Topical Tazarotene Therapy for Psoriasis, Acne Vulgaris, and ...

Click here for Skin Therapy Letter onlineSkinCareGuideV o l u m e 7 • N u m b e r 3 • M a r c h 2 0 0 2Indexed by the US National Library of Medicine and MEDLINETopical Tazarotene Therapy for Psoriasis,Acne Vulgaris, and PhotoagingL.C. Guenther, MD, FRCPCDivision of Dermatology, University of Western Ontario, London, Ontario, CanadaABSTRACTPsoriasis, acne vulgaris and photoaging are common conditions. Tazarotene is a pro-drug of tazarotenic acid, a receptor-selectiveretinoid, which has shown efficacy in the treatment of these disorders. In the treatment of acne vulgaris, it has greater comedolyticactivity than the currently available topical retinoids. In psoriasis, tazarotene normalizes keratinocyte differentiation, reverseskeratinocyte hyperproliferation and has better anti-inflammatory effects than any of the currently available topical retinoids. It ismost commonly used as combination therapy with a topical corticosteroid or phototherapy in psoriasis, or with an antibiotic in acne.KEY WORDS: tazarotene, retinoid, psoriasis, acne vulgaris, photoagingMechanism of ActionTazarotene is a pro-drug of the more water soluble tazarotenicacid, a receptor-selective acetylenic retinoid which binds toRARβ and RARγ and weakly to RARα. 1 Tazarotenic acid doesnot interconvert to any other retinoids that could potentiallyactivate other retinoid receptors. In psoriasis, tazarotenenormalizes keratinocyte differentiation, reverses keratinocytehyperproliferation and has anti-inflammatory effects. In acnevulgaris, the abnormal desquamation of the follicular epitheliumis normalized. 2 In October 2001, the US FDA approved Tazorac ®cream 0.1% (tazarotene, Allergan) for the treatment of acnevulgaris. Since 1997, Tazorac ® gel (0.05% and 0.1%) has beenavailable for the treatment of stable plaque psoriasis and the 0.1%gel is also indicated for the treatment of mild-to-moderatelysevere facial acne vulgaris. Tazorac ® cream (0.05% and 0.1%)was approved by the US FDA in 2000 for the treatment of plaquepsoriasis. Approval by the US FDA and TPP – Canada isexpected for the indication of photoaging sometime in 2002.PsoriasisPsoriasis affects approximately 2% of the population. 3 Plaquepsoriasis, the most common variant, is characterized by welldefinederythematous scaly plaques, with or without associatednail disease and arthritis. In most patients, the disease is localizedand amenable to topical therapy.Tazarotene is efficacious as monotherapy, 4 but is morecommonly used in combination with phototherapy or with atopical corticosteroid in order to enhance efficacy andtolerability. 5 Adjunctive use of a mid or high-potency steroidresults in greater reductions of overall disease severity, plaqueelevation and adverse events (see Table 1).Rebound does not appear to be a problem. Epidermal atrophyinduced by steroids can also be minimized by tazarotene. Thereduction of epidermal thickness was only 28% when tazarotenewas used in conjunction with diflorasone diacetate 0.05%compared to 43% when the steroid was used alone. 5 Use of the0.1% gel once daily in combination with mometasone furoate0.1% cream once daily is more efficacious than twice dailycalcipotriol ointment 6 or twice daily mometasone furoate 0.1%cream. 7 Superior maintenance of remission was seen with thriceweekly tazarotene 0.1% gel used in conjunction with twiceweekly clobetasol propionate 0.05% ointment than when thevehicle was used alone. 8Acne vulgarisApproximately 95% of the population suffers at some point in theirlifetime from acne vulgaris. 9 Papules, pustules, closed and opencomedones, cysts and scarring may be seen. Although morecommon in teenage years, it may persist into the fourth and fifthEDITOR-IN-CHIEF: Stuart Maddin ASSOCIATE EDITOR (International): Hugo Degreef, Catholic University, Leuven: ASSOCIATE EDITOR (Canada): Jason RiversINTERNET EDITOR: Harvey Lui PUBLICATIONS EDITOR: Penelope Gray-Allan EDITORIAL ADVISORY BOARD: Kenneth A. Arndt, Beth Israel Hospital & Harvard Medical School, Boston;Wilma Fowler Bergfeld, Cleveland Clinic, Cleveland; Jan D. Bos, University of Amsterdam, Amsterdam; Enno Christophers, Universitäts-Hautklinik, Kiel; Richard L. Dobson, Medical Universityof South