Liverpool HIV Interactions

Potential Interaction

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Multivitamins

Quality of Evidence: Very Low

Summary:

Coadministration with dolutegravir/abacavir/lamivudine has not been studied. No interaction is expected with abacavir or lamivudine. Dolutegravir binds to divalent cations such as magnesium, iron or calcium and forms a complex at the level of the gastro-intestinal tract which results in less dolutegravir being absorbed. Divalent cations can be found in multivitamins. The simultaneous coadministration of a multivitamin preparation decreased dolutegravir AUC by 33%. Triumeq and multivitamins can be taken together with food. If Triumeq is taken in a fasted state, multivitamins should be taken at least 2 hours after or 6 hours before Triumeq.

Description:

When taken with food, Triumeq and supplements or multivitamins containing calcium, iron or magnesium can be taken at the same time. If Triumeq is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Triumeq. Coadministration of multivitamins (containing calcium, iron and magnesium) and dolutegravir decreased dolutegravir AUC, Cmax and C24 by 33%, 35% and 32%, respectively. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir and these supplements during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state.

Triumeq Summary of Product Characteristics, ViiV Healthcare, July 2021.

Coadministration may decrease dolutegravir concentrations. Coadministration of a multivitamin preparation (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 subjects. Dolutegravir Cmax, AUC and Ctrough decreased by 35%, 33% and 32%, respectively. Administer Triumeq 2 hours before or 6 hours after taking medications containing polyvalent cations.

Triumeq US Prescribing Information, ViiV Healthcare, May 2019.

Coadministration of a multivitamin preparation with high metal divalent cation content (One-A-Day, single dose) and dolutegravir (50 mg, single dose) was studied in 16 HIV-negative subjects and was found to decrease dolutegravir AUC, Cmax and Ctrough by 33%, 35% and 32%, respectively.

Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. Patel P, Song, I, Borland J, et al. J Antimicrob Chemother, 2011, 66: 1567-1572.

Potential Interaction

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Ferrous fumarate

Summary:

Coadministration with Triumeq (dolutegravir/abacavir/lamivudine) has not been studied. No interaction is expected with abacavir or lamivudine. Administration of ferrous fumarate (324 mg) simultaneously under fed conditions or 2 hours after dolutegravir had no significant effect on dolutegravir exposure. However, when coadministered simultaneously in the fasted state, dolutegravir AUC and Cmax decreased by 54% and 57%, respectively. Triumeq and supplements containing iron can be taken together with food. If Triumeq is taken in a fasted state, iron supplements should be taken at least 2 hours after or 6 hours before Triumeq.

Description:

When taken with food, Triumeq and supplements or multivitamins containing calcium, iron or magnesium can be taken at the same time. If Triumeq is taken in a fasted state, such supplements should be taken a minimum 2 hours after or 6 hours before the intake of Triumeq. Coadministration of iron supplements and dolutegravir decreased dolutegravir AUC, Cmax and C24 by 54%, 57% and 56%, respectively, due to complex binding to polyvalent ions. The stated reductions in dolutegravir exposure were observed with the intake of dolutegravir and these supplements during fasted conditions. In fed state, the changes in exposure following intake together with calcium or iron supplements were modified by the food effect, resulting in an exposure similar to that obtained with dolutegravir administered in the fasted state.

Triumeq Summary of Product Characteristics, ViiV Healthcare, July 2021.

Coadministration may decrease dolutegravir concentrations. Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=11) decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and 56%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir (n=10) decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. Administer Triumeq 2 hours before or 6 hours after taking supplements containing iron. Alternatively, Triumeq and supplements containing iron can be taken together with food.

Triumeq US Prescribing Information, ViiV Healthcare, May 2019.

Coadministration of ferrous fumarate (324 mg) and dolutegravir (50 mg single dose) was studied under fasted, fed and temporally separated conditions. Simultaneous coadministration to fasting subjects (n=11) decreased dolutegravir Cmax, AUC and Cmin by 57%, 54% and 56%, respectively. Simultaneous coadministration to fed subjects (n=11) increased dolutegravir Cmax by 3%, decreased AUC by 2%, and had no effect on Cmin. Coadministration of ferrous fumarate 2 h after dolutegravir (n=10) decreased dolutegravir Cmax, AUC and Cmin by 1%, 5% and 8%, respectively. Dolutegravir and iron supplements can be co-administered if taken with a meal. Under fasted conditions, dolutegravir should be administered 2 hours before or 6 hours after iron supplements.

Pharmacokinetics of dolutegravir when administered with mineral supplements in healthy adult subjects. Song I, Borland J, Arya N, et al. J Clin Pharmacol. 2015 May;55(5):490-6. doi: 10.1002/jcph.439.

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Rifaximin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Dalteparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged by the kidneys.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Gabapentin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with abacavir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Insulin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linagliptin is mainly eliminated as parent compound in faeces, with metabolism by CYP3A4 representing a minor elimination pathway. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with abacavir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Amlodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolized by CYP3A4. Dolutegravir is not expected to inhibit or induce CYP450 enzymes at clinically relevant concentrations. No interaction is expected with abacavir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Lactulose

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of lactulose to lactic acid occurs via gastro-intestinal microbial flora only.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Senna

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant drug interactions are known.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Folic acid [alone]

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Furosemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). Dolutegravir is not expected to inhibit or induce UGTs at clinically relevant concentrations, or to inhibit OATs. No interaction is expected with abacavir. There is little potential for an interaction with lamivudine as lamivudine is excreted by different renal transporters.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7, whereas dolutegravir is glucuronidated by UGT1A1. No interaction is expected with abacavir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Ramipril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ramipril is hydrolysed to the active metabolite ramiprilat, and is metabolized to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Dolutegravir is not expected to interfere with these metabolic pathways. No interaction is expected with abacavir or lamivudine.

Description:

(See Summary)

No Interaction Expected

Dolutegravir/Abacavir/ Lamivudine (DTG/ABC/3TC)

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (via UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15) and sulfation and, to a lesser extent, by oxidation. Dolutegravir is not expected to inhibit or induce CYP450 or UGT enzymes at clinically relevant concentrations. No interaction is expected with abacavir or lamivudine.

Description:

(See Summary)

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