The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients

Ashok Kumar B. Jain, Raman Venkataramanan, Ron Shapiro, Velma P. Scantlebury, Santosh Potdar, C. Andrew Bonham, Margaret Ragni, John J. Fung

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Solid organ transplantations have been performed successfully in selected HIV-positive patients with highly active antiretrovirus therapy (HAART). However, some of the medications in the HAART regimen require metabolism via the cytochrome P4503A, the same enzyme complex responsible for clearance of the calcineurin inhibitors cyclosporine and tacrolimus. Several case reports have described significant interactions between the agents used in HAART and immunosuppressive drugs. The goal of this report is to examine the extent of potential drug interactions between antiretroviral agents and tacrolimus after liver and kidney transplantation. Seven liver transplant (LTx) patients (M = 6, F = 1) and four kidney transplant (KTx) patients (M = 4) infected with HIV underwent surgery between September 1997 and January 2001. Initial immunosuppression consisted of tacrolimus and steroids for LTx patients or tacrolimus, steroids, and mycophenolate mofetil for KTx recipients. Their current baseline immunosuppression and HAART regimen were examined retrospectively. Of the seven liver recipients, one (case 4) died 2 weeks after LTx and never received HAART therapy posttransplantation. The remaining six patients were placed on a regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI) (nelfinavir in 5, indinavir in 1) based on known viral sensitivities or history of a previous clinical response. Kidney recipients received NRTI and non-nucleoside reverse transcriptase inhibitors (NNRTI). The mean dose of tacrolimus in liver recipients was 0.6 mg/d, with mean trough concentration of 9.7 mg/mL. Compared with historic controls (liver transplant patients not on HAART), the average tacrolimus dose was 16-fold lower in patients on HAART. In contrast to liver recipients, HIV-positive kidney recipients not on PI therapy required a mean tacrolimus dose of 9.5 mg/d to maintain a mean trough concentration of 9.6 ng/mL. Of the two protease inhibitors used, nelfinavir seems to have a more profound effect than indinavir. When patients on nelfinavir alone (n = 5) were compared with a control group not on antiretroviral therapy, the need for a tacrolimus dose was 38 times lower (mean dose, 0.26 mg/d). Profound drug interactions between PI and tacrolimus have been observed requiring up to 50-fold reductions in dosage. This effect seems to be most pronounced with the use of nelfinavir as opposed to indinavir, although further experience is required to confirm this observation. In contrast, HAART using NRTI and NNRTI without the use of PI, as shown in kidney recipients, produces less significant effects on tacrolimus metabolism. Great caution and frequent drug level monitoring are necessary when HAART is introduced or withdrawn in HIV-positive recipients of organ transplants.

Original languageEnglish (US)
Pages (from-to)841-845
Number of pages5
JournalLiver Transplantation
Volume8
Issue number9
DOIs
StatePublished - Sep 2002

Fingerprint

Anti-Retroviral Agents
Tacrolimus
Transplants
Kidney
Liver
Reverse Transcriptase Inhibitors
Nelfinavir
Protease Inhibitors
Indinavir
Nucleosides
Therapeutics
HIV
Drug Interactions
Immunosuppression
Steroids
Mycophenolic Acid
Drug Monitoring
Organ Transplantation
Cytochromes
Immunosuppressive Agents

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hepatology
  • Transplantation

