Generic medication for glaucoma. pr. nordmann

1,169 views
989 views

Published on

Generic anti-glaucoma drugs : are they equivalent or not to brand drugs?

Published in: Health & Medicine, Business
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,169
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
62
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide
  • Generic substitution refers to switching between a branded drug and its therapeutically equivalent generic version ( Holmes et al. Circulation 2011;124:1290–1310).
  • http://www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf http://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/understandinggenericdrugs/ucm167991.htm
  • Generic medication for glaucoma. pr. nordmann

    1. 1. Generic medication forGeneric medication for glaucomaglaucoma Pr. Jean-Philippe NordmannPr. Jean-Philippe Nordmann University Paris V,University Paris V, Hôpital des Quinze-VingtsHôpital des Quinze-Vingts
    2. 2. Pfizer Xalatan Xalacom There is increasingly a choice of both branded andThere is increasingly a choice of both branded and generic IOP-lowering drugsgeneric IOP-lowering drugs EXCLUSIVITY EXPIRATION Merck/Santen Trusop tCosop t Novartis Azopt Duotrav Travatan Azarga Allergan Ganfort Lumigan 0.01%
    3. 3. France – Market share of Generic LatanoprostFrance – Market share of Generic Latanoprost 60%
    4. 4. Italy – Market share of Generic LatanoprostItaly – Market share of Generic Latanoprost 0 50 100 150 200 250 mai-10 juin-10 juil-10 août-10 sept-10 oct-10 nov-10 déc-10 NumberofUnitssold Generic latanoprost Xalatan 66%
    5. 5. What is the effect of generics inWhat is the effect of generics in clinical practice?clinical practice? Physicians • Possibility of less prescribing control due to generic substitution3,4 Third parties Patients • Payers: potential for cost-saving1 • Pharmacists: potential for generic substitution • Government regulators: could legislate that generics be prescribed where possible (as in France, Spain2, … ) 1. Pechlivanoglou et al. BMC Health Serv Res 2011;11:89. 2. Rada. BMJ 2011;343:epub. 3. Lindstrom. Ocular Surgery News US edition 25 May 2011. Available from: http://www.osnsupersite.com/view.aspx?rid=83789 .Accessed Jan 2012. 4. Holmes et al. Circulation 2011;124:1290–13104. 5. Greene. Lancet 2011;378:120−121. • Change in a drug’s appearance can influence compliance5
    6. 6. Generics and brands:Generics and brands: similar or identical?similar or identical? Generics and brands:Generics and brands: similar or identical?similar or identical?
    7. 7. Generic drugs: propertiesGeneric drugs: properties 1. Facts and myths about generic drugs. FDA. Available from: www.fda.gov .Accessed Jan 2012 2. EMEA Guideline on the Investigation of Bioequivalence, 2010. Available from: www.ema.europa.eu Accessed Jan 2012 Generic drugs must have the same quality and performance as the brand name drugs1 Same active ingredient, strength, dosage form and route of administration as the branded drug1,2 Bioequivalence i.e. blood levels similar to those of reference drug1,2 Properties of systemic generics However, inactive ingredients can differ from the brand product e.g. Preservatives, pH-adjusters, antioxidants, buffers, thickening agents
    8. 8. How is bioequivalence of systemic genericsHow is bioequivalence of systemic generics demonstrated?demonstrated?  A generic is consideredA generic is considered bioequivalent to the brand if thebioequivalent to the brand if the same levels of drug are shownsame levels of drug are shown to be absorbed into theto be absorbed into the bloodstreambloodstream  In other words, equivalentIn other words, equivalent bioavailability must be shown, asbioavailability must be shown, as assessed byassessed by − Maximum blood concentration (CMaximum blood concentration (Cmaxmax)) − Time to reach maximum concentration (TTime to reach maximum concentration (Tmaxmax)) − Area under the curve (AUC)Area under the curve (AUC) Drugconcentration(mg/mL) Time after dose (h) Cmax Tmax Brand Generic AUC
    9. 9. Non systemic generics:Non systemic generics: Bioequivalence does not need to be shownBioequivalence does not need to be shown  For agents with local rather than systemic activityFor agents with local rather than systemic activity (such as eye drops), bioavailability studies using(such as eye drops), bioavailability studies using blood samples are difficult to performblood samples are difficult to perform11  Bioequivalence thus does not need to beBioequivalence thus does not need to be demonstrated fordemonstrated for22 – GasesGases – Ophthalmic products prepared as aqueous solutionsOphthalmic products prepared as aqueous solutions – Topical products prepared as solutionsTopical products prepared as solutions 1. Cantor. J Glaucoma 1997;6:344–9. 2. EMEA Guideline on the Investigation of Bioequivalence, 2010. Available from: http://www.ema.europa.eu. 3. Vesga et al. Antimicrob. Agents Chemother 2010;54:3271–9. Therapeutic equivalence is often assumed3
