Presentation is loading. Please wait.

Presentation is loading. Please wait.

Drug-drug interaction Satellite Workshop

Published byWilfred Lawrence Modified over 9 years ago

Similar presentations

Presentation on theme: "Drug-drug interaction Satellite Workshop"— Presentation transcript:

1 Drug-drug interaction Satellite Workshop
HIV Malaria Co-infection M Lamorde MRCP, PhD

2 Malaria and HIV Malaria: major cause of morbidity and mortality in tropics Treatment: artemisinin derivatives are critical for eradication of plasmodium falciparum (responsible for greatest burden) Epidemiology: significant geographic overlap with HIV Complex interactions: pathogenesis, therapeutics Focus: malaria HIV drug interactions in resource-limited settings

3 Uganda: recommended drugs
Malaria treatment Uncomplicated malaria artemether/lumefantrine artesunate/amodiaquine Alternative: DHA/piperaquine (previously oral quinine) Severe malaria parenteral quinine parenteral artesunate

4 Uganda: recommended drugs
Antiretroviral therapy First-line (NNRTI-based) efavirenz nevirapine Second-line (PI-based) lopinavir/ritonavir atazanavir/ritonavir

5 Uganda: recommended drugs
Antiretroviral therapy First-line (NNRTI-based) efavirenz nevirapine Second-line (PI-based) lopinavir/ritonavir atazanavir/ritonavir CYP3A4 inducers

6 Uganda: recommended drugs
Antiretroviral therapy First-line (NNRTI-based) efavirenz nevirapine Second-line (PI-based) lopinavir/ritonavir atazanavir/ritonavir CYP3A4 inhibitors

7 Potential for interactions with ARVs
Antimalarial drug Metabolic pathway Quinine CYP3A4, 2C19 Artesunate/amodiaquine CYP3A4, 2A6 Artemether/lumefantrine CYP2C19, 3A4 Chloroquine CYP2C8, 2D6, 3A4 Atovaquone/proguanil Glucuronidation, 2C19 ATOVAQUONE/PROGUANIL NOT MENTIONED IN UGANDA GUIDELINES SO WILL YOU COMMENT?

8 Potential for interactions with ARVs
Antimalarial drug Metabolic pathway Quinine CYP3A4, 2C19 Artesunate/amodiaquine CYP3A4, 2A6 Artemether/lumefantrine CYP2C19, 3A4 Chloroquine CYP2C8, 2D6, 3A4 Atovaquone/proguanil Glucuronidation, 2C19 ATOVAQUONE/PROGUANIL NOT MENTIONED IN UGANDA GUIDELINES SO WILL YOU COMMENT?

9 Potential interactions
Malaria treatment Uncomplicated malaria artemether/lumefantrine artesunate/amodiaquine Alternative: DHA/piperaquine (previously oral quinine) Severe malaria parenteral quinine parenteral artesunate Antiretroviral therapy First-line (NNRTI-based) efavirenz nevirapine Second-line (PI-based) lopinavir/ritonavir atazanavir/ritonavir

10 Case May 2012 Loss of appetite, fever, occasional vomiting X 1 week
NGN, F, 43 yrs, HIV diagnosis (2005) Management CTX 960 mg OD (since 2005) AZT/3TC/EFV (since 2008) baseline CD4 108 cells/µL CD4 (2011) 765 cells/µL May 2012 Loss of appetite, fever, occasional vomiting X 1 week Self medication with antimalarials (likely artemether/lumefantrine) No improvement NICE CASE. MAYBE STOP AFTER THE NO IMPROVEMENT TO GET PANEL COMMENTS BEFORE PROCEEDING TO THE DIAGNOSIS? Infectious Diseases Institute, Kampala

11 plasmodium falciparum
Case NGN, F, 43 yrs, HIV diagnosis (2005) Management CTX 960 mg OD (since 2005) AZT/3TC/EFV (since 2008) baseline CD4 108 cells/µL CD4 (2011) 765 cells/µL May 2012 Loss of appetite, fever, occasional vomiting X 1 week Self medication with antimalarials (likely artemether/lumefantrine) No improvement NICE CASE. MAYBE STOP AFTER THE NO IMPROVEMENT TO GET PANEL COMMENTS BEFORE PROCEEDING TO THE DIAGNOSIS? plasmodium falciparum

12 Options: AZT/3TC/EFV plus
quinine ? Will you be asking the Panel if they would treat this patient with Quinine?

13 Options: AZT/3TC/EFV plus
quinine EVIDENCE: No data for efavirenz, some data for nevirapine PK: In healthy volunteers receiving nevirapine, 33% lower quinine AUC and 36% lower Cmax Soyinka et al. J Pharm Pharmacol (2009) Efficacy: 1 case report of worsening malaria during quinine therapy Uriel A. Int J STD AIDS (2011) Will you be asking the Panel if they would treat this patient with Quinine?