Cite this

Jain, A. K. B., Venkataramanan, R., Shapiro, R., Scantlebury, V. P., Potdar, S., Bonham, C. A., ... Fung, J. J. (2002). The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients. Liver Transplantation, 8(9), 841-845. https://doi.org/10.1053/jlts.2002.34880
Jain, Ashok Kumar B. ; Venkataramanan, Raman ; Shapiro, Ron ; Scantlebury, Velma P. ; Potdar, Santosh ; Bonham, C. Andrew ; Ragni, Margaret ; Fung, John J. / The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients. In: Liver Transplantation. 2002 ; Vol. 8, No. 9. pp. 841-845.
@article{bc0d3503dbee48d9b00d00b2a4eda694,
title = "The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients",
abstract = "Solid organ transplantations have been performed successfully in selected HIV-positive patients with highly active antiretrovirus therapy (HAART). However, some of the medications in the HAART regimen require metabolism via the cytochrome P4503A, the same enzyme complex responsible for clearance of the calcineurin inhibitors cyclosporine and tacrolimus. Several case reports have described significant interactions between the agents used in HAART and immunosuppressive drugs. The goal of this report is to examine the extent of potential drug interactions between antiretroviral agents and tacrolimus after liver and kidney transplantation. Seven liver transplant (LTx) patients (M = 6, F = 1) and four kidney transplant (KTx) patients (M = 4) infected with HIV underwent surgery between September 1997 and January 2001. Initial immunosuppression consisted of tacrolimus and steroids for LTx patients or tacrolimus, steroids, and mycophenolate mofetil for KTx recipients. Their current baseline immunosuppression and HAART regimen were examined retrospectively. Of the seven liver recipients, one (case 4) died 2 weeks after LTx and never received HAART therapy posttransplantation. The remaining six patients were placed on a regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI) (nelfinavir in 5, indinavir in 1) based on known viral sensitivities or history of a previous clinical response. Kidney recipients received NRTI and non-nucleoside reverse transcriptase inhibitors (NNRTI). The mean dose of tacrolimus in liver recipients was 0.6 mg/d, with mean trough concentration of 9.7 mg/mL. Compared with historic controls (liver transplant patients not on HAART), the average tacrolimus dose was 16-fold lower in patients on HAART. In contrast to liver recipients, HIV-positive kidney recipients not on PI therapy required a mean tacrolimus dose of 9.5 mg/d to maintain a mean trough concentration of 9.6 ng/mL. Of the two protease inhibitors used, nelfinavir seems to have a more profound effect than indinavir. When patients on nelfinavir alone (n = 5) were compared with a control group not on antiretroviral therapy, the need for a tacrolimus dose was 38 times lower (mean dose, 0.26 mg/d). Profound drug interactions between PI and tacrolimus have been observed requiring up to 50-fold reductions in dosage. This effect seems to be most pronounced with the use of nelfinavir as opposed to indinavir, although further experience is required to confirm this observation. In contrast, HAART using NRTI and NNRTI without the use of PI, as shown in kidney recipients, produces less significant effects on tacrolimus metabolism. Great caution and frequent drug level monitoring are necessary when HAART is introduced or withdrawn in HIV-positive recipients of organ transplants.",
author = "Jain, {Ashok Kumar B.} and Raman Venkataramanan and Ron Shapiro and Scantlebury, {Velma P.} and Santosh Potdar and Bonham, {C. Andrew} and Margaret Ragni and Fung, {John J.}",
year = "2002",
month = "9",
doi = "10.1053/jlts.2002.34880",
language = "English (US)",
volume = "8",
pages = "841--845",
journal = "Liver Transplantation",
issn = "1527-6465",
publisher = "John Wiley and Sons Ltd",
number = "9",

}

Jain, AKB, Venkataramanan, R, Shapiro, R, Scantlebury, VP, Potdar, S, Bonham, CA, Ragni, M & Fung, JJ 2002, 'The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients', Liver Transplantation, vol. 8, no. 9, pp. 841-845. https://doi.org/10.1053/jlts.2002.34880

The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients. / Jain, Ashok Kumar B.; Venkataramanan, Raman; Shapiro, Ron; Scantlebury, Velma P.; Potdar, Santosh; Bonham, C. Andrew; Ragni, Margaret; Fung, John J.

In: Liver Transplantation, Vol. 8, No. 9, 09.2002, p. 841-845.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients

AU - Jain, Ashok Kumar B.

AU - Venkataramanan, Raman

AU - Shapiro, Ron

AU - Scantlebury, Velma P.

AU - Potdar, Santosh

AU - Bonham, C. Andrew

AU - Ragni, Margaret

AU - Fung, John J.

