Oral Meds: Antivirals
These drugs are extremely valuable in managing patients with
varicella zoster virus (VZV) infections, and can be very helpful
in a subset of herpes simplex expressions. The cardinal symptom
in zoster dermatologic disease is pain. The first sign is skin
erythema. For any patient over age 50 who presents with unilateral,
facial skin pain and erythema, suspect VZV highly. If the diagnosis
is not certain at this stage, the appearance of vesicular eruptions
in a few days will seal the diagnosis.
 The first of the antivirals to be approved in 1989 was acyclovir
(ACV), and though generically available, is well known by its
original brand name, Zovirax. It has a relatively short half-life,
which explains its five-times-a-day dosing schedule.
During the past decade, two more oral anti-herpetic drugs
were synthesized: valacyclovir (Valtrex) and famciclovir (Famvir).
These newer drugs perform virtually identically to acyclovir,
except they have an extended half-life activity, which allows
them to be used q8h (tid).
 As with life in general, time and money are the two practical
prescribing considerations. If the cost of the medicine is
a prime concern (as would be the case for an indigent or uninsured
patient), then prescribe generic acyclovir; however, if the
patient is a busy executive, affluent, or has prescription
drug coverage, then prescribing one of the tid drugs may be
the preferred choice.
Antiviral drugs need to be taken within three days of vesicular
eruption to achieve maximal response; however, we recommend
a course of therapy even if there is a delay of several days
in seeking care and/or diagnosis. The standard course of therapy
is seven days, but for very severe cases, therapy can be prescribed
for 10 days.
 The main side effect of these drugs is occasional (usually
mild) nausea. Since these drugs are cleared through the kidneys,
it is critically important for the patient with renal disease
that the prescriber consult with the patient’s nephrologist
or primary care physician and/or pharmacist regarding dosing.
While these antivirals are primarily designed to treat VZV,
they are also well-suited for treating herpes simplex disease.
For perspective, the simplex viruses are about twice as easy
to kill as their zoster cousins; therefore, only half of the
standard (zoster) dosage is used. For example, acyclovir is
normally dosed at 800mg 5 x d for seven days; with simplex
disease, prescribe 400mg 5 x d for seven days. This dosing
ratio applies to all three of the antiviral drugs.
Here are some examples of where oral antivirals can be helpful
in simplex disease:
• The patient with an allergy to trifluridine (Viroptic)
• The patient with primary HSV blepharodermatitis (with or
without concurrent HSV keratitis)
• The patient with stromal herpetic keratitis where topical
corticosteroids must be used to suppress the inflammation.
In such cases, the corneal epithelium may be toxic from prior
treatment with trifluridine (or its preservatives), yet an
antiviral cover must be provided to prevent virus activation.
If the patient also has keratoconjunctivitis sicca, prescribing
orals would be more corneal-sparing than using the potentially
corneotoxic topical antiviral eyedrops.
Treatment for Recurrent Herpetic Disease
A new standard-of-care was set by an article in The New
England Journal of Medicine regarding the reduction
of recurrence rates in herpetic eye disease, both stromal
and epithelial. It showed that 400mg of acyclovir
taken twice a day for up to two years can reduce recurrence
rates about 50%. So, for that subset of patients plaqued
with chronic recurrence of herpetic eye disease, such
therapy has the potential to be of enormous help.
Herpetic Eye Disease Study Group. Acyclovir for the
prevention of recurrent herpes simplex virus eye disease.
N Eng J Med 1998 Jul 30, 339(5) 300-6. |
It is well established that oral antivirals can eradicate
live virus from the corneal epithelium, and does so on par
with topical therapy in almost all cases. There are uncommon
occasions where viral keratitis “breaks through” oral therapy,
and topical trifluridine needs to be added. However, we never
initiate therapy in these cases with both approaches, since
dual therapy is rarely needed.
Are these oral antivirals safe in children? You bet. When
there is an indication to treat chicken pox, the FDA-approved
dosage of ACV is 80mg/kg/day (divided into four dosages) not
to exceed 800mg qid for five days. This certainly confirms
the safety of this class of drugs! Furthermore, an article
in Ophthalmology suggests that children with herpetic epithelial
keratitis may be better treated via the oral route than topically.1
It certainly may be easier for the child (and parents) to swallow
ACV liquid than fight eyedrops.
Quoting from that article, “Acyclovir is safe to use in children
and is the drug of choice for many manifestations of HSV disease
found in pediatric patients. We believe that oral acyclovir
has three applications in treating children with HSV keratitis.
First, it is effective in treating active infectious epithelial
keratitis. Second, it is useful in prophylactically treating
children prone to recurrent infectious epithelial disease.
Third, when used prophylactically for children being treated
with topical corticosteroid medications for immune stromal
keratitis, it may likely prevent infectious disease.”
Analgesic & Antidepressant
Use with Oral Antivirals
Occasionally, patients may have significant pain during
and after herpes zoster infection. It can last for
months before it typically self-limits.
If pain is severe, prescribe a narcotic analgesic such
as acetaminophen with codeine (Tylenol #3) or oxycodone
with acetaminophen (Tylox or Percocet). The most comonly
used oral therapy for post-herpetic neuralgia is Elavil
(amitriptyline), a tricyclic antidepressant.
Although there are new generation antidepressants such
as the selective serotonin re-uptake inhibitors (SSRIs)
- Prozac, Zoloft, Paxil, Celexa, and others- the older
tricyclics perform better when treating zoster pain.
Another possible, though controversial, treatment for
pain and inflammation is prednisone 40mg po tapered over
10 days. |
The recommended dosage for treating children with herpes simplex
disease is 20mg/kg/day divided into four doses. Note that ACV
is available as 800mg and 400mg tablets; 200mg capsules, and
as a banana-flavored oral suspension of 200mg/5ml (5ml = one
teaspoon), which is ideal for children.
In summary, the oral antiviral drugs are wonderfully safe
and effective. They are enormously helpful in managing the
spectrum of herpes simplex and varicella zoster eye disease.
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