14 Options: AZT/3TC/EFV plus
artesunate/ amodiaquine ? Question to Panel – is this a realistic option?

15 Options: AZT/3TC/EFV plus
artesunate/ amodiaquine EVIDENCE: Safety: First two healthy volunteers in a trial developed significant transaminase elevations with amodiaquine exposure increased 115% & 302%. No artemisinin data. German P et al. J CID (2007) Safety: Higher risk of neutropenia among HIV-infected children on antiretroviral therapy Gasasira AF et al. CID (2008) Question to Panel – is this a realistic option?

16 Options: AZT/3TC/EFV plus
artemether/ lumefantrine This is what we did ? So the issues now are: the patient has already self-medicated with ART/LUM; the magnitude of the interaction To Panel – would you proceed?

17 Options: AZT/3TC/EFV plus
artemether/ lumefantrine EVIDENCE: PK: In 30 Ugandan HIV positive patients without malaria, artemether, DHA, lumefantrine concentrations were reduced by 77%, 75% and 55%, respectively. Byakika-Kibwika P IAC 2012 TUPE-054 PK: Similar reductions seen with rifampicin Lamorde et al 51st ICAAC 2011 So the issues now are: the patient has already self-medicated with ART/LUM; the magnitude of the interaction To Panel – would you proceed?

18 Outcome Symptoms resolved with artemether/lumefantrine treatment and patient continues ongoing HIV care at IDI

19 Issues for discussion Self-medication with antimalarials and limited capacity for pharmacovigilance in resource-limited settings Efavirenz and nevirapine lower exposure of critical malaria drugs Clinical outcomes data needed ? Potential for resistance

20 How about malaria treatment for patients receiving protease inhibitors?
Any chance that this could be made into a second case, even if it is brief. I think you could develop the cardiotoxicity issue a bit – this will certainly be of interest.

21 Case June 2012 Low grade fever (on and off) Blood film: malaria
AK, M, 52 yrs, city businessman HIV diagnosis (2004) Management CTX 960 mg OD (since 2004) d4T/3TC/NVP (since 2004) baseline CD4 77 cells/µL VL 17,000 copies (2008) TDF/3TC/LPV/r (since 2008) Last CD4 (2011) 350 cells/µL Referred to heart institute 2011 ECG normal Blood pressure normal Cholesterol Total: 230 mg/dL HDL: 50 mg/dL June 2012 Low grade fever (on and off) Blood film: malaria

22 Options: Lopinavir/ritonavir plus
quinine ?

23 Options: Lopinavir/ritonavir plus
quinine EVIDENCE: PK: In healthy volunteers, ritonavir increased the AUC and Cmax of quinine four-fold. Soyinka et al. Br J Clin Pharmacol (2010) Safety: ? Potential for increased toxicity at standard doses

24 Options: Lopinavir/ritonavir plus
artemether/ lumefantrine ?

25 Options: Lopinavir/ritonavir plus
artemether/ lumefantrine EVIDENCE: PK: Ugandan HIV+ patients without malaria (n = 32), lumefantrine concentrations increased by 386% while artemether decreased by 43% Byakika-Kibwika P, J Antimicrob Chemother (2012) PK: Lumefantrine markedly higher in SA patients on LPV/r T Kredo,CROI 2012 (Paper # 613) Efficacy: Randomized trial in Ugandan HIV+ children (n=176): 43% lower risk of malaria recurrence in lopinavir/ritonavir arm versus NNRTI arm. Achan J, CROI 2012 (Paper #26)

26 Safety?

27 Options: Lopinavir/ritonavir plus
artemether/ lumefantrine EVIDENCE: Safety: Structurally similar to halofantrine which causes QT prolongation Single dose studies: No QTc prolongation in healthy volunteers or Ugandan patients German P, JAIDS 2009; Byakika-Kibwika P, Chem Res and Pract, 2011 However, lumefantrine accumulates with repeated dosing and no safety data with six-dose regimen

28 Acknowledgements www.hiv-druginteractionslite.org
Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala Ivan Mambule Jane Achan Pauline Byakika-Kibwika Acknowledgements

Download ppt "Drug-drug interaction Satellite Workshop"

Similar presentations

TB & HIV Infection: Treatment

TB & HIV Infection: Treatment
ART in HIV-Infected Patients with TB: Research Priorities Group II Facilitator: David Cohn Rapporteur: Soumya Swaminathan.

ART in HIV-Infected Patients with TB: Research Priorities Group II Facilitator: David Cohn Rapporteur: Soumya Swaminathan.
Building Global HIV/AIDS Clinical Pharmacology Research Capacity HIV and TB: Capacity Challenges to the use of Current Drugs and Developing New Drugs Kimberly.

