Dolutegravir: Side effects like nausea and diarrhoea may potentially be porphyrinogenic through reduction in carbohydrate intake.

Lamivudine: Common adverse reactions of lamivudine that can be confused with an acute porphyric attack are nausea, vomiting, abdominal pain and diarrhoea. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake. Abacavir: Common adverse reactions of abacavir that can be confused with an acute porphyric attack are nausea, vomiting and diarrhoea. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake. Dolutegravir: Very common side effects of dolutegravir are nausea and diarrhoea. Other common side effects are vomiting and abdominal pains. These adverse reactions can be confused with an acute porphyric attack and may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.

Lamivudine: Lamivudine is not metabolized by CYP450 enzymes, and is not an inducer or a mechanism-based inhibitor of CYP450 enzymes. No pharmacokinetic porphyrinogenic effects are suspected. Abacavir: Abacavir is not a metabolized by CYP450 enzymes and is not an inducer or a mechanism-based inhibitor of CYP450 enzymes. Dolutegravir: Dolutegravir is not an inducer or an inhibitor of CYP450 enzymes and no pharmacokinetic porphyrinogenic effects are suspected.

Lamivudine: Nucleoside analogue Abacavir: Nucleoside analogue Dolutegravir: Pyridinecarboxylic acid

Lamivudine: Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV-1 and hepatitis B. It is administered orally. Abacavir: Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) indicated in the antiretroviral combination therapy for the treatment of HIV-1 infection in adults, adolescents and children. It is administered orally. Dolutegravir: Dolutegravir is an integrase strand transfer inhibitor (INSTI) indicated in combination with other anti-retroviral medicinal products for the treatment of HIV-1 infection. It is administered orally.

Lamivudine: 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). Abacavir: 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). Dolutegravir: Dolutegravir is mainly metabolized through glucuronidation, with minor contribution from CYP3A4 (SPC). About 50 % of the dose is excreted in unchanged form in feaces and about 30 % is excreted in the urine as glucuronide conjugate. In vitro, dolutegravir is not found to be an inhibitor of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 or 3A4, and is not found to be an inducer of CYP1A2, 2B6 or 3A4 (SPC). Dolutegravir does not alter drug-metabolizing enzymes and there are no CYP-dependent drug-drug interactions with dolutegravir as perpetrator (Kandel 2015). A drug-drug interaction study found that dolutegravir had no effect on the pharmacokinetics of an oral contraceptive containing norgestimate and ethinyl estradiol (Song 2015).