Download DRUG INTERACTIONS AND SIDE EFFECTS

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
Why is the “HIV Therapy” called “multiple
therapies”?
Ans. : Immune system
What is the “medical problem”?
Ans. : Drug interactions
How many types of HIV-drugs?
Ans. : 3 Types
Types of HIV-drugs
2 main groups
1. 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)
indinavir
ritonavir
What is HIV protease?
How do protease inhibitors work?
How do protease inhibitors differ from
other available anti-HIV drugs?
OUTLINE
Introduction
Ritonavir
Pharmacology
Drug Interactions
Side effects
RITONAVIR
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
OUTLINE
Introduction
Ritonavir
Pharmacology
Drug Interactions
Side effects
RITONAVIR
Combinations & Interactions
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
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
DRUG INTERACTION
Between Other drugs and Ritonavir
Interacting Drugs
Group of drugs Amiodarone
Astemizole
Beperidil
Cisapride
Clozapine
Ergotamine
Rifabutin etc.
Etoposide
Lovastatin
Rifampin
Fentanyl etc.
Amitriptyline
Fluoxetine
Haloperiol
Pindodol
Ketoconazole
Phenobabital
Digoxin etc.
Effect
Increase plasma con. of
antiretroviral
Potential for serious
toxicities
Do not coadminister
Mechanism
> 3X increase AUC of drug CYP3A4 inhibition
by ritonavir
1.5-3X increase AUC of
drug
CYP2D6 inhibition
by ritonavir
Possible increase AUC of
drug
Unknown
(1998)
http://www.hivinsite.UCSF.edu/topics/research_advances/2098.339b.html
DRUG INTERACTION
Between Other drugs and PIs
Drugs
Indinavir
Affected
(IDV)
Antifugals:
Levels :
Ketoconazole IDV  68%
Antimycobacterials:
Rifampin
Rifabutin
Ritonavir
(RTV)
Levels :
Keto.  3X
Saquinavir
Nelfinavir
*
(SQV)
(NFV)
Levels :
No dose
adjustment
SQV  3X
necessary
Levels :
IDV  89%
Levels :
Levels :
RTV  35% SQV  84%
Levels :
IDV  89%
Rifabutin
 2X
Levels :
Rifabutin
 4X
Levels :
SQV  40%
http://www.thebody.com/hivatis/agents1/table14.html
Levels :
NFV  82%
Amprenavir
(APV)
Levels :
APV  31%
Keto. 44%
Levels :
APV  82%
No change
rifampin
Levels :
Levels :
NFV  82%
NFV  32%
Rifabutin
Rifabu.  2X
193%
DRUG COMBINATION
Between PIs and PIs
Drug
Affected
Indinavir
(IDV)
Ritonavir
(RTV)
Saquinavir
(SQV)
Nelfinavir
(NFV)
Ritonavir
(RTV)
Levels :
IDV  2-5X
-
-
-
Saquinavir
(SQV)*
Nelfinavir
(NFV)
Levels :
IDV no effect
SQV  4-7X#
Levels :
RTV no effect
SQV  20X+#
-
Levels :
IDV  50%
NFV  80%
Levels :
RTV no effect
NFV  1.5X
Levels :
SQV  3-5X
NFV  20%#
-
-
Amprenavir
(APV)
Levels :
APV  33%
Levels :
APV  2.5X
Levels :
APV  32%
Levels :
APV  1.5X
* Invirase or Fortovase , + Conducted with Invirase , # with Fortovase
http://www.thebody.com/hivatis/agents1/table15.html
OUTLINE
Introduction
Ritonavir
Pharmacology
Drug Interactions
Side effects
SIDE EFFECTS
Adverse Drug Reaction
Name(s)
Vomiting
Nausea
Diarrhea
Numbness (mouth)
Asthenia & Anorexia
Fatigue /Tire
Taste disturbance
Increase liver
Transminases
Rash
GI problems
Nephrolithiasis
(Kidney stone)
Ritonavir
(RTV)

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
Indinavir
(INV)
Saquinavir
(SQV)

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http://www.utoledo.edu/pharmacy/clinical/aids.html
http://www.iapac.org/clinmgt/avtherapies/patient/proinbk.html#top
Nelfinavir
(NFV)

SIDE EFFECTS
HIV Drugs -Toxicities
HIV
Drugs
Ritonavir
Indinavir
Nelfinavir
All
Protease
Inhibitors
Pancreatitis Nephrotoxicity Hepatotoxicity Rash Diarrhea




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
http://www.thebody.com/hivatis/agents1/table16.html
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OUTLINE
Introduction
Ritonavir
Pharmacology
Drug Interactions
Side effects
Conclusion
CONCLUSIONS
Protease Inhibitors can cure or not!
Combination ; more efficiency
Side effects ; different ways
Resistance Problems
Cross resistance problems
THE END
THANK YOU
• Dr. SUVIT
• Dr. MARIA
• Mr. SOMJERD
• CRI OFFIER & OUR CLASS
……...
SIDE EFFECTS
Advantages & Disadvantages of
Class-Sparing Regimens
Regimen
Possible
Advantages
PI-based
-Well document
HAART
-Require multiple
mutations
-2 step inhibitors;
RT & PI
NNRTI-based -PI relate side
HAART
effects
(PI-sparing)
-Easier to use
Triple NRTI
-Easier to use
and PI-sparing -Side effect (+PI
and NNRTI)
-Not confer cross
resistance
Possible
Disadvantages
-Lipodystrophy,
hyperlipidemia and
insulin resistance
-Difficult to use
Drug Interaction
Complication
-Inhibition of
P450 partway
(not much)
-End point
unknown
-Single Resistance
-End point
unknown
-High baseline
viral load
-Fewer
interaction
problems
-General drug
interaction
problems
http://www.thebody.com/hivatis/agents1/table7.html
Impact on Future
Options
-Save NNRTIs for
use in treatment
failure
-cross resistance
with other PIs
-Save PIs for later
use
-cross resistance
-Save both PI and
NNRTI , later use
-Limited cross
resistance in
NRTI