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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
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
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
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
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