ACCUTANE FOR THE TREATMENT OF ACNE (1) "Rest" peiod before a second course (2) Accutane dosage (3) Low dose Accutane (4) Miscellaneous pearls (5) Night vision (6) Intracranial hypertension (7) Folliculitis barbae (8) Alopecia (9) Aseptic necrosis (10) Miscellaneous --------------------------------------------------------------------- ----------------------------------------------- "REST" PERIOD BEFORE SECOND COURSE OF ACCUTANE ----------------------------------------------- Does anyone know of any published suggestions or reccomendations on how long to wait to start a second Accutane course. I have a 16 y.o. male who is developing large cystic lesions 6 weeks off a 6 month course at 1 mg/kg/d. Mike Crowe, M.D. ================ It has been my understanding that it is recommended to "rest" for 3 months before starting a 2nd course of Accutane. This has been my practice and has worked fine for me. Jeff Marmelzat, M.D. ==================== I personally wait at least 6 months between courses of Accutane, and I always use at least 1 mg/kg for 4-5 months when I give Accutane. I don't use it in the suppressive, low dose, intermittant mode because I don't think the potential toxicity is worth the benefit when it is used that way. The 6 month "drug holiday" (to borrow from the psychiatrist's lexicon) is arbitrary. I don't know if anyone has studied this in a scientific way, but my otherwise uninformed opinion is that the wisest thing to do is to give the skeletal system a rest from the potent hormone-like effects of Accutane. This is an excellent question, and I would like to hear some comments from others on the list. Mark Naylor, M.D. Department of Dermatology University of Oklahoma Health Sciences Center ============================================= The minimum time that I wait between courses of accutane is 8 weeks. I often find that if the acne is confined to the chest and back that a dosage of up to 2 mg/kg may be necessary to bring about a remission. Of course this depends on patient tolerance and lab evaluations... Jason Rivers MD =============== I tend to do the same thing, i.e., full doses of Accutane for a full course because of the studies that show such an approach results in the best long term " cure ". I, too, wait about 6 months between courses. Incidentally, how often have you needed a second, or even a third course, of Accutane? Elliot Puritz MD ================ Naturally the likelihood of recurrence is inversely related to the age and directly related to the severity of a given patient. Among the patient population that I see, I am guessing that about 10 to 20% require a second course and that about 15 to 25% of those require a third course. I don't think I remember treating anyone a fourth time. Mark Naylor, M.D. Department of Dermatology University of Oklahoma Health Sciences Center ============================================= ---------------- ACCUTANE DOSAGE ---------------- Despite using 1mg/kg Accutane for 4-5 months, over the last 10 years i have had to use 2 or 3 courses of accutane quite a number of times. I have not calculated the exact percentage but, I would guess about 20 percent of the time. A well controlled study of this question would be appreciated. There would be many variables to control. Marty Kay MD ============ Thanks for the response Marty. Several years ago, Dr. Leyden, I believe, pointed out several instances in which a second course of Accutane might be anticipated. These included a tendency to Hidradenitis, and an earlier onset of severe acne. There might have been other "predictors". Marty, could you be abit more specific? Did you use higher then 1mg/kg in those with severe acne on the back? Is your sense that the need for retreatment is higher in those with acne on the chest and back? Male or female? Patients always ask about the need for another course...even before starting the first, and so it is certainly useful to have the experience of colleagues to call upon as we advise these individuals. Elliot Puritz MD ================ With patients who require multiple courses of Accutane, I customarily give 1 mg/kg on the second time around also. Now I wonder, perhaps these resistant patients would benefit from ratcheting up the Accutane dosage for the second cycle. Does anybody have advice? Marty Okun MD ============= I've used Accutane in 10 and 11 y.o kids with no problems - start at 20 mg/d and go to 40 if necessary. KC Smith MD FRCPC Niagara Falls ON ================ ------------------ LOW DOSE ACCUTANE ------------------ I have often wondered about the "potential toxicity" of intermittant low dose Accutane. Are there any good studies comparing toxicity of various regimens? I would like to see the data showing that at least 1mg/kg for 4-5 months is superior to longer term low dose, or intermittent low dose supressive treatment. For example, has anyone studied a dose regimen of say 40 mg per week in conjunction with other topical or oral therapy for treatment of inflamatory acne of mild to moderate severity? I suspect that Accutane should be indicated for any disorder where there is excess sebum production, not just "severe nodular inflammatory acne unresponsive to oral antibiotics". Furthermore, the dose and length of treatment should be adjusted to accomodate individual requirements and risk tolerances. Walter H. Wood, M.D. ==================== Walter makes a good point that there is very little evidence of toxicity of low dose intermittant Accutane in the literature (perhaps someone on the list knows differently?) That is not to say that there is none. As far as I am aware most of the reports of joint and tendon calcification/ossification are from individuals treated with substantial doses for relatively long periods (many months to years). However, I worry more about Accutane given long term than I do Minocin for example. Although I have used Accutane to treat sebaceous hyperplasia and similar conditions in low doses, my experience is that the problem always recurs, and the lack of information about long-term consequences disturbs me, particularly when we know what this drug can do, e.g., its potent hormone-like effects on the skeletal system, and its adverse effects on blood lipid profiles. I would not be at all surprized to learn that this drug increased the risk for heart disease given over several years in low doses, for example. Why use Accutane for suppressive therapy of severe acne when Minocin is less expensive and less risky? Finally, if you are going to use Accutane in the first place, why not cure the patient? Mark Naylor, M.D. University of Oklahoma Health Sciences Center ============================================= There are several studies that point towards a threshold of total accutane dose required for it to be effective over the long term in most people. It comes out roughly as about 1mg/kg for 4 or 5 mos. It seems to be borne out in my practice. Guy Webster MD ============== Mark, I have used low dose accutane with benefit in male patients in their late teens as a supplement to systemic antibiotics. These were cases which did not respond to 4 or 5 antibiotics,usually had deep pustules rather than cysts and were getting some scarring but didn't severe enough to justify full doses of accutane. Worked well at 40mg 2X/wk. Harold Rehbein MD ================= There are a number of cases in which low dose accutane is entirely appropriate. Macrocomedones respond poorly and slowly to everything except Accutane-- one or two months of 10 mg/daily usually clears patients to the point at which they can resume topical therapy. Patients and patient's parents who are concerned about all of the negative things they have heard about Accutane also do well with a month or two of low dose Accutane. This is especially effective in patients who have reached therapeutic plateaus with conventional therapy. As long as one explains up front that prolonged remissions will occur only with higher accutane doses, and that the goals is to obtain a degree of clearing that will allow the patient to revert back to the conventional therapy that was no longer working-- it is a good treatment modality. I track the total doses of accutane for all patients. I have a number of patients who initially were reluctant to use Accutane who later consented to full dose therapy after one or two uneventful courses of low-dose therapy (10 to 20 mg.day) Finally, teenage girls whose mothers are aghast at the prospect of oral contraceptives sometimes allow their children to go on an OCP for a short course of low dose accutane. The OCP frequently makes the acne more manageable, and the experience often leads to later acceptance of the full course of Accutane treatment. For the males, I try get a copy of recent labwork from the pediatrician or internist so I don't have to draw baseline labs. For females, I follow all of the Roche guidelines for initiating accutane. Alan Silverman MD ================= I wish now I kept better