Abstract and Introduction

Abstract

Objective: To evaluate pharmaceutical and pharmacotherapeutic differences in oral opioid modified-release products used in the management of chronic pain.
Data Sources: Searches of MEDLINE (1966-May 2006) and an extensive review of peer reviewed journals were conducted using the key search terms opioid, morphine, hydromorphone, and oxycodone. Supplemental information was gathered through the American Pain Society, and limited but relevant information was obtained from manufacturers' labeling.
Study Selection and Data Extraction: All articles identified from the data sources were evaluated. Information deemed relevant was included for this review if it introduced new or well supported concepts or clarified clinical practice issues.
Data Synthesis: The recognition and treatment of pain has become a major focus of healthcare professionals. The Joint Commission on Accreditation of Healthcare Organizations mandates compliance with recommended standards, outcome measures, and other initiatives. A general review of pain management and pharmacokinetic parameters are included.
Conclusions: Oral modified-release products have enabled patients to better maintain pain control due to convenient dosing intervals and sustained blood concentrations. The differences between available oral modified-release products are half-life, cost, and formulation (excipients and drug-release properties).

Introduction

The recognition and treatment of pain have become a major focus of healthcare professionals. Opioids have become the drugs of choice for the treatment of moderate-to-severe chronic pain.^[1,2] The American Pain Society noted that, in most cases, the preferred route of delivery for opioids is oral administration because of its flexibility, convenience, and ability to maintain relatively steady blood concentrations.^[3] For chronic pain, around-the-clock therapy provides the most effective analgesia and results in the fewest adverse drug effects (ADEs).^[1,2] However, this dosing regimen often requires frequent administration, especially for agents with a short elimination half-life. The inconvenience associated with frequent dosing may be overcome by using modified-release drug products. These formulations may also ensure uninterrupted sleep and allow patients to focus on their daily activities rather than on their pain, which facilitates adherence and optimizes therapy. Therefore, oral modified-release opioid products have become the standard of care for the management of moderate-to-severe chronic pain.^[1,2]

This review focuses on the oral modified-release opioid products currently used to treat moderate-to-severe chronic pain: morphine (Avinza, Kadian, Oramorph, MS Contin) and oxycodone (OxyContin). These products vary in regard to their active ingredient, dosage form, mechanism of drug release, dosing frequency, pharmacokinetic profile, and cost. To effectively manage chronic pain, healthcare providers must have a complete understanding of this class of drug products. Modified-release opioid formulations have also been designed for other forms of administration (eg, transdermal fentanyl), and some oral modified-release opioid products are delivered via alternate routes (eg, rectal administration of MS Contin tablets); however, this review focuses on orally administered products. Palladone (hydromorphone), which was recently withdrawn from the market due to safety concerns, and miscellaneous products in development are included in the discussion.

The delivery systems discussed here have been designated as extended-release, controlled-release, or sustainedrelease. However, these terms do not have specific definitions and have been used inconsistently within other published reports. One needs to examine each product to determine its exact mechanism of drug release. The formulations in this review are generally referred to as modified-release products.