Viral Hepatitis Pharm

Question 1

What is the goal of HBV treatment?

Answer 1

• HBV DNA suprpression to undetectable levels
• seronegativity to HBeAg (sometimes HBsAg
• reduction of transaminase

These correspond to:

• decreased liver damage
• decreased risk for cirrhosis and HCC
• decreased likelihood for need of liver transplant

Question 2

When is HBV treated (acute/chronic)?

Answer 2

• only chronic HBV is treated
• acute HBV will often resolve on its own

Question 3

What is the common mechanism of action in most drugs used to treat HBV?

What limitation does this give treatment of HBV?

Answer 3

nucleoside/nucleotide reverse transcriptase inhibitors (NTRI)

only effective against actively replicating virus due to MOA

Question 4

What side effects are commonly shared by HBV NTRIs?

Answer 4

• headache
• nausea
• fatigue
• nasal symptoms
• cough
• diarrhea

Question 5

What black box warning is common in most drugs used to treat HBV?

What HBV drug does not come with this warning?

Answer 5

• lactic acidosis
• severe exacerbation of HBV infection upon discontinuation

adefovir does not have this warning

Question 6

What is entecavir?

(indications)

Answer 6

HBV NTRI (nucleoside)

Indications: (active HBV)

• adults
• children >2

Question 7

What contraindications/adverse effects are associated with entecavir?

Answer 7

none

Question 8

What is tenofovir disoproxil?

(indications)

Answer 8

HIV1/HBV NTRI (nucleotide)

Indications:

• HIV-1 infection in adults or children >2
• HBV in adults and children >12

Question 9

What contraindications/adverse effects are associated with tenofovir disoproxil?

Answer 9

renal impairment

Question 10

What is adefovir?

(indications)

Answer 10

HBV NTRI (nucleotide)

Indications:

HBV infection in adult and children >12

Question 11

What contraindications/adverse effects are associated with adefovir?

Answer 11

• nephrotoxicity
• weakness and increased creatinine

Question 12

What is lamivudine?

(indications)

Answer 12

HIV-1/HBV NTRI (nucleoside)

Indications:

• HIV-1 infection in adults
• HBV infection in adults
• co-infection

Question 13

What contraindications/adverse effects are associated with entecavir?

Answer 13

-pancreatitis

Question 14

What is telbivudine?

(indications)

Answer 14

HBV NTRI (nucleoside)

Indications:

-HBV in adults

Question 15

What contraindications/adverse effects are associated with telbivudine?

Answer 15

not to be administered with PEG interferon alfa-2a -> peripheral neuropathy

Question 16

Which HBV treatments are also used in HIV-1 treatment?

Answer 16

• tenofovir disoproxil
• lamivudine

_{many of the others are effective against HIV-1 but at levels that are too high to be safe and are therefore not approved for use}

Question 17

What non-NTRI is used to treat HBV?

Answer 17

PEG interferon alfa-2a

Question 18

What are the two PEG interferon’s used to treat viral hepatitis?

Which viral hepatitis do they treat?

Answer 18

• PEG interferon alfa-2a -> HBV and HCV (HCV with ribivrin)
• PEG interferon alfa-2b -> HCV only

Question 19

What is the MOA of PEG interferons?

Answer 19

interferon analogs -> drive MHC I expression and stimulate cytotoxic T cell response (viral related immune responses)

Question 20

What black box warning is associated with PEG interferon alfa-2a/b?

Answer 20

causes or aggravates neurospsychiatric, autoimmune, ischemic, and infectious

Question 21

What are the side effects of PEG interferons?

Answer 21

flu-like symptoms

Question 22

What are contraindications of PEG interferon alfa-2a?

Answer 22

• autoimmune hepatitis (worsens CD8+ mediated destruction)
• decompensated liver disease
• neonates/infants (birth defects)

Question 23

What are contraindications of PEG interferon alfa-2b?

Answer 23

• autoimmune hepatitis (worsens CD8+ mediated destruction)
• decompensated liver disease

Question 24

What is the goal of HCV treatment?

