ritonavir interactions and side effects
DESCRIPTION
RITONAVIR INTERACTIONS AND SIDE EFFECTS. Present by PEERAKARN BANJERDKIJ. OUTLINE. Introduction HIV Therapy Types of HIV-drugs Protease Inhibitors work Ritonavir Pharmacology Drug Interactions Side effects Conclusion. INTRODUCTION. - PowerPoint PPT PresentationTRANSCRIPT
RITONAVIR INTERARITONAVIR INTERACTIONS AND SIDE ECTIONS AND SIDE E
FFECTSFFECTS
Present by Present by PEERAKARN BANJERDK PEERAKARN BANJERDK
IJIJ
OUTLINEOUTLINE• Introduction
• HIV Therapy
• Types of HIV-drugs
• Protease Inhibitors work
• Ritonavir• Pharmacology
• Drug Interactions
• Side effects
• Conclusion
INTRODUCTIONINTRODUCTION
Why is the “HIV Therapy” called “multiple therapies”?Ans. : Immune systemWhat is the “medical problem”?Ans. : Drug interactionsHow many types of HIV-drugs?Ans. : 3 Types
Types of HIV-drugs
2 main groups1. Reverse Transcriptase 1.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
zidovudine (AZT)didanosine (ddI)
1.2 Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
nevirapine delaviridine
2. Protease Inhibitors (PIs)indinavirritonavir
What is HIV protease?What is HIV protease?
How do protease inhibitors work?
How do protease inhibitors differ from other available anti-HIV drugs?
OUTLINEOUTLINEIntroductionRitonavir
PharmacologyDrug InteractionsSide effects
Pharmacology
• Block maturation of virus • By interfering
• Act at the stage of HIV replication cycle
• Produce resistance• Bound plasma 98-99%• Cross resistance
• combine with NNRTIs or NRTIs
• combine with PIs Cross resistance
RITONAVIR
OUTLINEOUTLINEIntroductionRitonavir
PharmacologyDrug InteractionsSide effects
What types of other medications can interact with PIs?Ans.1 : HIV-HIV drugs
- Combination Therapy- Double-Drug ; PIs + PIs , PIs +
NRTIs- Triple-Drug ; PIs+PIs+NNRTIs
Ans.2 : HIV-Other drugs ; PIs+Antivirals
Combinations & Interactions
RITONAVIR
Drug Interactions
• Metabolized by P450 at the liver • Combine with competition drugs ; can occur
1. Metabolism of these drugs
2. Concentration of Ritonavir and these drugs
RITONAVIR
Between Other drugs and RitonavirInteracting Drugs Effect Mechanism
Group of drugs AmiodaroneAstemizoleBeperidilCisaprideClozapineErgotamineRifabutin etc.
Increase plasma con. ofantiretroviralPotential for serioustoxicitiesDo not coadminister
EtoposideLovastatinRifampinFentanyl etc.
> 3X increase AUC of drug CYP3A4 inhibitionby ritonavir
AmitriptylineFluoxetineHaloperiolPindodol
1.5-3X increase AUC ofdrug
CYP2D6 inhibitionby ritonavir
KetoconazolePhenobabitalDigoxin etc.
