Emtricitabine should not be taken with medicinal products containing lamivudine. There is no clinical experience as yet on the co-administration of cytidine analogues. Consequently, the use of emtricitabine in combination with lamivudine for the treatment of HIV infection cannot be recommended at this time.
Emtriva Summary of Product Characteristics, Gilead Sciences Ltd, April 2019.

Lamivudine should not be administered concomitantly with with other cytidine analogues, such as emtricitabine. 
Epivir Summary of Product Characteristics, ViiV Healthcare UK Ltd, February 2019.

Coadministration of Kaletra and tenofovir (300 mg once daily) increased tenofovir AUC and Cmin by 32% and 51% respectively, but had no effect on Cmax. Higher tenofovir concentrations could potentiate tenofovir associated adverse events, including renal disorders. No dose adjustment necessary.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Coadministration of tenofovir (300 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) to 24 HIV- volunteers resulted in no change in tenofovir Cmax, but increases of 32% and 51% in tenofovir AUC and Cmin respectively. Patients receiving Kaletra and tenofovir should be monitored for adverse reactions associated with tenofovir.
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

When tenofovir disoproxil fumarate (300 mg once daily) was administered with lopinavir/ritonavir (400/100 mg twice daily), there was no significant effect on lopinavir/ritonavir PK parameters. Tenofovir AUC increased by 32%, Cmin increased by 51%, and there was no change in Cmax. No dose adjustment is recommended. The increased exposure of tenofovir could potentiate tenofovir associated adverse events, including renal disorders. A higher risk of renal impairment has been reported in patients receiving tenofovir disoproxil fumarate in combination with a ritonavir or cobicistat boosted protease inhibitor. A close monitoring of renal function is required in these patients. In patients with renal risk factors, the co-administration of tenofovir disoproxil fumarate with a boosted protease inhibitor should be carefully evaluated.
Viread Summary of Product Characteristics, Gilead Sciences Ltd, September 2016.

Coadministration of lopinavir/ritonavir (400/100 mg twice times daily for 14 days) and tenofovir-DF (300 mg once daily) was investigated in 24 healthy volunteers. There was no change in tenofovir Cmax; AUC and Cmin increased by 32% and 51% respectively. There was no change in Cmax, AUC or Cmin for lopinavir or ritonavir. Patients receiving tenofovir-DF concomitantly with lopinavir/ritonavir should be monitored for tenofovir-associated adverse reactions. Tenofovir-DF should be discontinued in patients who develop tenofovir-associated adverse reactions.
Viread Prescribing Information, Gilead Sciences Inc, February 2016.

Plasma concentrations of tenofovir (300 mg once daily) with lopinavir/ritonavir (400/100 mg twice daily, n=14) or nevirapine (400 mg once daily, n=13) were determined in HIV positive patients. Tenofovir AUC, Cmax and Ctrough were 50%, 33% and 72% higher, respectively, in the presence of lopinavir/ritonavir when compared to nevirapine. The authors suggest that observed increase in tenofovir exposure may involve intestinal P-gp inhibition by lopinavir and/or ritonavir.
Pilot pharmacokinetic study of Human Immunodeficiency Virus-infected patients receiving tenofovir disoproxil fumarate (TDF): Investigation of systemic and intracellular interactions between TDF and abacavir, lamivudine, or lopinavir-ritonavir. Pruvost A, Negredo E, Théodoro F, et al. Antimicrob Agents Chemother, 2009, 53(5): 1937-1943.

The pharmacokinetic interaction between tenofovir (300 mg once daily) and lopinavir (400/100 mg twice daily) was determined in 27 HIV-negative subjects. Coadministration of lopinavir/ritonavir increase tenofovir AUC (32%), Cmax (15%) and Cmin (51%). Lopinavir and ritonavir pharmacokinetics were unaffected by tenofovir (n=24). Clinical estimates of renal function were unaffected by administration of tenofovir alone or with lopinavir/ritonavir. The increase in tenofovir exposure is not believed to be clinically relevant based on the safety and efficacy of this combination in HIV-infected patients in long-term controlled clinical trials.
Pharmacokinetics and safety of tenofovir disoproxil fumarate on coadministration with lopinavir/ritonavir. Kearney BP, Mathias A, Mittan A, et al. J Acquir Immune Defic Syndr, 2006, 43: 278-283.