records of things like this. I'm still procrastinating on which pentium computer to buy for my own desk so I can really collect my clinical experience. Private practice is so overwhelming that I always marvel at my colleagues who also seem to conduct clinical trials, publish and lecture regularly. My impression of my accutane experience is that men and women have been equally resistant to accutane. I also have not been able to predict which ones will not respond nor which ones will recur quickly. I usually only go beyond 1mg/kg if the patients side effects are reasonable and they are responding slowly. I have been lucky with few patients with serious side effects so I have not changed my regimen. I also have used low dose for long term in afew women with severe oily skin or constant acne. These have been a very select group of educated people. I still wish we had more firm data on different ways of using the drug. I find some severe back acne responds before the face acne and sometimes the other way around?! Marty Kay MD ============ Accutane at a dose of 40 mg twice a week, which is sufficient to control acne in most adult patients, is about $10 a week, compared with about $15 a week for Dynacin, and more for Minocin. Generic minocycline is not much cheaper. I'm not suggesting low dose Accutane should be routine treatment, but it is not more expensive than minocycline, and it has worked marvelously in the half dozen patients in whom I have used it. Mark Valentine MD ================= I would love to see what folks think about doing just the opposite of what we always have done with Accutane-resistant acne. Specifically I'm referring to Albert Kligman's column in Cutis (feb or march of this year I believe) of using very low doses of Accutane (i.e. 10 qd, gradually tapering to 10 qweek) for an extended time (upwards of one year) as an alternative. He claims good results: I'd love to hear from anyone else who has read the article and thought about the approach. Mark Ling, M.D., Ph.D. Emory University Department of Dermatology Clinical Pharmacology Unit Atlanta, GA =========== Its an interesting concept, a bit heretical, and exactly what I always expect from Albert...an off-center view that is more often than not correct. I worry about long-term low dose accutane in women. The longer they're on it the greater the probability of a conception while on the drug. Having said that, I will occasionally use the regimen in either sex. Most recently, I've treated a 16 y/o man with 10mg/day for nodular zits because he runs triglycerides of over 1000 if on a higher dose. Interestingly enough, he's been able to tolerate higher doses lately and has kept his TGs wnl. The acne is nearly clear. In spite of this success, I'l still stick by the studies of John Strauss and others who show a relationship between total dose and long-term remission of acne. Guy Webster MD ============== -------------------- MISCELLANEOUS PEARLS -------------------- After 13 years and hundreds of patients I have the following anecdotal opinions 1. Women relapse about 30% of the time, the younger the more likely 2. I now use total dose seeking 125mg/kg as was published in BJD several years ago and don't worry about daily dose so much, its a good way to minimize side effects in those who suffer more. 3. Borderline candidates, that is pustular and microcystic relapse at a higher rate. 4. By continuing antibiotic tx (non-Tcn) for the first 4 weeks I avoid the severe early flares before the accutane takes effect. 5. I try to push"elective" courses to spring and summer, the sun is less a problem than the dry in winter. 6. I always warn of decreased night vision, it is very common during the third and later months. 7. Almost no one regrets having taken accutane once its over 8. Suppressive tx after second or third courses can be very valuable although I have used only sparingly in carefully chosen cases LJ Gregg, M.D.,Tulsa ------------ NIGHT VISION ------------ Concerning l.j. gregg's comments on accutane. Does one need to stop or lower the dose of accutane for complaints of decreased night vision? Is an ophtho referral necessary in order to continue the med? William.Liss MD Kaiser ====== In reply to my colleague I have just gone on and finished the course. The worst is usually late and from what the patients tell me I think it makes 16 year olds see at night like 45 year olds. My rudimentary understanding is that the isoretionoin replaces vitamin A in the rhodopsin cycle