Carolina, Charleston; Jeffrey S. Dover, Harvard Medical School, Boston; Boni E. Elewski, University of Alabama, Birmingham; Barbara A. Gilchrest, Boston University School ofMedicine, Boston; W. Andrew D. Griffiths, St. Johns Institute of Dermatology, London; Aditya K. Gupta, University of Toronto, Toronto;Vincent C.Y. Ho, University of British Columbia, Vancouver;Mark Lebwohl, Mount Sinai Medical Center, New York; James J. Leyden, University of Pennsylvania, Philadelphia; Howard I. Maibach, University of California Hospital, San Francisco;Larry E. Millikan, Tulane University Medical Center, New Orleans; Takeji Nishikawa, Keio University School of Medicine, Tokyo; Constantin E. Orfanos, Freie Universitäts Berlin,Universitätsklinikum Benjamin Franklin, Berlin; Stephen L. Sacks, Viridae Clinic Sciences, Vancouver; Alan R. Shalita, SUNY Health Sciences Center, Brooklyn; Richard Thomas, VancouverGeneral Hospital, Vancouver; Stephen K. Tyring, University of Texas Medical Branch, Galveston; John Voorhees, University of Michigan, Ann Arbor; Klaus Wolff, University of Vienna, Vienna

ComparatorsResultsTazarotene 0.1% gel +:• There was a lower median time to reach 50% improvement with (2 weeks) or• Fluocinolone acetonide 0.01% cream (LOW) vs. HIGH (3 weeks) vs. placebo (4 weeks) (p

ComparatorsResultsTazarotene 0.1% gel q.d. vs. Retin A ® gel q.d. 15 0.025% Tazarotene was more efficacious in reducing open comedo count (65% vs.44%, p=0.03), total noninflammatory lesion count (55% vs. 42% p=0.04) andtotal inflammatory lesion count (54% vs. 44% NS)Tazarotene 0.1% gel q.d. vs. Retin A Micro ® 0.1% q.d. 16 There were statistically significant reductions in overall disease severity (36%vs. 26%, p=0.02), global response scores (2.80 vs. 3.35, p=0.02), andnoninflammatory lesions (60% vs. 38%, p=0.02) with tazarotene.Tazarotene 0.1% gel q.d. vs. Differin ® Gel q.d. 17There was a greater reduction with tazarotene when compared to adapalene inmean global response score (2.38 vs. 3.41 at 12 weeks, p

Contraceptive counseling should be given to women ofchildbearing potential before topical tazarotene is used. Althoughabsorption is minimal, it should not be used by pregnant womensince systemic tazarotene is teratogenic.ConclusionsTopical tazarotene is very efficacious in the treatment ofpsoriasis, acne and photoaging. It is the most potent comedolytictopical retinoid currently available. Combination therapy withcorticosteroids or phototherapy in psoriasis, or antibiotics in acnevulgaris, can enhance efficacy and tolerance. Irritation can beminimized with patient education, and use of the 0.05% cream,on alternate day and short-contact regimens.References1. Chandraratna RA. Tazarotene—first of a new generation of receptor-selectiveretinoids. Br J Dermatol 135(Suppl 49):18-25 (1996 Oct).2. Bershad S, Poulin YP, Berson DS, et al. Topical retinoids in the treatment of acnevulgaris. Cutis 64(2 Suppl):8-20 (1999 Aug).3. Koo J. Population-based epidemiologic study of psoriasis with emphasis onquality of life assessment. Dermatol Clin 14(3):485-96 (1996 Jul).4. Weinstein GD, Krueger GG, Lowe NJ, et al. Tazarotene gel, a new retinoid fortopical therapy of psoriasis: vehicle-controlled study of safety, efficacy andduration of therapeutic effect. J Am Acad Dermatol 37(1):85-92 (1997 Jul).5. Guenther L. Tazarotene combination treatments in psoriasis. J Am AcadDermatol 43(2 Pt 3):S36-42 (2000 Aug).6. Guenther LC, Poulin YP, Pariser DM. A comparison of tazarotene 0.1% gel oncedaily plus mometasone furoate 0.1% cream once daily versus calcipotriene0.005% ointment twice daily in the treatment of plaque psoriasis. Clin Ther22(10):1225-38 (2000 Oct).7. Koo J, Martin D. Double-blind comparison of tazarotene gel q.d. plusmometasone furoate cream q.d. versus mometasone furoate cream b.i.d. Posterpresentation at: American Academy of Dermatology annual meeting, (1999 July28-August 1), New York, NY.8. Lebwohl M, Lombardi K, Tan MH. Duration of improvement in psoriasis aftertreatment with tazarotene 0.1% gel plus clobetasol propionate 0.05% ointment:comparison of maintenance treatments. Int J Dermatol 40(1):64-6 (2001 Jan).9. Ho V, Schacter D, Miller R, et al. Acne management for the 90s: currenttreatment guidelines. Can J Diagnosis 12(suppl):1-25 (1995).10. Lebwohl MG, Breneman DL, Goffe BS, et al. Tazarotene 0.1% gel pluscorticosteroid cream in the treatment of plaque psoriasis. J Am Acad Dermatol39(4 Pt 1):590-6 (1998 Oct).11. Green L, Sadoff W, and the Tazarotene Plus High-Potency or Mid-PotencySteroid Study Group. A clinical evaluation of tazarotene 0.1% gel, with andwithout a high- or mid-high-potency corticosteroid, in patients with stableplaque psoriasis. J Cut Med Surg. In Press 2002.12. Koo JY, Lowe NJ, Lew-Kaya DA, et al. Tazarotene plus UVB phototherapy inthe treatment of psoriasis. J Am Acad Dermatol 43(5 Pt 1):821-8 (2000 Nov).13. Behrens S, Grundmann-Kollmann M, Schiener R, Peter RU, Kerscher M.Combination phototherapy of psoriasis with narrow-band UVB irradiation andtopical tazarotene gel. J Am Acad Dermatol 42(3):493-5 (2000 Mar).14. Behrens S. Combination treatment of psoriasis with photochemotherapy andtazarotene gel, a receptor-selective topical retinoid. (Letter to Ed.) Br J Dermatol141:154-179 (1999).15. Webster GF, Berson D, Stein LF, Fivenson DP, Tanghetti EA, Ling M. Efficacyand tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin0.025% gel in the treatment of facial acne vulgaris: a randomized trial. Cutis67(6 Suppl):4-9 (2001 Jun).16. Leyden JJ, Tanghetti EA, Miller B, et al. Once-daily tazarotene 0.1% gel versusonce-daily tretinoin 0.1% microsponge gel for the treatment of facial acnevulgaris: a double-blind randomized trial. Cutis 69(suppl 2):12-19 (2002).17. Webster GF, Guenther L, Poulin YP, et al. A multicenter, double-blind,randomized comparison study of the efficacy and tolerability of once-dailytazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acnevulgaris. Cutis 69(suppl 2):4-11 (2002).18. Leyden J, Lowe N, Kakita L, Draelos Z. Comparison of treatment of acne vulgariswith alternate-day applications of tazarotene 0.1% gel and once-daily applicationsof adapalene 0.1% gel: a randomized trial. Cutis 67(6 suppl):10-6 (2001 Jun).19. Draelos ZD, Tanghetti EA, and the Tazarotene Combination Leads to EfficaciousAcne Results (CLEAR) Trial Study Group. Cutis 69(suppl 2):20-29 (2002).20. Sefton J, Kigman AM, Kopper SC, Lue JC, Gibson JR. Photodamage pilot study:a double-blind, vehicle-controlled study to assess the efficacy and safety oftazarotene 0.1% gel. J Am Acad Dermatol 43(4):656-63 (2000 Oct).21. Kang S, Leydon JJ, Lowe NJ, et al. Tazarotene cream for the treatment of facialphotodamage: a multicenter, investigator-masked, randomized, vehiclecontrolled,parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotenecreams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.Arch Dermatol 137(12):1597-604 (2001 Dec).————— INDUSTRY NEWS —————Roche Initiates an Enhanced Pregnancy Prevention Programto Prevent Accutane- Exposed PregnanciesIn January 2002, Hoffmann-LaRoche, working closely with the US FDA distributed an enhanced version of their Pregnancy Prevention Program for Womenon Accutane ® to more than 375,000 dermatologists, primary care prescribers and pharmacists in the US. The program is called S.M.A.R.T. (System to ManageAccutane ® Related Teratogenicity). It involves the prescriber, pharmacist and patient to ensure that female patients are not pregnant when they begin takingAccutane ® and that they do not become pregnant while taking the medication and for one month after stopping treatment. An innovative component of theprogram is the use of yellow self-adhesive Accutane ® Qualifications Stickers, which prescribers will apply to all Accutane ® prescriptions.To receive the first Accutane ® prescription, the female patient will be required to meet four qualifications:1. Have two negative pregnancy tests – the first as a screening test and the second as a confirmation test that will be administered during the first 5 daysof her next menstrual period.2. Select and commit to using two effective forms of birth control simultaneously one month prior to treatment, during treatment and for one month afterstopping treatment.3. Read and sign an informed consent agreement explaining the risk of potential birth defects associated with Accutane ® .4. Learn about and be encouraged to enroll in the Accutane ® Survey, a system to track female Accutane ® patients, learn about their experiences withpregnancy