Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone: A prospective, nonrandomized, crossover study in patients coinfected with hepatitis c and hiv receiving methadone maintenance treatment

Steven Ira Berk, Alain H. Litwin, Julia H. Arnsten, Evelyn Du, Irene Soloway, Marc N. Gourevitch

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Abstract

Background: Hepatitis C virus (HCV) infection is common among methadone-maintained HIV-positive individuals. Pegylated interferon (pegIFN) used in combination with ribavirin is conventional treatment for HCV. However, pegIFN has been associated with adverse effects (AEs) that may simulate opioid withdrawal and be confused with insufficient methadone dosage. Objective: The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients. Methods: This prospective, nonrandomized, crossover study was conducted at the Albert Einstein College of Medicine and Montefiore Medical Center (Bronx, New York). Patients who were aged ≥18 years, coinfected with chronic HCV and HIV, and had been receiving methadone maintenance treatment (dosage, 40-200 mg/d PO) for at least 8 weeks prior to enrollment were eligible. We determined mean methadone Cmax, Tmax, Cn,in, AUC, and oral clearance (CL/F) values over a 24-hour period before (baseline) and after the administration of pegIFN alfa-2b 1.5 μg/kg SC (2 doses given 1 week apart). To determine differences in opiate withdrawal symptoms, one of the primary investigators administered the Subjective Opiate Withdrawal Scale (SOWS) and Objective Opiate Withdrawal Scale (OOWS) at baseline and 7, 14, and 21 days after the administration of the first dose. Study participants underwent weekly clinical evaluation for signs and symptoms of methadone withdrawal and for AEs of pegIFN. Results: Nine patients were included in the study (7 men, 2 women; 7 Hispanic, 2 black; mean [SD] age, 41 [8.3] years; mean [SD] weight, 75.0 [12.3] kg). We did not observe any significant changes from baseline in mean Cmax, Tmax, Cmin, AUC, and CL/F values despite 80% power to detect a 30% change in either direction. Changes from baseline in SOWS and OOWS scores were not statistically significant. The only AEs reported were mild and consistent with those expected after pegIFN alfa-2b administration, such as inflammation at the injection site and mild, brief, flulike symptoms. Conclusion: Based on the results of this small, prospective, nonrandomized study, pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of methadone-maintained persons with HIV and chronic HCV coinfection; methadone dosage adjustments were unlikely to be needed.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalClinical Therapeutics
Volume29
Issue number1
DOIs
StatePublished - Jan 2007

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Methadone
Cross-Over Studies
Hepatitis
Opiate Alkaloids
Pharmacokinetics
Hepacivirus
HIV
Interferons
Therapeutics
Social Adjustment
Chronic Hepatitis C
Opioid Analgesics
Area Under Curve
peginterferon alfa-2b
Substance Withdrawal Syndrome
Ribavirin
Virus Diseases
Coinfection
Hispanic Americans
Signs and Symptoms

Keywords

  • hepatitis C
  • HIV
  • methadone
  • pegylated interferon

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{a7d3c1330a5143648e00b05cf5aca101,
title = "Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone: A prospective, nonrandomized, crossover study in patients coinfected with hepatitis c and hiv receiving methadone maintenance treatment",
abstract = "Background: Hepatitis C virus (HCV) infection is common among methadone-maintained HIV-positive individuals. Pegylated interferon (pegIFN) used in combination with ribavirin is conventional treatment for HCV. However, pegIFN has been associated with adverse effects (AEs) that may simulate opioid withdrawal and be confused with insufficient methadone dosage. Objective: The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients. Methods: This prospective, nonrandomized, crossover study was conducted at the Albert Einstein College of Medicine and Montefiore Medical Center (Bronx, New York). Patients who were aged ≥18 years, coinfected with chronic HCV and HIV, and had been receiving methadone maintenance treatment (dosage, 40-200 mg/d PO) for at least 8 weeks prior to enrollment were eligible. We determined mean methadone Cmax, Tmax, Cn,in, AUC, and oral clearance (CL/F) values over a 24-hour period before (baseline) and after the administration of pegIFN alfa-2b 1.5 μg/kg SC (2 doses given 1 week apart). To determine differences in opiate withdrawal symptoms, one of the primary investigators administered the Subjective Opiate Withdrawal Scale (SOWS) and Objective Opiate Withdrawal Scale (OOWS) at baseline and 7, 14, and 21 days after the administration of the first dose. Study participants underwent weekly clinical evaluation for signs and symptoms of methadone withdrawal and for AEs of pegIFN. Results: Nine patients were included in the study (7 men, 2 women; 7 Hispanic, 2 black; mean [SD] age, 41 [8.3] years; mean [SD] weight, 75.0 [12.3] kg). We did not observe any significant changes from baseline in mean Cmax, Tmax, Cmin, AUC, and CL/F values despite 80{\%} power to detect a 30{\%} change in either direction. Changes from baseline in SOWS and OOWS scores were not statistically significant. The only AEs reported were mild and consistent with those expected after pegIFN alfa-2b administration, such as inflammation at the injection site and mild, brief, flulike symptoms. Conclusion: Based on the results of this small, prospective, nonrandomized study, pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of methadone-maintained persons with HIV and chronic HCV coinfection; methadone dosage adjustments were unlikely to be needed.",
keywords = "hepatitis C, HIV, methadone, pegylated interferon",
author = "Berk, {Steven Ira} and Litwin, {Alain H.} and Arnsten, {Julia H.} and Evelyn Du and Irene Soloway and Gourevitch, {Marc N.}",
year = "2007",
month = "1",
doi = "10.1016/j.clinthera.2007.01.009",
language = "English (US)",
volume = "29",
pages = "131--138",
journal = "Clinical Therapeutics",
issn = "0149-2918",
publisher = "Excerpta Medica",
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}

