Skip to main content
Log in

Adverse Effects and Drug Interactions of Clinical Importance with Antiviral Drugs

  • Review Article
  • Drug Experience
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Most antiviral drugs are nucleoside analogues with potential teratogenic, embryotoxic, carcinogenic and antiproliferative activities. They must be administered with caution during pregnancy, because some are known teratogens (e.g. amantadine) and a similar propensity cannot be entirely excluded for others (e.g. aciclovir). Their adverse effects mostly involve bone marrow depression (e.g. granulocytopenia with ganciclovir, anaemia with zidovudine) or neurotoxicity (e.g. seizures with interferon-α, peripheral neuropathy with zalcitabine), although gastrointestinal effects are also seen. Idiosyncratic reactions include didanosine-induced acute pancreatitis. Only inosine pranobex is largely free from toxicity. Idoxuridine must be administered topically, given the severity of its systemic adverse effects.

Drug interactions involving antiviral agents mostly reflect shared toxicity with other agents (e.g. neutropenia with ganciclovir and zidovudine, pancreatitis with didanosine and alcohol), although renal excretion or hepatic metabolism may be implicated.

Given the possibility of severe adverse reactions and drug interactions, antiviral chemotherapy should only be used for potentially serious virus infections. Topical administration avoids systemic adverse effects but not mutagenic risks, and may result in exposure of individuals other than the patient (e.g. aerosolised ribavirin).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • ABPI Data Sheet Compendium 1993–1994, Datapharm Publications Ltd, London, 1993

  • Abrams DI, Goldman AI, Launer C, et al. A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. New England Journal of Medicine 330: 657–662, 1994

    Article  PubMed  CAS  Google Scholar 

  • Averbuch SD, AustinIII HA, Sherwin SA, Antonovych T, Bunn PA. Acute interstitial nephritis with the nephrotic syndrome following recombinant leukocyte A interferon therapy for mycosis fungoides. New England Journal of Medicine 310: 32–35, 1984

    Article  PubMed  CAS  Google Scholar 

  • Bach MC. Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS. New England Journal of Medicine 317:547, 1987

    Article  Google Scholar 

  • Blalock JE, Stanton JD. Common pathways of interferon and hormonal action. Nature 283: 406–408, 1980

    Article  PubMed  CAS  Google Scholar 

  • Boston Interhospital Virus Study Group and the NIAID-Sponsored Co-operative Antiviral Clinical Study. Failure of high dose 5-iodo-2-deoxyuridine in the therapy of herpes simplex virus encephalitis. Evidence of unacceptable toxicity. New England Journal of Medicine 292: 599–603, 1975

    Article  Google Scholar 

  • Burger DM, Meenhorst PL, Koks CHW, Beijnen JH. Drug interactions with zidovudine. AIDS 7: 445–460, 1993

    Article  PubMed  CAS  Google Scholar 

  • Capsey LJ, Jones KL, Snell NJC. Safety and tolerance of nebulised ribavirin in clinical usage. Acta Therapeutica 18: 133–147, 1992

    Google Scholar 

  • Centers for Disease Control. Prevention and control of influenza: recommendations of the Immunization Practices Advisory Committee (ACIP). Morbidity and Mortality Weekly Report 40: 1–15, 1991

    Google Scholar 

  • Centers for Disease Control. Pregnancy outcomes following systemic prenatal acyclovir exposure —June 1 1984 —June 30 1993. Morbidity and Mortality Weekly Report 42: 806–809, 1993

    Google Scholar 

  • Chang T-W, Heel RC. Ribavirin and inosplex: a review of their present status in viral diseases. Drugs 22: 111–128, 1981

    Article  PubMed  CAS  Google Scholar 

  • DeArmandT B. Safety consideration in the use of ganciclovir in immunocompromised patients. Transplant Proceedings 23 (2 Suppl. 1) 26–29, 1991

    Google Scholar 

  • Dorr RT. Interferon-α in malignant and viral diseases. Drugs 45: 177–211, 1993

    Article  PubMed  CAS  Google Scholar 

  • Dorr RT, Shipp NG. Effect of interferon, interleukin-2 and tumour necrosis factor on myocardial cell viability and doxorubicin cardiotoxicity in vitro. Immunopharmacology 18: 31–38, 1989

    Article  PubMed  CAS  Google Scholar 

  • Faulds D, Heel RC. Ganciclovir. A review of its antiviral activity, pharmacokinetic properties, and therapeutic efficacy in cytomegalovirus infections. Drugs 39: 597–638, 1990

    Article  PubMed  CAS  Google Scholar 

  • Goldstein D, Gockerman J, Krishnan R, et al. Effects of γ-interferon on the endocrine system: results from a phase I study. Cancer Research 47: 6397–6401, 1987

