One of my patients managed to get SkinCap spray from a London pharmacy -- incidentally in the UK it is NOT an OTC item. She used it for her intractable chronic plaque psoriasis on her legs and it almost cleared. Very impressive. However, she ran out a week ago. I saw her today. The rebound is quite severe, and it reminds me of the rebound patients get with superpotent topical steroids. I shall definitely be going to the archives to look up Dr. K. Smith's information sheet for patients on SkinCap! Melinda Tong, MRCP ---------------- Skin Cap is just getting off the ground here. I had a patient in the other day who had tried it on her own, improved a bit, then had a terrible flare (the worst she'd been in years). I've sent copies of my Skin Cap "LACK OF INFORMATION" handout to all the local pharmacies, and I'm giving it to my psoriasis patients as they come through, making it clear that this for information and (except in rare cases) I am NOT recommending Skin Cap. The handout has been much appreciated by the patients and pharmacies. I am trying it for a few things like vitiligo and alopecia areata. I'm attaching a copy of my handout. Feel free to use or modify it. Kevin C. Smith MD FRCPC - Dermatology -------------------- FOR: ___________________________ DATE: __________ Recently some patients have been asking about a product called Skin Cap (and about some other similar zinc pyrithione-containing products). Skin Cap can be very effective in controlling a number of unrelated inflammatory skin conditions, including psoriasis, lupus and lichen planus. Unfortunately there are many things which we will need to learn before Skin Cap can be safely recommended. I have prepared this "lack-of-information" sheet to help you decide whether or not you are willing to accept the risks and problems which could be associated with using Skin Cap. Skin Cap appears to be a VERY potent broad-spectrum anti-inflammatory and perhaps immunosuppressive or immune-modulating medication. Medications which are very potent often also have a great ability to cause serious problems under some circumstances. Other medications which are as potent as Skin Cap or even less potent (eg. clobetasol propionate - Dermovate) can cause serious side effects such as thinning of the skin, excessive hair growth and occasionally may even cause crippling problems with the bones and joints or other body systems if not used properly. It is certainly possible that when more information is available Skin Cap will be found to cause equally serious (but perhaps different) problems in some cases. Some people think that: "Because Skin Cap has the same active ingredient as Head and Shoulders Shampoo (zinc pyrithione) it must be as safe as Head and Shoulders." This may not be a safe assumption: 1. It is not known whether the zinc pyrithione or the other chemicals in Skin Cap is responsible for the very potent anti-inflammatory effect of Skin Cap. Because Skin Cap is not a prescription medicine the manufacturer is not required to tell anyone the names of the other chemicals in Skin Cap. 2. The anti-inflammatory effects of Skin Cap are very different from and much greater than the effects produced by other zinc pyrithione containing products, and it is likely that Skin Cap will eventually turn out to produce harmful effects different from and greater than those caused by other zinc pyrithione containing products. 3. Because the effects of Skin Cap on skin diseases such as psoriasis, lupus and lichen planus are vastly greater than and different from the effects of other zinc pyrithione containing products Skin Cap should be regarded as a NEW medicine by patients and physicians, and perhaps also by the goverment agencies which deal with the safety of medicines. Some people think that: "Because tens of thousands of cans of Skin Cap are being sold every month, and there has been little news of problems, Skin Cap must be pretty safe." This may not be a safe assumption. Because Skin Cap is not a prescription medicine the manufacturer and distributor are not required to maintain a detailed record of reports of adverse reactions to Skin Cap. Because animal and human experiments and followup studies of the quality necessary for prescription medicines have not been done, it is very likely that the frequency, severity and kinds of adverse reactions to Skin Cap have not been adequately studied and publicized. Because Skin Cap is not a prescription medicine we do not have the information from the laboratory experiments, experiments with animals, or experiments with humans that are available for virtually all of the other medicines and other treatments that we use in dermatology. Because medical and scientific information on the safety of Skin Cap is not available: 1. I do not know how Skin Cap works. 2. I cannot predict what kinds of problems you may develop after long-term (months to years) or in some cases even short-term (days to months) exposure to Skin Cap. 3. I do not know if there is a safe limit to the amount of Skin Cap you can be apply every day. 4. I do not know if there is a safe limit to the number of days or weeks Skin Cap can be applied. 5. I do not know if there are some parts of your body where Skin Cap should not be applied. 6. I do not know if Skin Cap might make some diseases worse (for example skin infections or skin cancer). 7. I do not know if there are some people (for example children, pregnant women, or old people) who may be at increased risk for problems if they are exposed to Skin Cap. 8. I do not know if there could be an increased risk of problems (for example, skin cancer) if Skin Cap is used in combination with or following other treatment, such as ultraviolet light, methotrexate, cyclosporine or corticosteroid creams. 9. I do not know if inhaling traces of Skin Cap while it is being sprayed, or absorbing it though the skin, could cause internal problems. For example, it is possible that the potent anti-inflammatory and possibly immunosuppressive effect of inhaled Skin Cap could increase the risk of yeast infections in the mouth and airway, and perhaps also increase the risk of dangerous lung infections like Pneumocystis carinii. The animal and human experiments which are necessary to deal with these issues (and which would have been required if Skin Cap was a prescription medication) have not been done. Because the risks of Skin Cap are unknown, it is not possible to accurately weigh the risks against the benefits. Because Skin Cap is not a prescription medicine, it is not required to be manufactured to the same high standards we expect of prescription medicines, and the manufacturer of Skin Cap may deliberately or accidentally change the amounts and types of chemicals in Skin Cap without telling anyone. Because there are a number of unanswered questions and unknown risks most of my patients prefer to avoid using Skin Cap for the time being. There are a few people with very bad skin conditions which are have not responded adequately to better understood treatments, and some of these people are willing to accept the possible risks and unknowns associated with using Skin Cap. You should not use Skin Cap unless you are willing to accept the possible risks and side effects (including risks and side effects we are not aware of yet.) If you decide to use Skin Cap, please keep a diary of: 1. when you start and stop using Skin Cap. 2. the amounts of skin Cap you use. 3. the other medications and treatments you use in