Answer 24

eradicatin of the virus -> “sustained viral response” (absence of detectable signs of infection 24 weeks after treatment completion)

Corresponds to

• decreased liver damage
• decreased risk for cirrhosis and HCC
• possible regression of cirrhosis

Question 25

When is HCV treated (acute/chronic)?

Answer 25

chronic \> acute but both are treated acute HCV is likley to progress to chronic HCV but some cases don't -\> treatment is usually delayed in the acute stage to see if virus is cleared on its own

Question 26

What are the main MOAs of HCV treatment? What suffix is associated with each?

Answer 26

- NS3/4A **protease inhibitors** -\> "**-previr**" - **NS**_5A_**** inhibitors -\> "**-asvir**" - NS**_5B_** **polymerase inhibitors** -\> "**-buvir**"

Question 27

What is ribivarin? | (indications)

Answer 27

HCV nucleoside polymerase inhibitor Indications: - HCV **with interferon alfa-2a** in **children \>5** - chronic HCV w/ HIV co-infection in adults

Question 28

What black box warning is associated with ribivarin?

Answer 28

risk of **birth defects or fetal death** - not to be used **during or 6 months prior to pregnancy** - not to be used by **male sexual partner of pregnant females**

Question 29

What contraindications/adverse effects are associated with ribivarin?

Answer 29

- **hemoglobinopathies** - pregnancy/males with pregnant partners (black box warning)

Question 30

What is elbasvir/grazoprevir? | (indication)

Answer 30

elb**_asvir_**/grazo**_previr_** combination drug; _NS5A inhibitor_ + NS3/4A _protease inhibitor_ Indications: -treatment of HCV in **adults**

Question 31

What contraindications/adverse effects are associated with elbasvir/grazoprevir?

Answer 31

-elevated ALT Contraindications: -moderate or severe **hepatic impairment** (these drugs are **metabolized in the liver**)

Question 32

What drug interactions occur with elbasvir/grazoprevir?

Answer 32

**CYP3A inducers** increase metabolism of elbasvir/grazoprevir

Question 33

What is ledipasvir/sofosbuvir? | (indications)

Answer 33

ledip**_asvir_**/sofos**_buvir_** combination drug; _NS5A inhibitor_ + nucleotide NS5B _polymerase inhibitor_ Indications: -treatment of HCV in **adults** **-only in combination with _ribavirn_**

Question 34

What contraindications/adverse effects are associated with ledipasvir/sofobuvir?

Answer 34

only **given in combo with ribavirn** -\> ribavirn contraindications apply - **pregnancy/ males with pregnant partners** - **hemoglobinopathies**

Question 35

What drug interactions occur with velpatasvir/sofobuvir?

Answer 35

- polyglycoprotein **(PGP) inducers** (rifampin, St. John's wort) - **CYP inducers**

Question 36

What is velpatasvir/sofosbuvir? | (indications)

Answer 36

velpat**_asvir_**/sofos**_buvir_** combination drug; **NS5A inhibitor** + nucleotide NS5B **polymerase inhibitor** Indications: - HCV **w/o cirrhosis** or with **compensated cirrhosis** in **adults** - HCV w/ **decompensated cirrhosis** in combination **_with ribivarin_** in **adults**

Question 37

What contraindications/adverse effects are associated with velpatasvir/sofobuvir?

Answer 37

**ribivarin contrainidcations** apply in **decompensated cirrhosis:** **-****pregnancy/ males with pregnant partners** -**hemoglobinopathies**

Question 38

What drug interactions occur with ledipasvir/sofobuvir?

Answer 38

polyglycoprotein **(PGP) inducers** (rifampin, St. John's wort)

Question 39

What is boceprevir? | (indications)

Answer 39

HCV **NS3/4A inhibitor** Must be given in combo with: -**PEG interferon alfa** and **ribivarin** Indications: -chronic HCV with **compensated** liver disease in **adults**

Question 40

What contraindications/adverse effects are associated with boceprevir?

Answer 40

When given _with ribivarin_: - **pregnancy/ males with pregnant partners** - **hemoglobinopathies**