Differin® Gel Adapalene 0.1% Topical Gel

Total Page:16

File Type:pdf, Size:1020Kb

Differin® Gel Adapalene 0.1% Topical Gel NDA 20380 NONPRESCRIPTION ADAPALENE 0.1% BRIEFING DOCUMENT FOR APRIL 15, 2016 TOPICAL GEL NONPRESCRIPTION DRUGS ADVISORY COMMITTEE MEETING FDA NONPRESCRIPTION DRUGS ADVISORY COMMITTEE BRIEFING DOCUMENT Differin® Gel Adapalene 0.1% Topical Gel Meeting Date: April 15, 2016 Available for Public Disclosure Without Redaction Page 1 NDA 20380 NONPRESCRIPTION ADAPALENE 0.1% BRIEFING DOCUMENT FOR APRIL 15, 2016 TOPICAL GEL NONPRESCRIPTION DRUGS ADVISORY COMMITTEE MEETING TABLE OF CONTENTS LIST OF ABBREVIATIONS ..................................................................................................................... 4 1 EXECUTIVE SUMMARY ............................................................................................................... 5 1.1 Program Overview ....................................................................................................................... 5 1.2 Acne: Prevalence and Impact on Quality of Life ...................................................................... 5 1.3 Current Self-Management of Acne ............................................................................................. 5 1.4 History of Adapalene ................................................................................................................... 6 1.5 Efficacy and Safety ....................................................................................................................... 7 1.5.1 Clinical Studies ........................................................................................................................ 7 1.5.2 Post-Marketing Surveillance .................................................................................................. 8 1.5.3 Clinical Pharmacokinetic Studies .......................................................................................... 8 1.5.4 Teratogenicity .......................................................................................................................... 9 1.5.5 Potential Off-Label Use ........................................................................................................ 12 1.5.6 Other Safety Considerations ................................................................................................ 13 1.6 Differin Gel OTC Development Program ................................................................................ 13 1.6.1 Label Comprehension Study ................................................................................................ 13 1.6.2 Actual Use Study ................................................................................................................... 14 1.6.3 Targeted Self-Selection Study .............................................................................................. 17 1.7 Benefit and Risk Considerations for Nonprescription Differin Gel ...................................... 18 1.8 Rationale for Nonprescription Access to Differin Gel ............................................................ 19 2 BACKGROUND ............................................................................................................................. 20 2.1 Overview of Acne ....................................................................................................................... 20 2.2 Current Self-Management of Acne ........................................................................................... 21 3 DEVELOPMENT OF DIFFERIN GEL ....................................................................................... 23 3.1 Properties of Adapalene and the Differin Gel Formulation ................................................... 23 3.2 Regulatory History ..................................................................................................................... 25 4 SUMMARY OF EFFICACY ......................................................................................................... 26 5 SUMMARY OF SAFETY .............................................................................................................. 27 5.1 Safety Data from Original Pivotal Clinical Studies ................................................................ 27 5.1.1 Cutaneous Tolerability ......................................................................................................... 29 5.1.2 Adverse Events ...................................................................................................................... 29 5.1.3 Serious adverse events .......................................................................................................... 32 5.2 Other Clinical Studies ................................................................................................................ 32 5.3 Post-Marketing Surveillance ..................................................................................................... 32 5.4 Clinical Pharmacokinetic Studies ............................................................................................. 33 5.4.1 Maximal Use Pharmacokinetic Study 18115 ...................................................................... 33 5.4.2 Maximal Use Pharmacokinetic Study 18097 ...................................................................... 35 5.4.3 Maximal Use Pharmacokinetic Study 18254 ...................................................................... 38 5.4.4 Conclusion of Maximal Use Clinical Pharmacokinetic Studies ........................................ 46 5.5 Teratogenicity and Fetotoxicity ................................................................................................ 