prevention efforts and determine their pregnancy status.Each month the patient must have a negative pregnancy test and receive contraception counseling from the prescriber before receiving a new prescription.If the patient meets these qualifications, or is male, the prescriber will then write a prescription for a 1-month supply, affix one of the yellow Accutane ®Qualification Stickers and date it. Prescriptions must be filled within 7 days of the qualification date on the sticker.This program is being phased in and the deadline for compliance is April 10, 2002.The S.M.A.R.T. program is only applicable for treating patients in the US. For other countries, including Canada, Roche has created uniquely tailoredprograms to address their distinctive health care needs.4Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 7 No. 3 • March 2002

Common Sense Dermatological Drug SuggestionsFor Women Who Are Breast-feedingC. Zip, MD, FRCPCDepartment of Medicine, University of Calgary, Calgary, Alberta, CanadaABSTRACTUse of medications by breast-feeding mothers is not uncommon. When prescribing a medication to a nursing mother, the physicianmust weigh the potential risk of exposing the infant to the medication or the risks of not breast-feeding against the benefits of themedication to the mother. Information regarding the safety of common dermatological medications during lactation will bereviewed. Based on this information, treatment recommendations will be made.Key Words: breast-feeding, antimicrobials, antihistimines, immunomodulators, antipsoriatics, steriods, scabicides, anti-acne agentsBreast-feeding provides optimal nutrition in the first 6 months oflife. Well documented benefits of breast-feeding include adecreased incidence of infantile diarrhea 1 and infection. 2 Otherstudies show a possible protective affect against sudden infantdeath syndrome, 3 insulin dependent diabetes mellitus, 4 Crohn’sdisease, 5 ulcerative colitis, 5 lymphoma, 6 and allergic disorders. 7The American Academy of Pediatrics (AAP) recommendsexclusive breastfeeding for the first six months of life, continuingto a year or beyond with the addition of solid food at 6 months ofage. 8 In Canada, approximately 80% of new mothers initiatebreast-feeding, 9 while 30-40% are still nursing 6 monthspostpartum. 10 Corresponding US figures are 64% and 29%,respectively. 11The use of prescription and over-the-counter (OTC) medicationsis common for nursing mothers. In one study of 14,000 pregnantor breastfeeding women, 79% of them took at least onemedication, while on average, 3.3 drugs were taken whilebreastfeeding. 12 Fortunately, severe adverse effects resultingfrom the presence of common medications in breast milk areuncommon. Of 838 infants exposed to medications throughbreast milk, 11% experienced minor reactions, and no seriousreactions requiring medical attention or cessation ofbreastfeeding occurred. 13 The adverse reactions that did occurwere consistent with the known pharmacological affects of thecausative agent.Transfer of Medications into Breast MilkA number of factors determine the passage of a drug into breastmilk. These include characteristics of the mother, the infant andthe drug itself. In general, drugs given to a nursing mother reachthe infant in much lower concentrations than those given to apregnant woman reach the fetus. 14AntimicrobialsPenicillins and cephalosporins are present only in trace amountsin breast milk, and are compatible with breast-feeding. 15 Theiruse is associated with a remote risk of alterations ingastrointestinal flora causing diarrhea and allergic sensitization ofthe infant. 16 Erythromycin is excreted into breast milk, but noadverse effects in infants exposed to this drug in breast milk havebeen reported, 16 and it is considered compatible withbreastfeeding by the AAP. Caution may be in order in whenprescribing erythromycin to lactating mothers of newbornshowever, because of recent reports of pyloric stenosis in neonatestreated with erythromycin. 17,18 It has been reported that thecalcium present in breast milk may inhibit absorption of the smallamount of tetracycline, however, use of tetracycline while breastfeedingis not advised, because the threshold for its affect on teethand bone is unknown. 