OXYMORPHONE HYDROCHLORIDE- oxymorphone hydrochloride tablet, film coated, extended release

United States - English - NLM (National Library of Medicine)

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Active ingredient:
OXYMORPHONE HYDROCHLORIDE (UNII: 5Y2EI94NBC) (OXYMORPHONE - UNII:9VXA968E0C)
Available from:
Ranbaxy Pharmaceuticals Inc.
INN (International Name):
OXYMORPHONE HYDROCHLORIDE
Composition:
OXYMORPHONE HYDROCHLORIDE 5 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Oxymorphone hydrochloride extended-release tablets are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Limitations of Usage Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve oxymorphone hydrochloride extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Oxymorphone hydrochloride extended-release tablets are not indicated as an as-needed (prn) analgesic. Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with: Clinical Considerations Fetal/neonatal adverse reactions Prolonged use of opioid analgesics during pregnanc
Product summary:
Oxymorphone hydrochloride extended-release tablets are supplied as follows: 5 mg Pink to light pink, round, biconvex film-coated tablets, debossed with ‘RH 29 ’ on one side and plain on the other side. NDC 63304-218-30 Bottles of 30 with child-resistant closure NDC 63304-218-05 Bottles of 500 7.5 mg Gray to light gray, round, biconvex film-coated tablets, debossed with ‘RI 36 ’ on one side and plain on the other side. NDC 63304-219-30 Bottles of 30 with child-resistant closure NDC 63304-219-05 Bottles of 500 10 mg Orange to light orange, round, biconvex film-coated tablets, debossed with ‘RH 30 ’ on one side and plain on the other side. NDC 63304-220-30 Bottles of 30 with child-resistant closure NDC 63304-220-05 Bottles of 500 15 mg White to off-white, round, biconvex film-coated tablets, debossed with ‘RI 37 ’ on one side and plain on the other side. NDC 63304-221-30 Bottles of 30 with child-resistant closure NDC 63304-221-05 Bottles of 500 20 mg Green to light green, round, biconvex film-coated tablets, debossed with ‘RH 31 ’ on one side and plain on the other side. NDC 63304-222-30 Bottles of 30 with child-resistant closure NDC 63304-222-05 Bottles of 500 30 mg Reddish brown, round, biconvex film-coated tablets, debossed with ‘RI 38 ’ on one side and plain on the other side. NDC 63304-223-30 Bottles of 30 with child-resistant closure NDC 63304-223-05 Bottles of 500 40 mg Yellow to light yellow, round, biconvex film-coated tablets, debossed with ‘RH 32 ’ on one side and plain on the other side. NDC 63304-224-30 Bottles of 30 with child-resistant closure NDC 63304-224-05 Bottles of 500 Store at 20° - 25° C (68° - 77° F) [See USP Controlled Room Temperature]. Dispense in tight container as defined in the USP, with a child-resistant closure (as required).
Authorization status:
Abbreviated New Drug Application
Authorization number:
63304-218-05, 63304-218-30, 63304-219-05, 63304-219-30, 63304-220-05, 63304-220-30, 63304-221-05, 63304-221-30, 63304-222-05, 63304-222-30, 63304-223-05, 63304-223-30, 63304-224-05, 63304-224-30

OXYMORPHONE HYDROCHLORIDE- oxymorphone hydrochloride tablet, film coated,

extended release

Ranbaxy Pharmaceuticals Inc.

Reference Label Set Id: 565fd727-e53c-4fd2-b10a-9c98018f1437

----------

MEDICATION GUIDE

OXYMORPHONE HYDROCHLORIDE EXTENDED-RELEASE TABLETS, FOR ORAL USE, CII

Rx only

Oxymorphone hydrochloride extended-release tablets are:

A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain

severe enough to require daily around-the-clock, long-term treatment with an opioid, when other

pain treatments such as non-opioid pain medicines or immediate-release opioid medicines do not

treat your pain well enough or you cannot tolerate them.

A long-acting (extended-release) opioid pain medicine that can put you at risk for overdose and

death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse,

and misuse that can lead to death.

Not for use to treat pain that is not around-the-clock.

Important information about oxymorphone hydrochloride extended-release tablets:

Get emergency help right away if you take too much oxymorphone hydrochloride extended-release

tablets (overdose). When you first start taking oxymorphone hydrochloride extended-release tablets,

when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing

problems that can lead to death may occur.

Taking oxymorphone hydrochloride extended-release tablets with other opioid medicines,

benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can

cause severe drowsiness, decreased awareness, breathing problems, coma, and death.

Never give anyone your oxymorphone hydrochloride extended-release tablets. They could die from

taking it. Store oxymorphone hydrochloride extended-release tablets away from children and in a

safe place to prevent stealing or abuse. Selling or giving away oxymorphone hydrochloride

extended-release tablets is against the law.

Do not take oxymorphone hydrochloride extended-release tablets if you have:

severe asthma, trouble breathing, or other lung problems.

a bowel blockage or have narrowing of the stomach or intestines.

Before taking oxymorphone hydrochloride extended-release tablets, tell your healthcare provider if you

have a history of:

head injury, seizures

liver, kidney, thyroid problems

problems urinating

pancreas or gallbladder problems

abuse of street or prescription drugs, alcohol addiction, or mental health problems.

Tell your healthcare provider if you are:

pregnant or planning to become pregnant. Prolonged use of oxymorphone hydrochloride extended-

release tablets during pregnancy can cause withdrawal symptoms in your newborn baby that could

be life-threatening if not recognized and treated.

breastfeeding. Oxymorphone hydrochloride passes into breast milk and may harm your baby.

taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking

oxymorphone hydrochloride extended-release tablets with certain other medicines can cause serious

side effects.

When taking oxymorphone hydrochloride extended-release tablets:

Do not change your dose. Take oxymorphone hydrochloride extended-release tablets exactly as

prescribed by your healthcare provider.

Take your prescribed dose every 12 hours at the same time every day on an empty stomach, at least

1 hour before or 2 hours after meals. Do not take more than your prescribed dose in 24 hours. If you

miss a dose, take your next dose at your usual time.

Swallow oxymorphone hydrochloride extended-release tablets whole. Do not cut, break, chew,

crush, dissolve, snort, or inject oxymorphone hydrochloride extended-release tablets because this

may cause you to overdose and die.

Call your healthcare provider if the dose you are taking does not control your pain.

Do not stop taking oxymorphone hydrochloride extended-release tablets without talking to your

healthcare provider.

After you stop taking oxymorphone hydrochloride extended-release tablets, flush any unused tablets

down the toilet.

While taking oxymorphone hydrochloride extended-release tablets DO NOT:

Drive or operate heavy machinery, until you know how oxymorphone hydrochloride extended-

release tablets affect you. Oxymorphone hydrochloride extended-release tablets can make you

sleepy, dizzy, or lightheaded.

Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using

products containing alcohol during treatment with oxymorphone hydrochloride extended-release

tablets may cause you to overdose and die.

The possible side effects of oxymorphone hydrochloride extended-release tablets:

constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your

healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue,

throat, or hands, hives, itching, rash, extreme drowsiness, light-headedness when changing

positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental

changes such as confusion.

These are not all the possible side effects of oxymorphone hydrochloride extended-release tablets. Call

your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-

1088. For more information go to dailymed.nlm.nih.gov

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Ranbaxy Pharmaceuticals Inc.

Jacksonville, FL 32257 USA

www.ranbaxyusa.com or call 1-888-726-2299

September 2016 FDA-06

Revised: 9/2016

Document Id: b6f91a0b-ca7e-4af1-8ea6-741af2050314

Set id: e6b1c980-bb0c-4805-8e0d-9f8f8e9bfdde

Version: 6

Effective Time: 20160913

Ranbaxy Pharmaceuticals Inc.

OXYMORPHONE HYDROCHLORIDE- oxymorphone hydrochloride tablet, film coated,

extended release

Ranbaxy Pharmaceuticals Inc.

Reference Label Set Id: 565fd727-e53c-4fd2-b10a-9c98018f1437

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use OXYMORPHONE hydrochloride Extended-

Release Tablets safely and effectively. See full prescribing information for OXYMORPHONE hydrochloride

Extended-Release Tablets.

OXYMORPHONE hydrochloride Extended-Release Tablets, for oral use, CII

Initial U.S. Approval: 1959

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION;

ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and INTERACTION WITH

ALCOHOL

See full prescribing information for complete boxed warning.

RECENT MAJOR CHANGES

Boxed Warning 4/2014

Indications and Usage (1) 4/2014

Dosage and Administration (2) 4/2014

Warnings and Precautions (5) 4/2014

INDICATIONS AND USAGE

Oxymorphone hydrochloride extended-release tablets are an opioid agonist indicated for the management of pain severe

enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are

inadequate. (1) (1)

Limitations of Use (1)

DOSAGE AND ADMINISTRATION

Oxymorphone hydrochloride extended-release tablets expose users to risks of addiction, abuse, and

misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and

monitor regularly for development of these behaviors or conditions. (5.1)

Serious life-threatening or fatal respiratory depression may occur. Monitor closely, especially upon

initiation or following a dose increase. Instruct patients to swallow oxymorphone hydrochloride

extended-release tablets whole to avoid exposure to a potentially fatal dose of oxymorphone. (5.2)

Accidental ingestion of oxymorphone hydrochloride extended-release tablets, especially in children,

can result in fatal overdose of oxymorphone. (5.2)

Prolonged use of oxymorphone hydrochloride extended-release tablets during pregnancy can result

in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and

treated. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of

the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be

available (5.3).

Instruct patients not to consume alcohol or any product containing alcohol while taking

oxymorphone hydrochloride extended-release tablets because co-ingestion can result in fatal

plasma oxymorphone levels. (5.4)

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the

greater risks of overdose and death with extended-release opioid formulations, reserve oxymorphone hydrochloride

extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or

immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient

management of pain. (1)

Oxymorphone hydrochloride extended-release tablets are not indicated as an as-needed (prn) analgesic. (1)

For opioid-naïve and opioid non-tolerant patients, initiate with 5 mg tablets orally every 12 hours. (2.1)

To convert to oxymorphone hydrochloride extended-release tablets from another opioid, use available conversion

factors to obtain estimated dose. (2.1)

DOSAGE FORMS AND STRENGTHS

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

Adverse reactions in ≥ 2% of patients in placebo-controlled trials: nausea, constipation, dizziness, somnolence, vomiting,

pruritus, headache, sweating increased, dry mouth, sedation, diarrhea, insomnia, fatigue, appetite decreased, and

abdominal pain. (6.1) (6)

To report SUSPECTED ADVERSE REACTIONS, contact Ranbaxy Pharmaceuticals Inc. at 1-888-Ranbaxy (726-

2299) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. (6)

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 9/2016

Dose can be increased every 3 to 7 days, using increments of 5 to 10 mg every 12 hours (i.e., 10 to 20 mg per day).

(2.2)

Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating. (2.1)

Do not abruptly discontinue oxymorphone hydrochloride extended-release tablets in a physically dependent patient.

(2.3, 5.15)

Instruct patients to swallow oxymorphone hydrochloride extended-release tablets intact. (2.4)

Reduce the dose of oxymorphone hydrochloride extended-release tablets in patients with mild hepatic impairment

and patients with renal impairment. (2.5, 2.6)

Extended-release tablets: 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg

Significant respiratory depression (4)

Acute or severe bronchial asthma (4)

Known or suspected paralytic ileus (4)

Hypersensitivity to oxymorphone (4)

Moderate or severe hepatic impairment (4)

See Boxed WARNINGS

Interaction with CNS depressants: Concomitant use may cause profound sedation, respiratory depression, and death.