46 5.5.1 Receptor-binding Properties of Adapalene ........................................................................ 47 5.5.2 Nonclinical Reproductive Toxicity Studies with Adapalene ............................................. 47 5.5.3 Calculation of Safety Margin ............................................................................................... 49 5.5.4 Exposure During Pregnancy ................................................................................................ 51 5.5.5 Evaluation of Additional Data Sources ............................................................................... 52 5.5.6 Summary of Teratogenic Risk ............................................................................................. 53 Page 2 NDA 20380 NONPRESCRIPTION ADAPALENE 0.1% BRIEFING DOCUMENT FOR APRIL 15, 2016 TOPICAL GEL NONPRESCRIPTION DRUGS ADVISORY COMMITTEE MEETING 5.6 Other Safety Considerations ..................................................................................................... 54 5.6.1 Potential Off-Label Use ........................................................................................................ 54 5.6.2 Concomitant Use with Other Acne Medications and Topical Products .......................... 55 5.6.3 Carcinogenesis and Mutagenesis ......................................................................................... 56 5.6.4 Phototoxicity .......................................................................................................................... 56 5.6.5 Lactation ................................................................................................................................ 56 6 DEVELOPMENT OF NONPRESCRIPTION DIFFERIN GEL ............................................... 57 6.1 Label Comprehension Testing .................................................................................................. 58 6.2 Actual Use Study ........................................................................................................................ 61 6.2.1 Study Design .......................................................................................................................... 61 6.2.2 Disposition of Subjects .......................................................................................................... 67 6.2.3 Actual Use Results ................................................................................................................. 67 6.3 Targeted Self-Selection Study ................................................................................................... 79 6.3.1 Study Design .......................................................................................................................... 79 6.3.2 Study Population ................................................................................................................... 80 6.3.3 Study Results ......................................................................................................................... 80 6.4 Conclusions of Differin Gel Nonprescription Development Program ................................... 81 6.5 Differin Gel Nonprescription DFL ........................................................................................... 81 7 BENEFIT AND RISK CONSIDERATIONS ............................................................................... 83 7.1 Benefits of Nonprescription Differin Gel ................................................................................. 83 7.2 Adverse Event Profile of Differin Gel ...................................................................................... 83 7.3 Teratogenicity ............................................................................................................................. 84 7.4 Potential Off-label Use ..............................................................................................................
Recommended publications
  • Targeted Topical Delivery of Retinoids in the Management of Acne Vulgaris: Current Formulations and Novel Delivery Systems
    pharmaceutics Review Targeted Topical Delivery of Retinoids in the Management of Acne Vulgaris: Current Formulations and Novel Delivery Systems Gemma Latter 1, Jeffrey E. Grice 2, Yousuf Mohammed 2 , Michael S. Roberts 2,3 and Heather A. E. Benson 1,* 1 School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth 6845, Australia; [email protected] 2 Therapeutics Research Group, The University of Queensland Diamantina Institute, School of Medicine, University of Queensland, Translational Research Institute, Brisbane 4109, Australia; jeff[email protected] (J.E.G.); [email protected] (Y.M.); [email protected] (M.S.R.) 3 School of Pharmacy and Medical Sciences, University of South Australia, Basil Hetzel Institute for Translational Health Research, Adelaide 5011, Australia * Correspondence: [email protected]; Tel.: +61-8-9266-2338 Received: 19 August 2019; Accepted: 17 September 2019; Published: 24 September 2019 Abstract: Acne vulgaris is a common inflammatory pilosebaceous condition that affects 80–90% of adolescents. Since the introduction of tretinoin over 40 years ago, topical retinoid products have been a mainstay of acne treatment. The retinoids are very effective in addressing multiple aspects of the acne pathology as they are comedolytic and anti-inflammatory, and do not contribute to antibiotic resistance or microbiome disturbance that can be associated with long-term antibiotic therapies that are a common alternative treatment. However, topical retinoids are associated with skin dryness, erythema and pain, and may exacerbate dermatitis or eczema. Thus, there is a clear need to target delivery of the retinoids to the pilosebaceous units to increase efficacy and minimise side effects in surrounding skin tissue.