14 Topical clindamycin is partially absorbedthrough the skin and small amounts may pass into breast milk. Noproblems have been reported in nursing infants with maternal useof topical clindamycin, 19 although bloody diarrhea was reportedin an infant of a mother on intravenous clindamycin. 20 Noadverse effects on the infant have been reported with use oftopical metronidazole during lactation, however the manufactureradvises against its use while breast-feeding. 21Acyclovir is considered safe during breast-feeding. 15,16Experience with the use of valacyclovir and famciclovir duringhuman lactation is lacking. 16Terbinafine and itraconazole are both excreted in breast milk, andthe safety of their use during lactation is unknown. Parenteralfluconazole has been safely used in neonates with candidiasis,and based on this, Briggs states that its use is probably safeduring breast-feeding. 16 The manufacturers of these threeantifungals do not recommend their use while breast-feeding andthe AAP has no rating. 22,23,24AntihistaminesSmall amounts of antihistamines are excreted in breast milk.Their use is not recommended during breast-feeding becauseinfants may be more susceptible to their adverse effects,particularly drowsiness and irritability. 19,25 Antihistamines mayalso reduce milk production in some women.ImmunomodulatorsBoth cyclosporine and methotrexate are excreted into breast milk,and considered contraindicated during breast-feeding by the AAPbecause of the possibility of immunosuppression, neutropenia,carcinogenesis and unknown affects on growth. 15Hydroxychloroquine is excreted in small amounts in breast milkand because of its slow elimination rate and potential toaccumulate to toxic levels in infants, caution is advised with dailySkin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 7 No. 3 • March 2002 5

dosing. 26 The AAP, however, considers hydroxychloroquine to becompatible with breast-feeding. 15 Tacrolimus is excreted in humanmilk. Topical tacrolimus is not recommended by the manufacturerduring breastfeeding, because of the potential for systemicabsorption with topical use. 27 The AAP does not rate tacrolimus.AntipsoriaticsIt is not known whether calcipotriol is excreted into breast milk.The manufacturer recommends its use only if the anticipatedbenefits outweigh the potential risks. 28 Methoxsalen excretion inhuman milk is also unknown and although there are no reports ofadverse effects with its use during lactation, the manufacturerrecommends use only when the probable benefits outweigh thepotential risks. 29 Briggs recommends that breast-feeding beinterrupted for at least 24 hours after administration of the drugbecause of its photosensitizing affect. 16SteroidsTrace amounts of prednisone and its metabolite prednisolone areexcreted in breast milk. 16 The AAP considers prednisone to becompatible with breastfeeding. 15 Hypertension was reported inthe infant of a woman who used a corticosteroid on the nipples. 30Use of topical corticosteroids on the breasts prior to nursingshould be avoided.Because estrogen decreases the quantity and protein content ofbreast milk, the use of combination oral contraceptive pillsshould be avoided whenever possible in lactating mothers,especially in the first two months postpartum. 31ScabicidesIt is not known if permethrin is excreted in human milk. Citingevidence of teratogenicity in animals, the manufacturerrecommends temporary discontinuation of nursing or avoidanceduring lactation. 32 Anderson considers its use to be safe duringlactation. 33AnalgesicsSignificant salicylate levels have been found in breast-fed neonatesof mothers taking salicylates, raising concerns about metabolicacidosis, bleeding, altered pulmonary circulation and Reye’ssyndrome. 26 There is one report of salicylate intoxication in aninfant exposed through her mother’s milk. 34 The AAPrecommends that it be used with caution in nursing mothers. 15Widespread use of topical salicylic acid should be avoided becauseof the potential for significant systemic absorption. Of thenonsteroidal anti-inflammatories, ibuprofen and flurbiprofen havethe best documentation of safety during lactation because they donot enter breast milk in significant quantities. 