treatment and/or postexposure prophylaxis of exposed individuals.71

Cidofovir Dosage and Administration

General

  • Assess renal function prior to initiation of cidofovir and monitor during therapy with the drug.1

  • Must not be initiated in patients with Scr >1.5 mg/dL, calculated Clcr ≤55 mL/minute, or urine protein concentration ≥100 mg/dL (equivalent to ≥2+).1 (See Renal Impairment under Dosage and Administration.)

  • To reduce risk of cidofovir-induced nephrotoxicity, patient must receive adequate hydration prior to each cidofovir dose and must receive a regimen of oral probenecid concomitantly with each cidofovir dose.1

  • Must not exceed recommended cidofovir dosage and recommended frequency and rate of administration.1

Hydration

  • All patients must receive ≥1 L of 0.9% sodium chloride infused IV over 1–2 hours immediately prior to each IV infusion of cidofovir.1

  • For patients who can tolerate additional fluid, administer an additional 1 L of 0.9% sodium chloride; initiate second infusion of 0.9% sodium chloride either concomitantly with or immediately after the cidofovir IV infusion and administer over 1–3 hours.1

  • Volume repletion and maintenance are particularly important in patients with potential volume depletion secondary to conditions such as chronic diarrhea, poor fluid intake, or HIV-related wasting.29

Concomitant Probenecid

  • All patients must receive a regimen of oral probenecid concomitantly with each cidofovir dose.1 3 7 Cidofovir undergoes renal tubular secretion, suggesting that use of probenecid may reduce risk of cidofovir renal toxicity by decreasing concentrations of the drug within proximal tubular cells.1 4 7

  • For each dose of IV cidofovir, the recommended regimen of oral probenecid is 2 g given 3 hours prior to initiation of the cidofovir infusion, followed by 1-g doses 2 and 8 hours after completion of the cidofovir infusion, for a total probenecid dose of 4 g.1

  • To reduce risk of nausea and/or vomiting associated with oral probenecid, food can be ingested prior to each probenecid dose and concomitant administration of an effective antiemetic can be considered.1

  • For patients who develop allergic or other hypersensitivity manifestations with probenecid, appropriate prophylactic or therapeutic use of antihistamines and/or acetaminophen can be considered.1 Because concomitant probenecid is required, cidofovir is contraindicated in patients with a history of severe hypersensitivity to probenecid or other sulfa-containing drugs.1 30

  • Because probenecid can affect the pharmacokinetics of many drugs, carefully assess other drugs that the patient may be receiving.1 (See Specific Drugs under Interactions.)

Administration

Administer by slow IV infusion using a controlled-infusion device (e.g., pump).1

Has been administered by intravitreal injection,6 20 24 25 26 but a preparation specifically for intravitreal administration not commercially available in US.1 Direct intraocular injection of the IV preparation (even if diluted) is contraindicated since such administration has been associated with iritis, ocular hypotony, and permanent visual impairment.1 30

Has been administered topically as a gel or cream for management of certain mucocutaneous viral infections (e.g., acyclovir-resistant HSV infections).43 75 78 155 156 344 Although topical preparations not commercially available in US, a topical gel containing 1% cidofovir has been prepared extemporaneously using the IV preparation.75 78 155 156 344

IV Infusion

Must be administered using a controlled-infusion device (e.g., pump).1

Commercially available as a concentrate for injection containing 75 mg of cidofovir per mL that must be diluted prior to IV infusion.1

Concentrate should appear clear and colorless;1 do not use if discolored or contains particles.1

Exercise caution when preparing, administering, and discarding solutions of cidofovir according to guidelines for handling mutagenic substances.1 If cidofovir concentrate or a diluted solution of the drug comes in contact with skin or mucosa, wash affected area immediately and thoroughly with soap and water.1 Discard partially used vials of cidofovir and diluted solutions of the drug by high-temperature incineration.1

Dilution

For IV infusion, withdraw appropriate dose of cidofovir concentrate from the vial and dilute in 100 mL of 0.9% sodium chloride injection in a compatible infusion container (e.g., PVC, glass, ethylene/propylene copolymer).1 Administer entire volume of diluted solution within 24 hours after preparation.1 (See Storage under Stability.)

Compatibility with Ringer’s, lactated Ringer’s, or bacteriostatic infusion solutions not evaluated.1

Rate of Administration

IV infusions should be given at a constant rate over 1 hour using a controlled-infusion device (e.g., pump).1

To minimize risk of nephrotoxicity, IV dose must not be infused over a shorter time period.1 29

Dosage

Available as cidofovir dihydrate; dosage is expressed in terms of anhydrous cidofovir.1

Pediatric Patients

CMV Retinitis in HIV-infected Adolescents
IV

Initial treatment (induction therapy): 5 mg/kg once weekly for 2 consecutive weeks.155

Maintenance therapy (secondary prophylaxis): 5 mg/kg once every 2 weeks (i.e., every other week).155 If renal function declines, reduce maintenance dosage or discontinue cidofovir depending on the degree of impairment.1 155 (See Renal Impairment under Dosage and Administration.)

Make decisions regarding discontinuance of CMV retinitis maintenance therapy in consultation with an ophthalmologist.155 (See Cytomegalovirus [CMV] Retinitis under Uses.)

