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Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Renal Impairment

Inactive Publication Date: 2008-12-25
ENDO PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008]One aspect of the invention is a method of using oxymorphone in the treatment of pain comprising providing a patient with a therapeutically effective amount of

Problems solved by technology

Pain is the most frequently reported symptom and it is a common clinical problem which confronts the clinician.
Many millions of people in the USA suffer from severe pain that, according to numerous recent reports, is chronically undertreated or inappropriately managed.
Non-compliance results in suboptimal pain control and poor quality of life outcomes.
Unfortunately, evidence from prior clinical trials and clinical experience suggests that the short duration of action of immediate release oxymorphone would necessitate administration every 4-6 hours in order to maintain optimal levels of analgesia in chronic pain.
There are two factors associated with the metabolism of some drugs that may present problems for their use in controlled release systems.
One is the ability of the drug to induce or inhibit enzyme synthesis, which may result in a fluctuating drug blood plasma level with chronic dosing.
Diseases of the kidney can cause impaired kidney function.
Impaired kidney function results in a potential build up of substances that are typically filtered out by the kidneys, such as waste products as well as some drugs.

Method used

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  • Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Renal Impairment
  • Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Renal Impairment
  • Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Renal Impairment

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0069]Two controlled release delivery systems are prepared by dry blending xanthan gum, locust bean gum, calcium sulfate dehydrate, and dextrose in a high speed mixed / granulator for 3 minutes. A slurry is prepared by mixing ethyl cellulose with alcohol. While running choppers / impellers, the slurry is added to the dry blended mixture, and granulated for another 3 minutes. The granulation is then dried to a LOD (loss on drying) of less than about 10% by weight. The granulation is then milled using 20 mesh screen. The relative quantities of the ingredients are listed in the table below.

TABLE 1Controlled Release Delivery SystemFormulation 1Formulation 2Excipient(%)(%)Locust Bean Gum, FCC  25.030.0Xanthan Gum, NF  25.030.0Dextrose, USP  35.040.0Calcium Sulfate Dihydrate, NF  10.00.0Ethylcellulose, NF  5.00.0Alcohol, SD3A (Anhydrous) (10)1(20.0)1Total 100.0100.0

[0070]A series of tablets containing different amounts of oxymorphone hydrochloride were prepared using the controlled release de...

examples 2 , 3 and 4

Examples 2, 3 and 4

[0071]Two batches of 20 mg tablets were prepared as described above, using the controlled release delivery system of Formulation 1. One batch was formulated to provide relatively fast controlled release, the other batch was formulated to provide relatively slow controlled release. Compositions of the tablets are shown in the following table.

TABLE 3Slow and Fast Release CompositionsExample 2Example 3Example 4IngredientsSlow (mg)Fast (mg)Fast (mg)Oxymorphone HCl, USP202020Controlled Release Delivery System360160160Silicified Microcrystalline Cellulose,202020NFSodium stearyl fumarate, NF422Total weight404202202Coating (color or clear)12129

[0072]The tablets of Examples 2, 3, and 4 were tested for in vitro release rate according to USP Procedure Drug Release U.S. Pat. No. 23. Release rate is a critical variable in attempting to control the blood plasma levels of oxymorphone and 6-hydroxyoxymorphone in a patient. Results are shown in the following Table 4.

TABLE 4Release...

example 5

[0138]Study Objectives

[0139]The objective of this study was to determine the effect of renal impairment on the pharmacokinetics and metabolism of oxymorphone following a single oral dose of EN3202 (oxymorphone HCl extended-release) tablets.

[0140]Methods

[0141]Clinical Study Design and Conduct

[0142]This study employed a single-dose, parallel-group study design in 24 subjects with chronic renal insufficiency (8 with mild renal impairment, creatinine clearance=51-80 mL / min; 8 with moderate renal impairment, creatinine clearance

[0143]=30-50 mL / min; and 8 with severe renal impairment, creatinine clearance80 mL / min). Attempts were made to match controls with the renal impaired patients with respect to age, gender, and weight. Each subject received a single 20 mg dose of EN3202 (oxymorphone ER). The oxymorphone ER tablets administered were according to the now-available commercial formula of Opana® 20 mg strength, which also contains the inactive ingredients hypromellose, iron oxide black, ...

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Abstract

The invention pertains to a method of using oxymorphone in the treatment of pain by providing a patient with an oxymorphone dosage form and informing the patient or prescribing physician that the bioavailability of oxymorphone is increased in patients with renal impairment.

Description

BACKGROUND OF THE INVENTION[0001]Pain is the most frequently reported symptom and it is a common clinical problem which confronts the clinician. Many millions of people in the USA suffer from severe pain that, according to numerous recent reports, is chronically undertreated or inappropriately managed. The clinical usefulness of the analgesic properties of opioids has been recognized for centuries, and morphine and its derivatives have been widely employed for analgesia for decades in a variety of clinical pain states.[0002]Oxymorphone HCl (14-hydroxydihydromorphinone hydrochloride) is a semi-synthetic phenanthrene-derivative opioid agonist, widely used in the treatment of acute and chronic pain, with analgesic efficacy comparable to other opioid analgesics. Oxymorphone is currently marketed as an injection (1 mg / ml in 1 ml ampules; 1.5 mg / ml in 1 ml ampules; 1.5 mg / ml in 10 ml multiple dose vials) for intramuscular, subcutaneous, and intravenous administration, and as 5 mg rectal s...

Claims

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Application Information

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IPC IPC(8): A61K31/485A61K9/44A61K9/22
CPCA61K9/2054A61K9/2059A61K31/485A61K47/38A61K47/10A61K47/26A61K47/36A61K47/02A61P13/12A61P25/00
Inventor AHDIEH, HARRY
Owner ENDO PHARMA INC
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