The effect of lopinavir/ritonavir (400/100 mg twice daily) on the renal clearance of tenofovir was investigated in HIV-infected subjects receiving tenofovir (300 mg once daily) alone or in combination with LPV/r. Tenofovir clearance was 16% lower in subjects receiving LPV/r, consistent with a renal interaction between tenofovir and LPV/r. There was no difference in tenofovir-diphosphate concentrations when tenofovir was given alone or in combination.
Effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. Kiser J, et al. 13th Conference on Opportunistic Infections and Retroviruses, Denver, February 2006, abstract 570.

Significant increases in TDF plasma exposure have been reported when coadministered with Kaletra. This study looked at the interaction at the intracellular level by investigating the effect of LPV/RTV (400/100 once daily) on TDF-DP concentrations in HIV+ patients taking TDF (300 mg once daily). There was a trend to higher TDF-DP concentrations when used in combination with LPV/r. However, due to interpatient variability, this did not reach statistical significance. Mean ± SD TDF-DP concentrations were 181.4 ± 80.1 and 280.3 ± 181.8 fmol/106 cells, alone and in combination with LPV/RTV respectively. Since target concentrations have yet to be defined for TDF-DP, the possible consequences of this increase remain unknown.
Possible interaction between tenofovir and boosted lopinavir; analysis at the intracellular level in HIV infected patients. Benech, H et al. 6th International Workshop on Clinical Pharmacology of HIV Therapy, Quebec, April 2005, abstract 34.

The effect of tenofovir on the pharmacokinetics of lopinavir and ritonavir was investigated in 18 treatment experienced HIV+ patients. Lopinavir concentrations decreased in the presence of tenofovir (Cmin from 4.61 to 3.06 µg/ml; Cmax from 10.68 to 9.65 µg/ml). Decreases in ritonavir concentrations were also observed (Cmin from 0.63 to 0.35 µg/ml; Cmax from 1.02 to 0.72 µg/ml). Therapeutic drug monitoring of lopinavir when coadministered with tenofovir may be useful to indicate if individual dose modification of lopinavir and/or ritonavir is required.
Pharmacokinetic drug interaction of lopinavir/ritonavir in combination with tenofovir in experienced HIV+ patients. Breilh D, Rouzes A, Djabarouti S, et al. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, October/November 2004, abstract A-445.

Lopinavir trough concentrations were obtained from 14 HIV+ patients receiving lopinavir with tenofovir and from 15 patients without tenofovir. Lopinavir Ctroughs were 5.6 µg/ml in the tenofovir group and 7.0 µg/ml without tenofovir.
Comparison of lopinavir/r plasma levels with and without tenofovir as part of HAART in HIV-1 infected patients. Scarsi K, Postelnick M, Murphy R. 5th International Workshop on Clinical Pharmacology of HIV Therapy, Rome, April 2004, abstract 26.