Mucocutaneous HSV Infections
Mucocutaneous Acyclovir-resistant HSV Infections in HIV-infected Adolescents
IV

CDC, NIH, IDSA, and others recommend 5 mg/kg once weekly for ≥2–4 weeks until a response is obtained.155

Topical

Extemporaneously prepared gel containing cidofovir 1%: Has been applied to affected area once daily for 5 days.43 344 In HIV-infected patients, treatment duration ≥3–4 weeks recommended depending on clinical response.155

Adults

CMV Retinitis in HIV-infected Adults
IV

Initial treatment (induction therapy): 5 mg/kg once weekly for 2 consecutive weeks.1 21 24 31 155 If patient has immediate sight-threatening CMV retinal lesions, CDC, NIH, and IDSA recommend that initial treatment also include an intravitreal antiviral.155 (See Cytomegalovirus [CMV] Retinitis under Uses.)

Maintenance therapy (secondary prophylaxis): 5 mg/kg once every 2 weeks (i.e., every other week).1 24 155 If renal function declines, reduce maintenance dosage or discontinue cidofovir depending on the degree of impairment.1 155 (See Renal Impairment under Dosage and Administration.)

Make decisions regarding discontinuance of CMV retinitis maintenance therapy in consultation with an ophthalmologist.155 (See Cytomegalovirus [CMV] Retinitis under Uses.)

Mucocutaneous HSV Infections
Mucocutaneous Acyclovir-resistant HSV Infections in immunocompromised Adults
IV

5 mg/kg once weekly for ≥2–4 weeks until a response is obtained.39 40 155

Topical

Extemporaneously prepared gel containing cidofovir 1%: Has been applied to affected area once daily for 5 days.43 344 In HIV-infected patients, treatment duration ≥3–4 weeks recommended depending on clinical response.155

Special Populations

Hepatic Impairment

Manufacturer makes no specific recommendation for dosage in patients with hepatic impairment;30 effect on cidofovir pharmacokinetics not evaluated.30

Renal Impairment

Assess renal function prior to initiation of cidofovir and monitor during therapy with the drug.1 (See Renal Effects under Cautions.)

Initiation of cidofovir contraindicated in patients with Scr >1.5 mg/dL, calculated Clcr ≤55 mL/minute, or urine protein concentration ≥100 mg/dL (equivalent to ≥2+).1

If Scr increases by 0.3–0.4 mg/dL above baseline, reduce dose to 3 mg/kg.1 155

If Scr increases by ≥0.5 mg/dL above baseline or if proteinuria ≥3+ develops, discontinue cidofovir.1 155

If 2+ proteinuria develops in the face of a stable Scr, observe closely (including close monitoring of Scr and urinary protein) to detect potential deterioration that would warrant dose reduction or discontinuance of cidofovir.29 30

CMV Retinitis in HIV-infected Adults and Adolescents
IV

If Scr increases by 0.3–0.4 mg/dL above baseline, reduce maintenance dosage to 3 mg/kg once every 2 weeks (i.e., every other week).1 155

If Scr increases by ≥0.5 mg/dL above baseline or if proteinuria ≥3+ develops, discontinue cidofovir.1 155

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.1 (See Geriatric Use under Cautions.)

Cautions for Cidofovir

Contraindications

  • Initiation in patients with Scr >1.5 mg/dL, calculated Clcr ≤55 mL/minute, or urine protein concentration ≥100 mg/dL (equivalent to ≥2+).1

  • Concomitant use with other nephrotoxic drugs.1 (See Interactions.)

  • Hypersensitivity to cidofovir.1

  • History of clinically severe hypersensitivity to probenecid or other sulfa-containing drugs.1

  • Direct intraocular injection of the IV preparation.1

Warnings/Precautions

Warnings

Renal Effects

Dose-dependent nephrotoxicity is the major dose-limiting toxicity.1 In clinical trials in adults with CMV retinitis, renal toxicity (manifested by increase in Scr of ≥0.4 mg/dL, decrease in Clcr to ≤55 mL/minute, or proteinuria ≥2+) occurred in 59% of patients receiving recommended cidofovir maintenance dosage.1

Acute renal failure resulting in dialysis and/or contributing to death has occurred with as few as 1 or 2 doses.1 29 35 In some cases, patients had risk factors for nephrotoxicity, such as preexisting mild renal insufficiency or cidofovir administration proximal to completion of aminoglycoside therapy.29

Proteinuria may be an early sign of cidofovir-induced nephrotoxicity.1 If proteinuria develops, manufacturer recommends that IV hydration be administered and the test repeated.1

If renal function deteriorates, dosage reduction or discontinuance of cidofovir may be required.1 29 (See Renal Impairment under Dosage and Administration.) Continued cidofovir may lead to additional proximal tubular cell injury, which may result in glycosuria; decreases in serum phosphate, uric acid, and bicarbonate concentrations; increases in Scr concentrations; and/or acute renal failure which may require dialysis.1

Occasionally, renal function may not return to baseline following discontinuance of cidofovir.1

Fanconi syndrome manifested by multiple abnormalities of proximal renal tubular function reported.1 (See Metabolic Acidosis under Cautions.)

To reduce risk of nephrotoxicity, IV hydration with 0.9% sodium chloride is required prior to each cidofovir dose and a regimen of oral probenecid is required with each cidofovir dose.1 (See General under Dosage and Administration.)