addition to Skin Cap 1. when you start and stop using Skin Cap. 4. the areas you apply Skin Cap to. 5. The lot number (printed usually on the bottom of the can), in case there are changes from batch to batch in the mixture of chemicals in Skin Cap. Please give me a copy of this information when you come to see me, so I can take it into account when I am working with you. Please keep me informed of your progress, If you have problems related to Skin Cap please let me know and I will try to help you. -------------------------------- How long was your patient using Skin Cap? Had she been on it for only a short period, I wonder if the period before signs of reoccurrence would have been longer than a week if the duration of therapy was longer. My thinking is that reoccurrence following cessation of Skin Cap therapy may be similar to reoccurrence post coal tar treatment. It is my understanding that the longer one treats with coal tar the longer the period before remission occurs after cessation of therapy and that duration of therapy might be related to knocking out more of the 'activated cells'. The duration of Skin Cap therapy may or may not relate to the severity of reoccurrence. Any thoughts from the others on the list? Daniel Bucks PhD The contents of this message are the opinion of the sender and do not necessarily reflect the opinion of Penederm Inc. or its management. ----------------------- I have received several telephone calls today informing me that at the American Academy of Dermatology Summer Meeting (New York) today, Friday, August 1, 1997, Professor Mark Lewohl, Chairman of the Department of Dermatology of Mt. Sinai School of Medicine announced, (in his presentation on the new treatments for psoriasis) that his department had several cans of Skin Cap analyzed and they were found to contain the superpotent steroid "clobetasol proprionate" . I would assume that the FDA and Federal Authorities are now being notified for the appropriate actions. Has anyone else heard of this report by Dr. Lebwohl? Dr. Crutchfield -------------------- This, if confirmed, is obviously sad news for all of us who have been seeing marvelous results with this agent. Most of you will agree that Temovate gel never cleared stubborn psoriatic scalps like Skin Cap does. The silver lining in the cloud is that now the mystery is solved, perhaps one of our orthodox pharmaceutical companies, maybe even Glaxo, will be able to duplicate the formula and get the stuff FDA approved. I certainly suspect it should be possible to prove that this formulation is more effective than other forms of clobetasol currently on the market, and if Tazorac can get away with $200 a tube pricing, then there is clearly money to be made in this arena once the insurance companies are in the prescribing loop. Mark Valentine --------------- Even if the FDA were to "crack down" on Skin Cap spray, we might consider continuing to evaluate similar agents. Many of us have remarked in the past that skin cap spray is more effective than high potency glucocorticoid preparations. Perhaps there is a synergistic effect between the glucocorticoid and the zinc pyrethione. What are the in vitro effects of the combination? Has anyone tested the combination of these agents to inhibit a lymphocyte phytohemaglutinin stimulation assay? Rhett Drugge, M.D. ------------- I do not think we should assume the report of clobetasol in Skin Cap is accurate until confirmed. Sorry, but its still unsubstantiated rumor, even though we got to read about it on the Internet. Jerry Eisner ----------- The penetration enhancers like isopropyl myristate would probably help the active ingredient in Skin Cap get into the skin; and in addition: as the vehicle evaporates the concentration of residual drug in the Skin Cap layer would increase greatly, increasing the concentration gradient driving drug into the skin. Kevin C. Smith MD FRCPC ---------------- The rumor that Skincap contains clobetasol is confirmed----I spoke briefly with Dr. Mark Lebwohl who confirmed this finding at the summer AAD meeting. For those who are not familiar with him, Dr. Lebwohl is the Chairman of Dermatology at Mt. Sinai Medical Center in New York City and has extensive research experience in psoriasis, among other areas of interest. There was no time for elaboration and I have no additional information. Stephen L. Comite, MD --------------- Perhaps this is one of the reasons that several have noticed an acneiform eruption on the face, either acne or perioral dermatitis? The isopropyl myristate as well could cause an irritant acne. Diane Thaler -------------- isopropyl myristate is comedogenic. Michael Fetterman --------------- Many thanks to Dr. K. Smith for the Skin Cap handout. Today another patient with psoriasis who has been using Skin Cap for the past three weeks said that her menstrual cycle had been affected. According to this patient, her menstrual cycle is very regular, and the only other times it has been affected was when she was using dermovate extensively. Boy, am I getting worried about Skin Cap Spray! Melinda Tong, MRCP --------------- While waiting for the dust to settle on what-is-skincap-anyway, I recalled a pearl from Bill Schorr. Bill always used Kenalog spray when treating discoid lupus. His instructions were to spray a small amount in one palm and use the fingers of the other hand to rub it into the lesions four times a day. Having seen failures (my own and others) with conventional supra-potent cortisones that have responded to Kenalog spray, I have adopted this treatment, but not tried it yet for psoriasis. I've always assumed that the vehicle was key. John Melski MD --------------- One of my patients obtained a can of skin cap from Madrid and the listed ingredients were Zn Piritionato 2mgm/ml and Metil etil Sulfato(de Sodio) 1 mgm/ml. I could translate most of the label and assume Caspa is the name for Sebborhea and Zinc Pyrithione was not difficult,however I would appreciate a Spanish understanding colleague to tell me what Metil etil Sulfato(de Sodia) is and its purpose. Stephen Wiener ------------- I called Dr. Lebwohl today (August 4,1997) and he confirms that clobetasol was found in Skin Cap - albeit at a "lower concentration then Temovate". He feels the other ingredients are playing a part in the results obtained by many with this product. Hopefully we'll hear more about this in print! Can someone contact him by E-mail, and ask him to comment in this forum? Robert I. Rudolph, M.D., FACP -------------------- Here is another way to explain the vehicle effect of Skin Cap spray. The lipid elements of the stratum corneum melt temporarily and reform quickly with greater airtightness. This transient stratum corneum meltdown allows the active ingredients to penetrate into the epidermis in the window of opportunity befor the stratum corneum reseals. This hypothesis accounts for the short-lived burning sensation which many patients report which I interpret as a transient increase in transepidermal water loss. I wonder if this is only isopropyl myrsitate, or is it also in part the spray propellant. Rhett Drugge, M.D. ----------- In addition to isopropyl myristate (IPM) acting as a potential penetration enhancer to facilitate the percutaneous absorption of 'active agent(s)' in Skin Cap as KC Smith wrote, sodium lauryl sulfate (SLS), if present, can also act as a very potent penetration enhancer by disruption of lipid bilayers and denaturation of proteins comprising the stratum