HERPES SIMPLEX -------------------------------------------------------------------- A query. A forty year old female has culture proven herpes type one and two at the lumbar and sacral dermatomes. She has frequent attacks associated with signs of miningitis and rosacea. Having seen many specialists, she was tried on courses of Acyclovir, Valtrex, and Famvir- no results. She gets attacks every few weeks, and is becoming depressed and debilitated. Suggestions appreciated. Foscarnet? She has mitral regurgitation from prolapse, and hypertension, takes tenormin. She has hyperadrenergic sysndrome, but no pheocchromocytoma. Elliot Puritz MD ================ Regarding the forty year-old female with frequent attacks of culture-proven lumbo-sacral HSV, associated with meningeal symptoms and rosacea: 1) HIV status should be checked. 2) Consider prophylactic regimen of one of the antivirals mentioned. I believe that only Acyclovir is FDA-approved for this indication at the moment. 3) Although culture-proven, these outbreaks may not always be HSV-related. This could be a recurrent Erythema Multiforme eruption, due to some intermittently-ingested medication (or from the HSV itself). Inquire about ALL medications. 4) I've seen lupus erythematosus look just like rosacea. I've seen nonspecific erythematous, edematous grouped papules on the buttocks be lupus on biopsy (in a patient with SLE). Tenormin has been associated with lupus (Drug Eruption Reference Manual). I would do a work-up for lupus, especially in the setting of "HSV not responding to any" of the antivirals mentioned. 5) Consider a re-culture for HSV next outbreak. T. Keith Vaughan, M.D. ====================== Thanks Keith. See my additional history about HIV status. I believe she was checked for lupus by her other consultatns, but I am obtaining the records. She haas had Herpes virus cultured several times from the sites, and the times I have seen her there was no doubt that these were grouped vesicles completely consistent with herpes. Elliot Puritz MD ================ Quite a case. Nothing specific to suggest, but I know that at one time, Burroughs Wellcome (nee Glaxo Wellcome) could culture HSV isolates and test for acyclovir resistance. Might be interesting if still available. Mark Ling, M.D., Ph.D. Emory University Department of Dermatology Clinical Pharmacology Unit Atlanta, GA =========== I have an unusual question to pose you that was posed to me by a patient and his wife. A 40 year old male presented to my office with a chronic burning in the perineum and scrotum (testicular) for eight years. He had seen numerous doctors and given all sorts of topicals and antibiotics, on and off. There is no significant past medical history, and he is on no meds; has no allergies; one sexual partner for the last eight years (she is asymptomatic). Examination revealed diffuse erythematous eruption of the perineum, tender to palpation, with scattered superficial erosions covered by a slightly yellow crust. My diagnosis was genital herpes. I treated the patient with oral acyclovir with complete clearing of lesions, pain and testicular pain. I have referred him to a urologist to verify any sequela of this chronic herpes on the testes. Simple, eh? Well here's the rub. He tells me, and his wife confirms, that he has had a significant personality alteration since the treatment. He sleeps well, he is pleasant. All office coworkers have noticed the difference. The patient asked me if I have ever seen personality changes in patients with active herpes genitalis. I have never noted that, although it is reasonable that a person with chronic pain and burning for eight years could be very irritable and difficult and impatient, I would imagine. However, I wonder. Have you seen any personality changes with herpes genitalis of the short course. Can patients present with even encephalitic like changes of neurologic function. He also described having intermittent episodes of what seem like myoclonic jerky movements in his sleep for YEARS which have since departed with the acyclovir. As the CNS and PNS are in essence a continuum, could irritation by recurrent viral infection at the level of the dorsal root ganglia cause stimulation of myoclonic jerking in the CNS? Your opinions are most appreciated. Warren Winkelman, MD, FRCPC --------------------------- The way the acyclovir rep is pushing away from acyclovir and to valtrex, you would think that the patent on acyclovir will be expired any minute now. Any info out there. Joel Schwartz ------------- To my knowledge, Acyclovir is still the only drug approved for long term prophylaxis of recurrent HSV, as opposed to Famvir which is only approved in the US for episodic use in this condition. Am I correct on this? Is there a protocol for Famvir for long term prophylaxis? Jerry Eisner ------------ SmithKline Beecham (Famvir) is competing effectively for market share with Glaxo-Welcome (Vatrex, Zovirax). Acyclovir was approved by the FDA