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Vistide (Cidofovir) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Probenecid

Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine). Concomitant medications should be carefully assessed. Zidovudine should either be temporarily discontinued or decreased by 50% when coadministered with probenecid on the day of VISTIDE infusion.

Nephrotoxic agents

Concomitant administration of VISTIDE and agents with nephrotoxic potential [e.g., intravenous aminoglycosides (e.g., tobramycin, gentamicin, and amikacin), amphotericin B, foscarnet, intravenous pentamidine, vancomycin, and nonsteroidal anti-inflammatory agents] is contraindicated. Such agents must be discontinued at least seven days prior to starting therapy with VISTIDE.

OVERDOSAGE

Two cases of cidofovir overdose have been reported. These patients received single doses of VISTIDE at 16.3 mg/kg and 17.4 mg/kg, respectively, with concomitant oral probenecid and intravenous hydration. In both cases, the patients were hospitalized and received oral probenecid (one gram three times daily) and vigorous intravenous hydration with normal saline for 3 to 5 days. Significant changes in renal function were not observed in either patient.

CONTRAINDICATIONS

Initiation of therapy with VISTIDE is contraindicated in patients with a serum creatinine > 1.5 mg/dL, a calculated creatinine clearance ≤ 55 mL/min, or a urine protein ≥ 100 mg/dL (equivalent to ≥ 2+ proteinuria).

VISTIDE is contraindicated in patients receiving agents with nephrotoxic potential. Such agents must be discontinued at least seven days prior to starting therapy with VISTIDE.

VISTIDE is contraindicated in patients with hypersensitivity to cidofovir.

VISTIDE is contraindicated in patients with a history of clinically severe hypersensitivity to probenecid or other sulfa-containing medications.

Direct intraocular injection of VISTIDE is contraindicated; direct injection of cidofovir has been associated with iritis, ocular hypotony, and permanent impairment of vision.

REFERENCES

  1. Ho HT, Woods KL, Bronson JJ, De Boeck H, Martin JC and Hitchcock MJM. Intracellular Metabolism of the Antiherpesvirus Agent (S)-1-[3-hydroxy-2-(phosphonylmethoxy) propyl]cytosine. Mol Pharmacol   41:197–202, 1992.
  2. Cherrington JM, Allen SJW, McKee BH, and Chen MS. Kinetic Analysis of the Interaction Between the Diphosphate of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, zalcitabineTP, zidovudineTP, and FIAUTP with Human DNA Polymerases b and g. Biochem Pharmacol   48:1986–1988, 1994.
  3. Xiong X, Smith JL, Kim C, Huang E, and Chen MS. Kinetic Analysis of the Interaction of Cidofovir Diphosphate with Human Cytomegalovirus DNA Polymerase. Biochem Pharmacol   51:1563–1567, 1996.
  4. Cherrington JM, Mulato AS, Fuller MD, Chen MS. In Vitro Selection of a Human Cytomegalovirus (HCMV) that is Resistant to Cidofovir. 35th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Francisco, CA. Abstract H117, 1995.
  5. Stanat SC, Reardon JE, Erice A, Jordan MC, Drew WL, and Biron KK. Ganciclovir-Resistant Cytomegalovirus Clinical Isolates: Mode of Resistance to Ganciclovir. Antimicrob Agents Chemother   35:2191–2197, 1991.
  6. Sullivan V, Biron KK, Talarico C, Stanat SC, Davis M, Pozzi M, and Coen DM. A Point Mutation in the Human Cytomegalovirus DNA Polymerase Gene Confers Resistance to Ganciclovir and phosphonylmethoxyalkyl Derivatives. Antimicrob Agents Chemother   37:19–25, 1993.
  7. Tatarowicz WA, Lurain NS, and Thompson KD. A Ganciclovir-Resistant Clinical Isolate of Human Cytomegalovirus Exhibiting Cross-Resistance to other DNA Polymerase Inhibitors. J Infect Dis   166:904–907, 1992.
  8. Lurain NS, Thompson KD, Holmes EW, and Read GS. Point Mutations in the DNA Polymerase Gene of Human Cytomegalovirus that Result in Resistance to Antiviral Agents. J Virol   66:7146–7152, 1992.
  9. Smith IL, Cherrington JM, Jiles RE, Fuller MD, Freeman WR, Spector SA. High-level Resistance of Cytomegalovirus to Ganciclovir is Associated with Alterations in both the UL97 and DNA Polymerase Genes. J Infect Dis   176:69–77, 1997.
  10. Sullivan V and Coen DM. Isolation of Foscarnet-Resistant Human Cytomegalovirus Patterns of Resistance and Sensitivity to Other Antiviral Drugs. J Infect Dis   164:781–784, 1991.
  11. Snoeck R, Andrei G, and De Clercq E. Patterns of Resistance and Sensitivity to Antiviral Compounds of Drug-Resistant Strains of Human Cytomegalovirus Selected in Vitro. Eur J Clin Microbiol Infect Dis   15:574–579, 1996.
  12. Baldanti F, Underwood MR, Stanat SC, Biron KK, Chou S, Sarasini A, Silini E, and Gerna G. Single Amino Acid Changes in the DNA Polymerase Confer Foscarnet Resistance and Slow-Growth Phenotype, While Mutations in the UL97-Encoded Phosphotransferase Confer Ganciclovir Resistance in Three Double-Resistant Human Cytomegalovirus Strains Recovered from Patients with AIDS. J Virol   70:1390–1395, 1996.
  13. The Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trials Group. Cidofovir (HPMPC) for the Treatment of Cytomegalovirus Retinitis in Patients with AIDS: the HPMPC Peripheral Cytomegalovirus Retinitis Trial. Ann Intern Med   126:264–274, 1997.
  14. Lalezari JP, Stagg RJ, Kupperman BD, et al. Intravenous Cidofovir for Peripheral Cytomegalovirus Retinitis in Patients with AIDS. A Randomized, Controlled Trial. Ann Intern Med   126:257–263, 1997.

© Gilead Sciences, Inc., 2000; all rights reserved.

Part Number: RM-1282
September 2000

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