Which medications are used in treatment of herpes simplex encephalitis (HSE)?

Updated: Jul 17, 2018
  • Author: Wayne E Anderson, DO, FAHS, FAAN; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Answer

Pharmacotherapy for HSE is available in the form of acyclovir. Patient outcome is improved after treatment with this agent. Acyclovir is the treatment of choice for HSE. [1, 3, 41] When the diagnosis of HSE is suspected or has been established, acyclovir (typically 30 mg/kg/d intravenously [IV] in adults) should be initiated immediately.

Through a series of in vivo reactions catalyzed by viral and host cellular enzymes, acyclovir is converted to acyclovir triphosphate, a potent inhibitor of HSV DNA polymerase, without which viral replication cannot occur. Human cells are not affected.

Acyclovir has relatively few serious adverse effects. Because of its high pH, IV acyclovir may cause phlebitis and local inflammation if extravasation occurs. Gastrointestinal (GI) disturbances, headache, and rash are among the more frequent adverse reactions.

The drug is excreted by the kidney, and the dose should be reduced in patients with renal dysfunction. Crystal-induced nephropathy may occur if the maximum solubility of free drug is exceeded. Risk factors for this are IV administration, rapid infusion, dehydration, concurrent use of nephrotoxic drugs, underlying renal disease, and high doses. The risk of renal toxicity is reduced by adequately hydrating the patient (eg, 1 mL/d of fluid for each 1 mg/d of acyclovir).

Acyclovir is considered appropriate for serious infections during pregnancy. The manufacturer cautions that it should be used in pregnancy only when the potential benefits outweigh the potential risks. However, a prospective registry of acyclovir use in pregnancy between 1984 and 1999, including 756 first-trimester exposures, demonstrated a 3.2% rate of birth defects, similar to that expected in the general population. [42]

In immunocompetent patients, viral resistance to acyclovir has been clinically insignificant, with a reported prevalence of less than 1%. [43] However, in immunocompromised patients, this figure rises to 6%. Degree of immunosuppression and duration of exposure to acyclovir appear to be the most important risk factors for the development of resistant strains.

Since most relapses occur within 3 months of completing an initial course of IV acyclovir, a prolonged course of an oral antiviral agent (eg, valacyclovir) has been suggested after initial treatment. An ongoing clinical trial is currently evaluating a 90-day course of valacyclovir versus placebo after treatment with acyclovir in patients with HSE. [44]

A 2009 Cochrane database review of data from 17 trials that compared interventions used for the prevention and treatment of HSV in patients being treated for cancer concluded that acyclovir is effective in preventing and treating HSV infections. Valacyclovir was not found to be more effective than acyclovir, nor did a higher dose of valacyclovir make a difference. Some evidence indicated that placebo, as a prophylaxis, is more effective than prostaglandin E, but the risk of bias was unclear in all trials. [45]

If long-term suppressive therapy is needed, acyclovir or famciclovir can be used orally.


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