in March 1982 and comes off patent in 1997. Rhett Drugge, M.D. ------------------ Has anyone used WB Shelley's STAT! 800 mg Acyclovir approach successfully as an alternative to long term prophylaxis with Acyclovir? Rhett Drugge, M.D. ------------------ Have tried it occasionally, mostly unsuccessfully. I try to use it in people with nuisance cold sores, such as occur on skiing trips or sunny weather. It seems worth a try. I give folks the instructions, but prompt them to use the standard dose the next day if it seems not to have helped. Most end up going on to standard dos. Perhaps I have too little faith. Jerry Eisner ------------ I have been recommending the Shelly's 800mg acyclovir loading dose for the past year, but cannot recall any feedback positive or negative. It makes too much sense not to do it. William Liss ------------ While I appreciate the cost savings of episodic acyclovir/valacyclovir/famcyclovir use, I beleive that suppressive therapy has been shown to reduce assymptomatic viral shedding, which is fairly common. Michael Fetterman ----------------- At present, my understanding is that both drugs (Valtrex and Famvir) are in active pursuit of the long-term suppression indication, but neither has it yet, so yes you're correct, acyclovir is the only one "officially" approved for this. I suspect you'll see the newer drugs gain approval soon. Regarding the original inquiry, I'm curious: what are the advantages of staying with original acyclovir versus Valtrex? Valtrex provides superior serum levels of acyclovir, has a much better dosing regimen (BID for simplex, TID for zoster), and at least in my area is cheaper than a comparable course of acyclovir. Famvir holds many of the same advantages, although of course it is a prodrug for penciclovir, not acyclovir. BTW, I AM theoretically biased as I am on the Glaxo speakers' bureau and have requested but not to date received research grant support. Mark Ling, M.D., Ph.D. ---------------------- A quick aside that I will try to back up in the future. I have talked with ID people here at NIH and been told that Famvir can cause severe hematologic problems in HIV (only) patients and they feel it is contraindicated in this population. I do not know of specific reports/frequencies but will try to find out and report it on the list. David J. Altman, MD, PhD ------------------------ David, please try to confirm that report as I am using Famvir in a very low CD4 count patient with a HSV2 chronic penile ulcer. I found the following citation which supports the safety of this agent in the AZT treated, low CD4 HIV population. Rhett Drugge ------------ This is a complex area with inadequate information. I know one area of concern is with TTP/HUS in Valtrex patients, but this occurs under extraordinary circumstances. Glaxo would have data to review on this issue: I'm sure the same is true for Famvir. I don't think these are relevant to otherwise healthy patients. Mark Ling, M.D., Ph.D. ---------------------- Valtrex is a much better way to get acyclovir into a person, because God put on enzyme (valacyclovirase) in the gut - the only known function of valacyclovirase is to remove valine from the valacyclovir pro-drug and facilitate its uptake, with the result that ~80% of the dose gets into the blood as acyclovir, giving iv-like levels, compared with ~15% uptake if a patient is given acyclovir. Here in Canada Valtrex is priced BELOW generic acyclovir and is in EVERY pharmacy, because Glaxo explicitly wants to "whack the generics". KC Smith MD FRCPC ----------------- For one who has suffered from recurrent, often severe, herpes labialis, I can testify to the efficacy of early, high dose Zovirax. I've been doing this for years. I have Zovirax everywhere: car, desk, my wife's purse, suitcase. As soon as I feel the telltale signs of impending herpes I take Zovirax. For me it works, and I tell my patients to use it. I've recently begun using Valtrex (1 gm) at the first sign of my herpes labialis. So far I've not noted any difference in efficacy. Robert I. Rudolph, M.D., FACP ----------------------------- I think that mouse report was biased because in humans the dose of Valtrex should be twice that of Famvir (eg. 1 gram tid vs. 500 mg / tid for Zoster). In the study the mice were given 50 mg/kg/dose of either drug, so -- if the pharmacokinetics are the same in mice as in men -- the mice in the Valtrex arm only got half of what they would have needed to be comparable with Famvir. As a practical matter, both are excellent medications. I prefer Valtrex: -- because we've got about 15 years of good, safe experience with the active product: acyclovir -- Valtrex is metabolized in one step to active drug, while Famvir needs 2 steps (1 in the liver) so there's an extra chance for something to go astray. -- Valtrex leads to an obligate chain terminator (acyclovir-triphosphate) while Valtrex leads to a reversible inhibitor -- Valtrex is cheap - less than generic acyclovir, and