If coadministration is required, consider dose reduction of one or both drugs because of additive pharmacological

effects. (5.4, 7.2)

Elderly, cachectic, and debilitated patients and those with chronic pulmonary disease: Monitor closely because of

increased risk for life-threatening respiratory depression. (5.5, 5.6)

Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions: If symptoms occur, stop administration

immediately, discontinue permanently, and do not rechallenge with any other oxymorphone formulation. (5.7)

Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the

opioid. (5.8)

Hypotensive effect: Monitor during dose initiation and titration. (5.10)

Patients with head injury or increased intracranial pressure: Monitor for sedation and respiratory depression. Avoid

use of oxymorphone hydrochloride extended-release tablets in patients with impaired consciousness or coma

susceptible to intracranial effects of CO retention. (5.11)

Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue oxymorphone hydrochloride

extended-release tablets if serotonin syndrome is suspected. (7.3)

Mixed agonist/antagonist and partial agonist opioid analgesics: Avoid use with oxymorphone hydrochloride extended-

release tablets because they may reduce analgesic effect of oxymorphone hydrochloride extended-release tablets or

precipitate withdrawal symptoms. (7.4)

Pregnancy: Based on animal data, may cause fetal harm. (8.1)

Nursing mothers: Closely monitor infants of nursing women receiving oxymorphone hydrochloride extended-

release tablets. (8.3)

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY

DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL

SYNDROME; and INTERACTION WITH ALCOHOL

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Initial Dosing

2.2 Titration and Maintenance of Therapy

2.3 Discontinuation of Oxymorphone Hydrochloride Extended-Release Tablets

2.4 Administration of Oxymorphone Hydrochloride Extended-Release Tablets

2.5 Patients with Hepatic Impairment

2.6 Patients with Renal Impairment

2.7 Geriatric Patients

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Addiction, Abuse, and Misuse

5.2 Life Threatening Respiratory Depression

5.3 Neonatal Opioid Withdrawal Syndrome

5.4 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

5.5 Use in Elderly, Cachectic, and Debilitated Patients

5.6 Use in Patients with Chronic Pulmonary Disease

5.7 Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions

5.8 Adrenal Insufficiency

5.9 Use in Patients with Hepatic Impairment

5.10 Hypotensive Effect

5.11 Use in Patients with Head Injury or Increased Intracranial Pressure

5.12 Use in Patients with Gastrointestinal Conditions

5.13 Use in Patients with Convulsive or Seizure Disorders

5.14 Avoidance of Withdrawal

5.15 Driving and Operating Machinery

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience

6.2 Post-marketing Experience

7 DRUG INTERACTIONS

7.1 Alcohol

7.2 Benzodiazepines and other Central Nervous System (CNS) Depressants

7.3 Serotonergic Drugs

7.4 Interactions with Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

7.5 Muscle Relaxants

7.6 Cimetidine

7.7 Anticholinergics

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Renal Impairment

8.8 Infertility

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

9.3 Dependence

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING

RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID

WITHDRAWAL SYNDROME; and INTERACTION WITH ALCOHOL

WARNING: RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR

OTHER CNS DEPRESSANTS

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS)

depressants, including alcohol, may result in profound sedation, respiratory depression,

coma, and death [see Warnings and Precautions (5.4), Drug Interactions (7.2)].

Limit dosages and durations to the minimum required.

Addiction, Abuse, and Misuse

Oxymorphone hydrochloride extended-release tablets expose patients and other users

to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and

death. Assess each patient’s risk prior to prescribing oxymorphone hydrochloride

extended-release tablets and monitor all patients regularly for the development of

these behaviors or conditions [see Warnings and Precautions (5.1)].

Life-threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of

oxymorphone hydrochloride extended-release tablets. Monitor for respiratory

depression, especially during initiation of oxymorphone hydrochloride extended-

release tablets or following a dose increase. Instruct patients to swallow oxymorphone

hydrochloride extended-release tablets whole; crushing, chewing, or dissolving

oxymorphone hydrochloride extended-release tablets can cause rapid release and

absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions

(5.2)].

Accidental Ingestion

Accidental ingestion of even one dose of oxymorphone hydrochloride extended-

release tablets, especially by children, can result in a fatal overdose of oxymorphone

[see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of oxymorphone hydrochloride extended-release tablets during

pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-

threatening if not recognized and treated, and requires management according to

protocols developed by neonatology experts. If opioid use is required for a prolonged

period in a pregnant woman, advise the patient of the risk of neonatal opioid

withdrawal syndrome and ensure that appropriate treatment will be available [see

Warnings and Precautions (5.3)].

Interaction with Alcohol

Instruct patients not to consume alcoholic beverages or use prescription or non-

prescription products that contain alcohol while taking oxymorphone hydrochloride

extended-release tablets. The co-ingestion of alcohol with oxymorphone

hydrochloride extended-release tablets may result in increased plasma levels and a

potentially fatal overdose of oxymorphone [see Warnings and Precautions (5.4)].

Reserve concomitant prescribing of oxymorphone hydrochloride extended-release

tablets and benzodiazepines or other CNS depressants for use in patients for whom

alternative treatment options are inadequate.

Follow patients for signs and symptoms of respiratory depression and sedation.

1 INDICATIONS AND USAGE

Oxymorphone hydrochloride extended-release tablets are indicated for the management of pain severe

enough to require daily, around-the-clock, long-term opioid treatment and for which alternative

treatment options are inadequate.

Limitations of Usage

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and

because of the greater risks of overdose and death with extended-release opioid formulations, reserve

oxymorphone hydrochloride extended-release tablets for use in patients for whom alternative treatment

options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or

would be otherwise inadequate to provide sufficient management of pain.

Oxymorphone hydrochloride extended-release tablets are not indicated as an as-needed (prn) analgesic.

2 DOSAGE AND ADMINISTRATION

2.1 Initial Dosing

To avoid medication errors, prescribers and pharmacists must be aware that oxymorphone is available

as both immediate-release 5 mg and 10 mg tablets and extended-release 5 mg and 10 mg tablets [see

Dosage Forms and Strengths].

Oxymorphone hydrochloride extended-release tablets should be prescribed only by healthcare

professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Initiate the dosing regimen for each patient individually, taking into account the patient’s prior analgesic

treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions

(5.1)]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of

initiating therapy with oxymorphone hydrochloride extended-release tablets [see Warnings and

Precautions (5.2)].

Oxymorphone hydrochloride extended-release tablets must be taken whole, one tablet at a time, with

enough water to ensure complete swallowing immediately after placing in the mouth [see Patient

Counseling Information (17)]. Crushing, chewing, or dissolving oxymorphone hydrochloride extended-

release tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or death

[see Warnings and Precautions (5.2)].

Oxymorphone hydrochloride extended-release tablets are administered at a frequency of twice daily

(every 12 hours). Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.

Use of Oxymorphone Hydrochloride Extended-Release Tablets as the First Opioid Analgesic

Initiate treatment with oxymorphone hydrochloride extended-release tablets with the 5 mg tablet orally

every 12-hours.

Use of Oxymorphone Hydrochloride Extended-Release Tablets in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is oxymorphone hydrochloride extended-

release tablets 5 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one

week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral

oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an

equianalgesic dose of another opioid.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory

depression.

Conversion from Oxymorphone Hydrochloride Tablets to Oxymorphone Hydrochloride Extended-Release

Tablets

Patients receiving oxymorphone hydrochloride tablets may be converted to oxymorphone

hydrochloride extended-release tablets by administering half the patient's total daily oral oxymorphone

hydrochloride dose as oxymorphone hydrochloride extended-release tablets, every 12 hours.

Conversion from Parenteral Oxymorphone to Oxymorphone Hydrochloride Extended-Release Tablets

The absolute oral bioavailability of oxymorphone hydrochloride extended-release tablets is

approximately 10%. Convert patients receiving parenteral oxymorphone to oxymorphone hydrochloride

extended-release tablets by administering 10 times the patient's total daily parenteral oxymorphone dose

as oxymorphone hydrochloride extended-release tablets in two equally divided doses (e.g., [IV dose x

10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion

monitor patients closely to evaluate for adequate analgesia and side effects.

Conversion from Other Oral Opioids to Oxymorphone Hydrochloride Extended-Release Tablets

Discontinue all other around-the-clock opioid drugs when oxymorphone hydrochloride extended-

release tablets therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient

variability in the relative potency of different opioid drugs and products. As such, it is preferable to

underestimate a patient’s 24-hour oral oxymorphone hydrochloride extended-release tablets

requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the

24-hour oral oxymorphone hydrochloride extended-release tablets requirements which could result in

adverse reactions. In an oxymorphone clinical trial with an open-label titration period, patients were

converted from their prior opioid to oxymorphone hydrochloride extended-release tablets using Table

1 as a guide for the initial oxymorphone hydrochloride extended-release tablets dose.

Consider the following when using the information in Table 1:

CONVERSION FACTORS TO OXYMORPHONE HYDROCHLORIDE EXTENDED-RELEASE

TABLETS

Prior Oral Opioid

Approximate Oral Conversion Factor

Oxymorphone

Hydrocodone

Oxycodone

Methadone

Morphine

0.333

To calculate the estimated oxymorphone hydrochloride extended-release tablets dose using Table 1:

This is not a table of equianalgesic doses.

The conversion factors in this table are only for the conversion from one of the listed oral opioid

analgesics to oxymorphone hydrochloride extended-release tablets.

This table cannot be used to convert from oxymorphone hydrochloride extended-release tablets

to another opioid. Doing so will result in an over-estimation of the dose of the new opioid and

may result in fatal overdose.

For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the

total daily dose by the conversion factor to calculate the approximate oral (active opioid) daily

dose.

For patients on a regimen of more than one opioid, calculate the approximate oral (active opioid)

dose for each opioid and sum the totals to obtain the approximate total (active opioid) daily dose.

Always round the dose down, if necessary, to the appropriate oxymorphone hydrochloride extended-

release tablets strength(s) available.

Example conversion from a single opioid to oxymorphone hydrochloride extended-release tablets:

Conversion from Methadone to Oxymorphone Hydrochloride Extended-Release Tablets

Close monitoring is of particular importance when converting from methadone to other opioid agonists.

The ratio between methadone and other opioid agonists may vary widely as a function of previous dose

exposure. Methadone has a long half-life and can accumulate in the plasma.

2.2 Titration and Maintenance of Therapy

Individually titrate oxymorphone hydrochloride extended-release tablets to a dose that provides

adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving

oxymorphone hydrochloride extended-release tablets to assess the maintenance of pain control and the

relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse,

and misuse. Frequent communication is important among the prescriber, other members of the healthcare

team, the patient, and the caregiver/family during periods of changing analgesic requirements, including

initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid

analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the

oxymorphone hydrochloride extended-release tablets dose to decrease the level of pain. Because

steady-state plasma concentrations are approximated within 3 days, oxymorphone hydrochloride

extended-release tablets dosage adjustments, preferably at increments of 5 to 10 mg every 12 hours, may

be done every 3 to 7 days.

Patients who experience breakthrough pain may require a dose increase of oxymorphone hydrochloride

extended-release tablets, or may need rescue medication with an appropriate dose of an immediate-

release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of

increased pain before increasing oxymorphone hydrochloride extended-release tablets dose.

If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced.

Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse

reactions.

