OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Ganciclovir	82410-32-0	C9-H13-N5-O4
Valganciclovir	175865-60-8	C14-H22-N6-O5

ANNOTATED BIBLIOGRAPHY

References updated: 06 March 2018

• Zimmerman HJ. Antiviral agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 621-3.

  (Expert review of antiviral agents and liver injury published in 1999; mentions that ganciclovir has not caused "overt hepatic injury").
• Núñez M. Hepatotoxicity of antiviral agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 505-18.

  (Review of hepatotoxicity of antiviral agents; ganciclovir and valganciclovir have been linked to serum enzyme elevations during therapy, and cases of clinically apparent liver injury have been reported to the sponsor).
• Acosta EP, Flexner C. Antiviral agents (nonretroviral). In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1593-1622.

  (Textbook of pharmacology and therapeutics).
• Styrt B, Freiman JP. Hepatotoxicity of antiviral agents. Gastroenterol Clin North Am 1995; 24: 839-52. [PubMed: 8749901]

  (Review of liver toxicity of antiviral agents; intravenous administration of ganciclovir has been reported to cause serum aminotransferase elevations in 2% of patients).
• Herraiz M, Beraza N, Solano A, Snagro B, Montoya J, Qian C, Prieto J, et al. Liver failure caused by herpes simplex virus thymidine kinase plus ganciclovir therapy is associated with mitochondrial dysfunction and mitochondrial DNA depletion. Human Gene Ther 2003; 14: 463-72. [PubMed: 12691611]

  (In a rat model, the adenoviral transfer of thymidine kinase followed by ganciclovir leads to acute hepatocellular injury with evidence of mitochondrial injury, lactic acid elevations and morphologic changes; this form of toxicity is only a concern for gene therapy studies in which there may be gene transfer of the viral kinase to normal hepatocytes).
• Reusser P. Oral valganciclovir: a new option for treatment of cytomegalovirus infection and disease in immunocompromised hosts. Expert Opin Investig Drugs 2001; 10: 1745-53. [PubMed: 11772283]

  (Review of valganciclovir, an oral prodrug of ganciclovir, which is active against CMV infection and disease; no mention of hepatotoxicity or ALT elevations with therapy).
• Shea BF, Hoffman S, Sesin GP, Hammer SM. Ganciclovir hepatotoxicity. Pharmacotherapy 1987; 7: 223-6. [PubMed: 2832836]

  (33 year old man with HIV infection, CMV retinitis and mycobacterium avium intracellulare [MAC] infections developed increases in preexisting elevated enzyme levels without bilirubin elevations during two courses of ganciclovir [ALT 133 rising to ~500 U/L, AlkP 181 rising to 1014 U/L], peaking several weeks after stopping and then decreasing; liver biopsy showed MAC and no evidence of hepatitis).
• Hochster H, Dieterich D, Bozzette S, Reichman RC, Connor JD, Liebes L, Sonke RL, et al. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS. An AIDS Clinical Trials Group Study. Ann Intern Med 1990; 113: 111-7. [PubMed: 2163228]

  (40 patients with HIV and CMV infection were treated with zidovudine and intravenous ganciclovir; anemia and neutropenia were common; 1 patient developed hepatitis thought to be zidovudine-related, resolving on stopping and recurred on restarting zidovudine [timing and details not given]).
• Figge HL, Bailie GR, Briceland LL, Kowalsky SF. Possible ganciclovir-induced hepatotoxicity in patients with AIDS. Clin Pharm 1992; 11: 432-4. [PubMed: 1316254]

  (Retrospective review of 14 courses of ganciclovir in 11 patients with HIV infection identified 5 with associated elevations in AST [29-36 rising to 55-110 U/L] or Alk P [61 rising to 360 U/L], but all were receiving other potentially hepatotoxic agents and no patient was reported to develop hepatitis or jaundice).
• Gish RG, Lau JY, Brooks L, Fang WS, Steady SL, Imperial JC, Garcia-Kennedy R, et al. Ganciclovir treatment of hepatitis B virus infection in liver transplant recipients. Hepatology 1996; 23: 1-7. [PubMed: 8550028]

  (9 patients with recurrent hepatitis B after liver transplant were treated with ganciclovir for 3-10 months; serum HBV DNA and ALT levels decreased on therapy and flare occurred in 3 when ganciclovir was stopped, one becoming jaundiced and developing hepatic decompensation).
• Noormohamed SE. Potential of ganciclovir to induce hepatotoxicity in patients with HIV disease. J Infect Dis Pharmacother 1997; 2: 95-101. Not in PubMed.
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008; 8 were attributed to antiviral agents including one attibuted to valacyclovir, but none were attributed to ganciclovir or valganciclovir).
• Witzke O, Hauser IA, Bartels M, Wolf G, Wolters H, Nitschke M; VIPP Study Group. Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: 1-year results of a randomized clinical trial. Transplantation 2012; 93: 61-8. [PubMed: 22094954]

  (Controlled trial of prophylaxis vs preemptive therapy of CMV infection in 296 renal allograft recipients; overall tolerability was good and no mention of ALT elevations or hepatotoxicity).
• Antiviral drugs. Treat Guidel Med Lett 2013; 11 (127): 19-30. [PubMed: 23459414]

  (Review of safety and efficacy of ganciclovir and valganciclovir treatment and prophylaxis against CMV infection; mentions that adverse effects include "abnormal liver function").
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, two cases were attributed to valacyclovir and one to acyclovir, but none to ganciclovir or valganciclovir).