    [Show full text]
  • Cumulative Irritation Comparison of Adapalene Gel and Solution with 2 Tazarotene Gels and 3 Tretinoin Formulations
    THERAPEUTICS FOR THE CLINICIAN Cumulative Irritation Comparison of Adapalene Gel and Solution With 2 Tazarotene Gels and 3 Tretinoin Formulations Alan Greenspan, MD; Christian Loesche, MD; Nancy Vendetti; Kathleen Georgeian; Richard Gilbert, PhD; Michel Poncet, PhD; Michael D. Baker, BS; Pascale Soto, RPh Forty-two subjects with normal skin were enrolled gel 0.025%, and 1 discontinued adapalene in a single-center study to assess the cumula- gel 0.1%. None of the subjects discontinued use tive irritancy potential of adapalene (Differin® of the white petrolatum or the adapalene solu- gel 0.1% and Differin solution 0.1%) compared tion 0.1%. Adapalene gel and solution 0.1% with tazarotene (Tazorac® gels 0.05% and 0.1%), were statistically (PϽ.01) less irritating than tretinoin (Retin-A Micro® gel 0.1%, Avita® cream both tazarotene gels 0.1% and 0.05%, tretinoin 0.025%, and Avita gel 0.025%), and white petro- microsphere gel 0.1%, and tretinoin gel 0.025%, latum (negative control). All test materials were and they were not statistically different from applied randomly, under occlusion, to sites tretinoin gel 0.025%. located on either side of the midline— the mid Cutis. 2003;72:76-81. thoracic area of the subjects’ backs. All patches were applied daily, Monday through Friday, to dapalene (Differin®) is a naphthoic-acid the same sites, unless the degree of reaction to derivative with retinoid activity that is a test product or adhesive necessitated removal A effective in the treatment of mild to moder- (grade 3). ate acne vulgaris.1-4 Adapalene, in both gel and Thirty-eight of the 42 subjects (90.5%) com- cream formulations, at the marketed and approved pleted the study.
    [Show full text]
  • 1 EMA Tender EMA/2017/09/PE, Lot 2 Impact of EU Label
    EMA tender EMA/2017/09/PE, Lot 2 Impact of EU label changes and revised pregnancy prevention programme for oral retinoid containing medicinal products: risk awareness and adherence Protocol • Prof. Anna Birna Almarsdóttir, Professor in Social and Clinical Pharmacy at the Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen • Prof. Marcel Bouvy, Professor of Pharmaceutical Care at the Division of Pharmacoepidemiology & Clinical Pharmacology of the Department of Pharmaceutical Sciences, Utrecht University. • Dr Rob Heerdink, Associate Professor at the Division of Pharmacoepidemiology & Clinical Pharmacology of the Department of Pharmaceutical Sciences, Utrecht University. • Dr Teresa Leonardo Alves, Researcher at the Centre for Health Protection, National Institute for Public Health and the Environment, The Netherlands. 1 Table of contents Background ...................................................................................................................... 3 Aims of the study ............................................................................................................. 4 Methods ........................................................................................................................... 4 Setting ........................................................................................... Error! Bookmark not defined. Study design ............................................................................................................................ 4 Population
    [Show full text]
  • Aetna Formulary Exclusions Drug List
    Covered and non-covered drugs Drugs not covered – and their covered alternatives 2020 Advanced Control Plan – Aetna Formulary Exclusions Drug List 05.03.525.1B (7/20) Below is a list of medications that will not be covered without a Key prior authorization for medical necessity. If you continue using one of these drugs without prior approval, you may be required UPPERCASE Brand-name medicine to pay the full cost. Ask your doctor to choose one of the generic lowercase italics Generic medicine or brand formulary options listed below. Preferred Options For Excluded Medications1 Excluded drug name(s) Preferred option(s) ABILIFY aripiprazole, clozapine, olanzapine, quetiapine, quetiapine ext-rel, risperidone, ziprasidone, VRAYLAR ABSORICA isotretinoin ACANYA adapalene, benzoyl peroxide, clindamycin gel (except NDC^ 68682046275), clindamycin solution, clindamycin-benzoyl peroxide, erythromycin solution, erythromycin-benzoyl peroxide, tretinoin, EPIDUO, ONEXTON, TAZORAC ACIPHEX, esomeprazole, lansoprazole, omeprazole, pantoprazole, DEXILANT ACIPHEX SPRINKLE ACTICLATE doxycycline hyclate capsule, doxycycline hyclate tablet (except doxycycline hyclate tablet 50 mg [NDC^ 72143021160 only], 75 mg, 150 mg), minocycline, tetracycline ACTOS pioglitazone ACUVAIL bromfenac, diclofenac, ketorolac, PROLENSA acyclovir cream acyclovir (except acyclovir cream), valacyclovir ADCIRCA sildenafil, tadalafil ADZENYS XR-ODT amphetamine-dextroamphetamine mixed salts ext-rel†, dexmethylphenidate ext-rel, dextroamphetamine ext-rel, methylphenidate ext-rel†, MYDAYIS,