corneum. IMHO combinations of IPM & SLS can be very irritating to the skin. R Drugge also raises the issue as to potential activity associated with the propellent. The addition of clobetasol dipropionate to an IPM/SLS vehicle may reduce the frequency and severity of irritation expressed. Addition of clobetasol dipropionate to Skin Cap Spray may account for the recent posts regarding rebound following termination of treatment (Drs. Tong and Thaler). It would be of interest if Dr. Crutchfield could have samples of Skin Cap Spray used in his psoriatic clinical trials analyzed for the presence of clobetasol dipropionate. Daniel Bucks The contents of this message are theopinion of the sender and do not necessarily reflect the opinion of Penederm Inc. or its management. ------------------------ Skin Cap just shows that if you administer enough corticosteroid psoriasis and other inflammatory disorders will back off. Big deal. We knew THAT 40 years ago. If Skin Cap was a prescription drug and had proper data to back it up I'd still be very reluctant to recommend it, because we have other better and safer treatments for psoriasis and other inflammatory disorders. I doubt like hell that it would ever get licensed, if for no other reason than because an aerosol of clobetasol propionate could be inhaled or get in the eyes (see below). What's needed today is an algorithm we can use for the patients who will be in the office TOMORROW, some of whom may have used large amounts of clobetasol propionate (who knows what concentration?) for up to 18 months, in a penetration-enhancing, rapidly evaporating vehicle system which included isopropyl myristate. I would not minimize the potential problems or be too reassuring. Here's my first iteration. As always, your input is needed to refine this thing: a. explain and document the risks of long-term high dose clobetasol propionate -- including in particular adrenal suppression, osteoporosis and avascular necrosis of bone (AVN). (The liability clock -- "discovery & disclosure" -- probably STARTS ticking as soon as you tell them this stuff, then runs out in 12-24 months, depending on your jurisdiction). b. get a 24 hour urine for cortisol to see if they are adrenal suppressed. If they appear suppressed, they'd best see an endocrinologist for formal determination of the degree of suppression and appropriate advice and therapy of that issue. c. cover them with other therapy (eg. cyclosporine, methotrexate, etretinate / acetretin, UV-B or PUVA, Dovonex, Taxorac) to reduce the risk of rebound when the Skin Cap is stopped. d. there may be considerable anger and reactive depression (possibly superimposed on steroid-associated mental changes) when Skin Cap is withdrawn. Patients should be monitored for this, and treated / counselled / referred as appropriate. My guess is that out of this large a patient population there will be some suicides, and a number of other lesser problems (job loss, marriage breakdown). With good pro-active psych care we should be able to minimize the incidence of these problems in the subset of patients we care for. e. Depending on duration of use and amount used bone densitometry to assess osteoporosis could be appropriate. Unfortunately most corticosteroid-associated bone loss happens in the first 6 months of therapy, so there may not be a lot that can be done with calcium / vitamin D / alendronate or other bisphosphonates at this point in time. The endocrinologist can maybe help in this area. f. If there is joint pain, in particular affecting the head of the humerus or the femur, rapid referral for assessment and treatment of avascular necrosis (AVN) of bone will be important. MRI of suspecious joints about the most sensitive and specific test that is readily available, and if there is evidence of AVN ***rapid*** referral for core decompression of the affected joint can reduce long-term disability and reduce the risk that joint replacement surgery will be needed. Patients should be counselled that the symptoms of AVN can come on months or even years after corticosteroids have been stopped, and if they notice symptoms suggestive of AVN (eg. sudden onset of pain, difficulty weight bearing, reduce range-of-motion) they should seek immediate medical advice and rapid treatment) - from you or from an orthopod, not just from some random doc who may not be familiar with AVN. They should be told that the risk of AVN may be reduced by avoiding obesity, smoking and alcohol consumption, and current status with regard to those risk factors ought to be documented. g. If a lot of Skin Cap spray has been used, in particular on the chest, face or scalp, it might be worth having an ophthalmologist rule out glaucoma and / or cataracts; and you might want to cover the patients for steroid-induced acne rosacea (eg. Minocin 100 mg hs or bid, and Metrogel or Sulfacet-R lotion bid). h. The rip-artists will be out in force trying to capitalize on the demise of Skin Cap. A flat warning to patients about quack remedies could be helpful. The NIH puts out a brochure about Quack Remedies, which I have found quite helpful in my attempts to "immunize" my patients who have chronic conditions like psoriasis against the quacks who are endlessly trying to prey on them. It is useful with people who have had psoriasis for a long time to say: "Many of my patients with psoriasis who have had psoriasis for a long time have seen a lot of quack remedies and ripoffs come and go over the years. What has your experience been?" This usually puts things in perspective, as they list for me all the time and money wasting over-the-counter, "health-food-store" and "natural" remedies they have tried. Currently most bitching is about Exorex -- very expensive, not very useful, manipulative 1-800 "support line", etc....... Kevin C. Smith MD FRCPC ------------- I would not minimize the potential problems or be too reassuring. >> Kevin, As usual your comments are complete, scientifically valid, and well reasoned, but the idea that patients who have used SkinCap have absorbed enough Clobetasol to cause all the side effects you mention is a big leap from the discovery of a little clobetasol in a few cans. Patients on systemic steroids USUALLY experience clinically apparent Cushingoid features before they experience osteoporosis, avascular necrosis, and severe adrenal suppression. If there are dozens of patients out there at risk for these dire complications, then there should be hundreds of patients with Cushingoid facies, buffalo humps, and obesity, and I've not heard of a single such case. While it may be appropriate for physicians to keep all your warnings in their heads, I would hate to see all the patients who have used Skin Cap subjected to an Alar-like scare campaign. Obviously the FDA had to remove this product from the market because of its disreputable origins. However, unlike you, I still harbor the strong suspicion that we are seeing more than just a steroid effect with this product, and that something similar could pass muster as a reasonably safe prescription remedy for psoriasis. Mark Valentine ------------- Thanks for posting the entire article: a huge help to SkinCap users like me. BTW, I'm struck and pretty unhappy over the hysterical tone the NPF appears to have taken. One, just because there's clobetasol in there doesn't mean that's the active: anyone who's used this stuff knows it is infinitely more effective than any Temovate formulation. Two, to overemphasize