Drugs to treat Viral Hepatitis Flashcards

1
Q

What is the treatment for Hep B infection?

A

No specific treatment for acute Hep B infection, most often it resolves spontaneously

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2
Q

What are the goals of chronic HBV therapy? (3)

A
  1. Suppress HBV DNA to undetectable levels
  2. Seroconversion of HbeAg (or HbsAg) from positive to negative
  3. Reduction in elevated serum aminotransferase levels
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3
Q

What are the goals of HBV therapy correlated with? (3)

A
  1. Improvement in necro-inflammatory dz
  2. Decreased risk of hepatocellular carcinoma and cirrhosis
  3. Decreased need for liver transplantation
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4
Q

Is HBV curable?

A

Yes, but it is RARE (so, no, ish)

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5
Q

What do current therapies for HBV do?

A

Suppress HBV replication only

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6
Q

Why is HBV so hard to cure?

A

B/c the covalently closed viral DNA is very stable and can exist indefinitely within the cell, serving as an HBV reservoir throughout the life of the cell so it can be reactivated

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7
Q

When is HBV relapse more common?

A

When patients are co-infected with Hep D virus

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8
Q

What is entecavir?

A

A Hep B virus nucleoSide analogue reverse transcriptase

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9
Q

When is entecavir indicated?

A

In treatment of chronic Hep B virus infection in adults and children AT LEAST 2 YEARS OF AGE w/active viral replication and either evidence of persistent elevation in serum AST or ALT or histologically active dz

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10
Q

Entecavir contraindications?

A

None

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11
Q

Entecavir adverse effects? (most common)

A

headache, fatigue, dizziness, nausea

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12
Q

Entecavir black box warning (4)

A
  1. Severe acute exacerbations of Hep B
  2. don’t use in patients co-infected w/ HIV and HBV
  3. It can cause lactic acidosis
  4. can cause hepatomegaly
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13
Q

What is tenofovir disoproxil?

A

A nucleoTide analog HIV-1 reverse transcriptase inhibitor, and an HBV reverse transcriptase inhibitor

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14
Q

When is tenofovir indicated?

A

Use in combo w/other antiretroviral agents to treat HIV-1 in adults and kids 2+

Use in treatment of chronic Hep B in adults and kids age 12 and older

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15
Q

What are warnings when using tenofovir?

A

Watch for new onset or worsening renal impairment (can include acute renal failure and Fanconi syndrome)

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16
Q

Tenofovir adverse effects?

A

in HBV infected pts with compensated liver dz: nausea

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17
Q

Tenofovir black box warning (2)

A
  1. Lactic acidosis/ severe hepatosplenomegaly w/steatosis

2. post treatment exacerbation of hepatitis

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18
Q

What is adefovir?

A

a nucleoTide analogue used for treatment of chronic Hep B in patients 12 and older

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19
Q

When is adefovir contraindicated?

A

In patients w/previously demonstrated hypersensitivity to any of the components of it

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20
Q

What are warnings for use of adefovir?

A

It is NEPHROTOXIC, renal function should be monitored during therapy for all patients, but esp those w/pre-existing or other risks of renal impairment

Can also severely exacerbate acute hepatitis

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21
Q

Adverse effects of adefovir

A

asthenia, increased creatinine in pre and post transplantation lamivudine-resistant liver disease patients

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22
Q

Adefovir drug interactions?

A

coadministering w/drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of adefovir or the coadministered drug

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23
Q

What is lamivudine?

A

A nucleoside analogue reverse transcriptase inhibitor

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24
Q

When is lamivudine contraindicated?

A

In pts w/previous hypersensitivity reaction to lamivudine

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25
Q

Warnings for lamivudine use:

A

In patients w/HIV-1 and HBV coinfection, emergence of lamivudine-resistant HBV variants associated w/ lamivudine-containing antiretrovirals has been reported, and you should monitor pts for treatment associated toxicities.

pancreatitis can occur, watch patients with significant risk factors for pancreatitis

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26
Q

Lamivudine adverse effects?