in an inefficient manner, thus when the drug is stopped the vision returns to normal. I certainly could stand correcting on this, however. Perhaps Dr. Rhett Drugge our clinical pharmacologist could shed some light on this phenomenon L.J. Gregg MD -------------- ------------------------- INTRACRANIAL HYPERTENSION ------------------------- I have a 27 year old female patient (incidently also a lawyer) with quite severe acne that has not responded well to oral antibiotics, topicals (azelaic acid and Isotretinoin gel) and Diane-35 (Cyproterone acetate2mg, Ethinylestradiol 35mcg). She has shown willingness to try a 4 month course of Roaccutane but has expressed reservations about the risk of Benign Intracranial Hypertension. What is the incidence or risk of developing Benign Intracranial Hypertension in a patient on treatment with Roaccutane (Accutane or isotretinoin) ? As she will also be required to be on contraception during the duration of her course of treatment with Roaccutane, can the Diane-35 be continued as the primary contraceptive or are there any contraindications for this? Dr J S Sidhu Kota Kinabalu ------------- ------------------- FOLLICULITIS BARBAE ------------------- Speaking of models and accutane. I have a 24 year old African American patient who is a model. Not only did Accutane clear her acne, oil, and her "smelly hair" (her diagnosis), it also cleared the folliculitis barbae pubis (she is a bathing suit model). Diane Thaler ------------ -------- ALOPECIA -------- Recently saw a 20 yo man who complained of red scalp and hair loss. He took accutane for 6 months, which cleared his cystic acne but it left his scalp constantly "dry and irritated". I saw redness all along his forehead hairlin and extending into the frontal scalp. Minimal scaling was noted. He did have significant thinning of his scalp from the forehead up to the vertex. I had put him on Minocin and Benzamycin 3 months after he had finished accutane and had acne returning. Evidently, he had continued to use the minocin off and on but he felt the benzamycin was aggravating his scalp! I'm not sure if this is androgenetic alopecia , drug irritation related, minocin related, or some sort of post accutane phenomenon. Any ideas? Martin H. Kay Ph.D.,M.D. ------------------------ Since dryness and even erythema are common under retinoids (so called retinoid dermatitis), I wouldn't be surprised to see it during therapy. However, these phenomena should soon be better after stopping. Minocyclin may be photosensitizing, and BPO is irritant in itself. Sounds to me like a little overtreatment (many patients are very im-patient...) and/or photo damage (is it possible to avoid the sun in LA?). Concerning androgenetic alopecia, I would expect the male pattern distribution without inflammatory signs. If your patient represents the rather seborrheic skin type (no doubt in acne), then I'd also take into account seborrheic dermatits (sometimes with hair loss). Hans Juergen Kammler -------------------- I have 2 similar cases that I decided eventually were seb derm exacerbated by accutane. Nizoral shampoo and septra ds qd has kept them quiet. Guy Webster ----------- I agree with Dr. Kamm's consideration of seb derm , but I usually find clearing of seb derm after accutane, which I assume is secondary to lack of grease for pityrosporum to grow in. Could he have mild psoriasis-check for itchy ear canals. I would give him a week of high potency topical steroids overnite, maybe even a non-irritating ointment, though stop with first sign of folliculitis. Diane Thaler ------------ ---------------- ASEPTIC NECROSIS ---------------- I had a patient complain of unilateral hip discomfort within an hour of her first dose of Accutane. This hip discomfort got progressively worse, so that after 3, 40 mg doses (bid intervals) she was wanting pain killers, and contacted me. I had her stop the Accutane and take some ibuprofen, and the hip pain is subsiding. There is one case report in the literature of aseptic necrosis of the hip, and obviously I was concerned that she might be headed for this (1). This does not seem like the usual arthralgias and muscle aches that are typically seen with the drug. Anyone else have a similar experience? I am afraid to even give her the drug again. Any suggestions from the group beyond what I have already done? (1) Bewley AP, Rankin EC, Levell NJ, et al.: Isotretinoin causing acute aseptic arthropathy [letter]. Clinical & Experimental Dermatology 20(3):279, 1995.