Concomitant use with potentially nephrotoxic drugs is contraindicated;1 discontinue such drugs ≥7 days prior to administration of cidofovir.1 29 (See Interactions.)

Prior to initiation of cidofovir therapy, must assess renal function.1 Cidofovir is contraindicated and should not be initiated in patients with Scr >1.5 mg/dL, calculated Clcr ≤55 mL/minute, or urine protein concentration ≥100 mg/dL (equivalent to proteinuria of ≥2+).1 Because Scr may not provide accurate assessment of renal function in patients with severe AIDS and CMV retinitis, use Cockcroft-Gault calculations initially to estimate Clcr more precisely when determining eligibility to receive cidofovir;1 29 for subsequent assessments, Scr should be used.29 30

During cidofovir therapy, must assess renal function (Scr and urine protein) within 48 hours prior to each cidofovir dose and adjust dosage or withhold the drug as appropriate based on any changes in renal function.1 (See Renal Impairment under Dosage and Administration.)

Hematologic Effects

Neutropenia (≤500/mm3) reported in 24% of adults in clinical trials receiving cidofovir maintenance therapy for CMV retinitis.1

Monitor neutrophil counts during cidofovir therapy.1

Carcinogenic and Mutagenic Potential

Cidofovir should be considered a potential carcinogen in humans.1 Has caused tumors (principally mammary adenocarcinomas) in rats.1

In vitro, cidofovir induced chromosomal aberrations in human peripheral blood lymphocytes without metabolic activation, but there was no evidence of mutagenicity in microbial mutagenicity assays in the presence or absence of metabolic activation.1

Effects on Fertility

In animals, cidofovir has caused reduced testes weight and hypospermia.1 Possibility exists that such effects could occur in humans and cause infertility.1

Advise women of childbearing potential and men to use an effective method of contraception during cidofovir therapy and for certain periods of time after the drug is discontinued.1 (See Pregnancy under Cautions.)

Selection and Use of Antivirals

Cidofovir is labeled by FDA only for treatment of CMV retinitis in HIV-infected patients, including those with AIDS.1

Safety and efficacy not established for treatment of other CMV infections or for treatment of CMV disease in individuals not infected with HIV.1

Other Warnings/Precautions

Administration Precautions

Administer cidofovir only by IV infusion;1 do not administer IV preparation by intraocular injection.1 (See Administration under Dosage and Administration.)

Patients must receive adequate IV hydration prior to each cidofovir dose and must receive a regimen of oral probenecid concomitantly with each cidofovir dose.1 (See General under Dosage and Administration.)

Because of the potential for nephrotoxicity, recommended cidofovir dose, frequency, and rate of administration must not be exceeded.1

Ophthalmologic Effects

Decreased IOP may occur and may be associated with decreased visual acuity.1 In adults in clinical trials receiving cidofovir maintenance therapy for CMV retinitis and whose IOP was monitored, 24% experienced ≥50% decrease in IOP from baseline;1 severe hypotony (i.e., IOP of 0–1 mm Hg) was reported in 3 patients.1 Risk of ocular hypotony may be increased in patients with preexisting diabetes mellitus.1

Uveitis or iritis reported in 11% of adults in clinical trials receiving cidofovir maintenance therapy for CMV retinitis.1

Patients should receive periodic ophthalmic examinations to monitor IOP and visual acuity and to monitor for symptoms of uveitis or iritis.1 35 36

If anterior uveitis or iritis develops, consider appropriate therapy (topical corticosteroids with or without cycloplegic therapy) as indicated.1 35

Metabolic Acidosis

Decreased serum bicarbonate associated with proximal tubule injury and renal wasting syndrome (including Fanconi syndrome) reported.1

Metabolic acidosis in association with liver dysfunction and pancreatitis has resulted in death.1

Specific Populations

Pregnancy

No adequate and well-controlled studies to date in pregnant women.1 Use during pregnancy only if potential benefits justify potential risks to fetus.1

In rats and rabbits, embryotoxicity (reduced fetal body weights) and maternal toxicity observed.1 In rabbits, maternal toxicity and increased incidence of fetal external, soft tissue, and skeletal anomalies (meningocele, short snout, and short maxillary bones) observed.1

Inform women of childbearing potential that cidofovir is embryotoxic in animals.1 Advise women of childbearing potential to use an effective method of contraception during and for 1 month after cidofovir therapy.1

Advise men to use a reliable method of barrier contraception during and for 3 months after cidofovir therapy.1

Lactation

Not known whether distributed into human milk.1

Discontinue nursing or the drug.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1 30

Because of risks of potential long-term carcinogenic and reproductive toxicity, manufacturer states use with extreme caution in children with AIDS and only after careful evaluation and only when potential benefits outweigh risks.1

Some experts state cidofovir has not been studied in children with CMV disease, but can be considered for management of CMV retinitis in HIV-infected children if other options cannot be used.156

Geriatric Use

Safety and efficacy not evaluated in adults >60 years of age.1

Because geriatric patients frequently have reduced GFR, pay particular attention to monitoring renal function prior to and during cidofovir therapy in this age group and modify dosage as indicated.1 (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Initiation of cidofovir contraindicated in patients with Scr >1.5 mg/dL, calculated Clcr ≤55 mL/minute, or urine protein concentration ≥100 mg/dL (equivalent to ≥2+).1 (See Renal Impairment under Dosage and Administration.)