Possible increase AUC ofdrug
Unknown(1998)
DRUG INTERACTION
http://www.hivinsite.UCSF.edu/topics/research_advances/2098.339b.html
Between Other drugs and PIsDrugs
AffectedIndinavir
(IDV)Ritonavir
(RTV)Saquinavir
(SQV)*Nelfinavir
(NFV)Amprenavir
(APV)Antifugals:Ketoconazole
Levels :IDV 68%
Levels :Keto. 3X
Levels :SQV 3X
No doseadjustmentnecessary
Levels :APV 31%Keto. 44%
Antimyco-bacterials:Rifampin Levels :
IDV 89%Levels :RTV 35%
Levels :SQV 84%
Levels :NFV 82%
Levels :APV 82%No changerifampin
Rifabutin Levels :IDV 89%Rifabutin 2X
Levels :Rifabutin 4X
Levels :SQV 40%
Levels :NFV 32%Rifabu. 2X
Levels :NFV 82%Rifabutin 193%
http://www.thebody.com/hivatis/agents1/table14.html
DRUG INTERACTION
Between PIs and PIs
DrugAffected
Ritonavir(RTV)
Saquinavir(SQV)*
Nelfinavir(NFV)
Amprenavir(APV)
Indinavir(IDV)
Levels :IDV 2-5X
Levels :IDV no effectSQV 4-7X#
Levels :IDV 50%NFV 80%
Levels :APV 33%
Ritonavir(RTV)
- Levels :RTV no effectSQV 20X+#
Levels :RTV no effectNFV 1.5X
Levels :APV 2.5X
Saquinavir(SQV)
- - Levels :SQV 3-5XNFV 20%#
Levels :APV 32%
Nelfinavir(NFV)
- - - Levels :APV 1.5X
* Invirase or Fortovase , + Conducted with Invirase , # with Fortovase
http://www.thebody.com/hivatis/agents1/table15.html
DRUG COMBINATION
OUTLINEOUTLINEIntroductionRitonavir
PharmacologyDrug InteractionsSide effects
Adverse Drug ReactionSIDE EFFECTS
http://www.utoledo.edu/pharmacy/clinical/aids.html
Name(s) Ritonavir(RTV)
Indinavir(INV)
Saquinavir(SQV)
Nelfinavir(NFV)
Vomiting Nausea Diarrhea Numbness (mouth) Asthenia & Anorexia Fatigue /Tire Taste disturbance Increase liverTransminases
Rash GI problems Nephrolithiasis(Kidney stone)
http://www.iapac.org/clinmgt/avtherapies/patient/proinbk.html#top
HIV Drugs -ToxicitiesHIV Drugs -Toxicities
SIDE EFFECTS
HIVDrugs
Pancreatitis Nephrotoxicity Hepatotoxicity Rash Diarrhea
Ritonavir
Indinavir Nelfinavir AllProteaseInhibitors
http://www.thebody.com/hivatis/agents1/table16.html
OUTLINEOUTLINEIntroductionRitonavir
PharmacologyDrug InteractionsSide effects
Conclusion
CONCLUSIONSCONCLUSIONS
Protease Inhibitors can cure or not!Combination ; more efficiencySide effects ; different waysResistance ProblemsCross resistance problems
THE ENDTHE END THANK YOU THANK YOU
• Dr. SUVIT Dr. SUVIT• Dr. MARIA Dr. MARIA• Mr. SOMJERD Mr. SOMJERD
• CRI OFFIER & OUR CLASS CRI OFFIER & OUR CLASS…………......
Advantages & Disadvantages ofAdvantages & Disadvantages ofClass-Sparing RegimensClass-Sparing Regimens
SIDE EFFECTS
Regimen PossibleAdvantages
PossibleDisadvantages
Drug InteractionComplication
Impact on FutureOptions
PI-basedHAART
-Well document-Require multiplemutations-2 step inhibitors;RT & PI
-Lipodystrophy,hyperlipidemia andinsulin resistance-Difficult to use
-Inhibition ofP450 partway(not much)
-Save NNRTIs foruse in treatmentfailure-cross resistancewith other PIs
NNRTI-basedHAART(PI-sparing)
-PI relate sideeffects-Easier to use
-End pointunknown-Single Resistance
-Fewerinteractionproblems
-Save PIs for lateruse-cross resistance
Triple NRTIand PI-sparing
-Easier to use-Side effect (+PIand NNRTI)-Not confer crossresistance
-End pointunknown-High baselineviral load
-General druginteractionproblems
-Save both PI andNNRTI , later use-Limited crossresistance inNRTI
http://www.thebody.com/hivatis/agents1/table7.html