Building Global HIV/AIDS Clinical Pharmacology Research Capacity HIV and TB: Capacity Challenges to the use of Current Drugs and Developing New Drugs Kimberly.
ARV overview and toxicity Dr Francois Venter Reproductive Health Research Unit University of the Witwatersrand.

ARV overview and toxicity Dr Francois Venter Reproductive Health Research Unit University of the Witwatersrand.
Slide #1 HIV Entry Inhibitors Trip Gulick, MD, MPH Director, Cornell HIV Clinical Trials Unit Associate Professor of Medicine Weill Medical College of.

Slide #1 HIV Entry Inhibitors Trip Gulick, MD, MPH Director, Cornell HIV Clinical Trials Unit Associate Professor of Medicine Weill Medical College of.
Daniel Everitt, MD; Erica Egizi MPH Global Alliance for TB Drug Development, New York Helen Winter, PhD University of Otago, New Zealand 2012 International.

Daniel Everitt, MD; Erica Egizi MPH Global Alliance for TB Drug Development, New York Helen Winter, PhD University of Otago, New Zealand 2012 International.
A daily dose of 400 mg efavirenz (EFV) is non-inferior to the standard 600 mg dose: week 48 data from the ENCORE1 study, a randomised, double-blind, placebo.

A daily dose of 400 mg efavirenz (EFV) is non-inferior to the standard 600 mg dose: week 48 data from the ENCORE1 study, a randomised, double-blind, placebo.
Scott Butler Infection Innovative Medicines Group AstraZeneca R&D, Boston CPTR Workshop, 2012 Arlington, VA AZD5847 Oxazolidinone for the treatment of.

Scott Butler Infection Innovative Medicines Group AstraZeneca R&D, Boston CPTR Workshop, 2012 Arlington, VA AZD5847 Oxazolidinone for the treatment of.
HIV and Malaria Dr Jane Achan Dept of Pediatrics, Makerere University College of Health Sciences Prof. Moses Kamya Makerere University College of Health.

HIV and Malaria Dr Jane Achan Dept of Pediatrics, Makerere University College of Health Sciences Prof. Moses Kamya Makerere University College of Health.
The new guidelines Dr Francois Venter Reproductive Health and HIV Research Unit University of the Witwatersrand Feb 2010.

The new guidelines Dr Francois Venter Reproductive Health and HIV Research Unit University of the Witwatersrand Feb 2010.
Developing child-appropriate formulations: what is in the research pipeline for paediatric ARVS? July 17, 2011 Challenges in the Development & Procurement.

Developing child-appropriate formulations: what is in the research pipeline for paediatric ARVS? July 17, 2011 Challenges in the Development & Procurement.
Summary of ARV prescribing guidelines in London These slides summarise the recommendations by the London HIV Consortium for prescribing antiretrovirals.

Summary of ARV prescribing guidelines in London These slides summarise the recommendations by the London HIV Consortium for prescribing antiretrovirals.
Management of HIV infection in HIV/HCV co-infected patients Mark Hull, MD, MHSc, FRCPC Division of AIDS University of British Columbia.

Management of HIV infection in HIV/HCV co-infected patients Mark Hull, MD, MHSc, FRCPC Division of AIDS University of British Columbia.
Journal Club Alcohol, Other Drugs, and Health: Current Evidence July–August 2013.

Journal Club Alcohol, Other Drugs, and Health: Current Evidence July–August 2013.
Switch to ATV + r-containing regimen - SWAN - SLOAT.

Switch to ATV + r-containing regimen - SWAN - SLOAT.
Malaria treatment. Dr abdulrahman al shaikh.. Introduction. 1-2.7 million patients died because of malaria every year. Most deaths due to Plasmodium Falciparum.

Malaria treatment. Dr abdulrahman al shaikh.. Introduction million patients died because of malaria every year. Most deaths due to Plasmodium Falciparum.
Cost-effectiveness of different starting criteria of antiretroviral therapy in Mexico. Caro Y., Colchero A., Valencia A., Bautista-Arredondo S., Sierra.

Cost-effectiveness of different starting criteria of antiretroviral therapy in Mexico. Caro Y., Colchero A., Valencia A., Bautista-Arredondo S., Sierra.
World Health Organization

World Health Organization
Choice of antimalarial drugs Malaria Medicines & Supplies Services RBM Partnership Secretariat.

Choice of antimalarial drugs Malaria Medicines & Supplies Services RBM Partnership Secretariat.
Moving forward in the diagnosis of infectious diseases in developing countries: a focus on malaria Forum organized by Fondation Mérieux & the Roll Back.

Moving forward in the diagnosis of infectious diseases in developing countries: a focus on malaria Forum organized by Fondation Mérieux & the Roll Back.

Similar presentations

Ads by Google