14 The AAPconsiders ibuprofen, indomethacin, and naprosyn to be compatiblewith breast-feeding. 15 There is one case report of seizures in aninfant exposed to indomethacin through breast milk. 35Antiacne AgentsThere have been no reports of adverse effects from use of topicalbenzoyl peroxide and topical tretinoin during lactation. 19 It is notknown whether adapalene or tazarotene pass into breast milk.The manufacturers recommend caution with their use duringClass of Choices Compatible CommentMedication with Breast-FeedingAntibiotics Penicillins, Cephalosporins, Possibility of diarrhea, thrush and allergic sensitization of theErythromycin (caution with neonates), infantTopical clindamycin, TopicalmetronidazoleAntivirals Acyclovir Considered safe during breastfeedingAntifungals Fluconazole Manufacturer does not recommend its use during lactation.Antihistamines None Infants may be more susceptible to their adverse effectsImmunomodulators Hydroxychloroquine Methotrexate and cyclosporine are not recommendedAntipsoriatics Calcipotriol No reports of adverse effectsSteroids Prednisone Trace amounts of prednisone are present in breast milk.Topical corticosteroidsCombination oral contraceptivesAvoid use of topical corticosteroids on breasts prior to nursing.Delay use until milk production established; may reduce milkproduction.Scabicides Permethrin Probably safe; consider temporary discontinuation ofbreastfeeding.Analgesics Ibuprofen Ibuprofen does not enter breast milk in significant amounts.Acetaminophen 15Antiacne Benzoyl peroxide No reports of adverse effectsTopical tretinoinTable 1: Compatibility of some dermatologic drugs during breastfeeding.6Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 7 No. 3 • March 2002

lactation. 36,37 Spironolactone may pass into breast milk, but hasnot been reported to cause problems in nursing babies. 19 TheAAP considered spironolactone to be compatible with breastfeeding,15 although its use during lactation is not recommendedby the manufacturer. 38ConclusionWhen considering a medication for a lactating mother, thebenefits of breast-feeding need to be weighed against thepotential risk of exposure of the infant to the drug in question.For the majority of dermatological conditions, alternatives thatare compatible with breast-feeding are available, or treatment canbe safely postponed until lactation is completed.References1. Popkin BM, Adair L, Akin JS, et al. Breast-feeding and diarrheal morbidity.Pediatrics 1990; 86: 874-882.2. Beaudry M., Dufour R, Marcoux S. Relation between infant feeding andinfections during the first six months of life. J Pediatr 1995; 126: 191-197.3. Ford RPK, Taylor BJ, Mitchell EA, et al. Breastfeeding and the risk of suddeninfant death syndrome. Int J Epidermiol 1993; 22: 885-890.4. Mayer EJ, Hamman RF, Gay EC, et al. Reduced risk of IDDM among breast-fedchildren. Diabetes 1988; 37:1625-1632.5. Rigas A, Rigas B, Glassman M, et al. Breast-feeding and maternal smoking inthe etiology of Crohn’s disease and ulcerative colitis in childhood. AnnEpidemiol 1993; 3:387-392.6. Davis MK, Savitz DA, Graubard BI. Infant feeding and childhood cancer. Lancet1988; 2:365-368.7. Gdalevich M, Mimouni D, David M, Mimouni M. Breast-feeding and the onsetof atopic dermatitis in childhood: A systematic review and meta-analysis ofprospective studies. J Am Acad Dermatol 2001; 45: 520-527.8. American Academy of Pediatrics, Work Group on Breastfeeding. Breastfeedingand the use of human milk. Pediatrics 1997; 100: 1035-1039.9. Barber CM, Abernathy T, Steinmetz B, Charlebois J. Using a breastfeedingprevalence survey to identify a population for targeted programs. Can J PublicHealth 1997; 88:242-245.10. Bourgoin G, Lahaie N, Rheaume B, et al. Factors influencing the duration ofbreastfeeding in the Sudbury region. Can J Public Health 1997; 88: 238-241.11. Ryan AS. The resurgence of breastfeeding in the United States. Pediatrics1997; 99:E12.12. Collaborative Group on Drug Use in Pregnancy. Medication during pregnancy:An intercontinental cooperative study. Int J Gynecol Obstet 1992; 39:185–196.13. Ito S, Blajchman A, Stephenson M, et al. Prospective follow-up of adversereactions in breastfed infants exposed to maternal medication. Am J ObstetGynecol 1993; 168:1393-1399.14. Howard CR, Lawrence RA. Drugs and