Pharmacokinetic data in individuals with renal impairment (Clcr as low as 11 mL/minute) indicate cidofovir clearance decreases proportionally with Clcr.1

High-flux hemodialysis reduces serum cidofovir concentrations by approximately 75%.1

Common Adverse Effects

Nephrotoxicity (proteinuria, elevated Scr), nausea and/or vomiting, fever, neutropenia, asthenia, headache, rash, infection, alopecia, diarrhea, pain, anemia, decreased IOP, anorexia, dyspnea, chills, increased cough, oral moniliasis, decreased serum bicarbonate.1

Interactions for Cidofovir

Nephrotoxic Drugs

Concomitant use with other nephrotoxic drugs is contraindicated since it may increase risk of nephrotoxicity.1 Other nephrotoxic agents must be discontinued ≥7 days prior to initiating cidofovir.1

Specific Drugs

Drug

Interaction

Comments

Acetaminophen

Probenecid may affect metabolism or renal tubular excretion of acetaminophen1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of acetaminophen1

Acyclovir

Probenecid may affect metabolism or renal tubular excretion of acyclovir1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of acyclovir1

Aminoglycosides (amikacin, gentamicin, tobramycin)

Possible increased risk of nephrotoxicity1

Concomitant use contraindicated;1 discontinue ≥7 days prior to initiating cidofovir1

Aminosalicylic acid

Probenecid may affect metabolism or renal tubular excretion of aminosalicylic acid1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of aminosalicylic acid1

Amphotericin B

Possible increased risk of nephrotoxicity1

Concomitant use contraindicated;1 discontinue ≥7 days prior to initiating cidofovir1

Angiotensin-converting enzyme (ACE) inhibitors

Probenecid may affect metabolism or renal tubular excretion of ACE inhibitors1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of ACE inhibitors1

Barbiturates

Probenecid may affect metabolism or renal tubular excretion of barbiturates1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of barbiturates1

Benzodiazepines

Probenecid may affect metabolism or renal tubular excretion of benzodiazepines1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of benzodiazepines1

Bumetanide

Probenecid may affect metabolism or renal tubular excretion of bumetanide1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of bumetanide1

Famotidine

Probenecid may affect metabolism or renal tubular excretion of famotidine1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of famotidine1

Foscarnet

Possible increased risk of nephrotoxicity1

Concomitant use contraindicated;1 discontinue ≥7 days prior to initiating cidofovir and monitor closely1

Furosemide

Probenecid may affect metabolism or renal tubular excretion of furosemide1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of furosemide1

Methotrexate

Probenecid may affect metabolism or renal tubular excretion of methotrexate1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of methotrexate1

Nonsteroidal anti-inflammatory agents (NSAIAs)

Possible increased risk of nephrotoxicity1

Probenecid may affect metabolism or renal tubular excretion of NSAIAs1

Concomitant use contraindicated;1 discontinue ≥7 days prior to initiating cidofovir1

Pentamidine

IV pentamidine: Possible increased risk of nephrotoxicity1

IV pentamidine: Concomitant use contraindicated;1 discontinue ≥7 days prior to initiating cidofovir1

Probenecid

Decreased renal clearance of cidofovir;1 can also affect pharmacokinetics of other drugs patient is receiving1

Used concomitantly with cidofovir for therapeutic advantage to reduce risk of cidofovir-associated nephrotoxicity;1 75 consider possible interactions with other drugs patient is receiving1

Theophylline

Probenecid may affect metabolism or renal tubular excretion of theophylline1

Since probenecid regimen must be used with each cidofovir dose, carefully assess concomitant use of theophylline1

Vancomycin

Possible increased risk of nephrotoxicity1

Concomitant use contraindicated;1 discontinue ≥7 days prior to initiating cidofovir1

Zidovudine

No evidence of pharmacokinetic interactions with cidofovir;1 concomitant probenecid reduces metabolic clearance of zidovudine1

Temporarily discontinue zidovudine or decrease zidovudine dosage by 50% on days patient receives probenecid1

Cidofovir Pharmacokinetics

Absorption

Bioavailability

Low concentrations of cidofovir are absorbed systemically following topical application of extemporaneously prepared gel containing cidofovir 1% to mucocutaneous HSV lesions.43

Distribution

Extent

Undetectable in CSF following IV administration in one patient.1

Not known whether distributed into human milk.1

Plasma Protein Binding

<6%.1

Elimination

Metabolism

Cidofovir is converted via cellular enzymes to the pharmacologically active diphosphate metabolite.1 2 3 5 7 11 12 13 15 16 18 24

Elimination Route

When administered with usual concomitant probenecid regimen (see Concomitant Probenecid under Dosage and Administration), 70–85% of an IV cidofovir dose is eliminated unchanged in urine within 24 hours.1 If administered without probenecid, 80–100% of the IV cidofovir dose is eliminated unchanged in urine within 24 hours.1

Removed by hemodialysis.1

Stability

Storage

Parenteral

Concentrate for IV Infusion

20–25°C.1

Following dilution with 0.9% sodium chloride, administer within 24 hours of preparation;1 do not refrigerate or freeze to extend storage period beyond 24 hours.1

