GI Pharm IV: HBV & HCV Flashcards
Interferon alfa 2A
MOA
Uses
Immune modulator & inhibitor of viral processes
Type 1 interferons lead to the activation of Jak/Stat pathway –> transcribes specific mRNAs to help cells respond to viruses
Uses: HBV & HVC
Interferon alfa 2A
ADME/Use
Use: younger pts
-Well compensated cirrhosis
-Pts who don’t want long-term tx
-IV for acute Hep B
-SubQ weekly for chronic Hep B
-Pegylated –> longer half-life (1x/wk)
Interferon alfa 2A
Adverse Effects
BB: May cause or aggravate fatal or life-threatening neuropsych, autoimmune, ischemic, and infectious disorders (worse in elderly)
Flu-like symptoms (fatigue)
long term use can cause neurotoxicity, myelosuppression, fatigue
Interferon alfa 2A
Contraindications/Monitor
DONT USE in PREGNANACY
Monitor:
CBC
TSH
Serum HCV RNA levels
Entecavir
MOA
Guanine nucleoside analog – inhibits HBV DNA Polymerase
Entecavir
Adverse Effects
HA, fatigue, dizziness, nausea.
Black Box- lactic acidosis and severe hepatomegaly with steatosis, and exacerbations of HBV when discontinued
Entecavir
Contraindications
Monitor
Don’t use if Lamivudine resistance
*Lactic acidosis by most nucleotide analogs occurs by inhibiting mitochondrial polymerase γ inside the liver and muscle cells
Tenofovir
1st line in HBV infection
MOA
Adenosine nucleotide analog (NRTI)
Interferes with the viral RNA dependent DNA polymerase resulting in inhibition of viral replication
Tenofovir
ADME/Use
Can also treat HIV
Two formulations, disoproxil fumarate and alafenamide
Alafenamide has fewer adverse effects on renal function and bone density
Tenofovir
Adverse Effects
GI effects (formulated with lactose so lactose intolerance increases these effects)
Renal tubulopathy → calcium and phosphate loss → monitor bone density in long-term use
Tenofovir
Contraindications
Monitor
Active against strains of HBV that are resistant to entecavir or lamivudine
Monitor: Serum phosphorus & creatinine, urine glucose & protein, LFTs, Bone density
Lamivudine
MOA
HBV –incorporated into the viral DNA by hepatitis B virus polymerase, resulting in DNA chain termination (cytidine analog)
NRTI in HIV therapy
Lamivudine
ADME/USE
Can also treat HIV
Lamivudine
Adverse Effects
- Headache, dizziness, insomnia
- GI effects
- Respiratory effects (cough, sore throat, nasal effects)
Black Box Warnings
- Lactic acidosis and severe hepatomegaly
- Exacerbations of hepatitis B on discontinuation
Ribavirin
MOA
Guanosine analog
Interferes with viral mRNA capping, inhibits synthesis of guanosine, inhibits viral RNA-dependent polymerase
Ribavirin
ADME/USE
- Needs phosphorylation to become active (triphosphate form)
- Oral v inhalation (RSV)
Ribavirin
Adverse Effects
Black Box Warning
-Don’t use as monotherapy (used in combination with interferon)
- Hemolytic Anemia (oral)
- HIGHLY teratogenic
o Central nervous system: Fatigue, headache, insomnia
o Gastrointestinal: Nausea, anorexia
o Hematologic: Anemia
For inhalation form, healthcare works experience- (Respiratory syncytial virus [RSV]) Headache (51%); conjunctivitis (32%); rhinitis, nausea, rash, dizziness, pharyngitis, and lacrimation (10% to 20%).
Ribavirin
Contraindications
Also treats RSV
VERY TERATOGENIC – DO NOT USE IN PREGNANCY. If using in women of childbearing age, must use TWO forms of birth control during + 6 months after termination of drug
Sofosbuvir
MOA
NS5B Inhibitor - (buvir)
Nucleotide analog (uracil) that inhibits the RNA-dependent RNA polymerase found in genotypes 1-6 (NS5B)
Pangenotypic
Sofosbuvir
Adverse Effects
CNS – Fever, HA, insomnia, chills, irritability
Dermatitis – Pruritus, skin rash
Hem/Onc – Decreased Hgb, anemia, neutropenia, decreased neutrophils
Neuromuscular: Weakness, myalgia
Respiratory: Flu-like sxs
Amiodarone: symptomatic bradycardia drug i/a
Sofosbuvir
Contraindications
Monitor
NS = nonstructural protein
Velpatasvir
MOA
Inhibits NS5A, likely viral transcription factor that might be involved in the induction of the viral RNA-dependent RNA polymerase
Velpatasvir
ADME
Uses
-Oral
-Half-life 15 hr
-Fixed dose with sofosbuvir for once per day dosing
Approved to be used in combination with sofosbuvir & effective w/o interferon/ribavirin
Velpatasvir
Adverse Effects
w/ sofobuvir- package alert HBV reactivation-check all patients for current or prior HBV infection
Diabetes – Caution for improvement of glucose metabolism, leading to hypoglycemia in pts taking antidiabetic agents
