# US 9,872,856 B2 · Systems and methods for treating an opioid-induced adverse pharmacodynamic response

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,872,856 B2
- Document ID: US9872856B2
- Status: Granted
- Kind: B2
- Application number: 14/612,941
- Filed: 2015-02-03
- Published: 2015-08-06
- Granted: 2018-01-23
- Earliest claimed: 2012-04-17
- Assignees: Purdue Pharma L.P.
- Applicants: Purdue Pharma L.P.
- Inventors: Michele Hummel; Donald J. Kyle; Garth Whiteside
- Web page: https://patentgrep.com/patent/US9872856B2

## CPC

- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
- A61K 31/451: having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
- A61K 31/4748: forming part of bridged ring systems (strychnine A61K31/475; morphinan derivatives A61K31/485)
- A61K 38/07: Tetrapeptides
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/06: Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
- A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics
- A61P 1/10: Laxatives
- A61P 1/12: Antidiarrhoeals
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/02: Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/14: Antitussive agents
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/30: for treating abuse or dependence
- A61P 25/36: Opioid-abuse
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 39/00: General protective or antinoxious agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/167: {with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073)}
- A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer}
- A61K 9/7023: {Transdermal patches and similar drug-containing composite devices, e.g. cataplasms (galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006)}
- A61K 31/445: Non condensed piperidines, e.g. piperocaine
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed in certain embodiments is a method of treating or preventing an opioid-induced adverse pharmacodynamic response comprising administering to a patient in need thereof an effective amount of buprenorphine.

## Claims

### Claim 1

A pharmaceutical unit dosage form comprising:
(a) an effective amount of an opioid other than buprenorphine to treat pain;
(b) an effective amount of buprenorphine to prevent or treat an opioid-induced adverse pharmacodynamic response that does not affect the analgesic effectiveness of the opioid; and
(c) a pharmaceutically acceptable excipient;
wherein the dosage form provides a plasma level of buprenorphine of about 1 ng/ml or less after administration to a human patient.

### Claim 2 (depends on 1)

The pharmaceutical unit dosage form of claim 1, wherein the dosage form is a solid dosage form for oral administration.

### Claim 3 (depends on 2)

The pharmaceutical unit dosage form of claim 2, wherein the dosage form is a tablet or capsule.

### Claim 4 (depends on 1)

The pharmaceutical unit dosage form of claim 1, wherein the opioid is selected from the group consisting of oxycodone, morphine, codeine, oxymorphone, fentanyl, hydrocodone, hydromorphone, tramadol and the pharmaceutically acceptable salts thereof.

### Claim 5 (depends on 1)

The pharmaceutical unit dosage form of claim 1, wherein the opioid-induced adverse pharmacodynamic response is selected from the group consisting of bowel dysfunction, nausea, vomiting, somnolence, dizziness, respiratory depression, headache, dry mouth, sedation, sweats, asthenia, hypotension, dysphoria, delirium, miosis, pruritis, urticaria, urinary retention, hyperalgesia, allodynia, physical dependence and tolerance.

### Claim 6 (depends on 1)

The pharmaceutical unit dosage form of claim 1, wherein the opioid-induced adverse pharmacodynamic response is bowel dysfunction or respiratory depression.

### Claim 7 (depends on 1)

The pharmaceutical unit dosage form of claim 1, wherein the dosage form provides a Cmax of buprenorphine of about 0.005 ng/ml to about 1 ng/ml after administration to a human patient.

### Claim 8 (depends on 1)

The pharmaceutical unit dosage form of claim 1, wherein the dosage form provides a Cmax of buprenorphine of about 0.05 ng/ml to about 0.5 ng/ml after administration to a human patient.

### Claim 9 (depends on 1)

The pharmaceutical unit dosage form of claim 1, wherein the dosage form provides a Cmax of buprenorphine of about 0.001 ng/ml to about 0.5 ng/ml after administration to a human patient.

