Lecture 4 - Antiviral Agent 3 Flashcards
Nevirapine ADE
Rash = dose titration
Most severe form - Erythema Multiforme
Hepatitis = AVOID in women with higher CD4 counts
Efavirenz ADE
CV - Dyslipidemia
Rash
CNS
Etravirine ADE
Rash
CNS, less than efavirenz
CV - Dyslipidemia
Rilpivirine ADE
Rash
CNS
CV - Dyslipidemia
Doravirine ADE
Rash
CNS = much less than Efavirenz, 8.8% vs 37% dizziness, 12.1 vs 25.5% abnormal dreams
** Positive effects on lipids **
NNRTI drugs are strong inducers so they will….
reduce lvls of substrate drug
Antidepressants that are less effected by NNRTI
Fluoxetine
Fluvoxamine
Paroxetine
Enzyme inducers reduce lvls of NNRTIs are….
Rifampin Rifabutin Phenytoin Phenobarbital Carbamazepine
Enzyme inhibitors that increase lvls of NNRTIs
Itraconazole Voriconazole Fluconazole Posaconazole Isavuconazonium Clarithromycin
Most common NNRTI Resistance Mutations
K103N = wipe out 1st gen NNRTI
Y181C
Importnat points about NNRTI resistance
Extensive cross-resistance between 1st gen, excludes….
Doravirine
Etravirine
Rilpivirine
Protease inhibitor MOA
interfere with viral replication by blocking the protease enzyme involved in the production of structural proteins-results in imperfect non-infectious virus
Protease inhibitors will do what to lvls of substrate drug?
increase
Ribavirin should be avoided with
didaosine
stavudine
zidovudine
Sofosbuvir should be avoided with
tipranavir
Ledipasvir/Sofosbuvir can be used with….
Most ARVs
Glecaprevir/Pibrentasvir should not be used with
atazanavir
ritonavir-containing regimens
efavirenz
etravirine
Elbasvir/Grazoprevir should not be used with…
Cobicistat efavirenz etravirine nevirapine or HIV protease inhibitors
Giving Azole with Protease inhib?
increased QT prolongation
Giving Protease inhib with anti-psychotics
increase side effects
Giving protease inhib with PDE5?
decrease dose for ED, dont use in PAH
Protease inhib effect on methadone?
lvl decreased**
Protease inhib with OC?
decrease in Hormone lvls
Protease inhib with Warfarin?
play with doses
Protease inhib with Steroids?
use beclomethasone as alternative inhalation steroid
use less potent steroids
pH altering with Protease inhibitors
Atazanavir = greatst risk for dec solubility an absorption Ritonavir = next Lopinavir = less risk for solubility changes
Unique SE Atazanavir
Asymptomatic jaundice
Unique SE Indinavir
Kidney Stones
Unique SE Fosamprenavir
Severe skin rash
Unique SE Tipranavir
Intracranial hemorrhage
Unique SE Saquinavir
QT prolongation
Lipodystrophy with Protease Inhibitors
up to 50-80% of pts after 12-18 months
Risk factors: > 65yrs old
low BW before therapy
using boosted PI combo
Prolonged used
Impact of PIs to Diabetes
Longer PI use associated with increased onset of diabetes
TGs also associated with diabetes
Special SE Indinavir
Lots of Kidney Stones, stay hydrated
SE Lopinavir/Ritonavir
Long PR interval
Atazanavir SE
Increased bilirubinemia = jaundice
Fosamprenavir SE
Hypersensitivity, sulfonamide allergy
Darunavir SE
Hepatitis
Caution w/ severe sulfa allergy
Tipranavir SE
Severe Hepatitis
Intracranial hemorrhage
Darunavir will…
maintain more activity through mutations compared to other drugs
Mariviroc (entry Inhibitor) MOA
CCR5 Antagonist
Binds to CCR5 co-receptor site on the host cell and prevents penetration of HIV
Mariviroc can only be used for….
R5 not X4
Prior to initiation, requires tropism test to evaluate the predominant virus
If virus is mixed x4/r5 or x4 virus, Mariviroc will fail
ADE Mariviroc
Hepatotoxicity
Mariviroc DI
Azole, PI
strong inhibition = increase in Mariviroc
Strong inducers = dec in Mariviroc so need to inc dose
How to avoid Mariviroc toxicity w/ enzyme inhibitor?
Decrease mariviroc dose to 150 BID
Enfuvirtide (T-20) MOA
Fusion inhibitor
Binds to viral gp41 and prevents a conformational change required for fusion of the virus to the CD4 cell
Enfuvirtide ADE
Injection site reactions
Hypersensitivity
Elevated CK
Enfuviritide clearance?
no renal or hepatic, no dose adjustments
Gas powered injection system?
Helps to to disperse drug so it doesn’t sit in one spot under the skin
leads to less injection site reactions
Enfuvirtide Mutations & Resistance?
Gp41 (binding site) amino acid substitutions
INSTI MOA
Prevents HIV integrase enzyme from inserting HIV genetic material into cellular DNA
Which INSTI has lower bioavailability?
Elvitegravir
INSTI SE profile?
***Weight gain
CNS
Rash
CK elevation
Highest CNS SE of INSTI?
Efavirenz
Raltegravir also has decent amount
ADE Elvitegravir
- need to use with Cobicistat, acts as booster
2. Cobicistat associated with more GI adverse effects
Dolutegravir ADE?
Marked by CNS side effects**weird dreams
Hypersensitivity
Increase in LFTs in pts co-infected with HBC or HCV
Which INSTIs avoided with Rifampin
EVG
BTG
CAB
DHHS guidelines for HIV?
DTG for persons of child bearing age
BIC only affected by…..
IRON
Dofetilide should be avoided with….
INSTI
When using Metformin with INSTI…..
dose has to be less than 1000mg daily
less so problem with BIC and CAB
PPI not significant interaction wit INSTI when….
using a boosted combo
INSTI resistance number
148Q
Mostly EV and RAL, less so BIC and DTG
How to get passed Q148 mutation?
using higher dose of DTG
BIC has most activity against….
wild type and G140S+Q140H mutation
Ibalizumab
Used for extremely drug resistant HIV
Q2weeks
ADE: infusion related
DI: none
Cl: no adjustments
Ibalizumab MOA
blocks postattachment HIV entry into CD4+ T-cells without altering normal cell function
Fostemsavir
Attachment inhibitor, prodrug
used as a salvage. so add on with others
no renal or hepatic dose adjustment
Fostemsavir ADE
QT prolonged
Hepatic dysfunction
Avoid Fostemsavir with….
Efavirenz
Etravirine
Rifampin
Carbamazepine + Phenytoin
will dc lvl
Fostemsavir effects on OATP1B1
inhibits it
need to dose adjust
Estrogen, Statins, Grazoprevir, Voxilaprevir
will inc lvl od drug elim