breastfeeding. Clin Perinatology 1999;26: 447-478.15. American Academy of Pediatrics Committee on Drugs. The transfer of drugs andother chemicals into human milk. Pediatrics 1994; 93:137-150.16. Briggs GG, Freeman RK, Yaffee SL. Drugs in pregnancy and lactation, FifthEdition, Baltimore: Williams and Wilkins, 1998.17. Anonymous. Erythromycin – induced pyloric stenosis in infants. PrescrireInternational 2001; 10:16.18. Honein MA, Paulozzi LJ, Himelright IM, et al. Infantile hypertrophic pyloricstenosis after pertussis prophylaxis with erythromycin: A case review and cohortstudy. Lancet 1999; 354: 2101-2105.19. USP- DI. Drug Information for the Health Care Professional, Vol. 1, NineteenthEdition, Taunton, MA: Rand McNally, 1999.20. Mann CF. Clindamycin and breast-feeding. Pediatrics 1980; 66:1030-1031.21. Metronidazole product monograph, Galderma Canada Inc., Thornhill, ON,Canada, 1996.22. Terbinafine product monograph, Novartis Pharmaceuticals Canada Inc., Dorval,QC, Canada, 2002.23. Itraconazole product monograph, Janssen-Ortho Inc., Toronto, ON, Canada, 2002.24. Fluconazole product monograph, Pfizer Canada Inc., Kirkland, QC, Canada, 2001.25. Reed BR, Dermatologic drug use during pregnancy and lactation. DermatolClinics 1997; 15:197-202.26. Janssen NM, Genta MS. The effects of immunosuppressive and antiinflammatorymedications on fertility, pregnancy and lactation. Arch Intern Med2000; 160:610-619.27. Tacrolimus product monograph, Fujisawa Canada Inc., Markham, ON,Canada, 2001.28. Calcipotriol product monograph, Leo Pharma Inc., Thornhill, ON, Canada, 2001.29. Methoxsalen product monograph, ICN Canada Ltd. Montreal, QC, Canada, 1992.30. DeStefano P, Bongo C, Borgna – Pignatti C, et al. Factitious hypertension withmineralocorticoid excess in infants. Helv Paediatr Acta 1983; 38:185-189.31. Spencer JP,Gonzalez LS, Barnhart DJ. Medications in the breast-feedingmother. Am Fam Phys 2001; 64:119-126.32. Permethin product monograph, Glaxo Smith Kline,Mississauga, ON, Canada, 2002.33. Anderson PO. Drug use during breast-feeding. Clin Pharm 1991; 10:594-624.34. Clark JH, Wilson WG. A 16-day-old breast-fed infant with metabolic acidosiscaused by salicylate. Clin Pediatr 1981; 20:53-54.35. Eeg-Olofsson O,Malmros I, Elwin CE, Steen B. Convulsions in a breast-fedinfant after maternal indomethacin. Lancet 1978; 2:215.36. Adapalene product monograph, Galderma Canada Inc., Thornhill, ON,Canada, 2002.37. Tazarotene product monograph, Allergan, Markham, ON, Canada, 2001.38. Spironolactone product monograph, Pharmacia Canada Inc., Mississauga, ON,Canada, 2001.WE’RE ON THE NET! www.skincareguide.com————— INDUSTRY NEWS —————Schering-Plough Recalls Specific Lots of Claritin-D 12-hour TabletsIn February 2002, Shering-Plough announced a voluntary recall of specific lots of Claritin-D ® 12-hour (5mg loratidine/120mg pseudoephedrine sulfate)tablets directed to wholesale accounts and retail pharmacies. These products were manufactured between August 1999, and June 2001. They are indicatedfor the relief of symptoms of seasonal allergic rhinitis.Schering-Plough as part of its standard quality-control procedures conducted stability testing of specific lots of this product including dissolution tests todetermine the rate that tablets dissolve and the amount of active ingredients released. Test results indicated that some tablets in these lots did not demonstratefull release of pseudoephedrine at the 5 th hour per specification, although be 25 minutes later all tested samples met specifications for releasing thedecongestant component. The company believes that this short delay poses no medical risk to patients.This recall is being conducted with the knowledge of the US FDA.Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 7 No. 3 • March 2002 7