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]
  • The Role of Specific Retinoid Receptors in Sebocyte Growth And
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector The Role of Speci®c Retinoid Receptors in Sebocyte Growth and Differentiation in Culture1 Mi-Jung Kim, Nancy Ciletti, Serge Michel,* Uwe Reichert,* and Robert L. Rosen®eld Departments of Pediatrics and Medicine, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, U.S.A.; *Galderma R&D, Sophia Antipolis, France Retinoic acid derivatives (retinoids) exert their pleio- (42.2 6 4.0% vs 22.6 6 2.7%, mean 6 SEM, lipid- tropic effects on cell development through speci®c forming colonies, p < 0.01). Furthermore, the RAR- nuclear receptors, the retinoic acid receptors and b,g antagonist CD2665 antagonized the suppressive retinoid X receptors. Despite recent progress in effects of all-trans retinoic acid, adapalene, and understanding the cellular and molecular mechan- CD2043 on both cell growth and differentiation. In isms of retinoid activity, it is unknown which of the contrast, the retinoid X receptor agonist CD2809 retinoid receptor pathways are involved in the speci- increased cell growth slightly and lipid-forming colo- ®c processes of sebocyte growth and development. nies dramatically in a clear dose-related manner to a In this study, we investigated the roles of speci®c maximum of 73.7% 6 6.7% at 10±6 M (p < 0.001). retinoid receptors in sebocyte growth and differen- Our data suggest that retinoic acid receptors and tiation, by testing the effects of selective retinoic acid retinoid X receptors differ in their roles in sebocyte receptor and retinoid X receptor ligands at concen- growth and differentiation: (i) retinoic acid recep- trations between 10±10 M and 10±6 M in a primary rat tors, especially the b and/or g subtypes, mediate preputial cell monolayer culture system.
    [Show full text]
  • Topical Acne Treatments and Pregnancy
    Topical Acne Treatments This sheet talks about exposure to topical acne treatments in a pregnancy and while breastfeeding. This information should not take the place of medical care and advice from your healthcare provider. What are topical acne treatments? Topical acne treatments are medications that are put directly on the skin. Topical acne treatments can be over-the- counter or prescription. Common active ingredients are benzoyl peroxide, azelaic acid, glycolic acid, and salicylic acid. Prescription acne medications include tretinoin, adapalene, dapsone, and antibiotics such as erythromycin and clindamycin. Can I use tretinoin (Retin A®) for severe acne during my pregnancy? Tretinoin is different from other topical treatments that will be discussed here. It belongs to a group of medications called retinoids, which can cause birth defects when taken by mouth. The amount of tretinoin absorbed through the skin is low, and studies have reported that women who used topical tretinoin during pregnancy did not have an increased chance for birth defects. However, due to the theoretical concerns and the availability of other topical acne products, tretinoin use is discouraged during pregnancy. Please refer to the MotherToBaby fact sheet Tretinoin at https://mothertobaby.org/fact-sheets/tretinoin-retin-a-pregnancy/pdf/ and Isotretinoin at https://mothertobaby.org/fact-sheets/isotretinoin-accutane-pregnancy/pdf/ for more information on this group of medications. Can I use adapalene gel during my pregnancy? Adapalene is a retinoid in the same group of medications as tretinoin. Studies have shown that only a small amount is absorbed through the skin when adapalene gel is used. Studies looking at adapalene in pregnancy include only a very small number of exposed pregnancies therefore, more studies are needed.