A

headache, nausea, malaise, fatigue, nasal signs and symptoms, diarrhea, cough

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27
Q

Lamivudine black box warnings? (3)

A
  1. lactic acidosis
  2. severe hepatomegaly
  3. exacerbation of Hep B
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28
Q

What is telbivudine?

A

A nucleoSide analogue reverse transcriptase inhibitor

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29
Q

When is telbivudine indicated?

A

In chronic Hep B adult patients w/evidence of viral replication and either evidence of persistent elevations in ALT/AST or histologically active disease

30
Q

When is telbivudine contraindicated?

A

contraindicated in combo w/ PEGylated interferon alfa-2a – increases risk of peripheral neuropathy

31
Q

Telbivudine adverse effects?

A

fatigue, increased CK, headache, cough, diarrhea, abdominal pain, nausea, arthralgia, pyrexia, rash, back pain, dizziness, myalgia, increased ALT, dyspepsia, insomnia, and abdominal distension (MOST ADVERSE EFFECTS)

32
Q

Telbivudine black box warning? (3)

A
  1. Can cause lactic acidosis
  2. Can cause severe hepatomegaly with steatosis
  3. Can cause severe acute exacerbation of Hep B
33
Q

When is PEG Interferon Alfa-2a indicated? (2)

A

In the treatment of chronic Hep C in people w/compensated liver dz not previously treated with interferon alpha, and in patients w/histological evidence of cirrhosis and compensated liver dz

in treatment of pts with chronic Hep B infection who have compensated liver dz and evidence of viral replication and liver inflammation

34
Q

When is PEG Interferon alfa-2a contraindicated? (3)

A
  • in patients with autoimmune hepatitis
  • in neonates and infants
  • in cases of hepatic decompensation in pts with cirrhosis
35
Q

PEG Ifn Alfa-2a adverse effects?

A

fatigue, pyrexia, myalgia, headache

36
Q

What is the goal of treatment for patients with HCV?

A

Viral eradication

37
Q

What is the primary efficacy end point in Hep C virus treatment?

A

Achievement of sustained viral response (SVR)

38
Q

What is sustained viral response? (SVR)

A

The absence of detectable viremia 24 weeks after completion of therapy

39
Q

What is SVR associated with? (3)

A
  • improvement in liver histology
  • reduction of end-stage liver disease and hepatocellular carcinoma
  • regression of cirrhosis (occasionally)
40
Q

Why do most practitioners choose to delay therapy after initial Hep C infection?

A

Because clearance rate w/o treatment is 20%-35%

41
Q

What is Elbasvir/Grazoprevir?

A

A fixed-dose combination product used to treat Hep C:

Elbasvir is a HCV NS5A inhibitor

Grazoprevir is a HCV NS3/4A protease inhibitor

42
Q

When is Elbasvir/Grazoprevir contraindicated?

A

in patients w/moderate or severe hepatic impairment

43
Q

What are warnings associated with Elbasvir/Grazoprevir?

A

can cause ALT elevations

44
Q

Elbasvir/Grazoprevir adverse effects?

A

fatigue, headache, nausea

45
Q

Elbasvir/Grazoprevir drug interactions?

A

Coadministration w/moderate CYP3A inducers isn’t recommended, may decrease plasma concentrations of Elbasvir/Grazoprevir

46
Q

What is Ledipasvir/Sofosbuvir?

A

A fixed-combination drug used to treat chronic Hep C infection in adults

Ledipasvir - NS5A inhibitor

Sofosbuvir - HCV nucleoTide analog (guanosine) NS5B polymerase inhibitor

47
Q

Warnings associated with Ledipasvir/Sofosbuvir?

A

Only recommended with some combination of ribavirin

48
Q

Ledipasvir/Sofosbuvir adverse effects?

A

fatigue, headache

49
Q

Ledipasvir/Sofosbuvir drug interactions?

A

polyglycoprotein inducers (rifampin, St. John’s wort) may alter concentrations of Ledipasvir/Sofosbuvir, so not recommended

50
Q

What is Velpatasvir/Sofosbuvir?