the risks of topical clobetasol the way this press release does (makes it sound worse than cis platinum) is unnecessary. Mark Ling, M.D., Ph.D. --------------- This morning's local papar had a wire service blurb on Skin Cap spray, saying that the FDA was warning nationwide about it containing powerful steroids, and for all patients to consult their physician regarding safely tapering off of them. The FDA is also having customs stop any new shipments from Spain. It is interesting that they used "This unapproved product" as a desription in the article, since many of us were led to believe that the FDA allowed this to be classified as OTC. The other question is: can Skin Cap still be dispensed by physicians as a presription product (ie clobetasol spray), since we deal with clobetasol on a regular basis. Hopefully there will be some attempt to get it approved (?Glaxo), but will the FDA be so pissed off that they will not approve it. I assume that web pages will sprout up outside the US, with psoriasis patients ordering Skin Cap offshore and having it mailed to them, to use unmonitored. An interesting situation. Mike Crowe, M.D. ------------- << It is interesting that they used "This unapproved product" as a desription in the article, since many of us were led to believe that the FDA allowed this to be classified as OTC. It was OTC under the monograph for seb derm, not psoriasis. So it was "unapproved" for this usage. >> The other question is: can Skin Cap still be dispensed by physicians as a presription product (ie clobetasol spray), since we deal with clobetasol on a regular basis. I doubt it. It will have to be tested to show that the ZPT doesn't add risk and does add benefit, just like any other combination drug eg benzamycin. Any drug company that tests it will run the risk that its results will be used to support the OTC usage for psoriasis and will have wasted its $$. As a combination with another Rx drug is a possibility though. Guy Webster ------------ The email is starting to flow in from patients who've found my Skin Cap "lack of info" sheet on the net. This is my reply to one such question: To: ksmithderm@aol.com I was just made aware of the FDA warning regarding Skin Cap today. I have been using this product for approximately a year and a half. As a result of that warning, my husband and I began searching the internet for information. I came across your e-mail message dated 7/2/97 regarding this product. While Skin Cap has all but "cured" my psorasis, I have recently noticed that I bruise easily and have experienced unexplained joint pain. As most people do, I associated this with other things, i.e. growing older, etc. (I am a 36 year old female). I am very concerned over yesterday's FDA ruling, and do not know who to contact. Should I see a dermatolgist, internal medicine dr., etc? Any comments or information you can provide will be greatly appreciated. Debbie Southerland Reply: Depending on how much Skin Cap (highly absorbed praparation of clobetasol propionate - an ultrapotent corticosteroid) you've been using, you could be looking at big trouble. There are a lot of things that can go wrong, but in particular get your doctors to look for ADRENAL SUPPRESSION, OSTEOPOROSIS, and (worst) AVASCULAR NECROSIS OF BONE (notably in the shoulder and hip). All of these very serious problems have already been described in patients who were using large amounts of clobetasol propionate on the skin. You'd best see a dermatologist and perhaps also an internist. Maybe print this for your doctors, together with my Skin Cap "Lack of Information" Sheet. Kevin C. Smith MD ---------- In this group some have reported that Skin Cap has helped patients who had severe psoriasis refractory to other treatments. Certainly this will make some feel the need to support the availability of the product. This should be weighed against the argument that we shouldn't support unscrupulous manufacturers who would make available through OTC channels a product which contains a potent topical corticosteroid. How many of us think triamcinolone should be available OTC? Fluocinonide? Clobetasol proprionate?! Can we possibly support a company that would make clobetasol proprionate available in a manner not subject to physician supervision, worse still, telling patients (and their physicians) that use of the product avoids the need for topical steroids and their inherent risks? And if the product does deliver the clobetasol proprionate in such a way as to have greater efficacy than Temovate, surely the risks of side effects are even higher. And would you trust such a company not to put other toxic agents in the product, to produce the product in a safe manner, or to have any degree of quality control whatsoever? I don't see this as a plot by "strong steroid" companies. In the U.S. we have a system that has allowed us great confidence in the products we prescribe or recommend to patients. The breakdown of this system would adversely affect our ability to care for all our patients. While I can see that if my patients with severe disease were benefitting from this product it would hurt them to lose access to the product, it is probably much worse to let this kind of abuse continue. If dermatology were to support this kind of abuse, what other deceitful, dangerous products might we see next. Steve Feldman, MD ----------- TYPE OF ALERT : Detention Without Physical Examination (Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the manufacturer(s) and/or product(s) at issue. It does not create or confer any rights for or on any person, and does not operate to bind FDA or the public.) PRODUCT : Skin-Cap Spray, Shampoo and Cream PRODUCT CODE : Spray: 61SAQ99, 61SAQ01, 61HBQ05, 62SAQ01, 53J02 Shampoo: 61HBL05, 62SAL01, 53E06 Cream: 62SAJ01, 53L03 PROBLEM : Product is an OTC product containing a prescription strength corticosteroid (clobetasol propionate). PAC FOR COLLECTION : 61D800 COUNTRY : Denmark (DK, 315) Spain (ES, 830) MANUFACTURER/ SHIPPER : Manufacturer: Laboratorios Cheminova Laboratorios Cheminova International Laboratorios Internacional, S.A. Madrid, Spain FEI# 3000384282 Shipper: Cheminova Holding A/S P.O. Box 9 DK-7620 Lemvig, Denmark FEI# 647 FEI# 1000195766 FEI# 1000645258 CHARGE : This article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a new drug within the meaning of Section 201(p) without an effective new drug application (NDA)[Unapproved New Drug, Section 505(a).] RECOMMENDING OFFICE : CDER, Office of Compliance, Division of Labeling and Non-Prescription Drug Compliance, HFD-310 REASON FOR ALERT : Skin-Cap, an over-the-counter (OTC) drug for psoriasis was found by FDA analysis to contain prescription levels of a potent medication, the topical steroid, clobetasol propionate, which can cause serious side effects if used incorrectly or unknowingly. Users would be unaware of the presence of this ingredient, as it is not declared on the labeling for the products. Side effects from long-term use of potent topical steroids can include stretch marks, thinning skin, and tiny dilated blood vessels. Use of large amounts, overuse or long-term use of potent topical steroids can also cause more serious side effects. Skin-Cap is an over-the counter (OTC) drug sold in various forms (spray, cream, shampoo) that is manufactured by Cheminova International Laboratories, Madrid, Spain, and is available through several U.S. distributors. Psoriasis is a chronic skin disorder that can be painful and disabling. It