Parenteral Acyclovir Short-age: Alternative Antiviral Agents for Adults and Pediatric/Neonatal Patients
Special Feature
By Jessica C. Song, MA, Pharm.D, Assistant Professor, Pharmacy Practice, University of the Pacific, Stockton, CA, Pharmacy Clerkship and Coordinator, Santa Clara Valley Medical Center Section Editor, Managed Care, is Associate Editor for Infectious Disease Alert.
By Hyunah Eom, PharmD at the University of the Pacific
Jessica C. Song and Hyunah Eom report no financial relationships relevant to this field of study.
Acyclovir (9-[2-Hydroxymethyl] Guanine) is a nucleoside analog known for its activity (in descending order of susceptibility) against Herpes Simplex virus (HSV) types 1 and 2, Varicella-Zoster virus (VZV), and Epstein-Barr virus (EBV).1-4 The intravenous formulation of acyclovir is used for the management of HSV encephalitis, VZV infections, HSV Zoster, and other severe HSV infections.4-10 Table 1 provides a summary of the key pharmacologic properties of the parenteral acyclovir formulation marketed in the United States.
A recent bulletin released by American Pharmaceutical Partner (APP), one of the two manufacturers of intravenous acyclovir in the U.S. market, indicated a critical shortage of this product secondary to increased demand and manufacturing delays. At present, resumption of full supply status is anticipated by May 2009.1
National guidelines for the management of HSV/VZV encephalitis,5 genital/severe HSV infections,8 and HSV/VZV infections in immunocompromised hosts,6,10 have consistently featured intravenous acyclovir as the first-line agent for all patient populations. Alternative antiviral agents with inhibitory activity against HSV and VZV include foscarnet and ganciclovir.4 However, the relative paucity of clinical trials utilizing these drugs in the management of HSV- and VZV-infected patients, along with problematic adverse effect profiles, have limited the use of these drugs to cytomegalovirus infections.5,6,10
Recommendations
Tables 2 and 3 highlight key recommendations from the Infectious Diseases Society of America, the CDC, the American Academy of Pediatrics, and from the U.S. Department of Health and Human Services with regard to the management of HSV encephalitis, VZV infections, HSV Zoster, and other severe HSV infections.5,6,8-10 Final recommendations for healthcare practitioners to consider during this period of limited supply of intravenous acyclovir include:
- Conserving use of existing supplies of intravenous acyclovir for neonatal HSV infections (including HSV encephalitis);
- Conserving use of existing supplies of intravenous acyclovir for patients (pediatric, adult) with HSV encephalitis;
- Conserving use of existing supplies of intravenous acyclovir for immunocompromised patients, including more critically ill pregnant females with visceral dissemination of HSV or VZV;
- For less serious HSV infections in immunocompetent hosts (e.g., recurrent herpes labialis) or for VZV infections in immunocompetent hosts, use oral valacyclovir or oral acyclovir;
- Due to the disadvantageous toxicity profile of foscarnet (renal dysfunction, hypocalcemia, hypophosphatemia, hypomagnesemia, hypokalemia), ganciclovir represents the first-line alternate agent for use in HSV/VZV infections;
- Ganciclovir should not be used if ANC < 500/mm3 or if platelet < 25,000/mm3. Renal dose adjustment is required (refer to Table 2), and seizure threshold lowering may occur when this drug is administered concomitantly with imipenem/cilastatin;
- Foscarnet has primarily been used as an alternative antiviral agent for immunocompromised patients displaying acyclovir-resistant HSV- or VZV- isolates. Renal dose adjustment (refer to Table 2) is required; and
- Use of acyclovir, ganciclovir, and foscarnet should be restricted to approval by an Infectious Disease Consult Service.
References
- FDA Alert Forwarding. Critical Shortage of Intravenous Acyclovir: FDA Approves New Supplier. http://www.idsociety.org/Content.aspx?id=13444. Accessed on February 12, 2009.
- Acyclovir for Injection prescribing information. Bedford, OH: Bedford Laboratories; 2005 June.
- Acyclovir for Injection prescribing information. Schaumberg, IL: American Pharmaceutical Partner Laboratories; 2008 January.
- Nucleosides and Nucleotides. In: McEvoy GK, Snow EK, Kester L, Litvak K, Miller J, Welsh OH, eds. AHFS 2008 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2008: 791-798.
- Tunkel AR, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008;47:303-327.
- Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. June 18, 2008. http://AIDSinfo.nih.gov. Accessed on February 10, 2009.
- Poscher ME. Successful treatment of varicella zoster virus meningoencephalitis in patients with AIDS: report of four cases and review. AIDS. 1994;8:1115-1117.
- Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55:1-94.
- American Academy of Pediatrics. Herpes Simplex. In: Pickering L, Baker CJ, Long SS, McMillan JA, ed. Red Book: 2009 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009: online-posting.
- Guidelines for Prevention and Treatment of Opportunistic Infections Among HIV-Exposed or HIV-Infected Children. June 20, 2008: http://AIDSinfo.nih.gov. Accessed on February 10, 2009.
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