NEOTIGASON Drug Class Description : Retinoids.

Generic Name : Acitretin 10 Drug description : Capsules with brown cap and white body with 10 printed in black on the body, containing 10mg acitretin. Excipients include glucose Presentation Capsules !or oral administration. Indications : "e#ere extensi#e psoriasis which is resistant to other !orms o! therapy. Palmo$plantar pustular psoriasis. "e#ere congenital ichthyosis. "e#ere %arier&s disease 'keratosis !ollicularis(. Adult Dosage : )t is recommended that *eotigason be gi#en only by, or under super#ision o!, a dermatological specialist. *eotigason capsules are !or oral administration. +he capsules should be taken once daily with meals or with milk. +here is a wide #ariation in the absorption and rate o! metabolism o! *eotigason. +his necessitates indi#idual ad,ustment o! dosage. -or this reason the !ollowing dosage recommendations can ser#e only as a guide. Adults )nitial daily dose should be ./mg or 00mg !or . to 1 weeks. 2!ter this initial treatment period the in#ol#ed areas o! the skin should show a marked response and3or side$e!!ects should be apparent. -ollowing assessment o! the initial

treatment period, titration o! the dose upwards or downwards may be necessary to achie#e the desired therapeutic response with the minimum o! side$e!!ects. )n general, a daily dosage o! ./ $ /0mg taken !or a !urther 4 to 5 weeks achie#es optimal therapeutic results. 6owe#er, it may be necessary in some cases to increase the dose up to a maximum o! 7/mg3day. )n patients with %arier&s disease a starting dose o! 10mg may be appropriate. +he dose should be increased cautiously as isomorphic reactions may occur. +herapy can be discontinued in patients with psoriasis whose lesions ha#e impro#ed su!!iciently. 8elapses should be treated as described abo#e. Patients with se#ere congenital ichthyosis and se#ere %arier&s disease may re9uire therapy beyond 0 months. +he lowest e!!ecti#e dosage, not exceeding /0mg3day, should be gi#en. Continuous use beyond 4 months is contra$indicated as only limited clinical data are a#ailable on patients treated beyond this length o! time. Combination therapy :ther dermatological therapy, particularly with keratolytics, should normally be stopped be!ore administration o! *eotigason. 6owe#er, the use o! topical corticosteroids or bland emollient ointment may be continued i! indicated. ;hen *eotigason is used in combination with other types o! therapy, it may be possible, depending on the indi#idual patient&s response, to reduce the dosage o! *eotigason. Child Dosage : )n #iew o! possible se#ere side$e!!ects associated with long$term treatment, *eotigason is contra$indicated in children unless, in the opinion o! the physician, the bene!its signi!icantly outweigh the risks. +he dosage should be established according to bodyweight. +he daily dosage is about 0./mg3kg. 6igher doses 'up to 1mg3kg daily( may be necessary in some cases !or limited periods, but only up to a maximum o! 0/mg3day. +he maintenance dose should be kept as low as possible in #iew o! possible long$term side$e!!ects.

Elderly Dosage : %osage recommendations are the same as !or other adults. Contra )ndications *eotigason is highly teratogenic. )ts use is contra$indicated in pregnant women and women who might become pregnant during or within . years o! the cessation o! treatment. +he use o! *eotigason is contra$indicated in women who are breast !eeding. *eotigason is contra$indicated in patients with hepatic or renal impairment and in patients with chronic abnormally ele#ated blood lipid #alues. 8are cases o! benign intracranial hypertension ha#e been reported a!ter *eotigason and a!ter tetracyclines. "upplementary treatment with antibiotics such as tetracyclines is there!ore contra$indicated. 2n increased risk o! hepatitis has been reported !ollowing the concomitant use o! methotrexate and etretinate. Conse9uently, the concomitant use o! methotrexate and *eotigason should be a#oided. Concomitant administration o! *eotigason with other retinoids or preparations containing high doses o! <itamin 2, 'i.e. more than the recommended dietary allowance o! 1,000 $ /,000 i.u. per day( is contra$indicated due to the risk o! hyper#itaminosis 2. *eotigason is contra$indicated in cases o! hypersensiti#ity to the preparation 'acitretin or excipients( or to other retinoids. :wing to the presence o! glucose, patients with rare glucose$galactose malabsorption should not take this medicine. Special Precautions : *eotigason should only be prescribed by physicians who are experienced in the use o! systemic retinoids and understand the risk o! teratogenicity associated with acitretin therapy.