^A Mark Naylor, M.D. ----------------- As one of our Canadian colleagues recently pointed out, there is a great article on A.N. in the Canadian Medical Journal this year. Accutane just does not seem to fit into any of the postulated mechanisms, especially following a single dose. I hope someone else has more concrete help for you. The following is simply my way of dealing with atypical or exagerrated symptoms on Accutane. I suggest stopping the drug for 3-14 days, and then a re-try at a significantly lower dose, such as 10-20 mg. If there seem to be other issues interfering with treatment, I just throw up my hands and say "it just seems that you can't tolerate this drug, as wonderful as it is, and I am sorry. But it appears to be the fact!" By the way, did your patient make any attempt to deal with the pain herself, such as several Advil? Also, in such cases I say stop the drug and see your primary care doctor or orthopedist as I cannot evaluate ortho symptoms accurately. Check out how they respond to that sort of advice. Diane Thaler ------------ ------------- MISCELLANEOUS ------------- I would like to include the potential for exacerbating atopic dermatitis, osteophyte development (there are some great slides of the spinal cord in long term retinoids), menometrorrhagia, malaise, weakness (the latter two seen esp. in elderly), and acute vitamin A toxicity. Of course, including the methods for management of early pregnancy in the face of retinoids such as miprositol and methotrexate, RU 486 as well as estrogen. Pose the uncertain question, should we be doing fat biopsies of women after accutane to assess the risk of teratogenicity. End with the concept that retinoids are quasi-chemotherapeutic agents which have been shown to have a maturation induction in vitro and a squamous cell carcinoma inhibiting function in vivo. .... Rhett Drugge, M.D. ------------------ Having followed the discussion on Accutane last week, I would like to offer my own contribution, albeit belatedly. In the past year I have lowered my threshold for using Accutane to treat moderate-severity inflammatory and comedonal acne that is only partially responsive to conventional Rx. My impression is that: 1. In the long run it is more cost-effective than antibiotics & topicals. 2. It may not be significantly more dangerous than years of antibiotics, especially sulfas and ampicillin, which I avoid except for gram neg. folliculitis. You don't get Stevens-Johnson Syndrome from Accutane. 3.If I'm going to give my patients a fair comparison of the risks of Accutane and its alternatives, I should show them the recent article on serious side effects of Minocin (Knowles) and tell them about maybe turning blue or having their teeth permanently stained. Although these may be rare, probably the number of cases of serious or permanent sequelae from Accutane is just as low. 4. Adult women with chronic perioral/jawline acne that is menstrually exacerbated tend to have only short remissions from Accutane. References: 1. The Journal of Dermatological Treatment, Vol 4, Supplement 2, 1993 - entire issue. Various authors. Marks,R and Finlay, A., eds. Martin Dunitz, Pubs. 2. Roujeau, JC et al: Medication Use and the risk of Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. NEJM 199:Dec. 14;333(24):1600-1607. 3. Knowles, SR: Serious Adverse Reactions Induced by Minocycline. Arch Derm 1996;132:934-939. 4.Hung, PH:Minocycline-induced Hyperpigmentation. J Fam Prac 1995, Aug;41(2): 183-5. 5. Practical Reviews in Dermatology, July-Aug 1996. Audiotape. Review & commentary by Ernst Epstein & Howard Maibach. Gene Sienkiewicz, M. D. ----------------------- 1. In the long run it (Accutane) is more cost-effective than antibiotics & topicals. I think alot about this position, so I have decided to share a few of my ruminations on the question of long term antibiotic treatment of acne. Reductions in antibiotic usages decreases the prevalence of antibiotic resistance (ref 1). Not all antibiotics are equivalent in their effects on antibiotic resistance. Tetracycline therapy tends to alter fecal flora resistance dramatically while erythromycin generates negligible perturbations (2). There is an antibiotic resistant bystander effect of chronic tetracycline usage in acne patients and domestic animals. Families of acne patients and farm dwellers are similarly affected by the intestinal flora of acne patients and domestic animals as are their neighbors (2,3). Tetracycline enhances