2.3 Discontinuation of Oxymorphone Hydrochloride Extended-Release Tablets

When a patient no longer requires therapy with oxymorphone hydrochloride extended-release tablets,

use a gradual downward titration of the dose every two to four days, to prevent signs and symptoms of

withdrawal in the physically-dependent patient. Do not abruptly discontinue oxymorphone

hydrochloride extended-release tablets.

For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid

component of these products in the conversion

Step 1: Sum the total daily dose of the opioid oxycodone 20 mg BID 20 mg former opioid 2 times

daily = 40 mg total daily dose of former opioid

Step 2: Calculate the approximate equivalent dose of oral (active opioid) based on the total daily

dose of the current opioid using Table 1 40 mg total daily dose of former opioid x 0.5 mg

Conversion Factor = 20 mg of oral (active opioid) daily

Step 3: Calculate the approximate starting dose of oxymorphone hydrochloride extended-release

tablets to be given every 12 hours. Round down, if necessary, to the appropriate oxymorphone

hydrochloride extended-release tablets strengths available. 10 mg oxymorphone hydrochloride

extended-release tablets every 12 hours

2.4 Administration of Oxymorphone Hydrochloride Extended-Release Tablets

Instruct patients to swallow oxymorphone hydrochloride extended-release tablets intact. The tablets are

not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially

fatal dose of oxymorphone [see Warnings and Precautions (5.2)]. Administer on an empty stomach, at

least 1 hour prior to or 2 hours after eating.

2.5 Patients with Hepatic Impairment

Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with moderate or

severe hepatic impairment.

In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose. For patients

on prior opioid therapy, start oxymorphone hydrochloride extended-release tablets at 50% lower than

the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly. Monitor

patients closely for signs of respiratory or central nervous system depression [see Warnings and

Precautions (5.2), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.6 Patients with Renal Impairment

In patients with creatinine clearance rates less than 50 mL/min, start oxymorphone hydrochloride

extended-release tablets in the opioid-naïve patient with the 5 mg dose. For patients on prior opioid

therapy, start oxymorphone hydrochloride extended-release tablets at 50% lower than the starting dose

for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients closely for

signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in

Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.7 Geriatric Patients

The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly

subjects than in young subjects. Initiate dosing with oxymorphone hydrochloride extended-release

tablets in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of

respiratory and central nervous system depression when initiating and titrating oxymorphone

hydrochloride extended-release tablets to adequate analgesia [see Warnings and Precautions (5.2), Use

in Specific Populations (8.5) and Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start

oxymorphone hydrochloride extended-release tablets at 50% lower than the starting dose for a younger

patient on prior opioids and titrate slowly.

3 DOSAGE FORMS AND STRENGTHS

The 5 mg dosage form is pink to light pink, round, biconvex film-coated tablet, debossed with ‘RH 29

on one side and plain on the other side.

The 7.5 mg dosage form is gray to light gray, round, biconvex film-coated tablet, debossed with ‘RI

36’ on one side and plain on the other side.

The 10 mg dosage form is orange to light orange, round, biconvex film-coated tablet, debossed with

RH 30’ on one side and plain on the other side.

The 15 mg dosage form is white to off-white, round, biconvex film-coated tablet, debossed with ‘RI

37’ on one side and plain on the other side.

The 20 mg dosage form is green to light green, round, biconvex film-coated tablet, debossed with ‘RH

31’ on one side and plain on the other side.

The 30 mg dosage form is reddish brown, round, biconvex film-coated tablet, debossed with ‘RI 38

on one side and plain on the other side.

The 40 mg dosage form is yellow to light yellow, round, biconvex film-coated tablet, debossed with

RH 32’ on one side and plain on the other side.

4 CONTRAINDICATIONS

Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with:

5 WARNINGS AND PRECAUTIONS

5.1 Addiction, Abuse, and Misuse

Oxymorphone hydrochloride extended-release tablets contain oxymorphone, a Schedule II controlled

substance. As an opioid, oxymorphone hydrochloride extended-release tablets expose users to the risks

of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)]. As modified-release products

such as oxymorphone hydrochloride extended-release tablets deliver the opioid over an extended

period of time, there is a greater risk for overdose and death due to the larger amount of oxymorphone

present.

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately

prescribed oxymorphone hydrochloride extended-release tablets and in those who obtain the drug

illicitly. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient’s risk for opioid abuse or addiction, abuse, or misuse prior to prescribing

oxymorphone hydrochloride extended-release tablets and monitor all patients receiving oxymorphone

hydrochloride extended-release tablets for the development of these behaviors or conditions. Risks are

increased in patients with a personal or family history of substance abuse (including drug or alcohol

addiction or abuse) or mental illness (e.g., major depression). The potential for these risks should not,

however, prevent the prescribing of oxymorphone hydrochloride extended-release tablets for the

proper management of pain in any given patient. Patients at increased risk may be prescribed modified-

release opioid formulations such as oxymorphone hydrochloride extended-release tablets, but use in

such patients necessitates intensive counseling about the risks and proper use of oxymorphone

hydrochloride extended-release tablets along with intensive monitoring for signs of addiction, abuse,

and misuse.

Abuse, or misuse of oxymorphone hydrochloride extended-release tablets by crushing, chewing,

snorting, or injecting the dissolved product will result in the uncontrolled delivery of the oxymorphone

and can result in overdose and death [see Overdosage (10)].

Opioid agonists such as oxymorphone hydrochloride extended-release tablets are sought by drug

abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks

when prescribing or dispensing oxymorphone hydrochloride extended-release tablets. Strategies to

reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the

patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local

state professional licensing board or state controlled substances authority for information on how to

prevent and detect abuse or diversion of this product.

5.2 Life Threatening Respiratory Depression

Significant respiratory depression

Acute or severe bronchial asthma or hypercarbia

Known or suspected paralytic ileus

Moderate and severe hepatic impairment [see Clinical Pharmacology (12.3), Warnings and

Precautions (5.9)].

Hypersensitivity (e.g. anaphylaxis) to oxymorphone, any other ingredients in oxymorphone

hydrochloride extended-release tablets, or to morphine analogs such as codeine [see Adverse

Reactions (6.1)].

Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified-

release opioids, even when used as recommended. Respiratory depression from opioid use, if not

immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory

depression may include close observation, supportive measures, and use of opioid antagonists,

depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO ) retention from

opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of

oxymorphone hydrochloride extended-release tablets, the risk is greatest during the initiation of therapy

or following a dose increase. Closely monitor patients for respiratory depression when initiating

therapy with oxymorphone hydrochloride extended-release tablets and following dose increases.

To reduce the risk of respiratory depression, proper dosing and titration of oxymorphone

hydrochloride extended-release tablets are essential [see Dosage and Administration (2.1, 2.2)].

Overestimating the oxymorphone hydrochloride extended-release tablets dose when converting patients

from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of oxymorphone hydrochloride extended-release tablets dose,

especially by children, can result in respiratory depression and death due to an overdose of

oxymorphone.

5.3 Neonatal Opioid Withdrawal Syndrome

Prolonged use of oxymorphone hydrochloride extended-release tablets during pregnancy can result in

withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal

syndrome in adults, may be life-threatening if not recognized and treated, and requires management

according to protocols developed by neonatology experts. If opioid use is required for a prolonged

period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and

ensure that appropriate treatment will be available.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern,

high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity

of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing

and amount of last maternal use, and rate of elimination of the drug by the newborn.

5.4 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of

oxymorphone hydrochloride with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine

sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics,

other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use

in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines

increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of

similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of

other CNS depressant drugs with opioid analgesics [see Drug Interactions (7)].

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an

opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In

patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or

other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response.

If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant,

prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow

patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when

oxymorphone hydrochloride is used with benzodiazepines or other CNS depressants (including alcohol

and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of

concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients

for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for

overdose and death associated with the use of additional CNS depressants including alcohol and illicit

drugs [see Drug Interactions (7) and Patient Counseling Information (17)].

5.5 Use in Elderly, Cachectic, and Debilitated Patients

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated

patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier

patients. Monitor such patients closely, particularly when initiating and titrating oxymorphone

hydrochloride extended-release tablets and when oxymorphone hydrochloride extended-release tablets

are given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.2)].

5.6 Use in Patients with Chronic Pulmonary Disease

Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients

having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory

depression for respiratory depression, particularly when initiating therapy and titrating with

oxymorphone hydrochloride extended-release tablets, as in these patients, even usual therapeutic doses

of oxymorphone hydrochloride extended-release tablets may decrease respiratory drive to the point of

apnea [see Warnings and Precautions (5.2)]. Consider the use of alternative non-opioid analgesics in

these patients if possible.

5.7 Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions

Potentially life-threatening hypersensitivity reactions, including anaphylaxis and angioedema, have

occurred in patients treated with oxymorphone hydrochloride extended-release tablets in the postmarket

setting. The most commonly described clinical features in these reports were swelling of the face,

eyes, mouth, lips, tongue, hands, and/or throat; dyspnea; hives, pruritus, and/or rash; and nausea/vomiting.

If anaphylaxis or other hypersensitivity occurs, stop administration of oxymorphone hydrochloride

extended-release tablets immediately, discontinue oxymorphone hydrochloride extended-release tablets

permanently, and do not rechallenge with any formulation of oxymorphone. Advise patients to seek

immediate medical attention if they experience any symptoms of a hypersensitivity reaction [see Patient

Counseling Information (17)].

5.8 Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than

one 1 month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs

including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal

insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal

insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the

patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until

adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid

without recurrence of adrenal insufficiency. The information available does not identify any particular

opioids as being more likely to be associated with adrenal insufficiency.

5.9 Use in Patients with Hepatic Impairment

A study of oxymorphone hydrochloride extended-release tablets in patients with hepatic disease

indicated greater plasma concentrations than those with normal hepatic function [see Clinical

Pharmacology (12.3)]. Oxymorphone hydrochloride extended-release tablets are contraindicated in

patients with moderate or severe hepatic impairment. In patients with mild hepatic impairment reduce the

starting dose to the lowest dose and monitor for signs of respiratory and central nervous system

depression [see Dosage and Administration (2.5)].

5.10 Hypotensive Effect

Oxymorphone hydrochloride extended-release tablets may cause severe hypotension including

orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose

ability to maintain blood pressure has already been compromised by a reduced blood volume or

concurrent administration of certain CNS depressant drugs (e.g. phenothiazines or general anesthetics)

[see Drug Interactions (7.2)]. Monitor these patients for signs of hypotension after initiating or titrating

the dose of oxymorphone hydrochloride extended-release tablets. In patients with circulatory shock,

oxymorphone hydrochloride extended-release tablets may cause vasodilation that can further reduce

cardiac output and blood pressure. Avoid the use of oxymorphone hydrochloride extended-release

tablets in patients with circulatory shock.

5.11 Use in Patients with Head Injury or Increased Intracranial Pressure

Monitor patients taking oxymorphone hydrochloride extended-release tablets who may be susceptible to

the intracranial effects of CO retention (e.g., those with evidence of increased intracranial pressure or

brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with

oxymorphone hydrochloride extended-release tablets. Oxymorphone hydrochloride extended-release

tablets may reduce respiratory drive, and the resultant CO retention can further increase intracranial

pressure. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of

oxymorphone hydrochloride extended-release tablets in patients with impaired consciousness or coma.

5.12 Use in Patients with Gastrointestinal Conditions

Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with paralytic

ileus. Avoid the use of oxymorphone hydrochloride extended-release tablets in patients with other GI

obstruction.