    10. 10. Is there therapeutic equivalence between brandedIs there therapeutic equivalence between branded and generic ophthalmic agents?and generic ophthalmic agents? • Some data show equivalence of brand toSome data show equivalence of brand to genericgeneric − A 6-week randomised, multicentre,A 6-week randomised, multicentre, investigator-masked study of 266investigator-masked study of 266 patients with POAG or OH foundpatients with POAG or OH found generic latanoprost was non-inferiorgeneric latanoprost was non-inferior to Xalatan in IOP-lowering efficacyto Xalatan in IOP-lowering efficacy11 1. Allaire et al. Eur J Ophthalmol 2012;22:19–27. -7.54 -7.29 -8 -7 -6 -5 -4 -3 -2 -1 0 Xalatan latanoprost MeanIOPreduction(mmHg)at6weeks p = ns IOP reduction Xalatan vs generic latanoprost1
    11. 11. Is there therapeutic equivalence between brandedIs there therapeutic equivalence between branded and generic ophthalmic agents?and generic ophthalmic agents? • Some show differencesSome show differences − A randomised, open-label,A randomised, open-label, crossover study of 30 patientscrossover study of 30 patients with glaucoma reported awith glaucoma reported a significant difference in IOPsignificant difference in IOP reduction between Xalatan and areduction between Xalatan and a generic productgeneric product22 1. Narayanaswamy et al. Indian J Ophthalmol 2007;55:127–31. Xalatan IOP reduction of Xalatan vs generic latanoprost1
    12. 12.  88 years old Japanese patient88 years old Japanese patient  Switch from Xalatan (Pfizer)Switch from Xalatan (Pfizer) to Latanoprost genericto Latanoprost generic (Kaken Pharmaceutical)(Kaken Pharmaceutical)  Corneal ulceration appearingCorneal ulceration appearing after each of the two attemptsafter each of the two attempts to switchto switch  May be due to a surfactantMay be due to a surfactant agent (Stearic Acid Polyester)agent (Stearic Acid Polyester) Takada Y, Okada Y, Fujita N, Saita S. A Patient with corneal epithelial disorder that developped after administration of aY, Okada Y, Fujita N, Saita S. A Patient with corneal epithelial disorder that developped after administration of a latanoprost generic, but not a brand-name drug eye drop. Case Rep Ophthalmol Med, 2012, 536746.latanoprost generic, but not a brand-name drug eye drop. Case Rep Ophthalmol Med, 2012, 536746.
    13. 13. Composition differences in genericsComposition differences in generics • A study compared concentration of active ingredients in brand vs generic glaucoma medications • Mean concentration of active ingredient in the brand (Xalatan) was unchanged by increasing temperature but was significantly reduced in the generic versions (LT1 and LT2) • Significantly higher levels of particulate matter were found in the generic bottles vs brand Kahook et al. Curr Eye Res 2011;epub a The summary of product characteristics for Xalatan states that the product should be stored in a refrigerator (2°C – 8°C) and, once open, stored below 25°C and used within 4 weeks. http://www.medicines.org.uk
    14. 14.  For Latanoprost generic : Yes!For Latanoprost generic : Yes!  For generic drugs before 1992: It depends!For generic drugs before 1992: It depends!
    15. 15. Current required policy for generic drugCurrent required policy for generic drug  Same active ingredientSame active ingredient andand  And the same inactive ones which are listed on theAnd the same inactive ones which are listed on the package insertpackage insert – In case of a solution, it is impossible to have differencesIn case of a solution, it is impossible to have differences between productsbetween products  In consequence, no utility to conduct clinical trialsIn consequence, no utility to conduct clinical trials – Better to evaluate the methodology to replicate theBetter to evaluate the methodology to replicate the productproduct – Variation of +/-10% is acceptableVariation of +/-10% is acceptable
    16. 16. Before 1992Before 1992  Inactive ingredients were not always identicalInactive ingredients were not always identical  May induce differences in efficacy and tolerabilityMay induce differences in efficacy and tolerability  In the US: brand-nameTimoptic XE vs genericIn the US: brand-nameTimoptic XE vs generic – Drop size : 38Drop size : 38 µµl vs 24l vs 24 µµll – Bottle tip : 3,5 vs 1Bottle tip : 3,5 vs 1 – Viscosity : 20 vs 1Viscosity : 20 vs 1 – Surface tension : 1,5 vs 1Surface tension : 1,5 vs 1 Mammo ZN, Flanagan JG, James DF, Trope GE. Generic versus brand-name North American topical glaucoma drops. Can J Ophthalmol, 2012, 47, 55-61.
    17. 17. Comments from patients with Latanoprost GenericComments from patients with Latanoprost Generic  « Does it have same efficacy? »« Does it have same efficacy? »  « I prefer the original brand for my eye »« I prefer the original brand for my eye »  Problem of packagingProblem of packaging  Problem of bottle quality (« squizzability »)Problem of bottle quality (« squizzability »)  Problem of color and shape of the bottleProblem of color and shape of the bottle
    18. 18. SummarySummary As more IOP-lowering agents lose their patent, generics are likely to occupy a greater space in the ophthalmology market Non-systemic generics such as IOP-lowering eye drops do not need to demonstrate bioequivalence to the brand Evidence suggests that generics should not be considered identical to brands due to differences in composition and, possibly, efficacy Re-evaluation of IOP reduction when switching to generic drug seems reasonable.

    ×