If prepared in advance, diluted solution may be refrigerated at 2–8°C but should be administered within 24 hours of preparation;1 allow solution to reach room temperature before administration.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Compatibility with Ringer’s, lactated Ringer’s, or bacteriostatic infusion fluids not evaluated.1

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.45%

Dextrose 5% in water

Sodium chloride 0.9%

Actions and Spectrum

  • Cidofovir is a prodrug with no antiviral activity until converted via cellular enzymes to the pharmacologically active diphosphate metabolite.2 3 13 15 16 18 20 75

  • Cidofovir diphosphate is a viral DNA polymerase inhibitor that interferes with viral DNA synthesis and inhibits viral replication1 6 10 11 13 14 16 20 75 by competitive inhibition of viral DNA polymerase6 14 16 75 and incorporation and termination of the growing viral DNA chain.1 3 75 The inhibitory activity of cidofovir diphosphate is highly selective1 9 10 11 12 20 because of its greater affinity for viral DNA polymerases than for human DNA polymerases.1 3 5 75

  • Active against various herpesviruses, including CMV, HSV-1 and HSV-2, VZV, and Epstein-Barr virus (EBV).1 3 16 24 33 75 Also active in vitro against adenovirus,3 16 24 75 human papillomavirus (HPV),3 24 33 75 and human polyomavirus.1 2 3 7 11 13 15 16 18 24 34 75

  • Has in vitro activity against poxviruses, including vaccinia virus (cowpox), monkeypox, and variola virus (causative agent of smallpox).45 46 47 53 57 67 68 71 75 Also has in vivo activity against monkeypox in animal models53 66 67 68 71 and against vaccinia virus in mice.47 48 53 54 55 56

  • May be active against some ganciclovir-resistant CMV1 2 9 27 and some acyclovir-resistant HSV;2 18 active against some, but not all, CMV isolates resistant to foscarnet.1

  • CMV isolates with reduced susceptibility to cidofovir have been selected in vitro.1 Consider possibility of cidofovir-resistant CMV in patients with CMV retinitis who fail to respond to cidofovir or experience recurrent CMV retinitis progression during cidofovir therapy.1 3

  • Some cidofovir-resistant CMV isolates selected in vitro have been cross-resistant to ganciclovir, but remained susceptible to foscarnet.1 75 Ganciclovir-resistant or ganciclovir- and foscarnet-resistant isolates that were cross-resistant to cidofovir have been obtained from drug-naive patients and patients who were treated with ganciclovir with or without foscarnet.1

Advice to Patients

  • Advise patients that cidofovir is not a cure for CMV retinitis; they may continue to experience progression of retinitis during or following treatment.1 Regular ophthalmologic examinations are necessary.1 Other manifestations of CMV disease may also occur.1

  • Advise HIV-infected patients who are receiving zidovudine to temporarily discontinue zidovudine or decrease the zidovudine dose by 50% on days cidofovir is administered because the probenecid regimen used with each cidofovir dose reduces metabolic clearance of zidovudine.1

  • Inform patients that the major toxicity of cidofovir is renal impairment; dosage modifications, including reduction, interruption, and, possibly, discontinuance of the drug may be required.1 Importance of close monitoring of renal function (routine urinalysis, Scr) during cidofovir therapy.1

  • Importance of receiving IV hydration prior to each cidofovir dose and importance of taking the recommended regimen of oral probenecid with each cidofovir dose to minimize risk of cidofovir-associated nephrotoxicity.1

  • Inform patients of possible adverse effects associated with the probenecid regimen, including headache, nausea, vomiting, and hypersensitivity reactions (e.g., rash, fever, chills, anaphylaxis).1 Advise patients that taking probenecid after a meal or concomitant use of an antiemetic may decrease nausea;1 antihistamines and/or acetaminophen can be used to ameliorate hypersensitivity reactions.1

  • Inform patients that cidofovir has caused tumors (principally mammary adenocarcinomas) in rats and the drug should be considered a potential carcinogen in humans.1

  • Inform patients that cidofovir has caused reduced testes weight and hypospermia in animals and such effects may occur in humans and cause infertility.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Inform women of childbearing potential that cidofovir is embryotoxic in animals and should not be used during pregnancy.1

  • Advise women of childbearing potential to use effective contraception during and for 1 month after cidofovir therapy.1 Advise men to practice barrier contraceptive methods during and for 3 months after cidofovir treatment.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

For the treatment of serious complications of smallpox vaccination or the treatment of human monkeypox, cidofovir is stored in the US Strategic National Stockpile (SNS).70 71 The SNS ensures that certain drugs and medical supplies are readily available to prevent or treat specific diseases, including during public health emergencies, and is managed by the US Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR).72 To request a drug from the SNS, state health departments can contact the CDC Emergency Operations Center at 770-488-7100 or the HHS Secretary's Operations Center at 202-619-7800.73

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cidofovir

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Concentrate, for injection, for IV infusion only

75 mg (of anhydrous cidofovir) per mL*

Cidofovir Injection

AHFS DI Essentials™. © Copyright 2019, Selected Revisions August 19, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Mylan Institutional LLC. Cidofovir anhydrous injection prescribing information. Rockford, IL; 2012 Nov.

2. Flaherty JF. Current and experimental therapeutic options for cytomegalovirus disease. Am J Health-Syst Pharm. 1996; 53(Suppl 2):S4-11.