The oxymorphone in oxymorphone hydrochloride extended-release tablets may cause spasm of the

sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for

worsening symptoms. Opioids may cause increases in the serum amylase.

5.13 Use in Patients with Convulsive or Seizure Disorders

The oxymorphone in oxymorphone hydrochloride extended-release tablets may aggravate convulsions

in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings.

Monitor patients with a history of seizure disorders for worsened seizure control during oxymorphone

hydrochloride extended-release tablets therapy.

5.14 Avoidance of Withdrawal

Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) and partial

agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy

with an opioid agonist analgesic, including oxymorphone hydrochloride extended-release tablets. In

these patients, mixed agonists/antagonist and partial agonist analgesics may reduce the analgesic effect

and/or may precipitate withdrawal symptoms.

When discontinuing oxymorphone hydrochloride extended-release tablets, gradually taper the dose [see

Dosage and Administration (2.3)]. Do not abruptly discontinue oxymorphone hydrochloride extended-

release tablets.

5.15 Driving and Operating Machinery

Oxymorphone hydrochloride extended-release tablets may impair the mental or physical abilities

needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn

patients not to drive or operate dangerous machinery unless they are tolerant to the effects of

oxymorphone hydrochloride extended-release tablets and know how they will react to the medication.

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed elsewhere in the labeling:

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in clinical practice.

The safety of oxymorphone hydrochloride extended-release tablets was evaluated in a total of 2011

patients in open-label and controlled clinical trials. The clinical trials enrolled of patients with moderate

to severe chronic non-malignant pain, cancer pain, and post surgical pain. The most common serious

adverse events reported with administration of oxymorphone hydrochloride extended-release tablets

were chest pain, pneumonia and vomiting.

Tables 1 and 2 list the most frequently occurring adverse reactions (in at least 5% of patients) from the

placebo-controlled trials in patients with low back pain.

Table 1: Treatment-Emergent Adverse Reactions Reported in ≥ 5% of Patients During the

Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term —Number

(%) of Treated Patients (12-Week Study In Opioid-Naïve Patients with Low Back Pain)

Open-Label Titration Period

Double-Blind Treatment Period

Oxymorphone Hydrochloride

Extended-Release Tablets

Oxymorphone Hydrochloride

Extended-Release Tablets

Placebo

Preferred Term

(N = 325)

(N = 105)

(N = 100)

Constipation

Somnolence

Nausea

Dizziness

Headache

Pruritus

Table 2. Treatment-Emergent Adverse Reactions Reported in ≥ 5% of Patients During the

Open-Label Titration Period and Double-Blind Treatment Period by Preferred Term —Number

(%) of Treated Patients (12-Week Study In Opioid-Experienced Patients with Low Back Pain)

Open-Label Titration Period

Double-Blind Treatment Period

Oxymorphone Hydrochloride

Extended-Release Tablets

Oxymorphone Hydrochloride

Extended-Release Tablets

Placebo

Preferred Term

(N = 250)

(N = 70)

(N = 72)

Nausea

Addicition, Abuse, and Misuse [see Warnings and Precautions (5.1)]

Life Threatening Respiratory Depression [see Warnings and Precautions (5.2)]

Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)]

Interactions with Other CNS Depressants [see Warnings and Precautions (5.4)]

Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions [see Warnings and Precautions

(5.7)]

Adrenal Insufficiency [see Warnings and Precautions (5.8)]

Hypotensive Effect [see Warnings and Precautions (5.10)]

Gastrointestinal Effects [see Warnings and Precautions (5.12)]

Seizures [see Warnings and Precautions (5.13)]

Constipation

Headache

Somnolence

Vomiting

Pruritus

Dizziness

The following table lists adverse reactions that were reported in at least 2% of patients in placebo-

controlled trials (N = 5).

Table 3: Adverse Reactions Reported in Placebo-Controlled Clinical Trials with Incidence ≥ 2%

in Patients Receiving Oxymorphone Hydrochloride Extended-Release Tablets.

MedDRA Preferred

Term

Oxymorphone Hydrochloride Extended-Release

Tablets (N = 1259)

Placebo (N =

461)

Nausea

Constipation

Dizziness (Excl Vertigo)

Somnolence

Vomiting

Pruritus

Headache

Sweating increased

Dry mouth

< 1%

Sedation

Diarrhea

Insomnia

Fatigue

Appetite decreased

< 1%

Abdominal pain

The common (≥ 1% to < 10%) adverse drug reactions reported at least once by patients treated with

oxymorphone hydrochloride extended-release tablets in the clinical trials organized by MedDRA’s

(Medical Dictionary for Regulatory Activities) System Organ Class and not represented in Table 1

were:

Eye disorders: vision blurred

Gastrointestinal disorders: diarrhea, abdominal pain, dyspepsia

General disorders and administration site conditions: dry mouth, appetite decreased, fatigue, lethargy,

weakness, pyrexia, dehydration, weight decreased, edema

Nervous system disorders: insomnia

Psychiatric disorders: anxiety, confusion, disorientation, restlessness, nervousness, depression

Respiratory, thoracic and mediastinal disorders: dyspnea

Vascular disorders: flushing and hypertension

Other less common adverse reactions known with opioid treatment that were seen < 1% in the

oxymorphone hydrochloride extended-release tablets trials include the following: Bradycardia,

palpitation, syncope, tachycardia, postural hypotension, miosis, abdominal distention, ileus, hot flashes,

allergic reactions, hypersensitivity, urticaria, oxygen saturation decreased, central nervous system

depression, depressed level of consciousness, agitation, dysphoria, euphoric mood, hallucination,

mental status changes, difficult micturition, urinary retention, hypoxia, respiratory depression,

respiratory distress, clamminess, dermatitis, hypotension.

6.2 Post-marketing Experience

The following adverse reactions have been identified during post approval use of oxymorphone

hydrochloride extended-release tablets. Because these reactions are reported voluntarily from a

population of uncertain size, it is not always possible to reliably estimate their frequency or establish a

causal relationship to drug exposure.

Nervous system disorder: amnesia, convulsion, memory impairment

Serotonin syndrome, adrenal insufficiency

Anaphylaxis, angioedema, and other hypersensitivity reactions

Androgen deficiency: Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis,

leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction,

amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is

unknown because the various medical, physical, lifestyle, and psychological stressors that may

influence gonadal hormone levels have not been adequately controlled for in studies conducted to date.

Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.

7 DRUG INTERACTIONS

7.1 Alcohol

Concomitant use of alcohol with oxymorphone hydrochloride extended-release tablets can result in an

increase of oxymorphone plasma levels and potentially fatal overdose of oxymorphone. Instruct patients

not to consume alcoholic beverages or use prescription or non-prescription products containing

alcohol while on oxymorphone hydrochloride extended-release tablets therapy [see Clinical

Pharmacology (12.3)].

7.2 Benzodiazepines and other Central Nervous System (CNS) Depressants

Clinical

Impact:

Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other

CNS depressants including alcohol, increases the risk of respiratory depression,

profound sedation, coma, and death.

Intervention:

Reserve concomitant prescribing of these drugs for use in patients for whom

alternative treatment options are inadequate. Limit dosages and durations to the minimum

required. Follow patients closely for signs of respiratory depression and sedation [see

Warnings and Precautions (5.4)].

Examples:

Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle

relaxants, general anesthetics, antipsychotics, other opioids, alcohol.

7.3 Serotonergic Drugs

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system,

such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors

(SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the

serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and monoamine oxidase

(MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and

intravenous methylene blue), has resulted in serotonin syndrome.

If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and

dose adjustment. Discontinue oxymorphone hydrochloride extended-release tablets if serotonin

dose adjustment. Discontinue oxymorphone hydrochloride extended-release tablets if serotonin

syndrome is suspected.

7.4 Interactions with Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

Mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol), and partial agonists

(buprenorphine) may reduce the analgesic effect of oxymorphone hydrochloride extended-release

tablets or precipitate withdrawal symptoms. Avoid the use of mixed agonist/antagonist and partial

agonist analgesics in patients receiving oxymorphone hydrochloride extended-release tablets.

7.5 Muscle Relaxants

Oxymorphone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce

an increased degree of respiratory depression. Monitor patients receiving muscle relaxants and

oxymorphone hydrochloride extended-release tablets for signs of respiratory depression that may be

greater than otherwise expected.

7.6 Cimetidine

Cimetidine can potentiate opioid-induced respiratory depression. Monitor patients for respiratory

depression when oxymorphone hydrochloride extended-release tablets and cimetidine are used

concurrently.

7.7 Anticholinergics

Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid

analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead

to paralytic ileus. Monitor patients for signs of respiratory and central nervous system depression when

oxymorphone hydrochloride extended-release tablets are used concurrently with anticholinergic drugs.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Clinical Considerations

Fetal/neonatal adverse reactions

Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in

physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding,

diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly [see Warnings and

Precautions (5.3)].

Teratogenic Effects - Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Oxymorphone hydrochloride

extended-release tablets should be used during pregnancy only if the potential benefit justifies the

potential risk to the fetus.

Oxymorphone hydrochloride administration did not cause malformations at any doses evaluated during

developmental toxicity studies in rats (≤ 25 mg/kg/day) or rabbits (≤ 50 mg/kg/day). These doses are ~3-

fold and ~12-fold the human dose of 40 mg every 12 hours, based on body surface area. There were no

developmental effects in rats treated with 5 mg/kg/day or rabbits treated with 25 mg/kg/day. Fetal

weights were reduced in rats and rabbits given doses of ≥ 10 mg/kg/day and 50 mg/kg/day, respectively.

These doses are ~1.2-fold and ~12-fold the human dose of 40 mg every 12 hours based on body

surface area, respectively. There were no effects of oxymorphone hydrochloride on intrauterine

survival in rats at doses ≤ 25 mg/kg/day, or rabbits at ≤ 50 mg/kg/day in these studies (see Non-

teratogenic Effects, below). In a study that was conducted prior to the establishment of Good

Laboratory Practices (GLP) and not according to current recommended methodology, a single

subcutaneous injection of oxymorphone hydrochloride on gestation day 8 was reported to produce

malformations in offspring of hamsters that received 15.5-fold the human dose of 40 mg every 12 hours

based on body surface area. This dose also produced 20% maternal lethality.

Non-teratogenic Effects

Oxymorphone hydrochloride administration to female rats during gestation in a pre- and postnatal

developmental toxicity study reduced mean litter size (18%) at a dose of 25 mg/kg/day, attributed to an

increased incidence of stillborn pups. An increase in neonatal death occurred at ≥ 5 mg/kg/day. Post-

natal survival of the pups was reduced throughout weaning following treatment of the dams with 25

mg/kg/day. Low pup birth weight and decreased postnatal weight gain occurred in pups born to

oxymorphone-treated pregnant rats given a dose of 25 mg/kg/day.

This dose is ~3-fold higher than the human dose of 40 mg every 12 hours on a body surface area basis.

8.2 Labor and Delivery

Opioids cross the placenta and may produce respiratory depression in neonates. Oxymorphone

hydrochloride extended-release tablets are not for use in women during and immediately prior to labor,

when shorter acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics

can prolong labor through actions that temporarily reduce the strength, duration, and frequency of

uterine contractions. However this effect is not consistent and may be offset by an increased rate of

cervical dilatation, which tends to shorten labor.

