1 / 32

Drug-Drug Interaction Satellite Workshop

Drug-Drug Interaction Satellite Workshop. David Back University of Liverpool UK. How the Drug Interactions web site started. Launched – July 2012. There is always room for improvement. Web site Improvement: Add WHO Essential Medicines. Anthelminics (11) Anti-TB (5) Antibiotics (15)

adolfo
Télécharger la présentation

Drug-Drug Interaction Satellite Workshop

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drug-Drug Interaction Satellite Workshop David Back University of Liverpool UK

  2. How the Drug Interactions web site started

  3. Launched – July 2012

  4. There is always room for improvement

  5. Web site Improvement:Add WHO Essential Medicines • Anthelminics (11) • Anti-TB (5) • Antibiotics (15) • Antifungal (2) • Antiprotozoal (4) • Cytotoxics (12) • Other antiinfectives (6) • Anaesthetics (5) • Miscellaneous (41)

  6. Web Site Improvement:Amber Project • Amber Project! Re-visit amber designations in the data base and re-classify if the interaction has a high likelihood of not being ‘clinically relevant’.

  7. What Constitutes a Clinically Relevant Drug-Drug Interaction? >20%, 30%, 50%, 70% change in PK? Therapeutic Window PK-PD

  8. Change in steady state concentration:Enzyme Induction Decrease in steady state Drug Conc. Target for efficacy Inducer Time

  9. Change in steady state concentration:Enzyme Induction Decrease in steady state Drug Conc. Target for efficacy Inducer Time

  10. Change in steady state concentration:Enzyme Inhibition Increase in steady state Drug Conc. Concern re toxicity Inhibiting Drug Time

  11. Change in steady state concentration:Enzyme Inhibition Increase in steady state Concern re toxicity Drug Conc. Inhibiting Drug Time

  12. Most Drug-Drug Interaction Studies are done in Healthy Volunteers

  13. Physiological changes (versus healthy volunteers) * Decreased albumin associated more with cirrhosis and significant liver damage † Significantly lower than HIV or HCV mono-infected patients 1Mehta SH, et al. AIDS Res Human Retrovir 2006;22:14–21; 2Graham SM, et al. AIDS Res Human Retrovir 2007;23:1197–12003Nagao Y & Sata M. Virology Journal 2010;7:375; 4Monga HK, et al. Clin Infect Dis 2001;33:240–7; 5Boffito M, et al. Drug MetabDispos 2002;30:859–60; 6Ozeki T, et al. Br J Exp Path 1988;69:589–95 7Welage LS, et al. Clin Infect Dis 1995;21:1431–38; 8Nam YJ, et al. Korean J Hepatol 2004;10:216–22

  14. PK differences (versus healthy volunteers) *Compared to HIV mono-infected; †Healthy individuals with & without mild/moderate hepatic impairment ҰHealthy individuals with and without moderate hepatic impairment

  15. Interactions with non-oral drugs

  16. Corticosteroids • Case report of Cushing’s syndrome and adrenal suppression in a patient on ATV/r and dexamethasone 0.1% eye drops1 • Cushing’s syndrome reported with the use of intra articular triamcinolone injections in patients on boosted PIs2–4 • Cushing’s syndrome and adrenal suppression in patients on budesonide and ritonavir (paediatrics) or boosted PIs5,6 • Several cases of Cushing’s syndrome with fluticasone and ritonavir7 1. Molloy A, et al. AIDS. 2011;25:1337–9. 2. Dort K, et al. AIDS Res Ther. 2009;6:10. 3. Danaher PJ, et al. Orthopedics 2009;32:450. 4. Ramanathan R, et al. Clin Infect Dis. 2008;47:e97–9. 5. Gray D, et al. S Afr Med J. 2010;100:296–7. 6. Frankel JK, & Packer CD. Ann Pharmacother. 2011;45:823–4. 7. Foisy MM, et al. HIV Medicine 2008;9:389–96.

  17. Corticosteroid metabolism and formulations                           Created from SmPCs for all included drugs. Available at: http://www.medicines.org.uk/emc/.

  18. Prevelance of Clinically Significant Drug Interactions in HIV Cohorts

  19. Prevelance of DDIs

  20. Clinically Significant Interactions in HIV+ patients

  21. B B < 50 years < 50 years A A 60 60 < 50 years < 50 years ? 50 years 50 50 *** *** *** 50 years ? >50 years 50 50 40 40 40 40 *** *** *** 30 30 patients (%) patients (%) 30 30 Patients (%) patients (%) 20 20 *** *** *** 20 20 *** *** *** *** *** *** *** *** *** ** ** ** ** ** ** *** *** *** 10 10 10 10 *** *** *** *** *** *** * * * 0 0 0 0 0 0 1 1 2 2 3 3 4 4 5 5 6 6 7 7 >8 >8 diuretics hormones analgesics methadone CNS agents antilipidemics ACE inhibitors Beta blockers anti-infectives Number of co-medications diuretics number of co-medications insulin/antidiabetics hormones analgesics methadone cardiovascular drugs gastrointestinal drugs angiotensin II inhibitors CNS agents antilipidemics ACE inhibitors Betablockers anti-infectives calcium channel inhibitors antiplatelets/anticoagulants insulin/antidiabetics angiotensin II inhibitors cardiovascular drugs gastrointestinaldrugs calciumchannelinhibitors antiplatelets/anticoagulants Drug Interactions will be greater as patients age > 50 years Marzolini C et al J AntimicrobChemother 2011;66:2107

  22. Numerous factors determine the pharmacokinetic phenotype

More Related