TY - JOUR

T1 - Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone

T2 - A prospective, nonrandomized, crossover study in patients coinfected with hepatitis c and hiv receiving methadone maintenance treatment

AU - Berk, Steven Ira

AU - Litwin, Alain H.

AU - Arnsten, Julia H.

AU - Du, Evelyn

AU - Soloway, Irene

AU - Gourevitch, Marc N.

PY - 2007/1

Y1 - 2007/1

N2 - Background: Hepatitis C virus (HCV) infection is common among methadone-maintained HIV-positive individuals. Pegylated interferon (pegIFN) used in combination with ribavirin is conventional treatment for HCV. However, pegIFN has been associated with adverse effects (AEs) that may simulate opioid withdrawal and be confused with insufficient methadone dosage. Objective: The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients. Methods: This prospective, nonrandomized, crossover study was conducted at the Albert Einstein College of Medicine and Montefiore Medical Center (Bronx, New York). Patients who were aged ≥18 years, coinfected with chronic HCV and HIV, and had been receiving methadone maintenance treatment (dosage, 40-200 mg/d PO) for at least 8 weeks prior to enrollment were eligible. We determined mean methadone Cmax, Tmax, Cn,in, AUC, and oral clearance (CL/F) values over a 24-hour period before (baseline) and after the administration of pegIFN alfa-2b 1.5 μg/kg SC (2 doses given 1 week apart). To determine differences in opiate withdrawal symptoms, one of the primary investigators administered the Subjective Opiate Withdrawal Scale (SOWS) and Objective Opiate Withdrawal Scale (OOWS) at baseline and 7, 14, and 21 days after the administration of the first dose. Study participants underwent weekly clinical evaluation for signs and symptoms of methadone withdrawal and for AEs of pegIFN. Results: Nine patients were included in the study (7 men, 2 women; 7 Hispanic, 2 black; mean [SD] age, 41 [8.3] years; mean [SD] weight, 75.0 [12.3] kg). We did not observe any significant changes from baseline in mean Cmax, Tmax, Cmin, AUC, and CL/F values despite 80% power to detect a 30% change in either direction. Changes from baseline in SOWS and OOWS scores were not statistically significant. The only AEs reported were mild and consistent with those expected after pegIFN alfa-2b administration, such as inflammation at the injection site and mild, brief, flulike symptoms. Conclusion: Based on the results of this small, prospective, nonrandomized study, pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of methadone-maintained persons with HIV and chronic HCV coinfection; methadone dosage adjustments were unlikely to be needed.

AB - Background: Hepatitis C virus (HCV) infection is common among methadone-maintained HIV-positive individuals. Pegylated interferon (pegIFN) used in combination with ribavirin is conventional treatment for HCV. However, pegIFN has been associated with adverse effects (AEs) that may simulate opioid withdrawal and be confused with insufficient methadone dosage. Objective: The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients. Methods: This prospective, nonrandomized, crossover study was conducted at the Albert Einstein College of Medicine and Montefiore Medical Center (Bronx, New York). Patients who were aged ≥18 years, coinfected with chronic HCV and HIV, and had been receiving methadone maintenance treatment (dosage, 40-200 mg/d PO) for at least 8 weeks prior to enrollment were eligible. We determined mean methadone Cmax, Tmax, Cn,in, AUC, and oral clearance (CL/F) values over a 24-hour period before (baseline) and after the administration of pegIFN alfa-2b 1.5 μg/kg SC (2 doses given 1 week apart). To determine differences in opiate withdrawal symptoms, one of the primary investigators administered the Subjective Opiate Withdrawal Scale (SOWS) and Objective Opiate Withdrawal Scale (OOWS) at baseline and 7, 14, and 21 days after the administration of the first dose. Study participants underwent weekly clinical evaluation for signs and symptoms of methadone withdrawal and for AEs of pegIFN. Results: Nine patients were included in the study (7 men, 2 women; 7 Hispanic, 2 black; mean [SD] age, 41 [8.3] years; mean [SD] weight, 75.0 [12.3] kg). We did not observe any significant changes from baseline in mean Cmax, Tmax, Cmin, AUC, and CL/F values despite 80% power to detect a 30% change in either direction. Changes from baseline in SOWS and OOWS scores were not statistically significant. The only AEs reported were mild and consistent with those expected after pegIFN alfa-2b administration, such as inflammation at the injection site and mild, brief, flulike symptoms. Conclusion: Based on the results of this small, prospective, nonrandomized study, pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of methadone-maintained persons with HIV and chronic HCV coinfection; methadone dosage adjustments were unlikely to be needed.

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KW - HIV

KW - methadone

KW - pegylated interferon

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