A

a fixed-dose combination used to treat Hep C

  • velpatasvir: a HCV HS5A inhibitor
  • Sofosbuvir - HCV nucleotide analog NS5B polymerase inhibitor
51
Q

When is Velpatasvir/Sofosbuvir indicated?

A

In treatment of adult chronic HCV patients:

  • WITHOUT cirrhosis or WITH compensated cirrhosis
  • with decompensated cirrhosis for use in combination with ribavirin
52
Q

When is Velpatasvir/Sofosbuvir contraindicated?

A

In patients for whom ribavirin is contraindicated

53
Q

Warnings for Velpatasvir/Sofosbuvir?

A
  • can potentiate bradycardia w/amiodarone co-administration

- caution in pts taking beta blockers or those with underlying cardiac comorbidities and/or advanced liver dz

54
Q

Velpatasvir/Sofosbuvir adverse effects? In combination w/ ribavirin?

A
  • headache and fatigue

- combo (in pts w/decompensated cirrhosis): fatigue, anemia, nausea, headache, insomnia, diarrhea

55
Q

Velpatasvir/Sofosbuvir drug interactions?

A
  • PGP inducers and/or moderate to potent CYP inducers (rifampin, St. John’s Wort, carbamazepine) may decrease concentrations of sofosbuvir and/or velpatasvir (not recommended)
56
Q

What is ribavirin?

A

A nucleoSide analogue indicated in treatment of chronic Hep C infection in combo w/ Interferon alfa-2a in pts 5 YEARS OF AGE AND OLDER w/compensated liver dz and not previously treated w/ interferon alpha

can also be used in adult CHC patients co-infected with HIV

57
Q

Ribavirin contraindications

A
  • don’t use in pregnant women or men whose female partners are pregnant (strongly teratogenic)
  • don’t use in people with hemoglobinopathies
58
Q

Ribavirin adverse effects

A

fatigue (asthenia), pyrexia, myalgia, headache

59
Q

Ribavirin black box warning

A

causes a risk of serious disorders and ribavirin-associated effects

  • can cause birth defects and fetal death; don’t use in pregnancy and for 6 months after treatment
60
Q

What is Boceprevir?

A

A HCV NS3/4A protease inhibitor indicated in treatment of chronic Hep C infection in combo with PEG-interferon alfa and ribavirin in adult patients w/compensated liver dz.

Use in patients who are previously untreated or who failed previous interferon and ribavirin therapy

61
Q

Boceprevir contraindications

A

all contraindications to PEG-interferon alfa and ribavirin apply (since must be administered w/)

62
Q

Boceprevir warnings

A

Ribavirin warning - may cause birth defects and fetal death. Don’t use in pregnant patients or males with pregnant partners

63
Q

Boceprevir adverse effects

A

fatigue, nausea, headache, ANEMIA, DYSGEUSIA (distorted sense of taste)

64
Q

PEG Interferon Alfa-2b indications?

A

Use in treatment of chronic Hep C patients 18+ years old with compensated liver dz who have a history of blood or blood product exposure and/or are HCV ab positive

65
Q

PEG Interferon Alfa-2b contraindications? (3)

A
  • hypersensitivity to interferon alpha or any component of product
  • autoimmune hepatitis
  • decompensated liver dz
66
Q

PEG Interferon Alfa-2b adverse reactions?

A

flu-like symptoms (fever, headache, myalgia, chills, fatigue)

more sever toxicities observed generally at higher doses, may be difficult for patients to tolerate

67
Q

Treatment amount/length for Velpatasvir/Sofosbuvir?

A

velpatasvir 100 mg
sofosbuvir 400 mg

all once daily for 12 weeks

68
Q

Treatment amount/length for Elbasvir/Grazoprevir?

A

Elbasvir 50 mg
Grazoprevir 100 mg

all once daily for 12 weeks

69
Q

Treatment amount/length for Ledipasvir/Sofosbuvir?

A

Ledipasvir 90 mg
Sofosbuvir 400 mg

all once daily for 12 weeks

70
Q

Treatment amount/length for Sofosbuvir?

A

400 mg once daily, PLUS weight-based Ribavirin for 12 weeks