3. Hitchcock MJM, Jaffe HS, Martin JC et al. Cidofovir, a new agent with potent anti-herpesvirus activity. Antivir Chem Chemother. 1996; 7:115-27.

4. Cundy KC, Petty BG, Flaherty J et al. Clinical pharmacokinetics of cidofovir in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1995; 39:1247- 52. http://www.ncbi.nlm.nih.gov/pubmed/7574510?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=162721&blobtype=pdf

5. Cherrington JM, Miner R, Hitchcock MJM et al. Susceptibility of human cytomegalovirus to cidofovir is unchanged after limited in vivo exposure to various clinical regimens of drug. J Infect Dis. 1996; 173:987-92. http://www.ncbi.nlm.nih.gov/pubmed/8603981?dopt=AbstractPlus

6. Kirsch LS, Arevalo JF, Chavez de la Paz E et al. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. 1995; 102:533-43. http://www.ncbi.nlm.nih.gov/pubmed/7724170?dopt=AbstractPlus

7. Polis MA, Spooner KM, Baird BF et al. Anticytomegaloviral activity and safety of cidofovir in patients with human immunodeficiency virus infection and cytomegalovirus viruria. Antimicrob Agents Chemother. 1995; 39:882-6. http://www.ncbi.nlm.nih.gov/pubmed/7785989?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=162647&blobtype=pdf

8. Minckler D. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. 1995; 253:702.

9. Flores-Aguilar M, Huang J-S, Wiley CA et al. Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. J Infect Dis. 1994; 169:642-7. http://www.ncbi.nlm.nih.gov/pubmed/8158041?dopt=AbstractPlus

10. Neyts J, Snoeck R, Schols D et al. Selective inhibition of human cytomegalovirus DNA synthesis by (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] and 9-(1,3- dihydroxy-2-propoxymethyl)guanine (DHPG). Virology. 1990; 179:41-50. http://www.ncbi.nlm.nih.gov/pubmed/2171213?dopt=AbstractPlus

11. Neyts J, Snoeck R, Balzarini J et al. Particular characteristics of the anti-human cytomegalovirus activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) in vitro. Antivir Res. 1991; 16:41-52. http://www.ncbi.nlm.nih.gov/pubmed/1663729?dopt=AbstractPlus

12. Snoeck R, Sakuma T, De Clercq E et al. (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother. 1988; 32:1839-44. http://www.ncbi.nlm.nih.gov/pubmed/2854454?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=176029&blobtype=pdf

13. Bronson JJ, Ghazzouli I, Hitchcock MJM et al. Synthesis and antiviral activity of the nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy) propyl]cytosine. J Med Chem. 1989; 32:1457-63. http://www.ncbi.nlm.nih.gov/pubmed/2544723?dopt=AbstractPlus

14. De Castro LM, Kern ER, De Clercq E et al. Phosphonylmethoxyalkyl purine and pyrimidine derivatives for the treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS. Antivir Res. 1991; 16:101-14. http://www.ncbi.nlm.nih.gov/pubmed/1663726?dopt=AbstractPlus

15. De Clercq E, Sakuma T, Baba M et al. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antivir Res. 1987; 8:261-72. http://www.ncbi.nlm.nih.gov/pubmed/3451698?dopt=AbstractPlus

16. Ho H-T, Woods KL, Bronson JJ et al. Intracellular metabolism of the antiherpes agent (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine. Mol Pharmacol. 1991; 41:197- 202.

17. Polis MA, Masur H. Promising new treatments for cytomegalovirus retinitis. JAMA. 1995; 273:1457-59. http://www.ncbi.nlm.nih.gov/pubmed/7723160?dopt=AbstractPlus

18. Lalezari JP, Drew WL, Glutzer E et al. (S)-1-[3-hydroxy-2- (phosphonylmethoxy)propyl]cytosine (cidofovir): results of a phase I/II study of a novel antiviral nucleotide analogue. J Infect Dis. 1995; 171:788-96. http://www.ncbi.nlm.nih.gov/pubmed/7706804?dopt=AbstractPlus

20. Kirsch LS, Arevalo JF, De Clercq E et al. Phase I/II study of intravitreal cidofovir for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol. 1995; 119:466-76. http://www.ncbi.nlm.nih.gov/pubmed/7709971?dopt=AbstractPlus

21. Lalezari JP, Stagg RJ, Kuppermann BD et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial. Ann Intern Med. 1997; 126:257-63. http://www.ncbi.nlm.nih.gov/pubmed/9036797?dopt=AbstractPlus

24. Masur H, Whitcup SM, Cartwright C et al. Advances in the management of AIDS-related cytomegalovirus retinitis. Ann Intern Med. 1996; 125:126-36. http://www.ncbi.nlm.nih.gov/pubmed/8678367?dopt=AbstractPlus

25. Jabs DA. Treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med. 1996; 125:144-5. http://www.ncbi.nlm.nih.gov/pubmed/8678370?dopt=AbstractPlus

26. Rahhal FM, Arevalo JF, Chavez de la Paz E et al. Treatment of cytomegalovirus retinitis with intravitreous cidofovir in patients with AIDS. Ann Intern Med. 1996; 125:98-103. http://www.ncbi.nlm.nih.gov/pubmed/8678386?dopt=AbstractPlus

27. Cantrill HL. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. 1995; 102:542.

28. Yuan LC, Samuels GJ, Visor GC. Stability of cidofovir in 9% sodium chloride injection and in 5% dextrose injection. Am J Health-Syst Pharm. 1996; 53:1939-43. http://www.ncbi.nlm.nih.gov/pubmed/8862207?dopt=AbstractPlus

29. Jaffe HS. Dear healthcare provider letter: reports of severe renal impairment. Foster City, CA: Gilead Sciences; 1996 Sept.

