Nucleoside Reverse Transcriptase Inhibitor

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

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II. Indications

  1. Backbone of Anti-Retroviral Therapy (nearly all regimens make use of nRTI agents)

III. Mechanism

  1. Incorporate into DNA of virus
  2. Stops building process
  3. Resulting DNA incomplete, cannot create new virus

IV. Preparations: Most commonly used nRTI agents

  1. Emtricitabine (FTC)
  2. Lamivudine (Epivir, 3TC)
  3. Tenofovir (Viread, TDF or TAF)
  4. Zidovudine (Retrovir, ZDV or AZT)

V. Preparations: Other nRTI agents

  1. Abacavir (Ziagen, ABC)
  2. Didanosine (Videx, ddI)
  3. Stavudine (Zerit, d4T)
  4. Zalcitabine (Hivid, ddC)

VI. Preparations: Combination Nucleotide-Nucleoside Reverse Transcriptase Inhibitor (nRTI)

  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)

VII. Combinations: nRTI agents commonly used together

  1. Stavudine (d4T) and Didanosine (ddI)
    1. Consider with Hydroxyurea 500 bid
  2. Stavudine (d4T) and Lamivudine (3TC)
  3. Zidovudine (AZT) and Didanosine (ddI)
  4. Zidovudine (AZT) and Zalcitabine (ddC)
  5. Zidovudine (AZT) and Lamivudine (3TC)

VIII. 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

IX. 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. Gastrointestinal upset or Diarrhea

X. References

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

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