8.3 Nursing Mothers

It is not known whether oxymorphone is excreted in human milk. Because many drugs, including some

opioids, are excreted in human milk, caution should be exercised when oxymorphone hydrochloride

extended-release tablets are administered to a nursing woman. Monitor infants who may be exposed to

oxymorphone hydrochloride extended-release tablets through breast milk for excess sedation and

respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal

administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

8.4 Pediatric Use

The safety and effectiveness of oxymorphone hydrochloride extended-release tablets in patients below

the age of 18 years have not been established.

8.5 Geriatric Use

Of the total number of subjects in clinical studies of oxymorphone hydrochloride extended-release

tablets, 27% were 65 and over, while 9% were 75 and over. No overall differences in effectiveness

were observed between these subjects and younger subjects. There were several adverse events that

were more frequently observed in subjects 65 and over compared to younger subjects. These adverse

events included dizziness, somnolence, confusion, and nausea. On average, age greater than 65 years

was associated with a 1.4-fold increase in oxymorphone AUC and a 1.5-fold increase in C

Initiate

dosing with oxymorphone hydrochloride extended-release tablets in patients 65 years of age and over

using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression

when initiating and titrating oxymorphone hydrochloride extended-release tablets. For patients on prior

opioid therapy, start at 50% of the starting dose for a younger patient on prior opioids and titrate

slowly.

8.6 Hepatic Impairment

Patients with mild hepatic impairment have an increase in oxymorphone bioavailability of 1.6-fold. In

opioid-naïve patients with mild hepatic impairment, initiate oxymorphone hydrochloride extended-

release tablets using the 5 mg dose and monitor closely for respiratory and central nervous system

depression. Oxymorphone hydrochloride extended-release tablets are contraindicated for patients with

max.

moderate and severe hepatic impairment [see Contraindications (4), Warnings and Precautions (5.9), and

Dosage and Administration (2.5)]. For patients on prior opioid therapy, start at the 50% of the dose for

that a patient with normal hepatic function on prior opioids and titrate slowly.

8.7 Renal Impairment

Patients with moderate to severe renal impairment were shown to have an increase in oxymorphone

bioavailability ranging from 57 to 65% [see Clinical Pharmacology (12.3)]. Start opioid-naïve patients

with the 5 mg dose of oxymorphone hydrochloride extended-release tablets and titrate slowly while

closely monitoring for respiratory and central nervous system depression [see Dosage and

Administration (2.6)]. For patients on prior opioid therapy, start at 50% of the dose for a patient with

normal renal function on prior opioids and titrate slowly.

8.8 Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is

not known whether these effects on fertility are reversible [see Adverse Reactions (6.2)].

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Oxymorphone hydrochloride extended-release tablets contain oxymorphone, a Schedule II controlled

substance with an abuse liability similar to other opioids including fentanyl, hydromorphone, methadone,

morphine, oxycodone and tapentadol. Oxymorphone hydrochloride extended-release tablets can be

abused and is subject to criminal diversion [see Warnings and Precautions (5.1)].

The high drug content in extended release formulations adds to the risk of adverse outcomes from

abuse and misuse.

9.2 Abuse

All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use

of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even

once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited

to the following examples: the use of a prescription or over-the counter drug to get "high", or the use

of steroids for performance enhancement and muscle build up.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after

repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use,

persisting in its use despite harmful consequences, a higher priority given to drug use than to other

activities and obligations, increased tolerance , and sometimes a physical withdrawal.

"Drug seeking" behavior is very common to addicts and drug abusers. Drug-seeking tactics include

emergency calls or visits near the end of office hours, refusal to undergo appropriate examination,

testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance

to provide prior medical records or contact information for other treating physician(s). “Doctor

shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug

abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain

relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians

should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of

physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true

addiction.

Oxymorphone hydrochloride extended-release tablets, like other opioids, can be diverted for non-

medical use into illicit channels of distribution. Careful record-keeping of prescribing information,

including quantity, frequency, and renewal requests as required by state law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and

proper dispensing and storage are appropriate measures that help to reduce abuse of opioid drugs.

Risks Specific to Abuse of Oxymorphone Hydrochloride Extended-Release Tablets

Oxymorphone hydrochloride extended-release tablets are for oral use only. Abuse of oxymorphone

hydrochloride extended-release tablets poses a risk of overdose and death. This risk is increased with

concurrent abuse of oxymorphone hydrochloride extended-release tablets with alcohol and other

substances. Taking cut, broken, chewed, crushed, or dissolved oxymorphone hydrochloride extended-

release tablets enhances drug release and increases the risk of over dose and death.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis

and HIV.

9.3 Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the

need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of

disease progression or other external factors). Tolerance may occur to both the desired and undesired

effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose

reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with

opioid antagonist activity, e.g., naloxone, nalmefene, mixed agonist/antagonist analgesics (pentazocine,

butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a

clinically significant degree until after several days to weeks of continued opioid usage.

Oxymorphone hydrochloride extended-release tablets should not be abruptly discontinued [see Dosage

and Administration (2.3)]. If oxymorphone hydrochloride extended-release tablets are abruptly

discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the

following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration,

chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability,

anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting,

diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may

exhibit respiratory difficulties and withdrawal symptoms [see Use in Specific Populations (8.2)].

10 OVERDOSAGE

Clinical Presentation

Acute overdosage with oxymorphone is manifested by respiratory depression, somnolence progressing

to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, sometimes,

pulmonary edema, bradycardia, hypotension, and death. Marked mydriasis rather than miosis may be seen

due to severe hypoxia in overdose situations.

Treatment of Overdose

In case of overdose, priorities are the re-establishment of a patent and protected airway and institution

of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen,

vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest

or arrhythmias will require advanced life support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression

resulting from opioid overdose. Opioid antagonists should not be administered in the absence of

clinically significant respiratory or circulatory depression secondary to oxymorphone overdose. Such

agents should be administered cautiously to patients who are known, or suspected to be, physically

dependent on oxymorphone hydrochloride extended-release tablets. In such cases, an abrupt or

complete reversal of opioid effects may precipitate an acute withdrawal syndrome.

Because the duration of reversal would be expected to be less than the duration of action of

oxymorphone in oxymorphone hydrochloride extended-release tablets, carefully monitor the patient

until spontaneous respiration is reliably re-established. Oxymorphone hydrochloride extended-release

tablets will continue to release oxymorphone adding to the oxymorphone load for up to 24 hours after

administration, necessitating prolonged monitoring. If the response to opioid antagonists is suboptimal

or not sustained, additional antagonist should be given as directed in the product’s prescribing

information.

In an individual physically dependent on opioids, administration of an opioid receptor antagonist may

precipitate an acute withdrawal. The severity of the withdrawal produced will depend on the degree of

physical dependence and the dose of the antagonist administered. If a decision is made to treat serious

respiratory depression in the physically dependent patient, administration of the antagonist should be

begun with care and by titration with smaller than usual doses of the antagonist.

11 DESCRIPTION

Oxymorphone hydrochloride extended-release tablets are for oral use and contain oxymorphone, a

semi-synthetic opioid analgesic. Oxymorphone hydrochloride extended-release tablets are supplied in

5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg tablet strengths for oral administration. The tablet

strength describes the amount of oxymorphone hydrochloride, USP per tablet.

The tablets contain the following inactive ingredients: hydrophobic colloidal silica, hypromellose,

polyethylene glycol, polyvinyl alcohol, silicified microcrystalline cellulose, sodium stearyl fumarate,

talc, and titanium dioxide.

In addition, the 5 mg and 30 mg tablets contain FD&C red No. 40. The 7.5 mg tablets contain ferric

oxide black, and ferric oxide yellow. The 10 mg tablets contain ferric oxide yellow and FD&C yellow

No. 6. The 20 mg tablets contain D&C yellow No. 10, FD&C blue No. 1, and FD&C yellow No. 6. The

30 mg tablets contain FD&C blue No. 1 and FD&C yellow No. 6. The 40 mg tablets contain D&C

yellow No. 10 and FD&C yellow No. 6.

The chemical name of oxymorphone hydrochloride is 4, 5α -epoxy-3, 14-dihydroxy-17-

methylmorphinan-6-one hydrochloride, a white to off-white powder, which is sparingly soluble in

alcohol, but freely soluble in water. The molecular weight of oxymorphone hydrochloride is 337.80.

The molecular formula of oxymorphone hydrochloride is C

H NO .HCl. The pK and pK of

oxymorphone at 37° C are 8.17 and 9.54, respectively. The octanol/aqueous partition coefficient at 37°

C and pH 7.4 is 0.98.

The structural formula for oxymorphone hydrochloride is as follows:

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Oxymorphone, an opioid agonist, is relatively selective for the mu receptor, although it can interact

with other opioid receptors at higher doses.

The precise mechanism of analgesia, the principal therapeutic action of oxymorphone, is unknown.

Specific central nervous system (CNS) opiate receptors and endogenous compounds with morphine-like

activity have been identified throughout the brain and spinal cord and are likely to play a role in the

expression and perception of analgesic effects. In addition, opioid receptors have also been identified

within the peripheral nervous system (PNS). The role that these receptors play in these drugs’ analgesic

effects is unknown.

12.2 Pharmacodynamics

Concentration-Efficacy Relationships

The minimum effective plasma concentration of oxymorphone for analgesia varies widely among

patients, especially among patients who have been previously treated with agonist opioids. As a result,

individually titrate patients to achieve a balance between therapeutic and adverse effects. The minimum

effective analgesic concentration of oxymorphone for any individual patient may increase over time due

to an increase in pain, progression of disease, development of a new pain syndrome and/or potential

development of analgesic tolerance.

Concentration-Adverse Experience Relationships

There is a general relationship between increasing opioid plasma concentration and increasing

frequency of adverse experiences such as nausea, vomiting, CNS effects, and respiratory depression.

CNS Depressant/Alcohol Interaction

Additive pharmacodynamic effects may be expected when oxymorphone hydrochloride extended-

release tablets are used in conjunction with alcohol, other opioids, or illicit drugs that cause central

nervous system depression.

Effects on the Central Nervous System (CNS)

The principal therapeutic action of oxymorphone is analgesia. Oxymorphone causes respiratory

depression, in part by a direct effect on the brainstem respiratory centers. The respiratory depression

involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in

carbon dioxide tension and electrical stimulation. Oxymorphone depresses the cough reflex by direct

effect on the cough center in the medulla.

Oxymorphone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but

are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar

findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see

Overdosage (10)]. Other therapeutic effects of oxymorphone include anxiolysis, euphoria, and feeling

of relaxation, drowsiness and changes in mood.

Effects on the Gastrointestinal Tract and on Other Smooth Muscle

Gastric, biliary and pancreatic secretions are decreased by oxymorphone. Oxymorphone causes a

reduction in motility and is associated with an increase in tone in the antrum of the stomach and

duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are

decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point

of spasm. The end result is constipation. Oxymorphone can cause a marked increase in biliary tract

pressure as a result of spasm of the sphincter of Oddi, and transient elevations in serum amylase.

Oxymorphone may also cause spasm of the sphincter of the urinary bladder.

Effects on the Cardiovascular System

Oxymorphone produces peripheral vasodilation which may result in orthostatic hypotension. Release of

histamine can occur and may contribute to opioid-induced hypotension. Manifestations of histamine

release may include orthostatic hypotension, pruritus, flushing, red eyes, and sweating.

Effects on the Endocrine System

Opioid agonists have been shown to have a variety of effects on the secretion of hormones. Opioids

inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate

prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.

Effects on the Immune System

Opioids have been shown to have a variety of effects on components of the immune system in in vitro

and animal models. The clinical significance of these findings is unknown.

