Acute Porphyria Drug Database

J05AR02 - Lamivudine and Abacavir
Propably not porphyrinogenic
PNP

Side effects
Common adverse reactions of lamivudine and abacavir that can be confused with an acute porphyric attack are nausea, vomiting, abdominal pains and diarrhoea. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
This combination product contains two substances: lamivudine (ATC-code: J05AF05) and abacavir (ATC-code: J05AF06). Neither lamivudine nor abacavir is a substrate, inhibitor or inducer of CYP450 enzymes, and both of them are safety classified as probably not porphyrinogenic. The classification of the combination is therefore safety classified as probably not porphyrinogenic. For more details please refer to the monographs of the two substances.
Chemical description
Lamivudine and abacavir are both nucleoside analogues
Therapeutic characteristics
This combination preparation of the two nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine and abacavir is indicated in antiretroviral combination therapy for the treatment of HIV-1 infection. The combination is administered orally.
Metabolism and pharmacokinetics
The majority of lamivudine is eliminated unchanged through the kidney, and only 5 % is metabolized to trans-sulfoxide (Kumar 2010). Lamivudine is not a substrate, inhibitor or inducer of CYP450 enzymes (Johnson 1999, SPC). Lamivudine is individually classified as probably not porphyrinogenic (see monograph with ATC-code: J05AF05). Abacavir is mainly metabolized in the liver by alcohol dehydrogenase and by glucuronidation (SPC). Abacavir is not metabolized by CYP450 enzymes, and has been shown in vitro not to inhibit or induce CYP3A4, 2C9 and 2D6 (SPC). No drug-drug interactions with abacavir as perpetrator have been reported in the literature (interaktionsdatabasen.dk, Yuen 2008). Abacavir is individually classified as probably not porphyrinogenic (see monograph with ATC-code: J05AF06).

References

  1. Scientific articles
  2. Johnson MA, Moore KH, et al. Clinical pharmacokinetics of lamivudine. Clin Pharmacokinet. 1999 Jan;36(1):41-66. #1809
  3. Kumar PN, Patel P. Lamivudine for the treatment of HIV. Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):105-14. PMID 20001611. #4543
  4. Yuen GJ, Weller S, et al. A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71. #1814
  5. Drug interaction databases
  6. Interaktionsdatabasen. Abacavir. #1812
  7. Summary of Product Characteristics
  8. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Kivexa). #1843

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