Kaletra must not be administered once daily in combination with nevirapine. Coadministration decreased lopinavir AUC, Cmax and Cmin by 27%, 19% and 51% respectively. The Kaletra tablets dosage should be increased to 500/125 mg twice daily when coadministered with nevirapine.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Kaletra ONCE DAILY in combination with nevirapine is not recommended. The dose of Kaletra must be increased when administered in combination with nevirapine.  The recommended dose of Kaletra tablets is 500/125 mg twice daily (such as two 200/50 tablets and one 100/25 tablet). The recommended dose of Kaletra oral solution for adults is 520/130 mg (6.5 mL) twice daily. Coadministration of nevirapine (200 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) to 22 HIV+ subjects resulted in decreases in lopinavir Cmax, AUC and Cmin of 19%, 27% and 51% respectively, when compared to data from 19 subjects receiving lopinavir/ritonavir alone. Coadministration of nevirapine (200 once daily for 14 days, escalating to 200 mg twice daily for 6 days) and lopinavir/ritonavir (400/100 mg for 20 days) to 5 HIV- subjects resulted in increases in nevirapine Cmax, AUC and Cmin of 5%, 8% and 15% respectively, when compared to data from 6 subjects receiving nevirapine alone.
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

Coadministration of nevirapine and lopinavir/ritonavir (400/100 mg twice daily) decreased lopinavir AUC, Cmax and Cmin by 27%, 19% and 46%, respectively. An increase in the dose of lopinavir/ritonavir to 533/133 mg (4 capsules) or 500/125 mg (5 tablets with 100/25 mg each) twice daily with food is recommended in combination with nevirapine. Dose adjustment of nevirapine is not required when co-administered with lopinavir. Coadministration of nevirapine and lopinavir/ritonavir oral solution (300/75 mg/m2) to paediatric patients decreased lopinavir AUC, Cmax and Cmin by 22%, 14% and 55%, respectively. For children, increase of the dose of lopinavir/ritonavir to 300/75 mg/m2 twice daily with food should be considered when used in combination with nevirapine, particularly for children in whom reduced susceptibility to lopinavir/ritonavir is suspected.
Viramune Summary of Product Characteristics, Boehringer Ingelheim Ltd, November 2019.

Coadministration of nevirapine (200 mg once daily for 2 weeks then 200 mg twice daily for 2 weeks) with Kaletra (400/100 mg lopinavir/ritonavir twice daily) in 22 patients was compared to lopinavir/ritonavir alone in 19 patients. Patients taking nevirapine had 27%, 19% and 51% lower lopinavir AUC, Cmax and Cmin, respectively. Coadministration of nevirapine (7 mg/kg or 4 mg/kg twice daily) and lopinavir/ritonavir (300/75 mg/m2 to was studied in 15 pediatric subjects (6 months to 12 years). When compared to data from 12 subjects taking lopinavir/ritonavir alone, nevirapine decreased lopinavir AUC, Cmax and Cmin by 22%, 14% and 55%, respectively. The effect on nevirapine pharmacokinetics was not significant when compared to adult and pediatric historical controls. Dosing in adult patients: A dose adjustment of lopinavir/ritonavir to 500/125 mg tablets twice daily or 533/133 mg (6.5 mL) oral solution twice daily is recommended when used in combination with nevirapine. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine. Dosing in pediatric patients: Please refer to the Kaletra® prescribing information for dosing recommendations based on body surface area and body weight. Neither lopinavir/ritonavir tablets nor oral solution should be administered once daily in combination with nevirapine.
Viramune Prescribing Information, Boehringer Ingelheim Pharmaceuticals Inc, October 2019.

The aim of this study was to assess the influence of nevirapine on lopinavir pharmacokinetics in order to optimise dosing regimens. The study included 15 HIV+ subjects, who received LPV/r (533/133 mg twice daily) and NVP (200 mg once daily for 2 weeks followed by NVP 200 mg twice daily). Steady state pharmacokinetic parameters were measured at week 4 and compared with data from patients (n=23) receiving LPV/r (400/100 mg twice daily) + 2 NRTIs. Following an increase in the LPV/r dosage, the mean ± sd LPV Ctrough was 5240 ± 4029 ng/ml, which was not significantly different from the mean Ctrough for LPV 400/100 mg bid + 2NRTI (4272 ± 3114 ng/ml, P=0.637). No statistically significant difference was observed in the mean AUC for LPV 400/100 mg bid + 2NRTI or with LPV/r 533/133 mg bid + NVP 200 mg bid (82746 ± 41019 vs 100940 ± 48871 ng.h/ml, P=0.3286). The findings suggest that an increase in LPV/r dose to 533/133 mg (4 capsules twice daily) is appropriate when co-administered with NVP. Data is awaited on the new tablet formulation of lopinavir in the presence of nevirapine.
The steady state pharmacokinetics (PK) of lopinavir/ritonavir 533/133 mg bid plus nevirapine (200 mg bid) in adult HIV-1-infected individuals (the NRTI sparing study). Youle M, et al. 16th International AIDS Conference, Toronto, August 2006, abstract TUPE0094.

