SAN FRANCISCO — A single, patient-initiated dose of famciclovir cut short recurrent outbreaks of herpes labialis by 2 days, Dr. Marcus Conant said at the annual meeting of the American Academy of Dermatology.
Viral replication of herpes simplex virus type 1 lasts 8 hours. Famciclovir remains in a cell for 10 hours, he explained. Given this “window of opportunity … you ought to be able to treat the patient with high-dose famciclovir if it's initiated early in the course of an outbreak,” he said. “That was the idea behind this study.”
Patients recruited from sites in the United States, Canada, and Australia had healthy immune function and a history of prodromal symptoms and vesicle formation associated with at least half of their previous facial herpes outbreaks. Of the 1,376 subjects, 477 experienced symptoms, initiated therapy within an hour, and developed vesicles.
The time to healing of primary vesicular lesions was 4.4 days in 152 patients randomized to receive 1,500 mg of famciclovir in a single dose, 4 days in 157 patients who took 2 doses of 750 mg each on the first day, and 6.2 days in 168 patients on placebo. The time to healing of all vesicular lesions was 4.5 days and 4.1 days in the single- and split-dose treatment groups and 6.6 days with placebo. Resolution of pain and tenderness was more rapid in patients taking the single-dose of famciclovir than in those taking a split dose, starting with 750 mg at the first prodromic sign and 750 mg later that day.
Adverse events included headache and nausea, but were similar in the active treatment and placebo arms.
The magnitude of benefit was significantly greater than that seen in studies of topical treatments, noted Dr. Spotswood Spruance of the University of Utah in a poster further detailing the findings. Acyclovir cream shortens outbreaks by 0.5–0.6 day; penciclovir cream by 0.7–1 day; and docosanol cream by 18 hours.
Still unclear is how efficient patient-initiated therapy was in aborting outbreaks altogether. There was no significant difference in the proportion of patients in the placebo and active treatment groups in progression to a full outbreak. “The problem is, when you say you're having a prodrome, are you really having an eruption or not? You can't really tell that,” said Dr. Conant, professor of dermatology at the University of California, San Francisco.
The challenge for physicians is to convince patients to keep 1,500 mg of famciclovir with them at all times so they can take it immediately. Women tend to keep the 3-tablet 1,500-mg dose in their purses, but men tend to think it will be fine if they wait until they get home, Dr. Conant said.
“Herpes is like a punch in the nose. If someone is going to hit you and you step aside, you're not going to have a black eye. If you don't move away, you're going to have a black eye for about a week,” he said.
A second Novartis-sponsored study showed that genital herpes lesions could be halted at the papule stage in about one of every four patients taking 1,000 mg of famciclovir in divided doses during the first day they recognized prodromal symptoms.
In that study, led by Dr. Stephen Tyring of the University of Texas Health Science Center in Houston, patient-initiated therapy reduced by 2 days the healing time of lesions in 163 patients receiving active drug, compared with 166 receiving placebo.
More than 30% of subjects in the active treatment arm developed no lesions or only papules after initiating therapy, vs. about 10% of patients in the placebo group.
In this study, patients obtained skin samples for polymerase chain reaction testing and visited the clinic for 3 consecutive days following symptoms and up to 14 days or total healing if lesions developed. The researchers concluded that famciclovir could reduce healing time as well as prevent development and/or progression of lesions in some patients with a history of recurrent genital herpes outbreaks.
The challenge for physicians is to convince patients to keep famciclovir with them so they can take it immediately. DR. CONANT