Elephant specific information, if available, is in blue.

Famciclovir is a human anti-viral drug that has been used to treat endotheliotrophic herpesvirus (EEHV) infection in Asian elephants.

Elephants:

Note: Herpesvirus infections in elephants are acute, severe and often fatal.  To date only 3 of the known cases have survived. Two of these were treated with famciclovir rectally  and one was treated orally.  At least 3 elephants treated with famciclovir have not survived.  In the surviving elephants, loading doses varied from 10.6 to 16.6 mg/kg and duration of treatment varied from 15 to 26 days. Dosages were adjusted during treatment and other supportive drugs were included in the treatment regimen. Veterinarians are urged to contact experienced colleagues for the latest treatment recommendations in suspected cases.

A study to determine the pharmacokinetic parameters is currently under way. Preliminary results suggest 5 mg/kg orally will result in drug levels that should be therapeutic in elephants (Ramiro Isaza, Kansas State University, personal communication).

Elephant References (Only those references that include treatment information are listed below.  For a complete list of elephant herpesvirus references see our Database – Herpesvirus)

a) Montali,R.J., Richman,L.K., Mikota,S.K., Schmitt,D.L., Larsen,R.S., Hildebrandt,T.B., Isaza,R., and Lindsay,W.A.  2001. Management Aspects of Herpesvirus Infections and Tuberculosis in Elephants. A Research Update on Elephants and Rhinos; Proceedings of the International Elephant and Rhino Research Symposium, Vienna, June 7-11, 2001. Pages: 87-95 Abstract: Elephant endotheliotropic herpesvirus (EEHV) infections and tuberculosis have emerged as causes of illness and mortality in captive elephants. Twenty-six confirmed EEHV cases are documented. Since 1995, 7 have occurred in North America, 10 in Europe and 2 in Asia. A PCR test was used to detect the virus in symptomatic animals; a serological test to identify carrier elephants is under development. The African elephant is a potential source of the EEHV that is lethal for Asian elephants. Fatal infections have also occurred in Asian elephants without African elephant contacts. Three of 6 elephants recovered after treatment with antiviral famciclovir; however, more research is needed to improve the usefulness of this drug. Asian elephants that are less than 10-years old and have been moved to another facility and/or have had contact with African elephants are at increased risk for contracting EEHV. Animals traveling between facilities with a history of EEHV cases may be at greater risk. All young elephants should be monitored daily for anorexia, lethargy, body swellings and blue discoloration (bruising) of the tongue, and be trained for blood sampling and potential oral and rectal treatment with famciclovir.

b) Schaftenaar,W., Mensink,J.M.C.H., Deboer,A.M., Hildebrandt,T.B., and Fickel,J.  2001. Successful treatment of a sub adult Asian elephant bull (Elephas maximus) infected with elephant herpes virus. Proc. of the  International Symposium for Diseases of Zoo and Wildlife Animals (Rotterdam).

c) Schmitt,D.L., Hardy,D.A., Montali,R.J., Richman,L.K., Lindsay,W.A., Isaza,R., and West,G. 2000. Use of famciclovir for the treatment of endotheliotrophic herpesvirus infections in Asian elephants (Elephas maximus). Journal of Zoo and Wildlife Medicine 31:(4):518-522  
Abstract: Two juvenile Asian elephants (E. maximus) presented with an acute onset of facial oedema and lethargy. Examination of the oral cavity of each animal revealed cyanosis of the tip and distal margins of the tongue suggestive of endothelial inclusion body disease (EIBD) of elephants. Whole-blood samples were obtained, and polymerase chain reaction tests confirmed the presence of elephant herpesvirus. The animals were administered famciclovir (Flamvir; 500 mg/70 kg body weight, with a loading dose of 1000 mg/70 kg body weight) a potent human anti-herpesvirus drug, in the course of their disease, and recovery followed a treatment regime of 3-4 wk. These are the first known cases of elephants surviving EIBD.

d) Schmitt,D.L., Hardy,D.A. 1998. Use of famciclovir for the treatment of herpesvirus in an Asian elephant. Journal of the Elephant Managers’ Association 9:103-10

e) Brock AP, Isaza R, Hunter RP, Richman LK, Montali RJ, Schmitt DL, Koch DE, Lindsay WA: Estimates of the pharmacokinetics of famciclovir and its active metabolite penciclovir in young Asian elephants (Elephas maximus). Am J Vet Res 2012, 73(12):1996-2000.

e) 8-15 mg/kg Po or per rectum at least q 8 hours (pharmacokinetic study)

 Abstract:

Objective—To determine plasma pharmacokinetics of penciclovir following oral and rectal administration of famciclovir to young Asian elephants (Elephas maximus).

Animals—6 healthy Asian elephants (5 females and 1 male), 4.5 to 9 years old and weighing 1,646 to 2,438 kg.

Procedures—Famciclovir was administered orally or rectally in accordance with an incomplete crossover design. Three treatment groups, each comprising 4 elephants, received single doses of famciclovir (5 mg/kg, PO, or 5 or 15 mg/kg, rectally); there was a minimum 12-week washout period between subsequent famciclovir administrations. Serial blood samples were collected after each administration. Samples were analyzed for famciclovir and penciclovir with a validated liquid chromatography–mass spectroscopy assay.

Results—Famciclovir was tolerated well for both routes of administration and underwent complete biotransformation to the active metabolite, penciclovir. Mean maximum plasma concentration of penciclovir was 1.3 μg/mL at 1.1 hours after oral administration of 5 mg/kg. Similar results were detected after rectal administration of 5 mg/kg. Mean maximum plasma concentration was 3.6 μg/mL at 0.66 hours after rectal administration of 15 mg/ kg; this concentration was similar to results reported for humans receiving 7 mg/kg orally.

Conclusions and Clinical Relevance—Juvenile Asian elephants are susceptible to elephant endotheliotropic herpesvirus. Although most infections are fatal, case reports indicate administration of famciclovir has been associated with survival of 3 elephants. In Asian elephants, a dose of 8 to 15 mg of famciclovir/kg given orally or rectally at least every 8 hours may result in penciclovir concentrations that are considered therapeutic in humans.