J05AR01 - Zidovudine and Lamivudine |
Propably not porphyrinogenic |
PNP |
Important Information
One very common side effect is nausea, and it may potentially be porphyrinogenic through reduction in carbohydrate intake.
Side effects
A very common side effect of zidovudine is nausea. Other common adverse reactions of zidovudine and lamivudine that can be confused with an acute porphyric attack are abdominal pains, vomiting and diarrhoea. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
This combination product contains two substances: zidovudine (ATC-code: J05AF01) and lamivudine (ATC-code: J05AF05). 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 zidovudine are nucleoside analogues
Therapeutic characteristics
This combination preparation of the two nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine and zidovudine is indicated in antiretroviral combination therapy for the treatment of HIV-1. It is administered orally.
Metabolism and pharmakokinetics
Zidovudine is mainly metabolized by glucuronide conjugation to an inactive metabolite (SPC), but several hepatic CYP enzymes are also suspected to be involved in the metabolism (Eagling 1994, Pan-Zhou 1998). Zidovudine is not reported to be a mechanism-based inhibitor or an inducer of CYP enzymes (Hisaka 2010, Isoherranen 2009, Pelkonen 2008), and no drug-drug interactions involving CYP enzymes with zidovudine as a perpetrator has been reported in the literature (SPC, interaktionsdatabasen.dk). Zidovudine is individually classified as probably not porphyrinogenic (see monograph with ATC-code: J05AF01).
Lamivudine is not a substrate, inhibitor or inducer of CYP450 enzymes (Johnson 1999, SPC). The majority of lamivudine is eliminated unchanged through the kidney, and only 5 % is metabolized to trans-sulfoxide (Kumar 2010). Lamivudine is individually classified as probably not porphyrinogenic (see monograph with ATC-code: J05AF05).
References
- Scientific articles
- Eagling VA, Howe JL, et al. The metabolism of zidovudine by human liver microsomes in vitro: formation of 3´-amino-3´-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76. #1803
- Hisaka A, Ohno Y, et al. Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information. Pharmacol Ther. 2010 Feb;125(2):230-48. #1138
- Isoherranen N, Hachad H, et al. Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Chem Res Toxicol. 2009 Feb;22(2):294-8. #1005
- Johnson MA, Moore KH, et al. Clinical pharmacokinetics of lamivudine. Clin Pharmacokinet. 1999 Jan;36(1):41-66. #1809
- Kumar PN, Patel P. Lamivudine for the treatment of HIV. Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):105-14. PMID 20001611. #4543
- Pan-Zhou XR, Cretton-Scott E, et al. Role of human liver P450s and cytochrome b5 in the reductive metabolism of 3´-azido-3´-deoxythymidine (AZT) to 3´-amino-3´-deoxythymidine. Biochem Pharmacol. 1998 Mar 15;55(6):757-66. PMID 9586947. #4541
- Pelkonen O, Turpeinen M, et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol. 2008 Oct;82(10):667-715. PMID 18618097. #4347
- Drug interaction databases
- Interaktionsdatabasen. Zidovudine. #1805
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Combivir). #1842
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