12.3 Pharmacokinetics

Abs orption

The absolute oral bioavailability of oxymorphone is approximately 10%.

Steady-state levels are achieved after three days of multiple dose administration. Under both single-

dose and steady-state conditions, dose proportionality has been established for the 5 mg, 10 mg, 20 mg,

and 40 mg doses of oxymorphone hydrochloride extended-release tablets, for both peak plasma levels

) and extent of absorption (AUC) (see Table 4).

Table 4: Mean (± SD) Oxymorphone Hydrochloride Extended-Release Tablets Pharmacokinetic

Parameters

Regimen

Dosage

(ng/mL)

AUC (nghr/mL)

(hr)

Single Dose

5 mg

0.27 ± 0.13

4.54 ± 2.04

11.30 ± 10.81

10 mg

0.65 ± 0.29

8.94 ± 4.16

9.83 ± 5.68

20 mg

1.21 ± 0.77

17.81 ± 7.22

9.89 ± 3.21

40 mg

2.59 ± 1.65

37.90 ± 16.20

9.35 ± 2.94

Multiple Dose

5 mg

0.70 ± 0.55

5.60 ± 3.87

10 mg

1.24 ± 0.56

9.77 ± 3.52

20 mg

2.54 ± 1.35

19.28 ± 8.32

40 mg

4.47 ± 1.91

36.98 ± 13.53

NA = not applicable

Results after 5 days of q12h dosing.

Food Effect

Two studies examined the effect of food on the bioavailability of single doses of 20 and 40 mg of

oxymorphone hydrochloride extended-release tablets in healthy volunteers. In both studies, after the

administration of oxymorphone hydrochloride extended-release tablets, the C

was increased by

approximately 50% in fed subjects compared to fasted subjects. A similar increase in C

was also

observed with oxymorphone solution.

The AUC was unchanged in one study and increased by approximately 18% in the other study in fed

subjects following the administration of oxymorphone hydrochloride extended-release tablets.

Examination of the AUC suggests that most of the difference between fed and fasting conditions occurs

in the first four hours after dose administration. After oral dosing with a single dose of 40 mg, a peak

oxymorphone plasma level of 2.8 ng/mL is achieved at 1 hour in fasted subjects and a peak of 4.25

ng/mL is achieved at 2 hours in fed subjects and that beyond the 12 hour time point, there is very little

difference in the curves. As a result, oxymorphone hydrochloride extended-release tablets should be

dosed at least one hour prior to or two hours after eating [see Dosage and Administration (2.1, 2.2)].

Dis tribution

Formal studies on the distribution of oxymorphone in various tissues have not been conducted.

Oxymorphone is not extensively bound to human plasma proteins; binding is in the range of 10% to 12%.

Metabolis m

Oxymorphone is highly metabolized, principally in the liver, and undergoes reduction or conjugation

with glucuronic acid to form both active and inactive metabolites. The two major metabolites of

oxymorphone are oxymorphone-3-glucuronide and 6-OH-oxymorphone. The mean plasma AUC for

oxymorphone-3-glucuronide is approximately 90-fold higher than the parent compound. The

pharmacologic activity of the glucuronide metabolite has not been evaluated. 6-OH-oxymorphone has

been shown in animal studies to have analgesic bioactivity. The mean plasma 6-OH-oxymorphone AUC

is approximately 70% of the oxymorphone AUC following single oral doses, but is essentially

equivalent to the parent compound at steady-state.

Excretion

Because oxymorphone is extensively metabolized, < 1% of the administered dose is excreted

unchanged in the urine. On average, 33% to 38% of the administered dose is excreted in the urine as

oxymorphone-3-glucuronide and less than 1% excreted as 6-OH-oxymorphone in subjects with normal

hepatic and renal function. In animals given radiolabeled oxymorphone, approximately 90% of the

administered radioactivity was recovered within 5 days of dosing. The majority of oxymorphone-

derived radioactivity was found in the urine and feces.

Specific Populations

Geriatric Patients

The steady-state plasma concentrations of oxymorphone, 6-OH-oxymorphone, and oxymorphone-3-

glucuronide are approximately 40% higher in elderly subjects (≥ 65 years of age) than in young

subjects (18 to 40 years of age). On average, age greater than 65 years was associated with a 1.4-fold

increase in oxymorphone AUC and a 1.5-fold increase in C

. This observation does not appear

related to a difference in body weight, metabolism, or excretion of oxymorphone [see Use in Specific

Populations (8.5)].

Gender

The effect of gender was evaluated following single- and multiple-doses of oxymorphone

hydrochloride extended-release tablets in male and female adult volunteers. There was a consistent

tendency for female subjects to have slightly higher AUC and C

values than male subjects;

however, gender differences were not observed when AUC and C

were adjusted by body weight.

Hepatic Impairment

The bioavailability of orally administered oxymorphone is markedly increased in patients with moderate

to severe liver disease. The disposition of oxymorphone was compared in six patients with mild, five

patients with moderate, and one patient with severe hepatic impairment and 12 subjects with normal

hepatic function. The bioavailability of oxymorphone was increased by 1.6-fold in patients with mild

hepatic impairment and by 3.7-fold in patients with moderate hepatic impairment. In one patient with

severe hepatic impairment, the bioavailability was increased by 12.2-fold. The half-life of

oxymorphone was not significantly affected by hepatic impairment.

Renal Impairment

Data from a pharmacokinetic study involving 24 patients with renal dysfunction show an increase of

26%, 57%, and 65% in oxymorphone bioavailability in mild (creatinine clearance 51 to 80 mL/min; n =

8), moderate (creatinine clearance 30 to 50 mL/min; n = 8), and severe (creatinine clearance < 30

mL/min; n = 8) patients, respectively, compared to healthy controls.

Drug Interaction/Alcohol Interaction

An in vivo study of the effect of alcohol (40%, 20%, 4% and 0%) on the bioavailability of a single dose

of 40 mg of oxymorphone hydrochloride extended-release tablets in healthy, fasted volunteers

demonstrated a highly variable effect on C

with concomitant administration of alcohol and

oxymorphone hydrochloride extended-release tablets. The change in C

ranged from a decrease of

50% to an increase of 270% across all conditions studied. Following administration of 240 mL of 40%

ethanol, the C

increased on average by 70% and up to 270% in individual subjects. Following the

concomitant administration of 240 mL of 20% ethanol, the C

increased on average by 31% and up to

260% in individual subjects. Following the concomitant administration of 240 mL of 4% ethanol, the

increased 7% on average and by as much as 110% for individual subjects. After oral dosing with a

single dose of 40 mg in fasted subjects, the mean peak oxymorphone plasma level is 2.4 ng/mL and the

median T

is 2 hours. Following co-administration of oxymorphone hydrochloride extended-release

tablets and alcohol (240 mL of 40% ethanol) in fasted subjects, the mean peak oxymorphone level is 3.9

ng/mL and the median T

is 1.5 hours (range 0.75 to 6 hours). The oxymorphone mean AUC was 13%

higher after co-administration of 240 mL of 40% alcohol. The AUC was essentially unaffected in

subjects following the co-administration of oxymorphone hydrochloride extended-release tablets and

ethanol (240 mL of 20% or 4% ethanol).

In vitro studies have demonstrated that oxymorphone hydrochloride extended-release tablets do not

release oxymorphone more rapidly in 500 mL of 0.1N HCl solutions containing ethanol (4%, 20%, and

40%),

Instruct patients to avoid use of alcohol when taking oxymorphone hydrochloride extended-release

tablets.

In vitro studies revealed little to no biotransformation of oxymorphone to 6-OH-oxymorphone by any of

the major cytochrome P450 (CYP P450) isoforms at therapeutically relevant oxymorphone plasma

concentrations.

No inhibition of any of the major CYP P450 isoforms was observed when oxymorphone was incubated

with human liver microsomes at concentrations of ≤ 15.1 mcg/mL. An inhibition of CYP3A4 activity

occurred at oxymorphone concentrations ≥ 45.3 mcg/mL. Therefore, it is not expected that

oxymorphone, or its metabolites will act as inhibitors of any of the major CYP P450 enzymes in vivo.

Increases in the activity of the CYP 2C9 and CYP 3A4 isoforms occurred when oxymorphone was

incubated with human hepatocytes. However, clinical drug interaction studies with oxymorphone

hydrochloride extended-release tablets showed no induction of CYP450 3A4 or 2C9 enzyme activity,

indicating that no dose adjustment for CYP 3A4- or 2C9-mediated drug-drug interactions is required.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies have been completed to evaluate the carcinogenic potential of oxymorphone in both

Sprague-Dawley rats and CD-1 mice. Oxymorphone HCl was administered to Sprague-Dawley rats (2.5,

5, and 10 mg/kg/day in males and 5, 10, and 25 mg/kg/day in females) for 2 years by oral gavage. The

systemic drug exposure (AUC ngh/mL) at the 10 mg/kg/day in male rats was 0.34-fold and at the 25

mg/kg/day dose in female rats was 1.5-fold the human exposure at a dose of 260 mg/day. No evidence

of carcinogenic potential was observed in rats. Oxymorphone was administered to CD-1 mice (10, 25,

75 and 150 mg/kg/day) for 2 years by oral gavage. The systemic drug exposure (AUC ngh/mL) at the

150 mg/kg/day dose in mice was 14.5-fold (in males) and 17.3-fold (in females) times the human

exposure at a dose of 260 mg/day. No evidence of carcinogenic potential was observed in mice.

Mutagenesis

Oxymorphone hydrochloride was not mutagenic when tested in the in vitro bacterial reverse mutation

assay (Ames test) at concentrations of ≤ 5270 mcg/plate, or in an in vitro mammalian cell chromosome

aberration assay performed with human peripheral blood lymphocytes at concentrations ≤ 5000 mcg/mL

with or without metabolic activation. Oxymorphone hydrochloride tested positive in both the rat and

mouse in vivo micronucleus assays. An increase in micronucleated polychromatic erythrocytes

occurred in mice given doses ≥ 250 mg/kg and in rats given doses of 20 and 40 mg/kg. A subsequent

study demonstrated that oxymorphone hydrochloride was not aneugenic in mice following

administration of up to 500 mg/kg. Additional studies indicate that the increased incidence of

micronucleated polychromatic erythrocytes in rats may be secondary to increased body temperature

following oxymorphone administration. Doses associated with increased micronucleated polychromatic

erythrocytes also produce a marked, rapid increase in body temperature. Pretreatment of animals with

sodium salicylate minimized the increase in body temperature and prevented the increase in

micronucleated polychromatic erythrocytes after administration of 40 mg/kg oxymorphone.

Impairment of Fertility

Oxymorphone hydrochloride did not affect reproductive function or sperm parameters in male rats at

any dose tested (≤ 50 mg/kg/day). The highest dose tested is ~6-fold the human dose of 40 mg every 12

hours, based on body surface area. In female rats, an increase in the length of the estrus cycle and

decrease in the mean number of viable embryos, implantation sites and corpora lutea were observed at

doses of oxymorphone ≥ 10 mg/kg/day. The dose of oxymorphone associated with reproductive

findings in female rats is 1.2-fold the human dose of 40 mg every 12 hours based on a body surface

area. The dose of oxymorphone that produced no adverse effects on reproductive findings in female

rats is 0.6-fold the human dose of 40 mg every 12 hours on a body surface area basis.

14 CLINICAL STUDIES

The efficacy and safety of oxymorphone hydrochloride extended-release tablets have been evaluated in

double-blind, controlled clinical trials in opioid-naïve and opioid-experienced patients with moderate to

severe pain including low back pain.

