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Antivirals for Hepatitis B and C: Nursing Pharmacology

Notes

Notes

ANTIVIRALS for HEPATITIS B and C
DRUG NAME
adefovir (Hepsera),
entecavir (Baraclude),
tenofovir (Vemlidy) - *High Alert Medication*

sofosbuvir (Sovaldi),
ribavirin (Copegus, Rebetol)

peginterferon alfa-2a (Pegasys)
CLASS
  • Nucleotide / nucleoside reverse transcriptase inhibitors (NRTIs)
  • Nucleotide polymerase inhibitors (sofosbuvir)
  • Nucleoside analogues (ribavirin)
  • Interferons
MECHANISM of ACTION
Interfere with DNA synthesis → decrease viral replication
Inhibit different viral proteins or enzymes required for viral replication → decrease viral replication
Induce innate antiviral immune response
INDICATIONS
Treatment of chronic hepatitis B infection
Treatment of chronic hepatitis C infection
Treatment of chronic hepatitis B and C infection
ROUTE(S) of ADMINISTRATION
PO
SubQ
SIDE EFFECTS
Common to all medications:
  • Boxed warning: severe, acute hepatitis exacerbations on therapy discontinuation
  • Boxed warning for adefovir and entecavir: lactic acidosis
  • Hepatotoxicity; increased serum transaminases
  • Hematuria 

Adefovir:
  • Fever, headache
  • Gastrointestinal toxicity (nausea, abdominal pain, vomiting, diarrhea)
  • Muscle weakness, back pain, joint pain
  • Boxed warning: severe hepatomegaly with steatosis

Entecavir:
  • Severe hepatomegaly with steatosis (boxed warning)

Tenofovir:
  • Nephrotoxicity
Both:
  • Boxed warning: HBV reactivation w/ concurrent HBV infection → life threatening, fulminant hepatitis
  • Neurotoxicity (fatigue, headache, insomnia, dizziness)
  • Dermatological toxicity (rashes, pruritus, eczema)
  • Gastrointestinal toxicity (nausea, diarrhea, anorexia, weight loss)
  • Flu-like symptoms
  • Myalgia, muscle weakness

Ribavirin:
  • Boxed warning: pregnancy
  • Boxed warning: hemolytic anemia
  • Alopecia


  • Boxed warning: can aggravate life-threatening neuropsychiatric, autoimmune, infectious and ischemic conditions
  • Gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain)
  • Dermatological toxicity (rashes, pruritus, alopecia)
  • Flu-like symptoms
  • Fatigue
  • Fever
  • Myalgia
  • Headache
  • Injection site reactions
  • Musculoskeletal pain

CONTRA-INDICATIONS and CAUTIONS
  • Breastfeeding
  • Pregnancy
  • Children
  • Geriatric clients
  • Severe renal disease

Entecavir:
  •  Impaired liver function
  • Pregnancy
  • Breastfeeding
  • Hepatic / renal disease
  • Diabetes

Ribavirin:
  • Hemoglobinopathies
  • Autoimmune hepatitis
  • Decompensated cirrhosis

Interactions
Sofosbuvir:
  • Do not use with potent cytochrome P450 inducers (e.g., rifampin, St. John’s wort)
  • Do not use with amiodarone (risk of bradycardia)
  • Pregnancy
  • Breastfeeding
  • Hepatic / renal impairment
  • Cardiac disease
  • Myelosuppression
  • Compromised CNS function 

Interactions
  • Increase theophylline levels; zidovudine: increases risk of neutropenia and/or anemia


NURSING CONSIDERATIONS: ANTIVIRALS for HEPATITIS B and C
ASSESSMENT AND MONITORING
Assessment
  • Current symptoms: fatigue, anorexia, nausea, vomiting, dark urine
  • Vital signs
  • Skin, eyes, and mucous membranes for yellowing
  • Laboratory test results: renal and liver function tests, bilirubin, albumin, PT, HBsAg, and urinalysis
  • Diagnostic test results: liver scan, biopsy

Monitoring
  • Side effects
  • Therapeutic response: improvement in their hepatitis B symptoms
CLIENT EDUCATION
  • Purpose of medication: lower the amount of the hepatitis B virus in their body
    • Will not completely eliminate the infection
    • Can transmit the virus to others
  • Take once each day with a full glass of water, with or without food
  • Powder form: measure medication using the supplied scoop, mix with 2–4 ounces of soft food; consume right after mixing
  • Medication adherence
    • Infection can worsen if discontinued
    • Routine follow-up blood tests needed to evaluate for side effects
  • Common side effects  
    • Neurological: headache, dizziness, insomnia
    • Gastrointestinal: nausea, flatulence, or diarrhea
      • Contact healthcare provider if they don’t resolve
  • Symptoms to report
    • Hepatotoxicity: fatigue, anorexia, abdominal pain, dark urine, yellowing of the eyes or skin
    • Nephrotoxicity: decreased urine output, difficulty urinating, blood in the urine, weight gain
    • Lactic acidosis: fast breathing or heartbeat, severe fatigue or dizziness, muscle pain or cramps
  • Lifestyle modifications
    • Annual influenza vaccine; hepatitis A vaccine
    • Smoking cessation
    • Avoid alcohol
    • Check with healthcare provider before taking any over the counter medication
      • Acetaminophen can further damage their liver
    • Regular screenings for liver cancer
Transcript