    PubMed  CAS  Google Scholar 

  • Groopman JE, Mitsuyasa RT, DeLeo MJ, Oette DH, Golde DW. Effect of recombinant human granulocyte-macrophage colony stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. New England Journal of Medicine 317: 593–598, 1987

    Article  PubMed  CAS  Google Scholar 

  • Gururangan S, Stevens R, Morris D. Ribavirin response in measles pneumonia. Journal of Infection 20: 219–221, 1990

    Article  PubMed  CAS  Google Scholar 

  • Hartshorn KL, Vogt MW, Chou TC, Blumberg RS, Byington R, et al. Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha A interferon. Antimicrobial Agents and Chemotherapy 31: 168–172, 1987

    Article  PubMed  CAS  Google Scholar 

  • Heylen R Miller R. Interactions with antiretroviral drugs. Pharmaceutical Journal (Feb. 13): 214–216, 1993

    Google Scholar 

  • Hicks R, Olson L, Jackson M, Barry V. Precipitation of ribavirin causing obstruction of a ventilator tube. Pédiatric Infectious Disease Journal 5: 707–708, 1986

    Article  CAS  Google Scholar 

  • Jones GJ, Itri LM. Safety and tolerance of recombinant interferon alpha-2a (Roferon-A® in cancer patients. Cancer 57: 1709–1715, 1986

    Article  PubMed  CAS  Google Scholar 

  • Krown SF, Gold JWM, Niedzwiecki D, et al. Interferon-α with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine 112:812–821, 1990

    PubMed  CAS  Google Scholar 

  • Lee BL, Safrin S. Interactions and toxicities of drugs used in patients with AIDS. Clinical Infectious Diseases 14: 773–779, 1992

    Article  PubMed  CAS  Google Scholar 

  • Merigan TC, Skowron G, Bozzett SA, et al. Circulating p24 antigen levels and response to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study. Annals of Internal Medicine 110: 189–194, 1989

    PubMed  CAS  Google Scholar 

  • Miller RL, Steis RG, Clark JW, et al. Randomized trial of recombinant (α2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. Cancer Research 49: 1871–1876, 1989

    PubMed  CAS  Google Scholar 

  • Morris DJ. Antiviral chemotherapy for cytomegalovirus disease. Journal of Antimicrobial Chemotherapy 21: 519–522, 1988a

    Article  CAS  Google Scholar 

  • Morris DJ. Antiviral chemoprophylaxis for cytomegalovirus disease. Journal of Antimicrobial Chemotherapy 22: 569, 1988b

    Article  CAS  Google Scholar 

  • Morris DJ. Clinical trials of antiviral agents. Journal of Antimicrobial Chemotherapy 29: 97–103, 1992

    Article  PubMed  CAS  Google Scholar 

  • Naito T, Shiota H, Mimura Y. Side effects in the treatment of herpetic keratitis. Current Eye Research 6: 237–239, 1987

    Article  PubMed  CAS  Google Scholar 

  • Palestine AG, Polis MA, De Smet MD, et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Annals of Internal Medicine 115: 665–673, 1991

    PubMed  CAS  Google Scholar 

  • Parkinson A, Lasker J, Kramer MJ, et al. Effect of three recombinant human leukocyte interferons on drug metabolism in mice. Drug Metabolism and Disposition 10: 579–585, 1982

    PubMed  CAS  Google Scholar 

  • Reines ED, Gross PA. Antiviral agents. Medical Clinics of North America 72: 691–715, 1988

    PubMed  CAS  Google Scholar 

  • Ross AV, Julia A, Balakrisnan C. Toxicity of adenine arabinoside in humans. Journal of Infectious Diseases 133 (Suppl. 1): A192–A198, 1976

    Article  PubMed  Google Scholar 

  • Rupprecht Rm, O’Brien L, Rosas D, Andersen J. Recombinant human interferon a A/D (F Hu IFN-α A/D) enhances the antiretroviral effect of 3′-arido-3′-deoxythymidine (AZT) in mice. Proceedings of the American Association of Cancer Research 28: 456,1987

    Google Scholar 

  • Smith O, Frankel L, Mathers L, Tang A, Ariagno R, et al. A controlled trial of aerosolised ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection. New England Journal of Medicine 325: 24–29, 1991

    Article  PubMed  CAS  Google Scholar 

  • Yarchoan R, Mitsuya H, Thomas RV, et al. In vivo activity against HIV and favourable toxicity profile of 2′,3′-dideoxyinosine. Science 245: 412–415, 1989

    Article  PubMed  CAS  Google Scholar 

  • Yarchoan R, Peno CF, Thomas RV, et al. Phase I studies of 2′, 3′-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). Lancet 1:76–81, 1988

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morris, D.J. Adverse Effects and Drug Interactions of Clinical Importance with Antiviral Drugs. Drug-Safety 10, 281–291 (1994). https://doi.org/10.2165/00002018-199410040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199410040-00002

Keywords

Navigation