*eotigason is highly teratogenic. +he risk o! gi#ing birth to a de!ormed child is exceptionally high i! *eotigason is taken be!ore or during pregnancy, no matter !or how long or at what dosage. -oetal exposure to *eotigason always in#ol#es a risk o! congenital mal!ormation. *eotigason is contra$indicated in women o! childbearing potential unless the !ollowing criteria are met 1. Pregnancy has been excluded be!ore instituting therapy with *eotigason 'negati#e pregnancy test within . weeks prior to therapy(. ;hene#er practicable a monthly repetition o! the pregnancy test is recommended during therapy. .. "he starts *eotigason therapy only on the second or third day o! the next menstrual cycle. 0. 6a#ing excluded pregnancy, any woman o! childbearing potential who is recei#ing *eotigason must practice e!!ecti#e contraception !or at least one month be!ore treatment, during the treatment period and !or at least . years !ollowing its cessation. E#en !emale patients who normally do not practice contraception because o! a history o! in!ertility should be ad#ised to do so, while taking *eotigason. 1. +he same e!!ecti#e and uninterrupted contracepti#e measures must also be taken e#ery time therapy is repeated, howe#er long the inter#ening period may ha#e been, and must be continued !or . years a!terwards. /. 2ny pregnancy occurring during treatment with *eotigason, or in the . years !ollowing its cessation, carries a high risk o! se#ere !oetal mal!ormation. +here!ore, be!ore instituting *eotigason the treating physician must explain clearly and in detail what precautions must be taken. +his should include the risks in#ol#ed and the possible conse9uences o! pregnancy occurring during *eotigason treatment or in the . years !ollowing its cessation. 4. "he is reliable and capable o! understanding the risk and complying with e!!ecti#e contraception, and con!irms that she has understood the warnings.

)n #iew o! the importance o! the abo#e precautions, *eotigason Patient )n!ormation =ea!lets are a#ailable to doctors and it is strongly recommended that these be gi#en to all patients. )! oral contraception is chosen as the most appropriate contracepti#e method !or women undergoing retinoid treatment, then a combined oestrogen$progestogen !ormulation is recommended. Patients should not donate blood either during or !or at least one year !ollowing discontinuation o! therapy with *eotigason. +heoretically there would be a small risk to a woman in the !irst trimester o! pregnancy who recei#ed blood donated by a patient on *eotigason therapy. 2citretin has been shown to a!!ect diaphyseal and spongy bone ad#ersely in animals at high doses in excess o! those recommended !or use in man. "ince skeletal hyperostosis and extraosseous calci!ication ha#e been reported !ollowing long$term treatment with etretinate in man, this e!!ect should be expected with acitretin therapy. "ince there ha#e been occasional reports o! bone changes in children, including premature epiphyseal closure, skeletal hyperostosis and extraosseous calci!ication a!ter long$term treatment with etretinate, these e!!ects may be expected with acitretin. *eotigason therapy in children is not, there!ore, recommended. )!, in exceptional circumstances, such therapy is undertaken the child should be care!ully monitored !or any abnormalities o! musculo$skeletal de#elopment. )n adults recei#ing longterm treatment with *eotigason, appropriate examinations should be periodically per!ormed in #iew o! possible ossi!ication abnormalities. 2ny patients complaining o! atypical musculo$skeletal symptoms on treatment with *eotigason should be promptly and !ully in#estigated to exclude possible acitretin$induced bone changes. )! clinically signi!icant bone or ,oint changes are !ound, *eotigason therapy should be discontinued. +he e!!ects o! >< light are enhanced by retinoid therapy, there!ore patients should a#oid excessi#e exposure to sunlight and the unsuper#ised use o! sun lamps. 6epatic !unction should be checked be!ore starting treatment with *eotigason, e#ery 1 $ . weeks !or the !irst . months a!ter commencement and then