Viral hepatitis is the inflammation of the liver caused by hepatitis viruses A, B, C, D, or E. Out of these, chronic hepatitis caused by hepatitis B virus, or HBV, and hepatitis C virus, or HCV, can be treated with antiviral medications.

Now, chronic HBV infection can be treated with a class of antiviral medications called NRTIs, which include nucleotide reverse transcriptase inhibitors like adefovir and tenofovir, as well as nucleoside reverse transcriptase inhibitors like entecavir; these medications are administered orally.

On the other hand, chronic HCV infection can be treated with antiviral medications that target different components of the virus, so they’re typically used in combination; these include nucleotide polymerase inhibitors like sofosbuvir, as well as nucleoside analogues like ribavirin, both of which are taken orally.

Finally, there’s a third class of medications that can be used to treat both chronic HBV and HCV; these include interferons like peginterferon alfa-2a, which is administered by subcutaneous injection.

Now, once administered, all of these antivirals have a different mechanism of action. NRTIs used to treat hepatitis B act by inserting into the replicating viral DNA. As a result, viral DNA synthesis is halted, ultimately stopping viral replication. On the other hand, medications used to treat hepatitis C work in different ways, inhibiting different viral proteins or enzymes required for viral replication. Interferons, on the other hand, induce the innate antiviral immune response that helps kill off cells that are infected by the virus.

Now, clients taking NRTIs for hepatitis B infection can have side effects. All these medications come with a boxed warning for severe, acute hepatitis exacerbations on discontinuation of therapy. These medications also cause lactic acidosis, which is a boxed warning for adefovir and entecavir, as well as severe hepatomegaly with steatosis; and a risk for individuals with concurrent HIV infection, that refers to the risk of developing HIV resistance to these agents. Other common side effects for these medications include hepatotoxicity and increased serum transaminase levels, as well as hematuria. Finally, adefovir can also cause fatigue; headache; muscle weakness; back pain and joint pain; and gastrointestinal toxicity, which can manifest as nausea, abdominal pain, diarrhea or vomiting; while tenofovir may cause nephrotoxicity.

Now let’s switch gears and look at the side effects of medications used to treat hepatitis C. All these medications come with a boxed warning for HBV reactivation in clients with concomitant HBV infections, which can cause potentially life-threatening fulminant hepatitis. Ribavirin also has two more boxed warnings, for use during pregnancy and for an increased risk of causing hemolytic anemia.

Another thing to bear in mind is that hepatitis C medications are usually part of a multi-drug regimen, so common side effects refer to those occurring with combination therapy. These include neurotoxicity, like fatigue, headache, insomnia and dizziness; dermatological reactions, like rashes, pruritus and eczema; as well as flu-like symptoms, myalgia and muscle weakness. Multidrug regimens containing ribavirin can also cause alopecia. Gastrointestinal toxicity is also a common side effect of these medications, and it can manifest as nausea, diarrhea, anorexia and subsequent weight loss.

Finally, let’s go over the side effects of peginterferon alfa 2a. First up, it comes with a boxed warning for aggravating life-threatening neuropsychiatric, autoimmune, infectious and ischemic conditions. Other common side effects include flu-like symptoms, fatigue, fever, myalgia, and headache, as well as injection site reaction; but it can also cause gastrointestinal toxicity, with nausea, vomiting, diarrhea or abdominal pain; and dermatological side effects like rashes, pruritus or alopecia.

As far as contraindications go, NRTIs should be used cautiously during breastfeeding, pregnancy, in children and the elderly, as well as those with severe renal disease. Entecavir in particular should be used with caution in clients with impaired hepatic function. Also remember that all clients with hepatitis B should be tested for an HIV infection before starting treatment with an NRTI.

Medications used to treat hepatitis C should be used cautiously during pregnancy, breastfeeding, and in clients with hepatic disease, renal disease or diabetes. Ribavirin is also contraindicated in clients with autoimmune hepatitis and decompensated cirrhosis. Now, since sofosbuvir is metabolized by cytochrome P450 in the liver, they shouldn’t be used with potent cytochrome inducers like rifampin or St. John’s wort, since they can decrease the medications’ level and effectiveness. Finally, be extra careful when sofosbuvir is used in combination with amiodarone, since the combo could cause severe bradycardia.

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