the long term hardiness of farm animals and probably humans by an unknown mechanism. Antibiotics are mixed with the feed of domestic farm animals as multiple studies in numerous species has demonstrated yield (i.e. they are larger and healthier) (ref 5). Unanswered questions abound, Is this a direct effect or do the bystanders who have fecal flora changes have benefit as well? Do we unintentionally made our antibiotic treated acne patients and their families healthier? What will be lost if we abandon the use of antibiotics for the treatment of acne? I use Accutane aggressively and early to cure acne. Are my patients healthier for this approach or am I missing something? (1) Eady EA Jones CE Tipper JL Cove JH Cunliffe WJ Layton AM Antibiotic resistant propionibacteria in acne: need for policies to modify antibiotic usage. BMJ 1993 Feb 27;306(6877):555-6 (2) Adams SJ Cunliffe WJ Cooke EM Long-term antibiotic therapy for acne vulgaris: effects on the bowel flora of patients and their relatives. J Invest Dermatol 1985 Jul;85(1):35-7 (3) Levy SB FitzGerald GB Macone AB Changes in intestinal flora of farm personnel after introduction of a tetracycline-supplemented feed on a farm. N Engl J Med 1976 Sep 9;295(11):583-8 (4) Nishijima S Akamatsu H Akamatsu M Kurokawa I Asada Y The antibiotic susceptibility of Propionibacterium acnes and Staphylococcus epidermidis isolated from acne. J Dermatol 1994 Mar;21(3):166-71 (5) Droumev D Review of antimicrobial growth promoting agents available. Vet Res Commun 1983 Dec;7(1-4):85-99 Rhett Drugge, M.D. ------------------ Two nice letters in this week's Lancet: Isotretinoin and azathioprine:a synergy that makes hair curl? By JW Van der Pijl et al. Three patients developed curly hair on the combination. Lancet 348:623:1996 The other: Isotretinoin dosage, JH Saurat, Lancet 1996:348:623 suggests that the total dose of accutane is 120-150mg/kg and that duration of treatment will depend on the daily dose. I like this approach a lot. One can give lower doses for longer time as long as the patient understands the rational: short course/highdose/lots of side effects. One might add longer remission. We all have patients who can't tolerate the side effects and for them lengthening treatment is a real pleasant option. Haines Ely MD -------------- I think many of us have been doing this for years, so I am so glad you found this in support. My one hesitation is with teen agers and the low dose chronic effect on the epiphysis and closure-without intermittant drug holiday. Any thoughts? For instance, would you consider treating a young man weighing l60 pounds in 9th grade at 20 mg/day for 20 months to avoid the dry lips? As you have probably noted before, I like long term low dose in the overmiddleaged with acne or greasy skin or Rosacea or sebaceous hyperplasia. Diane Thaler ------------ Very interesting re Accutane dosing in light of Albert Kligman's recent experience published in Cutis with extremely low dose, long course Accutane with good results. Mark Ling, M.D., Ph.D. ---------------------- In re KINKY HAIR, there are 2 references to kinky hair from Accutane alone: 1. (1990): Bunker CB+, Clin Exp Dermatol 15, 143. 2. (1985): Hays SB+, Cutis 25, 466. Jerry Litt ---------- Many years ago, I noted in the Schoch Letter that Accutane-produced curly hair in my patients was nothing more than trichorrhexis nodosa which resolved when the Accutane was discontinued. Any new observations on this subject? Philip Hughes, M.D. ------------------- Dan Siegal mentioned considering low dose Accutane in a patient who refuses low dose Tetracycline. I have not used Accutane in this way--have been concerned about the FDA's threat to remove it from the market if it is not used properly and have heard multiple comments about needing a certain threshhold dose for long term efficacy. Saw a case recently of a 60 year old man with multiple heel spurs. He had been given low-dose Accutane for *12 years* for mild rosacea. This particular dermatologist routinely gives long-term low dose Accutane with no bloodwork (including pregnancy tests). Barbara R. Reed, MD ------------------- I have given low dose and regular dose Accutane for Rosacea. I always feel that I am doing the patient a service-possibly zapping early bladder, bowel, breast, brain, promyelocytic leukemia etc. I think the man with heel spurs had a great possibility of developing them anyway. It also treats seb. hyperplasia. Diane Thaler ------------ ------ 10.28.96