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February 2009
Volume 19 Issue 2
Patient Care and Science
EIN Considers Alternatives to Acyclovir During Shortage

The Emerging Infections Network (EIN) is a forum for infectious diseases consultants and public health officials to report information on clinical phenomena and epidemiological issues with public health significance. Any diagnostic or therapeutic recommendations and all opinions presented are those of the individual contributor. They do not necessarily represent the views of EIN, IDSA (EIN's sponsor), or the Centers for Disease Control and Prevention, which funds the EIN. The reader assumes all risks in using this information.

A shortage of acyclovir for injection has EIN members considering alternatives for treating neonatal herpes simplex virus (HSV) or varicella zoster virus (VZV) infections and other pediatric central nervous system (CNS) infections.  

Several respondents reported that their institutions were almost out of IV acyclovir and were placing restrictions on orders. A respondent in Alabama noted that the American Academy of Pediatrics (AAP) Committee on Infectious Diseases recommends conserving intravenous (IV) acyclovir for immunocompromised patients.

The Alabama respondent said AAP recommends that, “When parenteral acyclovir is not available, intravenous ganciclovir should be substituted. This recommendation is based on in vitro susceptibility data and the relatively more manageable toxicities of ganciclovir as compared with foscarnet and cidofovir. Additionally, cidofovir does not cross the blood-brain barrier, further limiting its utility in central nervous system infections.”

The respondent continued, “Since there is a lack of clinical experience with ganciclovir in treatment of these diseases, close monitoring for therapeutic effect is warranted, including follow-up sampling of cerebrospinal fluid for HSV or VZV DNA PCR when central nervous system disease is present. Adverse events relating to use of an antiviral medication other than acyclovir should be reported to MedWatch.”

An article in AAP News describes the recommendations and the shortage in more detail.

Other EIN members discussed different options. For infections other than neonatal HSV, a member in Florida wrote, valacyclovir might be a good option. “Data in adults suggest that valacyclovir at 1 g Q 8 hours gives levels similar to IV acyclovir 5 mg/kg Q 8 hours. We might actually be using foscarnet for other pediatric CNS infections due to HSV or VZV after we run out [of acyclovir], since the pharmacokinetics look better than for ganciclovir.” A respondent in California agreed with these suggestions, citing a 2007 Medical Letter article (Abramowicz M, Ed. “Drugs for non-HIV viral infections.” Treatment Guidelines from The Medical Letter. 2007 Jul;5(59):59-70.)

However, a member in Georgia asked, “Can high dose oral valacyclovir be used in patients with HSV meningitis/meningoencephalitis? I thought that the bioavailability of acyclovir and valacyclovir were not adequate for CNS penetration.”

A respondent in California answered, “The problem with treatment of HSV CNS infections with oral therapy is that we are never completely sure how much drug is absorbed for a particular patient, with each particular dose; given that CNS levels are a function of levels in serum, we should attempt to achieve a high and reliable plasma AUC following each antiviral dose. Therefore, given the serious nature of CNS infection (suspected or documented), it seems prudent to use IV therapy. Ganciclovir is IT!”

More information on the shortage can be found on the Food and Drug Administration’s (FDA) drug shortages website.  An EIN respondent from FDA noted that the manufacturer, APP Pharmaceuticals, is currently distributing emergency supplies to meet patient needs until they are able to return to normal distribution, expected in March.

E-mail the Emerging Infections Network.

The Emerging Infections Network (EIN) is a provider-based sentinel network designed to help the public-health community detect trends in emerging infectious diseases.

A joint project of IDSA and the Pediatric Infectious Diseases Society (PIDS) and supported by funding from the Centers for Disease Control and Prevention, EIN tracks emerging infectious diseases and keeps the public-health community up to date with issues that are currently affecting or may soon affect members’ clinical practices.The Network provides a great opportunity for members to share knowledge quickly across large geographical distances. Both IDSA and PIDS members are eligible to join. The EIN listserve allows members to discuss new disease trends and difficult cases. Click here for more information or to join EIN.
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