e#ery 0 months during treatment. )! abnormal results are obtained, weekly checks should be instituted. )! hepatic !unction !ails to return to normal or deteriorates !urther, *eotigason must be withdrawn. )n such cases it is ad#isable to continue monitoring hepatic !unction !or at least 0 months. "erum cholesterol and serum triglycerides '!asting #alues( must be monitored, especially in highrisk patients 'disturbances o! lipid metabolism, diabetes mellitus, obesity, alcoholism( and during longterm treatment. )n diabetic patients, retinoids can alter glucose tolerance. ?lood sugar le#els should there!ore be checked more !re9uently than usual at the beginning o! the treatment period. Patients should be warned o! the possibility o! alopecia occurring. Interactions : Existing data suggests that concurrent intake o! acitretin with ethanol led to the !ormation o! etretinate. 6owe#er, etretinate !ormation without concurrent alcohol intake cannot be excluded. +here!ore, since the elimination hal!$li!e o! etretinate is 1.0 days the post$therapy contraception period in women o! childbearing potential must be . years. 2n increased risk o! hepatitis has been reported !ollowing the concomitant use o! methotrexate and etretinate. Conse9uently, the concomitant use o! methotrexate and *eotigason should be a#oided. )n concurrent treatment with phenytoin, it must be remembered that *eotigason partially reduces the protein binding o! phenytoin. +he clinical signi!icance o! this is as yet unknown. )nteraction studies show acitretin does not inter!ere with the anti$o#ulatory action o! the combined oral contracepti#es. )nteractions between *eotigason and other substances 'e.g. digoxin, cimetidine( ha#e not been obser#ed to date.

Ad erse !eactions : @ost o! the clinical side$e!!ects o! *eotigason are dose$related and are usually well$tolerated at the recommended dosages. 6owe#er, the toxic dose o! *eotigason is close to the therapeutic dose and most patients experience some side$e!!ects during the initial period whilst dosage is being ad,usted. +hey are usually re#ersible with reduction o! dosage or discontinuation o! therapy. +he skin and mucous membranes are most commonly a!!ected, and it is recommended that patients should be so ad#ised be!ore treatment is commenced. "kin %ryness o! the skin may be associated with scaling, thinning, erythema 'especially o! the !ace( and pruritus. Palmar and plantar ex!oliation may occur. "ticky skin and dermatitis occur !re9uently. Epidermal !ragility, nail !ragility and paronychia ha#e been obser#ed. :ccasionally bullous eruptions and abnormal hair texture ha#e been reported. 6air thinning and !rank alopecia may occur, usually noted 1 to 5 weeks a!ter starting therapy, and are re#ersible !ollowing discontinuation o! *eotigason. -ull reco#ery usually occurs within 4 months o! stopping treatment in the ma,ority o! patients. Aranulomatous lesions ha#e occasionally been obser#ed. "weating has been reported in!re9uently. 8arely, patients may experience photosensiti#ity reactions. @ucous membranes %ryness o! mucous membranes, sometimes with erosion, in#ol#ing the lips, mouth, con,uncti#ae and nasal mucosa ha#e been reported. Corneal ulcerations ha#e been obser#ed rarely. %ryness o! the con,uncti#ae may lead to mild$to$moderate con,uncti#itis or xerophthalmia and result in intolerance o! contact lensesB it may be alle#iated by lubrication with arti!icial tears or topical antibiotics. Cheilitis, rhagades o! the corner o! the mouth, dry mouth and thirst ha#e occurred. :ccasionally stomatitis, gingi#itis and taste disturbance ha#e been reported.

8hinitis and epistaxis ha#e been obser#ed. Central ner#ous system 6eadache has occurred in!re9uently. ?enign intracranial hypertension has been reported. Patients with se#ere headache, nausea, #omiting and #isual disturbance should discontinue *eotigason immediately and be re!erred !or neurological e#aluation and care. *euro$sensory system ?lurred or decreased night #ision has been reported occasionally. @usculo$skeletal system @yalgia and arthralgia may occur and be associated with reduced tolerance to exercise. ?one pain has also been reported. @aintenance treatment may result in hyperostosis and extraskeletal calci!ication, as obser#ed in long$term systemic treatment with other retinoids. Aastrointestinal tract *ausea has been reported in!re9uently. <omiting, diarrhoea and abdominal pain ha#e been obser#ed rarely. =i#er and biliary system disorders +ransient, usually re#ersible ele#ation o! serum le#els o! li#er enCymes may occur. ;hen signi!icant, dosage reduction or discontinuation o! therapy may be necessary. Daundice and hepatitis ha#e occurred rarely. @etabolic Ele#ation o! serum triglycerides abo#e the normal range has been obser#ed, especially where predisposing !actors such as a !amily history o! lipid disorders, obesity, alcohol abuse, diabetes mellitus or smoking are present. +he changes are dose$related and may be controlled by dietary means 'including restriction o! alcohol intake( and3or by reduction o! dosage o! *eotigason. )ncreases in serum cholesterol ha#e occurred. Cardio#ascular system :ccasionally peripheral oedema and !lushing ha#e been reported. @iscellaneous reactions )ncreased incidence o! #ul#o$#aginitis due to Candida albicans has been noted during treatment with acitretin. @alaise and drowsiness ha#e been in!re9uently reported.