12-Week Study in Opioid-Naïve Patients with Low Back Pain

Patients with chronic low back pain who were suboptimally responsive to their non-opioid therapy

entered a 4-week, open-label dose titration phase. Patients initiated therapy with two days of treatment

with oxymorphone hydrochloride extended-release tablets 5 mg, every 12 hours. Thereafter, patients

were titrated to a stabilized dose, at increments of 5 to 10 mg every 12 hours every 3 to 7 days. Of the

patients who were able to stabilize within the Open-Label Titration Period, the mean ± SD VAS score at

Screening was 69.4 ± 11.8 mm and at Baseline (beginning of Double-Blind Period) were 18.5 ± 11.2

mm and 19.3 ± 11.3 mm for the oxymorphone ER and placebo groups, respectively. Sixty three percent

of the patients enrolled were able to titrate to a tolerable dose and were randomized into a 12-week

double-blind treatment phase with placebo or their stabilized dose of oxymorphone hydrochloride

extended-release tablets. The mean ± SD stabilized doses were 39.2 ± 26.4 mg and 40.9 ± 25.3 mg for

the oxymorphone hydrochloride extended-release tablets and placebo groups, respectively; total daily

doses ranged from 10 to 140 mg. During the first 4 days of double-blind treatment patients were

allowed an unlimited number of oxymorphone hydrochloride tablets, an immediate-release (IR)

formulation of oxymorphone, 5 mg tablets, every 4 to 6 hours as supplemental analgesia; thereafter the

number of oxymorphone hydrochloride tablets was limited to two tablets per day. This served as a

tapering method to minimize opioid withdrawal symptoms in placebo patients. Sixty-eight percent of

patients treated with oxymorphone hydrochloride extended-release tablets completed the 12-week

treatment compared to 47% of patients treated with placebo. Oxymorphone hydrochloride extended-

release tablets provided superior analgesia compared to placebo. The analgesic effect of oxymorphone

hydrochloride extended-release tablets was maintained throughout the double-blind treatment period in

89% of patients who completed the study. These patients reported a decrease, no change, or a ≤ 10 mm

increase in VAS score from Day 7 until the end of the study.

The proportion of patients with various degrees of improvement from screening to study endpoint is

shown in Figure 1. The figure is cumulative, so that patients whose change from baseline is, for

example, 30%, are also included at every level of improvement below 30%. Patients who did not

complete the study were assigned 0% improvement.

Figure 1: Percent Reduction in Average Pain Intensity from Screening to Final Visit

12-Week Study in Opioid-Experienced Patients with Low Back Pain

Patients on chronic opioid therapy entered a 4-week, open-label titration phase with oxymorphone

hydrochloride extended-release tablets dosed every 12 hours at an approximated equianalgesic dose of

their pre-study opioid medication. Of the patients who were able to stabilize within the Open-Label

Titration Period, the mean ± SD VAS score at Screening was 69.5 ± 17 mm and at Baseline (beginning

of Double-Blind Period) were 23.9 ± 12.1 mm and 22.2 ± 10.8 mm for the oxymorphone ER and placebo

groups, respectively. Stabilized patients entered a 12-week double-blind treatment phase with placebo

or their stabilized dose of oxymorphone hydrochloride extended-release tablets. The mean ± SD

stabilized doses were 80.9 ± 59.3 mg and 93.3 ± 61.3 mg for the oxymorphone hydrochloride

extended-release tablets and placebo groups, respectively; total daily doses ranged from 20 to 260 mg.

During the first 4 days of double-blind treatment, patients were allowed an unlimited number of

oxymorphone hydrochloride 5 mg tablets, every 4 to 6 hours as supplemental analgesia; thereafter the

number of oxymorphone hydrochloride tablets was limited to two tablets per day. This served as a

tapering method to minimize opioid withdrawal symptoms in placebo patients. Fifty seven percent of

patients were titrated to a stabilized dose within approximately 4 weeks of oxymorphone hydrochloride

extended-release tablets dose titration. Seventy percent of patients treated with oxymorphone

hydrochloride extended-release tablets and 26% of patients treated with placebo completed the 12-

week treatment. Oxymorphone hydrochloride extended-release tablets provided superior analgesia

compared to placebo. The analgesic effect of oxymorphone hydrochloride extended-release tablets

was maintained throughout the double-blind treatment period in 80 % of patients who completed the

study. These patients reported a decrease, no change, or a ≤ 10 mm increase in VAS score from Day 7

until the end of the study.

The proportion of patients with various degrees of improvement from screening to study endpoint is

shown in Figure 2. The figure is cumulative, so that patients whose change from baseline is, for

example, 30%, are also included at every level of improvement below 30%. Patients who did not

complete the study were assigned 0% improvement.

Figure 2: Percent Reduction in Average Pain Intensity from Screening to Final Visit

16 HOW SUPPLIED/STORAGE AND HANDLING

Oxymorphone hydrochloride extended-release tablets are supplied as follows:

5 mg

Pink to light pink, round, biconvex film-coated tablets, debossed with ‘RH 29’ on one side and plain on

the other side.

NDC 63304-218-30 Bottles of 30 with child-resistant closure

NDC 63304-218-05 Bottles of 500

7.5 mg

Gray to light gray, round, biconvex film-coated tablets, debossed with ‘RI 36’ on one side and plain on

the other side.

NDC 63304-219-30 Bottles of 30 with child-resistant closure

NDC 63304-219-05 Bottles of 500

10 mg

Orange to light orange, round, biconvex film-coated tablets, debossed with ‘RH 30’ on one side and

plain on the other side.

NDC 63304-220-30 Bottles of 30 with child-resistant closure

NDC 63304-220-05 Bottles of 500

15 mg

White to off-white, round, biconvex film-coated tablets, debossed with ‘RI 37’ on one side and plain on

the other side.

NDC 63304-221-30 Bottles of 30 with child-resistant closure

NDC 63304-221-05 Bottles of 500

20 mg

Green to light green, round, biconvex film-coated tablets, debossed with ‘RH 31’ on one side and plain

on the other side.

NDC 63304-222-30 Bottles of 30 with child-resistant closure

NDC 63304-222-05 Bottles of 500

30 mg

Reddish brown, round, biconvex film-coated tablets, debossed with ‘RI 38’ on one side and plain on the

other side.

NDC 63304-223-30 Bottles of 30 with child-resistant closure

NDC 63304-223-05 Bottles of 500

40 mg

Yellow to light yellow, round, biconvex film-coated tablets, debossed with ‘RH 32’ on one side and

plain on the other side.

NDC 63304-224-30 Bottles of 30 with child-resistant closure

NDC 63304-224-05 Bottles of 500

Store at 20° - 25° C (68° - 77° F) [See USP Controlled Room Temperature].

Dispense in tight container as defined in the USP, with a child-resistant closure (as required).

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Addiction, Abuse, and Misuse

Inform patients that the use of oxymorphone hydrochloride extended-release tablets, even when taken as

recommended, can result in addiction, abuse, and misuse, which can lead to overdose or death [see

Warnings and Precautions (5.1)]. Instruct patients not to share oxymorphone hydrochloride extended-

release tablets with others and to take steps to protect oxymorphone hydrochloride extended-release

tablets from theft or misuse.

Life-threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk

is greatest when starting oxymorphone hydrochloride extended-release tablets or when the dose is

increased, and that it can occur even at recommended doses [see Warnings and Precautions (5.2)]. Advise

patients how to recognize respiratory depression and to seek medical attention if breathing difficulties

develop.

Accidental Ingestion

Inform patients that accidental ingestion, especially in children, may result in respiratory depression or

death [see Warnings and Precautions (5.2)]. Instruct patients to take steps to store oxymorphone

hydrochloride extended-release tablets securely to dispose of unused oxymorphone hydrochloride

extended-release tablets by flushing the tablets down the toilet.

Neonatal Opioid Withdrawal Syndrome

Inform female patients of reproductive potential that prolonged use of oxymorphone hydrochloride

extended-release tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which

may be life-threatening if not recognized and treated [see Warnings and Precautions (5.3)].

Interactions with Benzodiazepines and Other CNS Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if oxymorphone

hydrochloride extended-release tablets are used with benzodiazepines or other CNS depressants,

including alcohol, and not to use these concomitantly unless supervised by a health care provider [see

Warnings and Precautions (5.4), Drug Interactions (7)].

Anaphylaxis. Angioedema, and Other Hypersensitivity Reactions

Inform patients that anaphylaxis and other hypersensitivity reactions have been reported with ingredients

contained in oxymorphone hydrochloride extended-release tablets. Advise patients how to recognize

such a reaction and when to seek medical attention [see Contraindications (4), Warnings and Precautions

(5. 7), Adverse Reactions (6)].

Serotonin Syndrome

Inform patients that oxymorphone hydrochloride extended-release tablets could cause a rare but

potentially life-threatening condition resulting from concomitant administration of serotonergic drugs.

Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if

symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take

serotonergic medications [see Drug Interactions (7.3)].

Adrenal Insufficiency

Inform patients that oxymorphone hydrochloride extended-release tablets could cause adrenal

insufficiency, a potentially life threatening condition. Adrenal insufficiency may present with non-

specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low

blood pressure. Advise patients to seek medical attention if they experience a constellation of these

symptoms [see Warnings and Precautions (5.8)].

Important Administration Instructions

Instruct patients how to properly take oxymorphone hydrochloride extended-release tablets, including

the following:

Swallowing oxymorphone hydrochloride extended-release tablets whole

Not crushing, chewing, or dissolving the tablets

Hypotension

Inform patients that oxymorphone hydrochloride extended-release tablets may cause orthostatic

hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how

to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully

rise from a sitting or lying position).

Driving or Operating Heavy Machinery

Inform patients that oxymorphone hydrochloride extended-release tablets may impair the ability to

perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise

patients not to perform such tasks until they know how they will react to the medication.

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to

seek medical attention.

Pregnancy

Advise female patients that oxymorphone hydrochloride extended-release tablets can cause fetal harm

and to inform the prescriber if they are pregnant or plan to become pregnant.

Disposal of Unused Oxymorphone Hydrochloride Extended-Release Tablets

Advise patients to flush the unused tablets down the toilet when oxymorphone hydrochloride extended-

release tablets are no longer needed.

MEDICATION GUIDE

OXYMORPHONE HYDROCHLORIDE EXTENDED-RELEASE TABLETS, FOR ORAL USE,

CII

Rx only

Oxymorphone hydrochloride extended-release tablets are:

Important information about oxymorphone hydrochloride extended-release tablets:

Using oxymorphone hydrochloride extended-release tablets exactly as prescribed to reduce the

risk of life-threatening adverse reactions (e.g., respiratory depression)

Not discontinuing oxymorphone hydrochloride extended-release tablets without first discussing

the need for a tapering regimen with the prescriber

A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain

severe enough to require daily around-the-clock, long-term treatment with an opioid, when other

pain treatments such as non-opioid pain medicines or immediate-release opioid medicines do not

treat your pain well enough or you cannot tolerate them.

A long-acting (extended-release) opioid pain medicine that can put you at risk for overdose and

death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction,

abuse, and misuse that can lead to death.

Not for use to treat pain that is not around-the-clock.

Get emergency help right away if you take too much oxymorphone hydrochloride extended-

release tablets (overdose). When you first start taking oxymorphone hydrochloride extended-

release tablets, when your dose is changed, or if you take too much (overdose), serious or life-

threatening breathing problems that can lead to death may occur.