is characterized by inflamed, red, scaly lesions, caused when affected skin cells reproduce six times faster than normal skin cells. According to Cheminova International, the active ingredient in Skin-Cap is zinc pyrithione (ZnP). ZnP is the same active ingredient found in some dandruff shampoos, for which there is no history as an effective psoriasis treatment. Zinc pyrithione (ZnP) has never been found safe and effective for the treatment of psoriasis. ZnP is acceptable as an OTC product for the treatment of seborrheic dermatitis and dandruff only. GUIDANCE : Districts may detain, without physical examination all shipments of Skin-Cap Spray, Shampoo and Cream. For questions or issues concerning science, science policy, sample collection, analysis, preparation, or analytical methodology, contact the Division of Field Science at (301) 443-3320 or 3007. If private laboratory analysis DOES NOT INDICATE the presence of clobetasol proprionate, please contact Robert Eshelman of CDER's Division of Labeling and Non- Prescription Compliance at (301) 594-1065. PRIORITIZATION GUIDANCE : I FOI : No purging is required. KEYWORDS : Cheminova, dandruff, psoriasis, seborrheic dermatitis, unapproved prescription drug, corticosteroid, OTC PREPARED BY : Deborah Browning/Fredda Shere-Valenti, HFC-172, (301) 443-6553 DATE LOADED INTO FIARS : August 8, 1997 OTC psoriasis drug potentially harmful, warns National Psoriasis Foundation Skin-Cap, a popular over-the-counter (OTC) drug used for psoriasis, may contain an undisclosed superpotent prescription medication which can cause serious side effects if used unknowingly. The National Psoriasis Foundation (NPF) is urging anyone using this product to consult with their dermatologist. FDA analysis has shown this product contains prescription levels of a superpotent topical steroid, clobetasol propionate, and the agency is warning people about the product. Mass spectrometric analyses of Skin-Cap performed by investigators at the Mayo Clinic in Rochester, Minnesota, also suggest the presence of clobetasol propionate. In addition, tests performed by labs at Glaxo Dermatology, a division of pharmaceutical company Glaxo Wellcome Inc., found clobetasol propionate in Skin-Cap, and Glaxo confirmed those findings with an outside independent laboratory. Anyone using Skin-Cap should immediately discuss these findings with their dermatologist. When used as prescribed by a physician, clobetasol propionate can be a safe and highly effective treatment for psoriasis. However, side effects from long-term use of potent topical steroids can include stretch marks, thinning skin, and tiny dilated blood vessels. High doses, overuse or long-term use of potent topical steroids can cause very serious internal side effects. Note: If you have psoriasis, you should not stop using any product containing topical steroids without the guidance of a dermatologist, because abrupt withdrawal from topical steroids can significantly worsen psoriasis, and cause the disease to flare. Skin-Cap is manufactured by Cheminova International in Madrid, Spain. It has been available in the US through several distributors. Cheminova International claims that the active ingredient in Skin-Cap is zinc pyrithione (ZnP). ZnP is an active ingredient found in some dandruff shampoos, which have no history as effective psoriasis treatments. Cheminova has repeatedly denied the presence of corticosteroids in Skin-Cap, most recently in a letter to the NPF dated August 4. ZnP has never been found to be safe or effective for the treatment of psoriasis. As an OTC product, Skin-Cap has never been approved by the FDA. ZnP is approved as an OTC active ingredient for seborrheic dermatitis and dandruff only. Previous reports from several European countries that Skin-Cap contained topical steroids led the NPF to ask investigators to perform tests in the US. The Dutch Health Ministry ordered Skin-Cap banned from sale in late May because the product contained unreported steroids. Psoriasis is a noncontagious, chronic skin disorder that can be painful and disabling. Over six million individuals in the US are affected by psoriasis. Uncontrolled, psoriasis can limit a person's ability to walk, bend, grasp, or sit. In rare instances, people can die from complications of psoriasis. Psoriasis is characterized by inflamed, red, scaly lesions caused when affected skin cells reproduce six times faster than normal skin cells. Approximately 10% of people with psoriasis also develop a form of arthritis (psoriatic arthritis). There is currently no known cure for psoriasis, which is believed to be an autoimmune disease like rheumatoid arthritis. The NPF is a lay, nonprofit health organization with a mission to provide information and support to people with psoriasis. Through public education, the NPF hopes to stimulate research to find a cure for the men, women, and children who suffer from this disease. For more information on all treatments for psoriasis, call NPF at 1.800.723.9166. ---------------- Three scenarios: 1. For patients who have used a small amount for short periods: Stop using the product. See your physician for other treatment options. Risks of stopping are unlikely. 2. For patients using large amounts for short periods (less than 2 weeks): Stop the product. See your physician for other treatment options. If you experience signs of adrenal insufficiency (nausea or vomiting, abdominal pain, muscle weakness or fatigue), contact your physician. If you are in an accident or require surgery, let your physician know in case supplemental stress doses of corticosteroids are indicated. 3. If you have been using large amounts for prolonged periods: Stop the product under the guidance of your physician. See your dermatologist for other treatment of your psoriasis (as the disease may flare when stopping the medication). See your internist for consideration of testing for adrenal suppression and/or long-term corticosteroid taper to prevent acute adrenal insufficiency. If you have any unusual symptoms of hip or shoulder joint pain, see an orthopedist for evaluation of avascular necrosis. If you experience signs of adrenal insufficiency (nausea or vomiting, abdominal pain, muscle weakness or fatigue), contact your physician. If you are in an accident or require surgery, let your physician know in case supplemental stress doses of corticosteroids are indicated. Does that sound reasonable? Steve Feldman, MD ------------- I really like your practical stepwise approach to the problem of getting people off Skin Cap. I'd add that where Skin Cap was used on the face or forehead for more than a few weeks an eye exam to rule out glaucoma and/or cataracts might be useful. If a lot (eg. 1 can per week?) of Skin Cap has been applied for more than a couple of months, I'd get a bone densitometry to assess for osteoporosis, and then if necessary send them to someone who knows about that problem for advice and therapy. Does anyone know the concentration of clobetasol in Skin Cap? eg. if it is 0.05%, then 200 grams of Skin Cap = probably MORE than 200 grams of Temovate / Dermovate, because absorbtion of clobetasol from the penetration-enhancer delivery system of Skin Cap is probably higher than from cream or ointment. If Skin Cap is 0.1% clobetasol propionate, then 200 grams of Skin Cap probably = more than 400 grams of Temovate / Dermovate. And so on up the scale, depending on what the clobetasol concentration turns out to be. In a worst case