30. Gilead Sciences, Foster City, CA: Personal communication.

31. Lalezari JP, Holland GN, Kramer F et al. Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 17:339-44. http://www.ncbi.nlm.nih.gov/pubmed/9525435?dopt=AbstractPlus

33. Alrabiah FA, Sacks SL. New antiherpesvirus agents. Drugs. 1996; 52:17-32. http://www.ncbi.nlm.nih.gov/pubmed/8799682?dopt=AbstractPlus

34. Adrei G, Snoeck R, Vandeputte M et al. Activities of various compounds against murine and primate polyomaviruses. Antimicrob Agents Chemother. 1997; 41:587-93. http://www.ncbi.nlm.nih.gov/pubmed/9055998?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=163756&blobtype=pdf

35. Safrin SF. Dear health care professional. Reinforcement of guidelines to prevent nephrotoxicity with vistide use, and reports of uveitis/iritis, hearing loss. Foster City, CA: Gilead Sciences; 1998 Aug.

36. Palau LA, Tufty GT, Pankey GA. Recurrent iritis after intravenous administration of cidofovir. Clin Infect Dis. 1997; 25:337-8. http://www.ncbi.nlm.nih.gov/pubmed/9332544?dopt=AbstractPlus

37. Whitley RS, Jacobson MA, Friedberg DN et al. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy - recommendations of an international panel. Arch Intern Med. 1998; 158:957-69. http://www.ncbi.nlm.nih.gov/pubmed/9588429?dopt=AbstractPlus

39. LoPresti AE, Levine JF, Munk GB et al. Successful treatment of an acyclovir- and foscarnet-resistant herpes simplex virus type 1 lesion with intravenous cidofovir. Clin Infect Dis. 1998; 26:512-3. http://www.ncbi.nlm.nih.gov/pubmed/9502489?dopt=AbstractPlus

40. Martinez CM, Luks-Golger DB. Cidofovir use in acyclovir-resistant herpes infection. Ann Pharmacother. 1997; 31:1519-21. http://www.ncbi.nlm.nih.gov/pubmed/9416391?dopt=AbstractPlus

42. Balfour HH. Antiviral drugs. N Engl J Med. 1999; 340:1255-68. http://www.ncbi.nlm.nih.gov/pubmed/10210711?dopt=AbstractPlus

43. Lalezari J, Schacker T, Feinberg J et al. A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS. J Infect Dis. 1997; 176:892-8. http://www.ncbi.nlm.nih.gov/pubmed/9333146?dopt=AbstractPlus

44. Martin DF, Dunn JP, Davis JL et al. Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: recommendations of the International AIDS Society-USA Panel. Am J Ophthalmol. 1999; 127:329-39. http://www.ncbi.nlm.nih.gov/pubmed/10088745?dopt=AbstractPlus

45. LeDuc JW, Jahrling PB. Strengthening national preparedness for smallpox: an update. Emerg Infect Dis. 2001; 7:155-7. http://www.ncbi.nlm.nih.gov/pubmed/11266310?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2631676&blobtype=pdf

46. World Health Organization. Smallpox eradication: temporary retention of variola stocks. Report of the secretariat. Fifty-fourth world health assembly A54/16, 2001 April.

47. DeClerq E. Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infection. Clin Microbiol Rev. 2001; 14:382-97. http://www.ncbi.nlm.nih.gov/pubmed/11292644?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=88980&blobtype=pdf

48. Smee DF, Bailey KW, Wong M et al. Intranasal treatment of cowpox virus infections in mice with cidofovir. Antiviral Res. 2000; 47:171-7. http://www.ncbi.nlm.nih.gov/pubmed/10974369?dopt=AbstractPlus

49. Rotz LD, Dotson DA, Damon IK et al. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001. MMWR Recomm Rep. 2001; 50(RR-10):1-25; quiz CE1-7. http://www.ncbi.nlm.nih.gov/pubmed/15580803?dopt=AbstractPlus

50. Henderson DA, Inglesby TV, Bartlett JG et al. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 1999; 281:2127-37. http://www.ncbi.nlm.nih.gov/pubmed/10367824?dopt=AbstractPlus

51. US Army Medical Research Institute of Infectious Diseases. USAMRIID’s medical management of biologic casualties handbook. 8th ed. Fort Detrick, MD: USAMRIID; 2014 Sep.

53. De Clercq E. Cidofovir in the treatment of poxvirus infections. Antiviral Res. 2002; 55:1-13. http://www.ncbi.nlm.nih.gov/pubmed/12076747?dopt=AbstractPlus

54. Bray M, Martinez M, Smee DF et al. Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge. J Infect Dis. 2000; 181:10-9. http://www.ncbi.nlm.nih.gov/pubmed/10608745?dopt=AbstractPlus

55. Smee DF, Bailey KW, Sidwell RW. Treatment of lethal vaccinia virus respiratory infections in mice with cidofovir. Antiviral Chem Chemother. 2001; 12:71-6.