Taking oxymorphone hydrochloride extended-release tablets with other opioid medicines,

Do not take oxymorphone hydrochloride extended-release tablets if you have:

Before taking oxymorphone hydrochloride extended-release tablets, tell your healthcare provider

if you have a history of:

Tell your healthcare provider if you are:

When taking oxymorphone hydrochloride extended-release tablets:

benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can

cause severe drowsiness, decreased awareness, breathing problems, coma, and death.

Never give anyone your oxymorphone hydrochloride extended-release tablets. They could die

from taking it. Store oxymorphone hydrochloride extended-release tablets away from children and

in a safe place to prevent stealing or abuse. Selling or giving away oxymorphone hydrochloride

extended-release tablets is against the law.

severe asthma, trouble breathing, or other lung problems.

a bowel blockage or have narrowing of the stomach or intestines.

head injury, seizures

liver, kidney, thyroid problems

problems urinating

pancreas or gallbladder problems

abuse of street or prescription drugs, alcohol addiction, or mental health problems.

pregnant or planning to become pregnant. Prolonged use of oxymorphone hydrochloride

extended-release tablets during pregnancy can cause withdrawal symptoms in your newborn baby

that could be life-threatening if not recognized and treated.

breastfeeding. Oxymorphone hydrochloride passes into breast milk and may harm your baby.

taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking

oxymorphone hydrochloride extended-release tablets with certain other medicines can cause

serious side effects.

Do not change your dose. Take oxymorphone hydrochloride extended-release tablets exactly as

prescribed by your healthcare provider.

Take your prescribed dose every 12 hours at the same time every day on an empty stomach, at

least 1 hour before or 2 hours after meals. Do not take more than your prescribed dose in 24

hours. If you miss a dose, take your next dose at your usual time.

Swallow oxymorphone hydrochloride extended-release tablets whole. Do not cut, break, chew,

crush, dissolve, snort, or inject oxymorphone hydrochloride extended-release tablets because this

may cause you to overdose and die.

Call your healthcare provider if the dose you are taking does not control your pain.

Do not stop taking oxymorphone hydrochloride extended-release tablets without talking to

your healthcare provider.

After you stop taking oxymorphone hydrochloride extended-release tablets, flush any unused

tablets down the toilet.

While taking oxymorphone hydrochloride extended-release tablets DO NOT:

The possible side effects of oxymorphone hydrochloride extended-release tablets:

Get emergency medical help if you have:

These are not all the possible side effects of oxymorphone hydrochloride extended-release tablets.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088. For more information go to dailymed.nlm.nih.gov

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Ranbaxy Pharmaceuticals Inc.

Jacksonville, FL 32257 USA

www.ranbaxyusa.com or call 1-888-726-2299

PACKAGE LABEL. PRINCIPAL DISPLAY PANEL

RANBAXY

NDC 63304-218-30

Twice-A-Day (every 12 hours)

OXYMORPHONE HCl EXTENDED-RELEASE TABLETS, CII

5 mg

DISPENSE ACCOMPANYING MEDICATION GUIDE TO EACH PATIENT

Drive or operate heavy machinery, until you know how oxymorphone hydrochloride extended-

release tablets affect you. Oxymorphone hydrochloride extended-release tablets can make you

sleepy, dizzy, or lightheaded.

Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using

products containing alcohol during treatment with oxymorphone hydrochloride extended-release

tablets may cause you to overdose and die.

constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call

your healthcare provider if you have any of these symptoms and they are severe.

trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue,

throat, or hands, hives, itching, rash, extreme drowsiness, light-headedness when changing

positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental

changes such as confusion.

September 2016 FDA-06

Rx only 30 Tablets

Package/Label Display Panel

RANBAXY

NDC 63304-219-30

Twice-A-Day (every 12 hours)

OXYMORPHONE HCl EXTENDED-RELEASE TABLETS, CII

7.5 mg

DISPENSE ACCOMPANYING MEDICATION GUIDE TO EACH PATIENT

Package/Label Display Panel

RANBAXY

NDC 63304-220-30

Twice-A-Day (every 12 hours)

OXYMORPHONE HCl EXTENDED-RELEASE TABLETS, CII

10 mg

DISPENSE ACCOMPANYING MEDICATION GUIDE TO EACH PATIENT

Rx only 30 Tablets

Rx only 30 Tablets

Package/Label Display Panel

RANBAXY

NDC 63304-221-30

Twice-A-Day (every 12 hours)

OXYMORPHONE HCl EXTENDED-RELEASE TABLETS, CII

15 mg

DISPENSE ACCOMPANYING MEDICATION GUIDE TO EACH PATIENT

Package/Label Display Panel

RANBAXY

NDC 63304-222-30

Twice-A-Day (every 12 hours)

OXYMORPHONE HCl EXTENDED-RELEASE TABLETS, CII

20 mg

DISPENSE ACCOMPANYING MEDICATION GUIDE TO EACH PATIENT

Rx only 30 Tablets

Rx only 30 Tablets

Package/Label Display Panel

RANBAXY

NDC 63304-223-30

Twice-A-Day (every 12 hours)

OXYMORPHONE HCl EXTENDED-RELEASE TABLETS, CII

30 mg

DISPENSE ACCOMPANYING MEDICATION GUIDE TO EACH PATIENT

Package/Label Display Panel

RANBAXY

NDC 63304-224-30

Twice-A-Day (every 12 hours)

OXYMORPHONE HCl EXTENDED-RELEASE TABLETS, CII

40 mg

DISPENSE ACCOMPANYING MEDICATION GUIDE TO EACH PATIENT

Rx only 30 Tablets

Rx only 30 Tablets

OXYMORPHONE HYDROCHLORIDE

oxymorphone hydrochloride tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 330 4-218

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYMO RPHO NE HYDRO CHLO RIDE (UNII: 5Y2EI9 4NBC) (OXYMORPHONE -

UNII:9 VXA9 6 8 E0 C)

OXYMORPHONE

HYDROCHLORIDE

5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PO LYETHYLENE GLYCO LS (UNII: 3WJQ0 SDW1A)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

Product Characteristics

Color

pink (pink to light pink)

S core

no sco re

S hap e

ROUND (bico nvex)

S iz e

9 mm

Flavor

Imprint Code

RH29

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 330 4-218 -30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

2

NDC:6 330 4-218 -0 5

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 350 6

0 4/13/20 15

OXYMORPHONE HYDROCHLORIDE

oxymorphone hydrochloride tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 330 4-219

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYMO RPHO NE HYDRO CHLO RIDE (UNII: 5Y2EI9 4NBC) (OXYMORPHONE -

UNII:9 VXA9 6 8 E0 C)

OXYMORPHONE

HYDROCHLORIDE

7.5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PO LYETHYLENE GLYCO LS (UNII: 3WJQ0 SDW1A)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

Product Characteristics

Color

gray (gray to light gray)

S core

no sco re

S hap e

ROUND (bico nvex)

S iz e

9 mm

Flavor

Imprint Code

RI36

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 330 4-219 -30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

2

NDC:6 330 4-219 -0 5

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 350 6

0 4/13/20 15

OXYMORPHONE HYDROCHLORIDE

oxymorphone hydrochloride tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 330 4-220

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYMO RPHO NE HYDRO CHLO RIDE (UNII: 5Y2EI9 4NBC) (OXYMORPHONE -

UNII:9 VXA9 6 8 E0 C)

OXYMORPHONE

HYDROCHLORIDE

10 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PO LYETHYLENE GLYCO LS (UNII: 3WJQ0 SDW1A)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

Product Characteristics

Color

o range (o range to light o range)

S core

no sco re

S hap e

ROUND (bico nvex)

S iz e

9 mm

Flavor

Imprint Code

RH30

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 330 4-220 -30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

2

NDC:6 330 4-220 -0 5

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 350 6

0 4/13/20 15

OXYMORPHONE HYDROCHLORIDE

oxymorphone hydrochloride tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 330 4-221

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYMO RPHO NE HYDRO CHLO RIDE (UNII: 5Y2EI9 4NBC) (OXYMORPHONE -

UNII:9 VXA9 6 8 E0 C)

OXYMORPHONE

HYDROCHLORIDE

15 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PO LYETHYLENE GLYCO LS (UNII: 3WJQ0 SDW1A)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

Product Characteristics

Color

white (white to o ff-white)

S core

no sco re

S hap e

ROUND (bico nvex)

S iz e

9 mm

Flavor

Imprint Code

RI37

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 330 4-221-30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

2

NDC:6 330 4-221-0 5

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 350 6

0 4/13/20 15

OXYMORPHONE HYDROCHLORIDE

oxymorphone hydrochloride tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 330 4-222

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYMO RPHO NE HYDRO CHLO RIDE (UNII: 5Y2EI9 4NBC) (OXYMORPHONE -

UNII:9 VXA9 6 8 E0 C)

OXYMORPHONE

HYDROCHLORIDE

20 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PO LYETHYLENE GLYCO LS (UNII: 3WJQ0 SDW1A)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FD&C BLUE NO . 1 (UNII: H3R47K3TBD)

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

Product Characteristics

Color

green (green to light green)

S core

no sco re

S hap e

ROUND (bico nvex)

S iz e

9 mm

Flavor

Imprint Code

RH31

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 330 4-222-30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

2

NDC:6 330 4-222-0 5

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 350 6

0 4/13/20 15

OXYMORPHONE HYDROCHLORIDE

oxymorphone hydrochloride tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 330 4-223

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYMO RPHO NE HYDRO CHLO RIDE (UNII: 5Y2EI9 4NBC) (OXYMORPHONE -

UNII:9 VXA9 6 8 E0 C)

OXYMORPHONE

HYDROCHLORIDE

30 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PO LYETHYLENE GLYCO LS (UNII: 3WJQ0 SDW1A)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

FD&C BLUE NO . 1 (UNII: H3R47K3TBD)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

Product Characteristics

Color

red (reddish bro wn)

S core

no sco re

S hap e

ROUND (bico nvex)

S iz e

9 mm

Flavor

Imprint Code

RI38

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 330 4-223-30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

2

NDC:6 330 4-223-0 5

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 350 6

0 4/13/20 15

OXYMORPHONE HYDROCHLORIDE

oxymorphone hydrochloride tablet, film coated, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 330 4-224

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYMO RPHO NE HYDRO CHLO RIDE (UNII: 5Y2EI9 4NBC) (OXYMORPHONE -

UNII:9 VXA9 6 8 E0 C)

OXYMORPHONE

HYDROCHLORIDE

40 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

PO LYETHYLENE GLYCO LS (UNII: 3WJQ0 SDW1A)

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STEARYL FUMARATE (UNII: 7CV7WJK4UI)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

Product Characteristics

Color

yello w (yello w to light yello w)

S core

no sco re

S hap e

ROUND (bico nvex)

S iz e

9 mm

Flavor

Imprint Code

RH32

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 330 4-224-30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

2

NDC:6 330 4-224-0 5

50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 4/13/20 15

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

Ranbaxy Pharmaceuticals Inc.

ANDA

ANDA20 350 6

0 4/13/20 15

Labeler -

Ranbaxy Pharmaceuticals Inc. (937890044)

Registrant -

Ranbaxy Pharmaceuticals Inc. (937890044)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Ohm Labo rato ries

Inc ._Te rmina l

18 476 9 0 29

MANUFACTURE(6 330 4-218 , 6 330 4-219 , 6 330 4-220 , 6 330 4-221, 6 330 4-222,

6 330 4-223, 6 330 4-224)

Revised: 9/2016

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