scenario, where the dose in a can of Skin Cap was equivalent to say 400 grams of Temovate / Dermovate per week, a wide range of serious problems could be anticipated with high frequency, starting after a month or two. People with experience with Skin Cap please: what is the typical range of amounts and durations of use of Skin Cap? What proportion of patients are likely to have used more than half a can a week for more than a month or two? You see why I am kind of spooked by the potential risks. Kevin C. Smith MD ----------- I've always warned pts about risks of the unknown with SkinCap. I'm just a little concerned that the current response, which I find a bit overwrought, will end up losing a real opportunity to help explore psoriasis therapy. I use Temovate a ton, and with a little discretion don't feel it poses a significant risk to my pts. I understand the regulatory issues well, but wish the psoriasis community in dermatology was willing to debate this further (as we are doing here) before issuing a final stance, a la NPF. Mark Ling, M.D., Ph.D. ----------- Nope, as a heavy SkinCap user I beg to disagree, Steve. One of many anecdotes: female pt with worst scalp psoriasis I've ever seen. Absolutely no response to, among other things, MTX, cyclosporine, Accutane, PUVA (she was compliant enough to shave her entire scalp and wear a wig for months!), RePUVA using isotretinoin, gallons of topical Temovate lotion faithfully applied, Dovonex, anthralin, oral antibiotics, long course of suppressive Diflucan, and a few other things I cant remember. Huge, hyperkeratotic plaques, often staph superinfected to the point of focal scarring alopecia. Repeatedly biopsied and confirmed as psoriasis. Bottom line: she's CLEAR on NOTHING but SkinCap now. Compared to what she's been on before, SkinCap is like water from a safety standpoint. She would be crazy to stop using it. I've got plenty of other stories which I feel strongly argue that this stuff ain't just compliant Temovate. Mark Ling, M.D., Ph.D. ------------- Mark, I'm sure you're right, both about this and about the need for moderation with respect to warning patients. However, I don't thing the zinc is the active ingredient in Skin Cap; otherwise, this horrendoma story you describe would have cleared with Head and Shoulders. Up to now, the only thing that makes any sense is the clobetasol. Now perhaps your patient absorbed enough to have a systemic effect with a response (and presumably potential for side effects) akin to what would have happened if you put her on oral prednisone in high enough doses. I think the patient you described is the best reason yet to be very worried about the systemic corticosteroid side effects of Skin Cap. Steve Feldman ---------- The first two patients I saw this morning were herded in here by the scare stories on the evening news. One I had treated for psoriasis with chronic intertrigo. He brought in an empty tube of Nizoral and said since it didn't work he used Skin Cap from the health food store. He has been using it intermittently in the groin for a year+.Now I ask, have any of you seen a potent steroid used in the groin for a year NOT produce striae? I have seen striae from Lotrisone repeatedly, even after one month usage.If this stuff is clobetasol, why don't wee see the usual steroid side effects? Haines Ely ------------- Let me clarify before I give a very incorrect impression. I think that Skin Cap is "like water" regarding toxicity COMPARED TO WHAT SHE'S BEEN ON BEFORE (cyclosporine, MTX, etc). I'm still not convinced that this effect is systemic steroids. She is able to keep her scalp in control with a once a day 1/2 second spray to about 1/3 of her scalp. A bottle is about a two to three month supply. Roughly this means she's using perhaps 0.5 to 1.0 cc of spray a day. At a putative concentration of 0.1%, she is getting up to 1 mg. of clobetasol a day. Given that a substantial portion is sprayed onto hair, her husband, the mirror etc., and presuming that total absorption of the clobetasol that actually gets onto the skin is less than 100%, the total steroid she's absorbing is rather small I suspect. I'll check a number of my pts for evidence of adrenal suppression in the coming weeks/months, and if I'm wrong and it is happening you all will be informed immediately. Very interesting if annoying situation: as always I am indebted to the list for keeping me current. Mark Ling, M.D., Ph.D. ------------ Before we all (including the FDA I might add) conclude from one report by apparently one observer that skin cap = clobetasol, why not do something scientific like sample a dozen or so different lots to see if this is real or not. My understanding is that it has been assayed for steroid before and none have been found. Now that we have a single positive report we are supposed to believe that over all of the negative ones? Even if the stuff is clobetasol it seems to work better than any topical steroid I have ever seen, and I hope that the makers of clobetasol come out with a similar approved product, because whatever Skin Cap turns out to be, I still consider it a major advance in topical therapy and probably the most potent topical ever for psoriasis. That much seems true, regardless of the ethical or unethical behavior of the manufacturer. Our patients will be the losers if the drug is withdrawn from the market permanently. Mark Naylor, M.D. ---------- For sure. I thyink the story, from Holland to here, is that steroids have intermittently been in SkinCap (in Holland I think they reported triamcinolone, here clobetasol), but that is sort of besides the therapeutic point ( though not the ethical or legal ones). I'll join the speculative fray and repeat that I suspect skin cap contains a potent, unidentified antimetabolite (as opposed to antiinflammatory) agent. Michael Fetterman ----------- Having had a night to sleep on this, let me amend some of my comments: I do agree fully with Steve Feldman that the unethical behavior of the company is highly unethical, and dangerous, and I agree fully with taking it off the market while this is clarified. I also agree that patients on Skin Cap need to have information made available on what the implications of these findings are, and at least until the steroid issue is worked out, need to be weaned off. There's no way in the world I want clobetasol available OTC! Still, I am in the "something besides steroid" camp on this stuff. Based on Charles Crutchfield's experience, I suspect I'll see how DermaZinc works in my hand. I'll also follow up with any potentially steroid related side effects as I see my patients again. Mark Ling, M.D., Ph.D. -------------- i have a very compliant japanese patient who used temovate bid to his right forearm for 4 weeks with about 15% improvement and skin cap to his left forearm for 2 weeks...and the skin cap side was perfectly clear...and i have a severe atope responding only a bit to oral corticosteroids (from another md), not at all to temovate...and is clear on skin cap... steve Emmet CLOBETASOL has been found in Skin Cap by, among others, Mayo Medical Labs (state-of-the-art) and Glaxo (state-of-the-art), the Dutch government and a lab in Canada. What we need to know is the concentration, because this will help with risk asessment and drug withdrawl. The US government ought to ask the Spanish government to lean on the Skin Cap weasles and get proper answers, if qantitative testing here is not producing adequate answers. Kevin