FIXED DOSE COMBINATION: CLINICAL & PHARMACEUTICAL PERSPECTIVES

FIXED DOSE COMBINATION: CLINICAL & PHARMACEUTICAL PERSPECTIVES Cape Winelands Anova Conference 2013 Worcester Lindsay Wilson 3 June 2013

What is a fixed dose combination [FDC]? Pharmaceutical formulation that contains more than one active ingredient in specific proportions Many ARV and other FDC products available : AVOID using terminology SA just not accessed them until now Zidovudine / Lamivudine / Nevirapine Stavudine / Lamivudine / Efavirenz Tenofovir Emtricitabine Efavirenz Benefits: improve reliability / security of supplies: only ONE product to manage BUT converse applies: needs careful management ensures correct dosages reduce work loads: depot level to facility level reduce storage space: depot level to facility level reduce transport costs deduce: reduced pilferage reduced pill burden promotes adherence [evidence? likely but extent not quantifiable.. DON T rely on it patients still need support and counselling. Could argue easier to forget 1 tablet vrs 3?] 2

Who is eligible? National notice: signed 12 th Feb 2013 1. New patients [adults; adolescents and pregnant eligible to start ART] 2. All pregnant women needing triple therapy and breastfeeding mothers currently on a FDC compatible regimen 3. Virally suppressed patients currently on first line regimen requiring a switch due to toxicity [stavudine] 4. Patients currently stable on a TDF based regimen with TB comorbidity 5. Patients currently stable on a TDF based regimen with other comorbidities [e.g.hypertension ] 6. Patients currently stable on TDF based regimen and who request a switch to a FDC 7. Patients currently stable on TDF based regimen and who after counselling agree to a switch to FDC QUANTIFIABLE? 3

WC notice H38 2013 [21 st March 2013] The use of this product will initially be limited ONLY for use in patients who are INITIATING antiretroviral therapy [ART] from the 1 st April 2013 [or as and when stock is received at a facility level]. deviation from this shall jeopardize patients who have been placed on this product. Sites are requested to ACTIVELY manage the monthly increased requirements of this product and subsequent reduction in use of the individual products by: Liaising with the ART clinic staff regarding numbers of new patients initiating treatment Accurately completing the ARV month end report and ordering accordingly, based on both usage and expected need. Kindly note: medicine wastage through expiry of individual product line items is not acceptable. Kindly note: any change of guidelines should only be implemented on receipt of a formal circular from the Western Cape Department of Health. 4

What they look like more coming! 5

Roll out time-frame: we don t know! 14 th May 2013 ARV depot stock on hand: 80 583 ARV depot stock on order: 141 640 Total: 222 223 Adults RIC: 127 000 New adults per month: 2 500 Suggestion is to go with club patients through CDU first.. Comments? Need: Stock holding: minimum ARV depot: 2 months Site level: 1 to 2 months Aim: October 2013: New patients: 52 500 Old patients: [101 600 x 3] 304 800 Total: 357 300 62% of the way there 6

Considerations Tender only awarded: 29 th November 2012 Christmas period: shut down Gear up period required: 3 to 6 months Production: raise capital: new machines / space / staff and implement Source large quantities of API [active pharmaceutical ingredient: all from same source!] Import: sea time [3 months] Regulatory requirements: MCC [all of above!] Quality assurance on all changes Strike season: June: affecting most of suppliers Gear up for Nov / Dec NDOH notice: 1 month x 3 and then 3 months at a time! SA: 16.5% of international need [5.6mil of 34 mil] 7

Monitoring: stock Facility month end report: unfortunately still required: amended 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Total number of patients [second line] Total number of patients [first line "average"] / month Province: 2 weekly stock situation reports to NDOH 2 and a half years! [TDF never over 3 weeks stock] 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% QUARTER 1 QUARTER QUARTER QUARTER 2 3 4 Average FDC per month Average tenofovir usage per month 8

Monitoring: prescribing APP: top 10 ARV s vrs proportion of patients Province Cape W Q3 cum forecast Q3 cum usage % deviance % deviance Tenofovir 300mg tablets 30 258 300 248989-4 15 Efavirenz 600mg tablets 30 241 972 235 620-3 12 Lamivudine 300mg tablets 30 196 911 176 260-10 20 Lamivudine 150mg tablets 60 131 151 135 318 3 19 Nevirapine 200mg tablets 60 112 887 92266-18 -13 Stavudine 30mg capsules 60 51 000 52 809 4 12 Lamivudine/Zidovudine 150/300mg tablets 60 52 500 50 502-4 -25 Lopinavir/Ritonavir 200/50mg tablets 120 32 039 35 942 12 27 Lopinavir/Ritonavir 80/20mg/ml solution 60ml 18 589 17080-8 37 Abacavir 20mg/ml solution 240ml 14 227 16 155 14 48 9

Monitoring: Clinical Side Effects / Interactions / Efficacy: assume all the same as individual products: not tested renal impairment: will have to use individual products Interactions of ONE of the products have to use individual products and tailor doses or change medicine No reduced side effects and increased efficacy [as per NDOH advertising] Take on an empty stomach [contrary to NDOH notices take with food] - at night [reduce side effects of Efavirenz] 10

Per protocol, how clinical stationery must be completed Western Cape Government 2012

How to document FDC Indicate FDC FDC TDF 300mg/FTC 200mg /EFV 600mg FDC must be written on one line Please note: watch for differences between 3TC and FTC Western Cape Government 2012 Please do NOT write Odumine

How to capture in TIER.net and ekapa Western Cape Government 2012