Nucleoside Reverse Transcriptase Inhibitor

Aka: Nucleoside Reverse Transcriptase Inhibitor, Nucleotide Reverse Transcriptase Inhibitor, nRTI, Double nRTI

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II. Indications

  1. HIV Infection
    1. nRTIs form the backbone of Anti-Retroviral Therapy (nearly all regimens make use of nRTI agents)
  2. Chronic Hepatitis B Infection
    1. Agents include Tenofovir, Lamivudine, Emtricitabine, Adefovir and Entecavir

III. Mechanism

  1. nRTIs are Nucleoside analogs, delivered as prodrugs, and metabolized intracellularly to their active form
  2. nRTIs incorporate into DNA of virus
    1. Block continued reverse transcriptase activity
    2. Block DNA chain continuation and viral replication

IV. Medications: Specific Agents

  1. Most commonly used nRTI agents
    1. Tenofovir (Viread, TDF or TAF)
    2. Emtricitabine (FTC)
    3. Lamivudine (Epivir, 3TC)
    4. Zidovudine (Retrovir, ZDV or AZT)
  2. Other nRTI agents (most have been replaced by other nRTIs in U.S.)
    1. Abacavir (Ziagen, ABC)
    2. Didanosine (Videx, ddI)
    3. Stavudine (Zerit, d4T)
    4. Zalcitabine (Hivid, ddC)

V. Medications Combination Nucleotide-Nucleoside Reverse Transcriptase Inhibitor (nRTI)

  1. Common
    1. Atripla: Efavirenz (EFV), Emtricitabine (FTC) and Tenofovir (TDF)
    2. Combivir: Lamivudine (3TC) and Zidovudine (ZDV)
    3. Epzicom: Abacavir (ABC) and Lamivudine (3TC)
    4. Trizivir: Abacavir (ABC), Lamivudine (3TC), and Zidovudine (ZDV)
    5. Truvada (or Descovy): Emtricitabine (FTC) and Tenofovir (TDF or TAF)
  2. Older nRTI combinations with other nRTIs (largely replaced by newer nRTIs)
    1. Stavudine (d4T) and Didanosine (ddI) and sometimes with Hydroxyurea 500 m g twice daily)
    2. Stavudine (d4T) and Lamivudine (3TC)
    3. Zidovudine (AZT) and Didanosine (ddI)
    4. Zidovudine (AZT) and Zalcitabine (ddC)
    5. Zidovudine (AZT) and Lamivudine (3TC)

VI. Adverse Effects: Most common

  1. Lactic Acidosis (uncommon, but life-threatening)
    1. My present with Fatigue, GI distress, abnormal Liver Function Tests, elevated Lipase
    2. Stop nRTI immediately if Lactic Acidosis >45 mg/dl occurs (switch to nonthymidine nRTI)
  2. Lipodystrophy
    1. See Lipodystrophy
    2. Associated with prolonged nRTI use and more common with Protease Inhibitors
  3. Miscellaneous
    1. Fever
    2. Rash
    3. Gastrointestinal upset (Nausea or Vomiting, Abdominal Pain, Diarrhea)
    4. Fatigue
    5. Shortness of Breath

VII. Adverse Effects: Miscellaneous

  1. See individual agents regarding specific adverse effects
  2. Neuropathy (occurs with 3 D's: DDI, DDC, D4T)
    1. Didanosine (ddI)
    2. Zalcitabine (ddC)
    3. Stavudine (d4T)
  3. Pancreatitis (occurs with 3 D's: DDI, DDC, D4T)
    1. Didanosine (ddI)
    2. Zalcitabine (ddC)
    3. Stavudine (d4T)
  4. Hepatomegaly and Steatosis
    1. (1995) Am J Gastroenterol 90(9):1433-6 [PubMed]
  5. Severe lethal Hypersensitivity Reaction
    1. Abacavir (occurs on rechallenge after reaction)
  6. Bone Marrow suppression (e.g. Neutropenia, Anemia)
    1. Zidovudine

VIII. References

  1. (2009) Treat Guidel Med Lett 7(78): 11-22 [PubMed]

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