C. Smith MD FRCPC -------- Posted on alt.support.psoriasis" Subject: The truth about skin-cap From: vilana@earthlink.net Date: Mon, 11 Aug 1997 20:27:04 -0700 Message-ID: <33EFD808.3334@earthlink.net> The rumors you have heard on the media about the FDA and the National Psoriasis Foundation mentioning harmful effects using Skin-Cap are not true. We can assure you FROM THE CHIEF OFFICE OF CHEMINOVA LABORATORIES ( http://home.earthlink.net/~vilana/chemdoc.jpg )- THERE ARE NO STEROIDS IN SKIN-CAP. The rumors started with an article published in the National Psoriasis Foundation Newspaper, about a test study published in the Netherlands, which stated that there were steroids in Skin-Cap's formula, which caused a temporary I interruption of sales in that country . According to the National Psoriasis Foundation the product seems to be very effective, their concern is that they couldn't find any published test studies in the United States. Cheminova Laboratories, has taken all legal measures in this matter and was successful in proving that the test was in error. According to the General Manager of Cheminova Mr. Aly Santa MArta, The Dutch Authorities allowed immediate return of Skin-Cap to the Dutch market. Our competition is afraid of the success of our product and is trying to exploit this fact to their favor. Cheminova Laboratories is conducting right now, in conjunction with the F.D.A., the development of American studies to prove the safety and effectiveness of our product and the absence of any steroids in the formula. There are more than 100,000 Skin-Cap users in the United States and millions in over 35 countries world wide using the product fir the past 9 years without any reproted side effects. Skin-Cap is the most successful treatment in the world for severe skin disorders. For more information on the subject, please feel free to contact us with more questions at 800 321-SKIN (800 321-7546). If you want, give us your Fax number and we will send you more detailed information. The VILANA Company --------------- For the slightly-paranoid among us, note that today's AAD FAX about skin cap spray said that the initial studies finding steroids in Skin Cap Spray were done by Glaxo! I agree with Dr. Ling that this is a remarkable product and needs further study. Philip Hughes, M.D. ------------ Samples of Skin Cap purchased in several Canadian cities were (surprise! surprise!) all found to contain clobetasol propionate and the Health Protection Branch of our federal government banned Skin Cap Wednesday 13 August. The Canadian Skin Cap weasels (eg. Andrew Two-Names, et al.) tried to pre-empt the feds by "voluntarily withdrawing Skin Cap" but they still got slapped with a "cease and desist order", and the feds issued the by-now standard press release about the dangers of clobetasol propionate, in particular if used in large quantities (eg. more than half a can of Skin Cap per week) and for longer than a couple of months. Kevin C. Smith MD FRCPC ------------ I heard Dr. Koo speak last night on Tazorac but he gave what sounded like well-informed commentary on Skin Cap. He said there were four independent labs that found clobetasol (I don't remember Glaxo). He said the zinc concentrations were all over the map (0.2% to greater than the 2% listed) and that is part of what got FDA and others even more suspicious if that was the main "active" ingredient. Like others, I'm still interested in the truth of this matter, since there is no doubt that the product worked better than anything else in our "formulary" for psoriasis (especially scalp). Eliot Mostow, MD ------------- 2% zinc anything is a strong fixative! Furthermore it is highly corrosive and will bubble and strip paint. Terry L Marshall ------------ have seen about 5 skin cap users so far this week. all have universally been highly upset about losing this treatment, and not very concerned re toxicity (to a person, they all have used lots of Temovate in the past and were surprised at the dangers listed). Mark Ling, M.D., Ph.D. -------------- The Dutch DID find clobetasol according to a private email I got from someone at the NPF. Betamethasone was also found in one jurisdiction, but I can't recall if that was the Netherlands. I kind of think it was Austria. Kevin C. Smith MD FRCPC ------------- Reading the steady stream of testimonials for Skin Cap on this list and in alt.support.psoriasis my position remains unchanged. The fact that we know it has clobetasol does not make Skin Cap a whole lot safer to use. To quote from my fatwah on Skin Cap, promulgated in July: Skin Cap can be very effective in controlling a number of unrelated inflammatory skin conditions, including psoriasis, lupus and lichen planus. Unfortunately there are many things which we will need to learn before Skin Cap can be safely recommended. Skin Cap appears to be a VERY potent broad-spectrum anti-inflammatory and perhaps immunosuppressive or immune-modulating medication. Medications which are very potent often also have a great ability to cause serious problems under some circumstances. Because Skin Cap is not a prescription medicine we do not have the information from the laboratory experiments, experiments with animals, or experiments with humans that are available for virtually all of the other medicines and other treatments that we use in dermatology. Because medical and scientific information on the safety of Skin Cap is not available: 1. I do not know how Skin Cap works. 2. I cannot predict what kinds of problems you may develop after long-term (months to years) or in some cases even short-term (days to months) exposure to Skin Cap. 3. I do not know if there is a safe limit to the amount of Skin Cap you can be apply every day. 4. I do not know if there is a safe limit to the number of days or weeks Skin Cap can be applied. 5. I do not know if there are some parts of your body where Skin Cap should not be applied. 6. I do not know if Skin Cap might make some diseases worse (for example skin infections or skin cancer). 7. I do not know if there are some people (for example children, pregnant women, or old people) who may be at increased risk for problems if they are exposed to Skin Cap. 8. I do not know if there could be an increased risk of problems (for example, skin cancer) if Skin Cap is used in combination with or following other treatment, such as ultraviolet light, methotrexate, cyclosporine or corticosteroid creams. 