Coadministration of an NNRTI (n=25; nevirapine n=9, efavirenz n=16) with lopinavir/ritonavir (400/100 mg twice daily) resulted in a 39% decrease in lopinavir Ctrough but no change in Cmax, compared in patients taking lopinavir/ritonavir (400/100 mg twice daily alone n=125). There was no difference in lopinavir Ctrough between patients taking efavirenz and nevirapine. There was no difference in lopinavir Ctrough between patients taking lopinavir (400/100 mg twice daily, n=125) and those taking lopinavir/ritonavir (533/133 mg twice daily, n=32) with an NNRTI (NVP n=3, EFV n=29). There was no statistically significant difference in ritonavir Ctrough or Cmax in patients taking lopinavir/ritonavir 400/100 mg twice daily with or without an NNRTI but patients taking lopinavir ritonavir 533/133 mg twice daily with an NNRTI had higher ritonavir Ctrough and Cmax. The number of patients with lopinavir concentrations below the 3000 ng/ml threshold was higher in those taking lopinavir/ritonavir 400/100 with an NNRTI compared to those without an NNRTI. However, the number of patients with suboptimal levels was comparable between those taking lopinavir/ritonavir 400/100 mg alone to those taking lopinavir/ritonavir 533/133 mg plus an NNRTI. Similar results were observed when a lower threshold (1500 ng/ml) was used.
Therapeutic drug monitoring of lopinavir/ritonavir given alone or with an non-nucleoside reverse transcriptase inhibitor. Solas C, Poizot-Martin I, Drogoul M, et al., Br J Pharmacol, 2003, 57: 436-440.

The coadministration of nevirapine to 2 patients receiving lopinavir/ritonavir resulted in lopinavir Cmin values of 1420 and 5240 ng/ml and Cmax values of 3920 and 12300 ng/ml. Mean lopinavir concentrations in a group of patients (n=4) receiving lopinavir/ritonavir alone were 5690 (1420-11120) ng/ml for Cmin and 12400 (3920-17300) ng/ml for Cmax. Nevirapine concentrations were 769 and 1610 ng/ml for Cmin and 2290 and 2490 ng/ml for Cmax.
Steady state pharmacokinetics of lopinavir in combination with nevirapine or efavirenz. Degen O, Kurowski M, van Lunzen J, et al. 14th International AIDS Conference, Barcelona, July 2002, abstract TuPeB4573.

Five HIV+ patients receiving nevirapine (200 mg bd), amprenavir (600 mg bd) and lopinavir/ritonavir (400/100 mg bd) were studied. Amprenavir concentrations were in the expected ranges (Cmin 560-3090 ng/ml; Cmax 1760-8040 ng/ml; AUC0-12h 13230-75170 ng/ml.h). However, lopinavir concentrations were quite variable (Cmin 620-5980 ng/ml; Cmax 2710-12600 ng/ml; AUC0-12h 998-175140 ng/ml.h) and 40-60% lower than reported by the manufacturer. The combination of amprenavir, lopinavir and nevirapine may result in unpredictable lopinavir concentrations and pharmacological monitoring is advisable in patients treated with such combinations.
Pharmacokinetics of amprenavir and lopinavir in combination with nevirapine in highly pretreated HIV-infected patients. Fatkenheuer G, Romer K, Kamps R, et al. AIDS, 2001, 15:2334-2335.