    [Show full text]
  • Cumulative Irritation Potential of Adapalene 0.1% Cream and Gel Compared with Tazarotene Cream 0.05% and 0.1%
    THERAPEUTICS FOR THE CLINICIAN Cumulative Irritation Potential of Adapalene 0.1% Cream and Gel Compared With Tazarotene Cream 0.05% and 0.1% Jonathan S. Dosik, MD; Kenneth Homer, MS; Stéphanie Arsonnaud Despite the many beneficial effects of dermato- The mean 21-day cumulative irritancy indices for logic applications, most of the current treatments adapalene 0.1% cream and gel were significantly for acne cause local irritation. The objective of lower (Pϭ.05) than those for tazarotene cream this study was to compare the ability of the epi- 0.05% and 0.1% and not notably higher than that of dermis to tolerate adapalene 0.1% cream and gel the negative control product. and tazarotene cream in concentrations of 0.05% Cutis. 2005;75:289-293. and 0.1%. A total of 30 subjects were enrolled in the study. The test products were applied under occlusive dressings at randomized sites on the cne vulgaris is the most common dermato- upper back for approximately 24 hours, 4 times logic disorder, affecting approximately 85% a week, and for 72 hours, once a week, for a A of individuals at some time between the ages period of 3 weeks. Skin reactions (erythema of 12 and 14 years.1 Although acne is most preva- score plus other local reactions) at the product lent in this age group, the disease is reported in application sites were assessed 15 to 30 minutes 8% of adults between the ages of 25 and 34 years after dressing removal. and in 3% of adults between the ages of 35 and Twenty-six subjects completed the study.
    [Show full text]
  • Written Submissions of Board Staff
    PATENTED MEDICINE PRICES REVIEW BOARD IN THE MATTER OF the Patent Act R.S.C. 1985, c. P-4 as amended IN THE MATTER OF the Medicines DIFFERIN® (adapalene) DIFFERIN XP® (adapalene) TACTUPUMP® (adapalene/benzoyl peroxide) TACTUPUMP FORTE® (adapalene/benzoyl peroxide) (Collectively, " the Adapalene Medicines" ) Sold in Canada by GALDERMA CANADA Inc. (the "Respondent") WRITTEN SUBMISSIONS OF BOARD STAFF Conway Baxter Wilson LLP/s.r.l. 401-1111 Prince of Wales Dr. Ottawa, ON K2C 3T2 David K. Wilson [email protected] Calina Ritchie [email protected] Julie Mouris [email protected] Tel: 613-288-0149 Fax: 613-688-0271 Lawyers for Board Staff Table of Contents PART I - SUMMARY AND ORDER SOUGHT ...................................................................................... 2 PART II - BACKGROUND OF THIS APPLICATION .............................................................................. 6 A. The Adapalene Medicines and Acne Vulgaris ...................................................................... 6 Differin and Differin XP................................................................................................... 8 TactuPump and TactuPump Forte.................................................................................. 9 B. Adapalene Medicines and the Anatomical Therapeutic Classification (ATC) System ......... 9 C. Adapalene and Clinical Treatment Considerations ........................................................... 11 D. The Patents at Issue ..........................................................................................................
    [Show full text]
  • A Comparative Study of Efficacy of Once Daily 0.1% Tazarotene and Adapalene Gel for the Treatment of Facial Acne Vulgaris
    Original Research A Comparative Study of Efficacy of once Daily 0.1% Tazarotene and Adapalene Gel for the Treatment of Facial Acne Vulgaris Mukunda Ranga Swaroop Associate Professor, Adichunchanagiri Institute of Medical Sciences, Mandya, Karnataka Email: [email protected] ABSTRACT Background: Acne is a self-limiting chronic inflammatory disorder of pilo- sebaceous follicles seen among young adults with significant psychological and social impact. Tretinoin which was widely used for many years is being replaced gradually by newer generation agents like Tazarotene and Adapalene which unlike Tretinoin are specific for a subset of retinoic acid receptors. Objectives: To compare the efficacy of once daily topical 0.1% Tazarotene and Adapalene gel in the treatment of mild to moderate facial acne vulgaris. Method: A total number of 60 patients with mild to moderate facial acne vulgaris attending out-patient department of Dermatology, Venereology and Leprosy from Oct.2004 – April. 2006 were studied. Patients were allocated alternately to group A and group B. Group A received 0.1% Tazarotene gel and group B patients received 0.1% Adapalene gel and were advised to apply topically once daily in the evening. Patients were followed up on 4th, 8th and 12th week. Results: At the 4thweek of post treatment evaluation, the non-inflammatory lesions (comedones) responded early to Tazarotene 0.1% gel than to Adapalene 0.1% gel. At the end of 12th week treatment period, Tazarotene 0.1% gel had an overall superiority to Adapalene 0.1% gel as an antiacne agent. Conclusion: The results of the study show that Tazarotene 0.1% gel is a better anticomedogenic agent with rapid rate of clinical improvement when compared with Adapalene 0.1% gel.