9. I do not know if inhaling traces of Skin Cap while it is being sprayed, or absorbing it though the skin, could cause internal problems. For example, it is possible that the potent anti-inflammatory and possibly immunosuppressive effect of inhaled Skin Cap could increase the risk of yeast infections in the mouth and airway, and perhaps also increase the risk of dangerous lung infections like Pneumocystis carinii. The animal and human experiments which are necessary to deal with these issues (and which would have been required if Skin Cap was a prescription medication) have not been done. Because the risks of Skin Cap are unknown, it is not possible to accurately weigh the risks against the benefits. You should not use Skin Cap unless you are willing to accept the possible risks and side effects (including risks and side effects we are not aware of yet.) Kevin C. Smith MD FRCPC -------------- In many ways what you're saying is exactly what I say, but with a different slant. Imagine a world without lawyers, or fear of malpractice-- a world where personal responsibility for one's own actions is taken for granted. This would be a world where it was recognized that society can't be help responsible for decisions an individual makes, good or bad. In such a utopian setting, I would argue that the decision to use skin cap would ultimately be the patient's, and that our job as physicians would be to advise capably. The notion that a patient could use a product like Skin Cap, recognizing full well that the physician could in no way guarantee safety for perpetuity, would be just fine in my mind as long as they realized it was their decision. Many of my patients are perfectly clear in their minds that this stuff was potentially risky, but elected to make that decision to use it because the toxicity of their uncontrolled psoriasis was worse in their minds. You or I might not choose to use it, but it's sad that our screwed up societal standards of responsibility makes us unwilling to offer patients opportunities. NOT to say that skin cap should stay on the market--I believe they were crooked and unethical--but in a more general sense, this is why I feel the FDA has been much too overprotective in a misguided attempt to protect us from any possible risk. Mark Ling, M.D., Ph.D. ------------ If the isopropyl myristate in SKIN-CAP really enhances transepidermal penetration that much, why isn't it more widely used? Steve A. McClain, MD -------------- At the Canadian Derm last month Bill Danby reported seeing early striae and possibly hypertrichosis, I think after only a few months of use. Kevin C. Smith MD FRCPC --------------- I have recently treated a teenage girl with severe linear morphea of one thigh and leg with Lidex cream; she developed striae of the proximal thigh in less than a month, in areas that she was not applying Lidex. I agree it is puzzling that no striae are showing up 2ndary to Skin Cap, supposedly with a much stronger steroid. I admit teenagers and young adults seem to develope striae easier, probably from growth spurts, rapid wt. gain, exercise, etc. Hal Rehbein ------------ I have actually called a sample of my psoriasis patients to whom I recommended or monitored the use of Skin Cap. Several have stopped because of expense. Most are using it with high success only a couple of times a week, with better control than anything before. One patient has told me she had a brisk inflamatory reaction to it and stopped. I believe that any physician who has used this product open-mindedly cannot help but be impressed with the results in an amazing proportion of difficult patients. Regardless of the alleged transgressions of the company I think it would be a shame to throw out the baby with the bathwater here. If the NPF really cares about its constituency, it should be using all its clout to get FDA to do appropriate studies on this product, as is, and find out how it can be used in a responsible and safe manner. Some of the comments from this group have been examples, I think, of how not to react in a situation like this. Instead of inflaming the issue with visions of adrenal insufficiency and suicidal patients ( I have yet to see atrophy or striae), we should be working toward better understanding of this product. We should be taking action to protect the best interests of our patients instead of perhaps needlessly frightening them - and each other. I think it is appropriate to keep our patients informed of what we know about the situation as it unfolds, offer alternatives (such as Derma Zinc, plus/minus a steroid) where necessary. For myself, I have contacted a few patients by phone to see the general reaction. I plan to write a letter and send it to those whom I have placed on it or know are using it. The letter will outline the current situation as I understand it, outline the small risk of side effects depending on dose, offer help to those who are concerned they may be at risk for or experiencing side effects, and offer help in finding alternatives until more is known. Other than having sold 50 cans of Skin Cap fom my office approximately at cost, I have no financial interest in any product. Jerry Eisner --------- Sprayed skin cap on my arm, and applied Diprolene. Vasoconstriction remains 5 hours after application of Diprolene, none where Skin Cap was applied. And this is from a can which made miracles in one patient. Diane Thaler ----------- Received a fax from Cheminova Internacional,S.A. 8-14-97.It was a copy of a fax forwarded to Mrs Tara Rolstad of the National Psoriasis Foundation from Aly E. Santa Marta, General Manager(fax 213 3847155).This letter indicated that " tests showing no presence of any Corticosteroids in our product Skin-Cap as proof of the analysis test of molecular weight carrying out with Maldi-tof test..." "This analysis confirm that the component of the Skin-Cap which was in doubt, has a molecular weight of MW325 so far away from the range of steroids that oscillate between 380 and 480," "We confirm that Holland authorities have allowed the return to the Dutch market of the Skin-Cap immediately." Two pages follow which detail the Maldi-TOF test.... Whatever the outcome of all this, it IS interesting stuff and hopefully some group ?FDA ?NPF will help define this therapeutic agent so that our pts can have an additional option. Pierre Jaffe, MD --------------- My position is simply that we should apply the same principles to Skin Cap - and ask the same questions - as we do with any other therapy - principles we learned in introductory pharmacology. These generally are the questions I ask drug reps about new meds when they come to my office. These protect my patients and ME. (I haven't done it, but I have a piece of software on the Mac that records sound: 1 hour takes 14 MB, and you can annotate as you go along. Handy for meetings -- could be great documentation of what was said by a drug rep during a drug launch). These are the questions I would have asked if a Skin Cap rep had come to see me: 1. Powerful drugs usually have the ability to cause harm. What is the side effect profile of Skin Cap? How do I detect and deal with these side effects? 2. What is the mechanism of action? I am going to run a literature search - will you get me copies of the relevant papers from the scientific literature if I give you the references? (This line has blown out a couple of hucksters (eg. glycolic acid salesmen): " .... well, there's nothing published yet ...." Reply: so, come back when you have data. Goodbye. End of interview.) 3.. Is there a maximum safe dose? 4. Is there a maximum safe duration of use? 5. What is in this apart from the active ingredient? (eg. it was helpful to know that some of the older forms of cyclosporine had ethanol in them -- patients on Antabuse needed to avoid that). 6. Are there some parts of the body where this should not be used? 7. Are there some people who should not use this? *Kids (yeah, I know nothing is ever tested on kids, but are there any data suggesting that kids should avoid your stuff?) * Pregnant women (as above) * old people (as above) * people with cancer, herpes, fungi etc? 8. Are there some treatments that should not be used before, with or after this treatment? (eg. PUVA) Pity the poor unprepared drug rep who hits me with a manager in tow, trying to launch a new product. On the other hand, someone who is prepared to answer these reasonable questions will look great. I wonder how the Skin Cap rep would have done? Kevin C. Smith MD FRCPC ----------------