The influence of antiretroviral medications on the pharmacokinetics of prednisolone (a CYP3A4 substrate) was investigated in three groups of ten HIV-infected subjects receiving either lopinavir/ritonavir or efavirenz or no antiretrovirals. Each subject received a single prednisone dose (20 mg) followed by serial blood sampling for determining prednisolone pharmacokinetics. Prednisolone AUC was 20% lower in the presence of efavirenz than in subjects on no antiretrovirals. Prednisolone AUC was significantly lower in the presence of efavirenz versus lopinavir/ritonavir (GMR=0.60, p=0.01) and was higher in the subjects taking lopinavir/ritonavir than in subjects on no antiretrovirals, but this was not significant (p>0.05). The authors conclude that prednisolone concentrations may fluctuate widely when patients on efavirenz switch to lopinavir/ritonavir or vice versa.
Influence of antiretroviral drugs on the pharmacokinetics of prednisolone in HIV-infected individuals. Busse KH, Formentini E, Alfaro RM, Kovacs JA, Penzak SR. J Acquir Immune Defic Syndr, 2008, 48(5): 561-566.

Efavirenz and Lopinavir/ritonavir/amprenavir

The effect of efavirenz (600 mg once daily) on lopinavir/ritonavir/amprenavir (533/133/750 mg twice daily) was investigated in 19 HIV-infected subjects. Subjects received lopinavir/ritonavir/amprenavir without (n=12) or with efavirenz (n=7). Lopinavir concentrations were similar to historical controls receiving lopinavir/ritonavir 400/100 mg twice daily, while amprenavir concentrations were lower than those measured following the administration of amprenavir/ritonavir or fosamprenavir/ritonavir in the absence of lopinavir, but similar to those observed in a previous pharmacokinetic study which investigated the pharmacokinetics of lopinavir/ritonavir/fosamprenavir 533/133/1400 mg twice daily. At the doses studied in this small pilot study, efavirenz did not seem to have any inducing effect on either lopinavir or amprenavir, since when comparing drug concentrations in the two groups of subjects, no significant different was observed. However, a wider inter-individual variability in both lopinavir and amprenavir concentrations was observed in the efavirenz group.

Abacavir concentrations may be reduced due to increased glucuronidation by lopinavir. The clinical significance of this reduced abacavir concentrations is unknown.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Lopinavir induces glucuronidation and therefore has the potential to reduce abacavir plasma concentrations. The clinical significance of this potential interaction is unknown.
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

Coadministration of tenofovir-DF and raltegravir (400 mg twice daily) increased raltegravir AUC by 49%, Cmax by 64% and Cmin by 3%. Tenofovir AUC decreased by 10%, Cmax by 33% and Cmin by 13%. These findings can be extended to raltegravir 1,200 mg once daily. No dose adjustment required for raltegravir (400 mg twice daily and 1,200 mg once daily) or tenofovir disoproxil fumarate.
Isentress 600 mg Summary of Product Characteristics, Merck Sharp & Dohme Ltd, September 2021.

Coadministration of tenofovir-DF (300 mg once daily) and raltegravir (400 mg twice daily) increased raltegravir Cmax by 64%, AUC by 49% and Cmin by 3% (n=9). In drug interaction studies performed using raltegravir film-coated tablets 400 mg twice daily dose, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of tenofovir (tenofovir Cmax, AUC and C24 decreased by 23%, 10% and 13%; n=9). No dose adjustment is required when raltegravir 400 mg twice daily or 1200 mg once daily is coadministered.
Isentress Prescribing Information, Merck & Co Inc, August 2021.