PY - 2002/9

Y1 - 2002/9

N2 - Solid organ transplantations have been performed successfully in selected HIV-positive patients with highly active antiretrovirus therapy (HAART). However, some of the medications in the HAART regimen require metabolism via the cytochrome P4503A, the same enzyme complex responsible for clearance of the calcineurin inhibitors cyclosporine and tacrolimus. Several case reports have described significant interactions between the agents used in HAART and immunosuppressive drugs. The goal of this report is to examine the extent of potential drug interactions between antiretroviral agents and tacrolimus after liver and kidney transplantation. Seven liver transplant (LTx) patients (M = 6, F = 1) and four kidney transplant (KTx) patients (M = 4) infected with HIV underwent surgery between September 1997 and January 2001. Initial immunosuppression consisted of tacrolimus and steroids for LTx patients or tacrolimus, steroids, and mycophenolate mofetil for KTx recipients. Their current baseline immunosuppression and HAART regimen were examined retrospectively. Of the seven liver recipients, one (case 4) died 2 weeks after LTx and never received HAART therapy posttransplantation. The remaining six patients were placed on a regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI) (nelfinavir in 5, indinavir in 1) based on known viral sensitivities or history of a previous clinical response. Kidney recipients received NRTI and non-nucleoside reverse transcriptase inhibitors (NNRTI). The mean dose of tacrolimus in liver recipients was 0.6 mg/d, with mean trough concentration of 9.7 mg/mL. Compared with historic controls (liver transplant patients not on HAART), the average tacrolimus dose was 16-fold lower in patients on HAART. In contrast to liver recipients, HIV-positive kidney recipients not on PI therapy required a mean tacrolimus dose of 9.5 mg/d to maintain a mean trough concentration of 9.6 ng/mL. Of the two protease inhibitors used, nelfinavir seems to have a more profound effect than indinavir. When patients on nelfinavir alone (n = 5) were compared with a control group not on antiretroviral therapy, the need for a tacrolimus dose was 38 times lower (mean dose, 0.26 mg/d). Profound drug interactions between PI and tacrolimus have been observed requiring up to 50-fold reductions in dosage. This effect seems to be most pronounced with the use of nelfinavir as opposed to indinavir, although further experience is required to confirm this observation. In contrast, HAART using NRTI and NNRTI without the use of PI, as shown in kidney recipients, produces less significant effects on tacrolimus metabolism. Great caution and frequent drug level monitoring are necessary when HAART is introduced or withdrawn in HIV-positive recipients of organ transplants.

AB - Solid organ transplantations have been performed successfully in selected HIV-positive patients with highly active antiretrovirus therapy (HAART). However, some of the medications in the HAART regimen require metabolism via the cytochrome P4503A, the same enzyme complex responsible for clearance of the calcineurin inhibitors cyclosporine and tacrolimus. Several case reports have described significant interactions between the agents used in HAART and immunosuppressive drugs. The goal of this report is to examine the extent of potential drug interactions between antiretroviral agents and tacrolimus after liver and kidney transplantation. Seven liver transplant (LTx) patients (M = 6, F = 1) and four kidney transplant (KTx) patients (M = 4) infected with HIV underwent surgery between September 1997 and January 2001. Initial immunosuppression consisted of tacrolimus and steroids for LTx patients or tacrolimus, steroids, and mycophenolate mofetil for KTx recipients. Their current baseline immunosuppression and HAART regimen were examined retrospectively. Of the seven liver recipients, one (case 4) died 2 weeks after LTx and never received HAART therapy posttransplantation. The remaining six patients were placed on a regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI) (nelfinavir in 5, indinavir in 1) based on known viral sensitivities or history of a previous clinical response. Kidney recipients received NRTI and non-nucleoside reverse transcriptase inhibitors (NNRTI). The mean dose of tacrolimus in liver recipients was 0.6 mg/d, with mean trough concentration of 9.7 mg/mL. Compared with historic controls (liver transplant patients not on HAART), the average tacrolimus dose was 16-fold lower in patients on HAART. In contrast to liver recipients, HIV-positive kidney recipients not on PI therapy required a mean tacrolimus dose of 9.5 mg/d to maintain a mean trough concentration of 9.6 ng/mL. Of the two protease inhibitors used, nelfinavir seems to have a more profound effect than indinavir. When patients on nelfinavir alone (n = 5) were compared with a control group not on antiretroviral therapy, the need for a tacrolimus dose was 38 times lower (mean dose, 0.26 mg/d). Profound drug interactions between PI and tacrolimus have been observed requiring up to 50-fold reductions in dosage. This effect seems to be most pronounced with the use of nelfinavir as opposed to indinavir, although further experience is required to confirm this observation. In contrast, HAART using NRTI and NNRTI without the use of PI, as shown in kidney recipients, produces less significant effects on tacrolimus metabolism. Great caution and frequent drug level monitoring are necessary when HAART is introduced or withdrawn in HIV-positive recipients of organ transplants.

UR - http://www.scopus.com/inward/record.url?scp=0036712014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036712014&partnerID=8YFLogxK

U2 - 10.1053/jlts.2002.34880

DO - 10.1053/jlts.2002.34880

M3 - Article

C2 - 12200788

AN - SCOPUS:0036712014

VL - 8

SP - 841

EP - 845

JO - Liver Transplantation

JF - Liver Transplantation

SN - 1527-6465

IS - 9

ER -