Concentrations of ciclosporin, sirolimus (rapamycin) and tacrolimus may be increased when co-administered with Kaletra due to CYP3A inhibition by Kaletra. More frequent therapeutic concentration monitoring is recommended until plasma levels of these products have been stabilised.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Coadministration may result in increased plasma concentrations of tacrolimus and could increase or prolong its therapeutic and adverse events. Therapeutic concentration monitoring is recommended for immunosuppressants when coadministered with Kaletra.
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

The interaction between tacrolimus and antiretroviral therapy (ART) was studied in 7 HIV/HCV coinfected patients who had received liver transplants. Tacrolimus pharmacokinetics were determined at steady state during the post operative period before and after the reintroduction of ART once tacrolimus concentrations and liver function had stabilised. Lopinavir/ritonavir markedly inhibited tacrolimus concentrations. Following the reintroduction of lopinavir/ritonavir, the tacrolimus dose fell by 99% to 0.02-0.25 mg/day (administered as 0.5-1.5 mg once every 7-25 days). Tacrolimus oral clearance decreased from 492 to 5 ml/min. Concentrations of lopinavir were within the ranges published for patients with normal liver function tests.
Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study. Teicher E, Vincent I, Bonhomme-Faivre L, et al. Clin Pharmacokinet, 2007, 46(11): 941-952.

Tacrolimus concentrations were monitored following kidney transplantation in two HIV+ patients receiving LPV/RTV + EFV (Patient X) or LPV/RTV (Patient Y). Tacrolimus target concentrations were defined as 15 20 ng/ml immediately post transplant and then 8-12 ng/ml. Tacrolimus was initiated at doses of 0.5 mg for Patient X and 1 mg for Patient Y. Target concentrations were reached within 2 days for Patient X and 12 h for Patient Y. Patient X had to stop tacrolimus due to high concentrations (62 ng/ml). Tacrolimus half lives were calculated as 5.5 days for Patient X and 8 days for patient Y. After reintroduction of reduced doses of tacrolimus, target concentrations were maintained with doses of 0.5 mg given every 2 days for Patient X and given every 8 days for Patient Y. When given with boosted PIs, the initial dose of tacrolimus is critical, but unpredictable with reduced doses and daily TDM required.
Effect of coadministered boosted protease inhibitors regimen on tacrolimus blood concentration in 3 kidney transplant HIV-infected patients. Barrail-Tran, A et al. 8th International Workshop on Clinical Pharmacology of HIV Therapy, Budapest, April 2007, abstract 58.

Tacrolimus pharmacokinetics were reported in 8 HIV+ patients who received liver transplants for end-stage chronic hepatitis C. Tacrolimus concentrations were determined ~10 days post transplantation (just prior to reintroduction of HAART) and 10 days after the reintroduction of standards doses of HAART (NFV n=2; LPV/RTV n=3; EFV n=2; NRTI n=1). During the post transplantation period, prior to the reintroduction of HAART, tacrolimus oral clearance (CL/F) ranged from 5.3 to 19.4 L/h. A large decrease in tacrolimus CL/F was observed following the reintroduction of LPV/RTV (0.5-0.9 L/h) or with NFV (1.1 and 3.0 L/h). Reintroduction of NRTIs or EFV resulted in little change in tacrolimus pharmacokinetics. Coadministration of tacrolimus with LPV/RTV required dose reduction of tacrolimus to once every 5-10 days to maintain tacrolimus within the target range.
Potent drug interactions between tacrolimus and lopinavir/ritonavir therapy in HIV-infected liver transplant recipients. Taburet AM et al. 6th International Workshop on Clinical Pharmacology of HIV Therapy, Quebec, April 2005, abstract 26.

The management of drug-drug interactions between antiretroviral agents and tacrolimus in 10 HIV patients was reported. Antiretroviral agents were stopped on the day of liver transplantation and reintroduced 10 days later. All patients received tacrolimus and prednisolone as immunosuppressive agents and fluconazole, trimethoprim/sulfamethoxazole, and ganciclovir as primary prophylaxis. Tacrolimus pharmacokinetic parameters were measured 10 days following liver transplantation and 10 days following antiretroviral re-initiation. Tacrolimus target blood concentrations were 8-20 ng/ml from baseline to week 6 and 5-15 ng/ml after week 6; tacrolimus doses were individually adjusted according to the Ctrough measured. Among the patients studied, two were on nelfinavir, three on lopinavir/ritonavir, two on efavirenz and one on three NRTIs. While the NRTIs and efavirenz led to a slight change in tacrolimus pharmacokinetics, nelfinavir and lopinavir/ritonavir caused a large inhibition of tacrolimus metabolism, resulting in an increase in its half-life and a decrease in its clearance. Therefore, tacrolimus plasma concentrations should be monitored and drug dose adjustments performed. No alteration in the antiretroviral pharmacokinetic parameters was observed.
Teicher E, Taburet AM, Vincent I, et al. 12th Conference on Retroviruses and Opportunistic Infections, Boston, February 2005, abstract 662.

Data were reported from three transplant patients where tacrolimus concentrations were profoundly increased following initiation of lopinavir/ritonavir (400/100 mg twice daily). Patient 1 was stable on tacrolimus 5 mg twice daily (Ctrough = 10.6 ng/ml). Lopinavir/ritonavir was started and tacrolimus reduced to 6 mg/day; 2 days later Ctrough had increased to 78.5 ng/ml and tacrolimus was stopped. It was restarted after 21 days and the dose adjusted over two weeks to 0.5 mg/week which gave a Ctrough of 12.0 ng/ml. Patient 2 was stable on tacrolimus 4 mg twice daily (Ctrough 8.2-20.9 ng/ml). Lopinavir/ritonavir was started with a single tacrolimus dose of 2 mg followed by a further 1 mg dose 2 days later. Tacrolimus concentrations were 49 ng/ml (24 h), 20.6 ng/ml (60 h) and 7.2 ng/ml (38 days). Lopinavir/ritonavir was discontinued due to suspected toxicity with recurrent hepatitis C and the patient switched to nelfinavir. Patient 3 was initially stable on tacrolimus 2 mg twice daily (Ctrough 9.5-11.9 ng/ml), but discontinued tacrolimus from weeks 6 to 11 post transplant. Lopinavir/ritonavir was commenced 1 week prior to restarting tacrolimus; tacrolimus doses were adjusted until the patient stablised on 1 mg/week (Ctrough 2.9-5.4 ng/ml).
Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplant patients. Jain AB, Venkataramanan R, Eghtesad B, et al. Liver Transpl, 2003, 9: 954-960.

A case was reported where addition of lopinavir/ritonavir to a patient stable on tacrolimus (5 mg twice daily) resulted in toxic concentrations of tacrolimus three days after initiation of lopinavir/ritonavir. Tacrolimus was stopped until concentrations normalised (15 days) and then restarted at a much lower dose of 0.5 mg once weekly.
Tacrolimus and lopinavir/ritonavir interaction in liver transplantation. Schonder KS, Shullo MA, Okusanya O. Ann Pharmacother, 2003, 37: 1793-1796.