Coadministration of raltegravir (400 mg twice daily for 4 days) and tenofovir-DF (300 mg once daily for 7 days) alone and in combination for 4 days was studied in HIV- subjects. Pharmacokinetic profiles were also determined in HIV+ patients given raltegravir monotherapy alone or in combination with tenofovir-DF/lamivudine. In healthy volunteers raltegravir AUC and Cmax were modestly increased in the presence of tenofovir-DF (49% and 64%, respectively), while there was no effect of tenofovir-DF on raltegravir Cmin (3% increase). However, there was a modest increase of 42% in Cmin in HIV-infected patients. Raltegravir only had a small effect on tenofovir-DF AUC (10% decrease), Cmax (23% decrease) and Cmin (13% decrease). The authors conclude that coadministration of raltegravir and tenofovir-DF does not change the pharmacokinetics of either drug to a clinically meaningful degree and consequently may be coadministered without dose adjustments.
Lack of a significant interaction between raltegravir and tenofovir. Wenning LA, Friedman EJ, Kost JT, et al. Antimicrob Agents Chemother, 2008, 52(9): 3253-3258.

In drug interaction studies, efavirenz did not have a clinically meaningful effect on the pharmacokinetics of raltegravir 1,200 mg once daily; therefore, other less potent inducers (e.g., nevirapine) may be used with the recommended dose of raltegravir.
Isentress 600 mg Summary of Product Characteristics, Merck Sharp & Dohme Ltd, September 2021.

No clinical data available. Due to the metabolic pathway of raltegravir no interaction is expected. Raltegravir and nevirapine can be co-administered without dose adjustments.
Viramune Summary of Product Characteristics, Boehringer Ingelheim Ltd, November 2019.

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The pharmacokinetics of lamivudine (150 mg twice daily) were determined using non-linear mixed effects modelling on samples from HIV-infected subjects receiving lamivudine alone (n=47) or with nevirapine (200 mg twice daily, n=43). The results of the modelling analysis revealed that nevirapine had no effect on the pharmacokinetics of lamivudine. The pharmacokinetics of nevirapine were consistent with those of several earlier trials.
Pharmacokinetics of nevirapine and lamivudine in patients with HIV-1 infection. Sabo JP et al. AAPS Pharm Sci, 2002, 2: E1.

The effect of sorbitol on the single dose pharmacokinetics of 3TC oral solution was evaluated in 16 HIV-negative subjects. Sorbitol had a dose-dependent effect on 3TC PK with decreases of 28%, 52%, and 55% in Cmax and decreases of 20%, 39%, and 44% in AUC when co-administered with 3.2 g, 10.2 g, and 13.4 g sorbitol, respectively.
Effect of sorbitol on 3TC PK after administration of lamivudine solution in adults. Adkinson KK, McCoig C, Wolstenholm A, et al. CROI 2017, Seattle USA, February 2017, abstract 428.

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Clinical studies have shown that there are no clinically significant interactions between abacavir, zidovudine, and lamivudine. There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when abacavir was combined with tenofovir disoproxil fumarate and lamivudine as a once daily regimen.
Ziagen Summary of Product Characteristics, ViiV Healthcare UK Ltd, December 2018.

Fifteen HIV-infected patients were enrolled in a crossover-designed drug interaction trial evaluating single doses of abacavir (600 mg), lamivudine (150 mg), and zidovudine (300 mg) alone or in combination. Analysis showed no clinically relevant changes in the pharmacokinetics of abacavir with the addition of lamivudine or zidovudine or the combination of lamivudine and zidovudine. Lamivudine exposure (AUC decreased 15%) and zidovudine exposure (AUC increased 10%) did not show clinically relevant changes with concurrent abacavir.
Ziagen Prescribing Information, ViiV Healthcare, June 2019.

There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when lamivudine was combined with tenofovir disoproxil fumarate and abacavir as well as with tenofovir disoproxil fumarate and didanosine as a once daily regimen. Coadministration of sorbitol solution (3.2 g, 10.2 g, 13.4 g) with a single 300 mg dose of lamivudine oral solution resulted in dose-dependent decreases of 14%, 32%, and 36% in lamivudine exposure (AUC) and 28%, 52%, and 55% in the Cmax of lamivudine in adults. When possible, avoid chronic coadministration of Epivir with medicinal products containing sorbitol. Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided.
Epivir Summary of Product Characteristics, ViiV Healthcare UK Ltd, February 2019.

Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine. Lamivudine and sorbitol solutions were coadministered to 16 healthy adult subjects in an open-label, randomized-sequence, 4-period, crossover trial. Each subject received a single 300-mg dose of lamivudine oral solution alone or coadministered with a single dose of 3.2 grams, 10.2 grams, or 13.4 grams of sorbitol in solution. Coadministration of lamivudine with sorbitol resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC(0-24), 14%, 32%, and 36% in the AUC(infinity), and 28%, 52%, and 55% in the Cmax; of lamivudine, respectively.
Epivir US Prescribing Information, ViiV Healthcare, May 2019.

The pharmacokinetics and safety of single doses of abacavir (600 mg), zidovudine (300 mg) and lamivudine (150 mg) were evaluated when given alone or with either or both of the other drugs to 13 HIV-infected subjects. Coadministration of abacavir with lamivudine (with or without zidovudine) decreased lamivudine AUC by ~15%, decreased Cmax by ~ 35% and delayed Tmax by ~1 h. While these changes are statistically significant, they are not considered to be clinically significant. There were no differences in the pharmacokinetics of abacavir when given alone, or with zidovudine or lamivudine, or with both zidovudine and lamivudine.
Single dose pharmacokinetics and safety of abacavir (1592U98), zidovudine, and lamivudine administered alone and in combination in adults with human immunodeficiency virus infection. Wang LH, et al. Antimicrob Agents Chemother, 1999, 43: 1708-1715.

The effect of sorbitol on the single dose pharmacokinetics of 3TC oral solution was evaluated in 16 HIV-negative subjects. Sorbitol had a dose-dependent effect on 3TC PK with decreases of 28%, 52%, and 55% in Cmax and decreases of 20%, 39%, and 44% in AUC when co-administered with 3.2 g, 10.2 g, and 13.4 g sorbitol, respectively.
Effect of sorbitol on 3TC PK after administration of lamivudine solution in adults. Adkinson KK, McCoig C, Wolstenholm A, et al. CROI 2017, Seattle USA, February 2017, abstract 428.

Triple NRTI Therapy
There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when abacavir was combined with tenofovir disoproxil fumarate and lamivudine as a once daily regimen.
Ziagen Summary of Product Characteristics, ViiV Healthcare UK Ltd, December 2018.

Triple NRTI Therapy:
There have been reports of a high rate of virological failure and of emergence of resistance at early stage when tenofovir disoproxil fumarate was combined with lamivudine and abacavir as well as with lamivudine and didanosine as a once daily regimen.
Viread Summary of Product Characteristics, Gilead Sciences Ltd, September 2016.

Coadministration of tenofovir-DF (300 mg once daily) and abacavir (300 mg single dose) was studied in 8 HIV-negative subjects. There was no change in tenofovir pharmacokinetic parameters; abacavir AUC was unaltered and Cmax increased by 12%.
Viread Prescribing Information, Gilead Sciences International Inc, February 2016.

The plasma and intracellular pharmacokinetic interaction between tenofovir and abacavir, lamivudine or lopinavir was investigated in HIV+ subjects receiving TDF + 3TC/LPV (n=7), TDF + 3TC/NVP (n=8), TDF + ABC/LPV (n=7) or TDF + ABC/NVP (n=5). Between group comparisons showed no significant interaction between tenofovir and abacavir or lamivudine.
A pharmacokinetic study in HIV infected patients under tenofovir fumarate: investigation of systemic and intracellular interaction between TDF and abacavir, or lamivudine or lopinavir/ritonavir. Pruvost A, et al. 8th International Workshop on Clinical Pharmacology of HIV Therapy, Budapest, April 2007, abstract 56.