much less than Famvir. -- Valtrex is in every pharmacy (I don't want to order Famvir for Zoster on Friday and have the patient be told at the pharmacy: "We'll order it in for you -- should be here Tuesday." Disclaimer: I've given advice to Glaxo about Valtrex, and have lectured on the subject for them. KC Smith MD FRCPC ----------------- In St. Louis, Famvir is cheaper than Valtrex by quite a bit; how is it in the rest of the lower 48? John Uhlemann -------------- Despite claims by their respective drug reps, both Valtrex and Famvir are only minimally cheaper than Zovirax in south Florida. Their marketing here has been less aggressive than in Canada. I prefer Valtrex for the safety record of acyclovir, as well as some concern for possible hematologic effects of Famvir, which I have the impression is less specific for herpes than the former. I have also seen studies that suggest Famvir may have pahrmacokinetics to suggest quicker thymidine kinase inhibition, however, which would theoretically mean better clinical efficacy, which has not been reported. Michael Fetterman ----------------- 1. There was a statement that in St. Louis Famvir is cheaper than Valtrex by "quite a bit." The January Medical Letter published the prevailing AWP's of both drugs: for equivalent course (7 days at zoster dosing) the costs were: Valtrex 96.60, Famvir 129.15, and Zovirax 128.95. These have not substantively changed nationally since then to my knowledge. In Georgia, retail pricing appears to reflect these wholesale price differences. 2. I would be very careful about publicizing purported toxicities of drugs in a public forum like this one without clear evidence to support claims. I'm not a Famvir expert but would like to see the evidence regarding hematologic toxicity first before starting a perception which may be unjustified. I know similar problems occurred with the issue of TTP/HUS and Valtrex. The data there suggest that it is an extemely rare event, occurring only in select populations of sick patients, using extraordinary drug doses. Despite this, the TTP/HUS claim has been used by some to try and discredit Valtrex. Hopefully the same will not occur with Famvir as well. Mark Ling, M.D., Ph.D. ---------------------- At Grand Rounds yesterday, I heard it discussed that there was somewhere a suggestion that valcyclovir may have evidcenced a slightly higher incidence of postherpetic neuralgia than acyclovir. where was that reported? How strong was the evidence ? Michael Fetterman ----------------- I'd be cautious about small differences in different studies: PHN studies are very difficult to design and execute and I don't think small "statistically significant" differences are often clinically significant. Of course, too, since valtrex is simply a "delivery system" for acyclovir, it's difficult to imagine why it would be LESS effective. The Famvir-Valtrex PHN issue is cloudier, although one should reference the Beuttner study on PHN with valtrex to see where different studies show different results (he did find a significant reduction in PHN with Valtrex use). Mark Ling, M.D., Ph.D. ---------------------- CASE 1: Had a woman 6 months pregnant with what looked like a rip-roaring genital herpes (culture was Type 2). I put her on Valtrex (valacyclovir) 1 gram po stat and 1 gram po tid for a week and she did great. Now I'll keep her on Valtrex 500 mg daily at least until the kid is born, both to prevent premature labor secondary to herpes and to prevent neonatal herpes. The kid should have good transplacental antibodies in a month or so anyway. Told the family doc she can have a vaginal delivery as far as I'm concerned. CASE 2: Yesterday had a woman 9 months pregnant, dilated 3 cm, having contractions, with a 1 week history of painful grouped vesicles on the left labia minora. No previous history of similar problems. Her OB told her: "Go see Kevin, maybe he'll have some suggestions, then head over to the hospital." I gave her 1 gram of Valtrex po stat in the office, another gram 3 hours later and another at bedtime, with an Rx to continue until the kid is born. This morning the contractions had stopped, she was having less discomfort, and she was looking forward to a vaginal delivery today or tomorrow. The OB cancelled the section. Why such a whopping dose of Valtrex? Because I thought in each case it MIGHT be shingles, and because I wanted to punch through the placenta and give the kids a real high blood level of acyclovir real fast, in case the moms went into labor shortly after seeing me. Kevin C. Smith MD ----------------- This past week I have had 2 patients develop herpes labialis 2 days after a combined face peel (Jessner's soln., 35% trichloroacetic acid) while on famciclovir (Valtrex) 250 mgm BID starting the AM before the procedure. I have used acyclovir (Zovirax) with better results! I am now switching to valacyclovir (Valtrex) and anticipate better herpes prophylaxis. Philip Hughes, M.D. -------------------------