Update on DrugsClass Name/Company Approval Dates and CommentsAntiviral AgentNaturally-Derived AlphaInterferonViragenThe Swedish Regulatory Authorities approved expanded use in January2002, to include the treatment of patients afflicted with any and alldiseases in which patients were or became resistant to treatments usingrecombinant (synthetic) interferon. Recombinant interferons usuallycontain only one subtype of interferon as compared to multiplesubtypes in naturally derived interferon, which is produced by humanwhite blood cells.HIV/AIDSOralContraceptiveOncologicAgentHIV/AIDSAntihistamineEfavirenzSustiva ®Bristol-Myers SquibbEstradiol/LevonorgestrelAlesse ®Wyeth-Ayerst CanadaHSPPC-96Oncophage ®AntigenicsTenofovir Disoproxil FumerateViread ®Gilead SciencesDesloratidineClarinex ® 5mg. TabletsSchering-PloughThe US FDA approved a new one-tablet 600mg. formulation inFebruary 2002, of this non-nucleoside reverse transcriptase inhibitorused in combination treatment for HIV. The new formulation willprovide doctors with the option of prescribing one 600mg. tablet oncedaily instead of three 200mg. capsules once daily.TPP – Canada approved this birth control pill in January 2002, for thetreatment of moderate acne in women.The US FDA granted fast-track designation in February 2002, for thiscancer vaccine for the treatment of metastatic melanoma.The EMEA granted marketing approval in all 15 member states of theEuropean Union in February 2002, for use in combination with otherantiretroviral agents for the treatment of HIV infection in patients whoare experiencing early virological failure.The US FDA approved additional indications for this antihistaminein February 2002, to treat chronic idiopathic urticaria andsymptoms of allergies caused by indoor and outdoor allergens inadults and children >12 years of age.Drug NewsHIV/AIDS Many scientists have believed that HIV acts to deplete its primary target, CD4+ T-cells by blocking new T-cell production. According to a report from the US National Institutes of Health, two independent studiesdemonstrated that HIV does not block such production, but acts to accelerate the division of existing T-cells. Consequently, the increases in CD4+ T-cell counts seen following highly active antiretroviral therapy(HAART) are not due to a boost in the production of new T-cells. Instead, they are caused by a slowdownin the loss of existing T-cells.SunscreensAccording to an article published in the Journal of the American Academy of Dermatology* sunscreenshould be reapplied 15-30 minutes after sun exposure begins for maximum benefit. An individual whodoes this will have 15-40% less exposure to ultraviolet rays than someone who waits for 2 hours beforereapplying sunscreen.*J Amer Acad Dermatol 45:882-5 (2001).Skin Therapy Letter(ISSN 1201–5989) Copyright 2002 by SkinCareGuide.com. The Skin Therapy Letter © is published 10 times annually by SkinCareGuide.com Ltd, 450 – 688 West Hastings, Vancouver, British Columbia,Canada, V6B 1P1. Publications Editor: Penelope Gray-Allan: 604-633-1926, email: grayallan@skincareguide.com. All rights reserved. Reproduction in whole or in part by any process is strictly forbidden without prior consentof the publisher in writing. While every effort is made to see that no inaccurate or misleading data, opinion or statement appears in the Skin Therapy Letter © , the Publishers and Editorial Board wish to make it clear that the dataand opinions appearing in the articles herein are the responsibility of the contributor. Accordingly, the Publishers, the Editorial Committee and their respective employees, officers and agents accept no liability whatsoever forthe consequences of any such inaccurate or misleading data, opinion or statement. While every effort is made to ensure that drug doses and other quantities are presented accurately, readers are advised that new methods andtechniques involving drug usage, and described herein should only be followed in conjunction with the drug manufacturer’s own published literature. Printed on acid free paper effective with Volume 1, Issue 1, 1995.Subscription Information. Annual subscription: Canadian $95 individual; $165 institutional (plus GST); US $65 individual; $115 institutional. Outside North America: US$85 individual; $135 institutional. We sell reprints in bulk(100 copies of the same article or more). For individual reprints, we sell photocopies of the articles. The cost is $20 to fax and $15 to mail. Prepayment is required. Student rates available upon request. Director of Sales: EileenLarkin: 604-833-9437, email: elarkin@skincareguide.com. Fax: 604-633-1921.8Skin Therapy Letter • Editor: Dr. Stuart Maddin • Vol. 7 No. 3 • March 2002Click here for Skin Therapy Letter onlineSkinCareGuide