The effect of stopping abacavir on the intracellular pharmacokinetics of tenofovir was studied in 7 HIV-infected subjects initially receiving abacavir and tenofovir with lamivudine or stavudine. Intracellular levels of tenofovir-diphosphate did not demonstrate evidence of substantial changes over time after discontinuation of abacavir. Median TDF-DP concentrations prior to and 1 month after discontinuation were 89.9 and 89.6 fmol/10^6 cells, respectively.
Intracellular pharmacokinetics of tenofovir disphosphate, carbovir triphosphate and lamivudine triphosphate in patients receiving triple-nucleoside regimens. Hawkins T, et al. J Acquir Immune Defic Syndr, 2005, 39: 406-411.

There have been reports of a high rate of virological failure and of emergence of resistance at an early stage when lamivudine was combined with tenofovir disoproxil fumarate and abacavir as well as with tenofovir disoproxil fumarate and didanosine as a once daily regimen.
Epivir Summary of Product Characteristics, ViiV Healthcare UK Ltd, February 2019.

There were no clinically significant pharmacokinetic interactions when tenofovir disoproxil fumarate was coadministered with lamivudine.
Triple NRTI Therapy:
There have been reports of a high rate of virological failure and of emergence of resistance at early stage when tenofovir disoproxil fumarate was combined with lamivudine and abacavir as well as with lamivudine and didanosine as a once daily regimen.
Viread Summary of Product Characteristics, Gilead Sciences Ltd, September 2016.

Coadministration of tenofovir-DF (300 mg once daily) and lamivudine (150 mg twice daily for 7 days) was studied in 15 HIV-negative subjects. There was no change in tenofovir pharmacokinetic parameters. Lamivudine AUC and Cmin were unaltered, and there was a 24% decrease in Cmax.
Viread Prescribing Information, Gilead Sciences International Inc, February 2016.

There are no clinically significant interactions when emtricitabine is co-administered with indinavir, zidovudine, stavudine, famciclovir or tenofovir disoproxil fumarate.
Emtriva Summary of Product Characteristics, Gilead Sciences Ltd, April 2019.

No significant interactions were observed between emtricitabine and tenofovir. Coadministration of emtricitabine (200 mg once daily for 7 days) and tenofovir (300 mg once daily for 7 days) was studied in 17 HIV-negative subjects. There was no change in emtricitabine AUC and Cmax and a 20% increase in Cmin. Tenofovir AUC, Cmax and Cmin were unaltered.
Emtriva Prescribing Information, Gilead Sciences Inc, December 2018.

There were no clinically significant pharmacokinetic interactions when tenofovir disoproxil fumarate was coadministered with emtricitabine.
Viread Summary of Product Characteristics, Gilead Sciences Ltd, September 2016.

Coadministration of tenofovir-DF (300 mg once daily) and emtricitabine (200 mg once daily for 7 days) was studied in 17 HIV-negative subjects. There was no change in tenofovir pharmacokinetic parameters. Emtricitabine AUC and Cmax were unaltered and there was a 20% increase in Cmin.
Viread Prescribing Information, Gilead Sciences International Inc, February 2016.

The steady-state pharmacokinetics of abacavir (600 mg once daily plus two NRTIs – excluding tenofovir ) were investigated when coadministered with raltegravir (400 mg twice daily) to 19 HIV+ subjects in a cross-over study. Abacavir AUC and Cmax increased by 3% and 6% and Cmin decreased by 17% in the presence of raltegravir. Exposure of abacavir’s active intracellular carbovir triphosphate anabolite was decreased, however, the clinical significance of this decrease is unclear.
Pharmacokinetics of abacavir and its anabolite carbovir triphosphate without and with darunavir/ritonavir or raltegravir in HIV-infected subjects. Jackson A, Moyle, G, Dickinson L, et al. Antivir Ther, 2012, 17(1): 19-24.

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