### Claim 10

A kit comprising:
(i) a unit dosage form comprising an opioid other than buprenorphine, in an effective amount to treat pain; and
(ii) a unit dosage form comprising an effective amount of buprenorphine to prevent or treat an opioid-induced adverse pharmacodynamics response that does not affect the analgesic effectiveness of the opioid;
wherein the unit dosage form comprising buprenorphine provides a plasma level of buprenorphine of about 1 ng/ml or less after administration to a human patient.

### Claim 11 (depends on 10)

The kit of claim 10, wherein the unit dosage form comprising buprenorphine is a transdermal patch, and wherein the unit dosage form comprising the opioid is a controlled release oral solid dosage form comprising oxycodone or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 11)

The kit of claim 11, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising oxycodone or pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 3 days.

### Claim 13 (depends on 10)

The kit of claim 10, wherein the unit dosage form comprising buprenorphine is a transdermal patch and wherein the unit dosage form comprising the opioid is a controlled release oral dosage form comprising oxymorphone or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 13)

The kit of claim 13, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising oxymorphone or pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 3 days.

### Claim 15 (depends on 10)

The kit of claim 10, wherein the unit dosage form comprising buprenorphine is a transdermal patch and wherein the unit dosage form comprising the opioid is a controlled release oral solid dosage form comprising hydrocodone or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 15)

The kit of claim 15, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising hydrocodone of a pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 3 days.

### Claim 17 (depends on 10)

The kit of claim 10, wherein the unit dosage form comprising buprenorphine is a transdermal patch, and wherein the unit dosage form comprising the opioid is a controlled release oral solid dosage form comprising hydromorphone or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 17)

The kit of claim 17, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising hydromorphone or a pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 3 days.

### Claim 19 (depends on 10)

The kit of claim 10, wherein the unit dosage form comprising buprenorphine is an oral solid dosage form, and wherein the unit dosage form comprising the opioid is an oral solid dosage form, the opioid selected from the group consisting of oxycodone, morphine, codeine, oxymorphone, fentanyl, hydrocodone, hydromorphone, tramadol and pharmaceutically acceptable salts thereof.

### Claim 20 (depends on 11)

The kit of claim 11, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising oxycodone or pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 7 days.

### Claim 21 (depends on 13)

The kit of claim 13, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising oxymorphone or pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 7 days.

### Claim 22 (depends on 15)

The kit of claim 15, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising hydrocodone or pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 7 days.

### Claim 23 (depends on 17)

The kit of claim 17, wherein the unit dosage form comprising buprenorphine and the unit dosage form comprising hydromorphone or pharmaceutically acceptable salt thereof are in an amount to provide treatment for about 7 days.

### Claim 24 (depends on 10)

The kit of claim 10, wherein the opioid-induced adverse pharmacodynamic response is selected from the group consisting of bowel dysfunction, nausea, vomiting, somnolence, dizziness, respiratory depression, headache, dry mouth, sedation, sweats, asthenia, hypotension, dysphoria, delirium, miosis, pruritis, urticaria, urinary retention, hyperalgesia, allodynia, physical dependence and tolerance.

### Claim 25 (depends on 10)

The kit of claim 10, wherein the opioid-induced adverse pharmacodynamic response is bowel dysfunction or respiratory depression.

### Claim 26 (depends on 10)

The kit of claim 10, wherein the dosage form comprising buprenorphine provides a Cmax of buprenorphine of about 0.005 ng/ml to about 1 ng/ml after administration to a human patient.

### Claim 27 (depends on 10)

The kit of claim 10, wherein the dosage form comprising buprenorphine provides a Cmax of buprenorphine of about 0.05 ng/ml to about 0.5 ng/ml after administration to a human patient.

### Claim 28 (depends on 10)

The kit of claim 10, wherein the dosage form comprising buprenorphine provides a Cmax of buprenorphine of about 0.001 ng/ml to about 0.5 ng/ml after administration to a human patient.