    [Show full text]
  • Review of (1) Pregnancy Prevention Measures
    Isotretinoin Safety Issues CONFIDENTIAL Medicines Adverse Reactions Committee Meeting date: 3 July 2018 Agenda item: 3.2.4 Isotretinoin: review of (1) pregnancy prevention measures and(2) obsessive Title: compulsive disorder Submitted by: Medsafe Pharmacovigilance Team Paper type: For advice Active constituent Medicine Sponsor Isotretinoin Isotane 10 Soft gelatin capsule, 10 mg Mylan New Zealand Ltd Isotane 20 Soft gelatin capsule, 20 mg Mylan New Zealand Ltd Oratane Soft gelatin capsule, 5 mg Douglas Pharmaceuticals Ltd Oratane Soft gelatin capsule, 10 mg Douglas Pharmaceuticals Ltd Oratane Soft gelatin capsule, 20 mg Douglas Pharmaceuticals Ltd Tretinoin ReTrieve Topical cream, 0.5mg/g iNova Pharmaceuticals (New Zealand) Ltd Adapalene Differin Topical cream, 0.1% w/w Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics Differin Topical gel, 0.1% Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics Adapalene; Epiduo Topical gel, 0.1% / 2.5 % Pharmacy Retailing (NZ) Ltd t/a Benzoyl peroxide Healthcare Logistics Funding Oral retinoids Isotane 10 and Isotane 20 Soft gelatin capsules (Mylan) – Special Authority Oratane Soft gelatin capsules 10 mg and 20 mg capsules (Douglas) – Special Authority From 1 August 2018 Oratane 5mg capsule will also be funded. From 1 October 2018 a part payment may be required for Isotane From 1 January 2019 Isotane will not be funded; Oratane will continue to be fully funded. Topical retinoids ReTrieve Topical cream (iNova) Differin Topical cream and gel (Pharmacy Retailing) Schedule Prescription medicine Previous MARC Isotretinoin and the need for pregnancy prevention has been discussed meetings previously at the following meetings: − 109th Meeting — 27 March 2002 Isotretinoin and reducing pregnancy risk: The MARC voted not to adopt new restrictions that would come into effect on 1 April 2002 in the US to reduce risk of pregnancy.
    [Show full text]
  • Estonian Statistics on Medicines 2013 1/44
    Estonian Statistics on Medicines 2013 DDD/1000/ ATC code ATC group / INN (rout of admin.) Quantity sold Unit DDD Unit day A ALIMENTARY TRACT AND METABOLISM 146,8152 A01 STOMATOLOGICAL PREPARATIONS 0,0760 A01A STOMATOLOGICAL PREPARATIONS 0,0760 A01AB Antiinfectives and antiseptics for local oral treatment 0,0760 A01AB09 Miconazole(O) 7139,2 g 0,2 g 0,0760 A01AB12 Hexetidine(O) 1541120 ml A01AB81 Neomycin+Benzocaine(C) 23900 pieces A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+Thymol(dental) 2639 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+Cetylpyridinium chloride(gingival) 179340 g A01AD81 Lidocaine+Cetrimide(O) 23565 g A01AD82 Choline salicylate(O) 824240 pieces A01AD83 Lidocaine+Chamomille extract(O) 317140 g A01AD86 Lidocaine+Eugenol(gingival) 1128 g A02 DRUGS FOR ACID RELATED DISORDERS 35,6598 A02A ANTACIDS 0,9596 Combinations and complexes of aluminium, calcium and A02AD 0,9596 magnesium compounds A02AD81 Aluminium hydroxide+Magnesium hydroxide(O) 591680 pieces 10 pieces 0,1261 A02AD81 Aluminium hydroxide+Magnesium hydroxide(O) 1998558 ml 50 ml 0,0852 A02AD82 Aluminium aminoacetate+Magnesium oxide(O) 463540 pieces 10 pieces 0,0988 A02AD83 Calcium carbonate+Magnesium carbonate(O) 3049560 pieces 10 pieces 0,6497 A02AF Antacids with antiflatulents Aluminium hydroxide+Magnesium A02AF80 1000790 ml hydroxide+Simeticone(O) DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 34,7001 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 3,5364 A02BA02 Ranitidine(O) 494352,3 g 0,3 g 3,5106 A02BA02 Ranitidine(P)
    [Show full text]