56. Bray M, Martinez M, Kefauver D et al. Treatment of aerosolized cowpox virus infection in mice with aerosolized cidofovir. Antiviral Res. 2002; 54:129-42. http://www.ncbi.nlm.nih.gov/pubmed/12062386?dopt=AbstractPlus

57. Snoeck R, Holy A, Dewolf-Peeters C et al. Antivaccinia activities of acyclic nucleoside phosphonate derivatives in epithelial cells and organotypic cultures. Antimicrob Agents Chemother. 2002; 46:3356-61. http://www.ncbi.nlm.nih.gov/pubmed/12384336?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=128754&blobtype=pdf

59. De Clercq E. Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infection. Clin Microbiol Rev. 2001; 14:382-97. http://www.ncbi.nlm.nih.gov/pubmed/11292644?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=88980&blobtype=pdf

60. Smee DF, Bailey KW, Wong M et al. Intranasal treatment of cowpox virus infections in mice with cidofovir. Antiviral Res. 2000; 47:171-7. http://www.ncbi.nlm.nih.gov/pubmed/10974369?dopt=AbstractPlus

63. Centers for Disease Control and Prevention. Smallpox vaccination and adverse reactions: guidance for clinicians. MMWR Recomm Rep. 2003; 52(RR-4):1-28.

64. Smee DF, Bailey KW, Wong MH et al. Effects of cidofovir on the pathogenesis of a lethal vaccinia virus respiratory infection in mice. Antiviral Res. 2001; 52:55-62. http://www.ncbi.nlm.nih.gov/pubmed/11530188?dopt=AbstractPlus

65. Wharton M, Strikas RA, Harpaz R et al. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 2003; 52(RR-7):1-16. http://www.ncbi.nlm.nih.gov/pubmed/12710832?dopt=AbstractPlus

66. Smee DF, Sidwell RW. A review of compounds exhibiting anti-orthopoxvirus activity in animal models. Antiviral Res. 2003; 57:41-52. http://www.ncbi.nlm.nih.gov/pubmed/12615302?dopt=AbstractPlus

67. Huggins JW, Smee D, Martinez MJ et al. Cidofovir (HPMPC) treatment of monkeypox. Antiviral Res. 1998; 37:A73.

68. Baker RO, Bray M, Huggins JW. Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections. Antiviral Res. 2003; 57:13-23. http://www.ncbi.nlm.nih.gov/pubmed/12615299?dopt=AbstractPlus

70. Centers for Disease Control and Prevention. Smallpox: Medical management of adverse reactions. 2016 Dec 5. From the CDC website. Accessed 2019 Jan 21. https://www.cdc.gov/smallpox/clinicians/vaccine-medical-management6.html

71. Centers for Disease Control and Prevention. Monkeypox: Treatment. 22016 Dec 7. From the CDC website. Accessed 2019 Jan 21. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html

72. HHS Office of the Assistant Secretary for Preparedness and Response (ASPR). Strategic National Stockpile. From the Public Health Emergency website. Accessed 2019 Feb 25. https://www.phe.gov/about/sns/Pages/default.aspx

73. Bialek SM (Office of the Assistant Secretary for Preparedness and Response). Personal communication.

75. Andrei G, Snoeck R. Cidofovir and brincidofovir. In: Grayson ML, ed. Kucers' the use of antibiotics: a clinical review of antibacterial, antifungal, antiparasitic, and antiviral drugs. 7th ed. Boca Raton, FL: CRC Press; 2018:3531-71.

76. De Clercq E. Acyclic nucleoside phosphonates: past, present and future. Bridging chemistry to HIV, HBV, HCV, HPV, adeno-, herpes-, and poxvirus infections: the phosphonate bridge. Biochem Pharmacol. 2007; 73:911-22. http://www.ncbi.nlm.nih.gov/pubmed/17045247?dopt=AbstractPlus

77. Magee WC, Hostetler KY, Evans DH. Mechanism of inhibition of vaccinia virus DNA polymerase by cidofovir diphosphate. Antimicrob Agents Chemother. 2005; 49:3153-62. http://www.ncbi.nlm.nih.gov/pubmed/16048917?dopt=AbstractPlus

78. Usoro A, Batts A, Sarria JC. Intravenous Foscarnet With Topical Cidofovir for Chronic Refractory Genital Herpes in a Patient With AIDS. J Investig Med High Impact Case Rep. 2015 Oct-Dec; 3:2324709615621095. http://www.ncbi.nlm.nih.gov/pubmed/26788527?dopt=AbstractPlus

155. Panel on Opportunistic Infection in HIV-infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (Accessed February 6, 2019). Updates may be available at HHS AIDS Information (AIDSinfo) website https://aidsinfo.nih.gov/guidelines

156. Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, and the Pediatric Infectious Diseases Society (Accessed February 6, 2019). Updates may be available at HHS AIDS Information (AIDSinfo) website https://aidsinfo.nih.gov/guidelines

344. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep. 2015; 64(RR-03):1-137. http://www.ncbi.nlm.nih.gov/pubmed/26042815?dopt=AbstractPlus

HID. ASHP’s interactive handbook on injectable drugs. McEvoy, GK, ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc; Updated April 20, 2015. From HID website http://www.interactivehandbook.com/

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