Monograph

J05AR01 - Zidovudine and Lamivudine

Propably not porphyrinogenic

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 pharmacokinetics

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

#	Citation details	PMID
*	Scientific articles
1.	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3´-amino-3´-deoxythymidine. Eagling VA, Howe JL, et al. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
2.	Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information. Hisaka A, Ohno Y, et al. Pharmacol Ther. 2010 Feb;125(2):230-48.
3.	Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Isoherranen N, Hachad H, et al. Chem Res Toxicol. 2009 Feb;22(2):294-8.
4.	Clinical pharmacokinetics of lamivudine. Johnson MA, Moore KH, et al. Clin Pharmacokinet. 1999 Jan;36(1):41-66.
5.	Kumar PN, Patel P. Lamivudine for the treatment of HIV. Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):105-14.	20001611
6.	Role of human liver P450s and cytochrome b5 in the reductive metabolism of 3´-azido-3´-deoxythymidine (AZT) to 3´-amino-3´-deoxythymidine. Pan-Zhou XR, Cretton-Scott E, et al. Biochem Pharmacol. 1998 Mar 15;55(6):757-66.	9586947
7.	Inhibition and induction of human cytochrome P450 enzymes: current status. Pelkonen O, Turpeinen M, et al. Arch Toxicol. 2008 Oct;82(10):667-715.	18618097
*	Drug interaction databases
8.	Interaktionsdatabasen. Zidovudine.
*	Summary of Product Characteristics
9.	The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Combivir).

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Netherlands

Combivir · Combivir, tabletten 150/300 mg · Zidovudine / Lamivudine · Lamivudine/Zidovudine Aurobindo 150/300 mg, filmomhulde tabletten · Lamivudine/Zidovudine Viatris 150/300 mg, filmomhulde tabletten

Belgium