Oxymorphone

Oxymorphone is part of the drug class:

• Natural opium alkaloids

Take oxymorphone exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of oxymorphone is taken for a long time, it may become habit-forming (causing mental or physical dependence).

oxymorphone comes with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

It is best to take oxymorphone on an empty stomach, at least 1 hour before or 2 hours after a meal.

If you are using the extended-release tablets:

• Take the tablets whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing it in the mouth. Do not crush, break, cut, dissolve, lick, or chew it.
• While taking oxymorphone, part of the tablet may pass into your stools. This is normal and is nothing to worry about.

Dosing

The dose of oxymorphone will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of oxymorphone. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • For moderate to severe pain:
    • For patients who are not taking narcotic medicines:
      • Adults—At first, 5 milligrams (mg) every 12 hours. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For patients switching from Opana® to Opana® ER:
      • Adults—At first, the dose is half of the total oral Opana® that you are taking per day, every 12 hours. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For patients switching from oxymorphone injection to Opana® ER:
      • Adults—At first, the dose is 10 times the total oxymorphone injection dose that you are receiving per day divided into two equal doses. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For patients switching from oral opioids to Opana® ER:
      • Adults—At first, the dose is half of the total daily dose that you are taking per day, every 12 hours. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
• For oral dosage form (tablets):
  • For moderate to severe pain:
    • For patients who are not taking narcotic medicines:
      • Adults—At first, 10 to 20 milligrams (mg) every 4 to 6 hours per day. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For patients switching from oxymorphone injection to Opana®:
      • Adults—At first, the dose is 10 times the total oxymorphone injection dose that you are receiving per day, divided into 4 to 6 equal doses. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For patients switching from oral opioids to Opana®:
      • Adults—At first, the dose is half of the total daily dose that you are taking per day, divided into 4 to 6 equal doses, every 4 to 6 hours. Your doctor may adjust your dose as needed.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of oxymorphone, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Oxymorphone can cause serious unwanted effects if taken by adults who are not used to strong narcotic pain medicines, children, or pets. Make sure you store the medicine in a safe and secure place to prevent others from getting it.

Important Dosage and Administration Instructions

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:

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)]. Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, 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 and following dosage increases with Oxymorphone Hydrochloride Extended-Release Tablets and adjust the dosage accordingly [see Warnings and Precautions (5.2)].

Instruct patients to swallow Oxymorphone Hydrochloride Extended-Release Tablets whole [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)].

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

Oxymorphone Hydrochloride Extended-Release Tablets are administered orally twice daily (every 12 hours).

  Initial Dosing

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 considered opioid tolerant are those taking, 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 tablets 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 × 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 Tablet 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 requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral Oxymorphone requirements which could result in adverse reactions. In an Oxymorphone Hydrochloride Extended-Release Tablets clinical trial with an open-label titration period, patients were converted from their prior opioid to Oxymorphone Hydrochloride Extended-Release Tablets using the table below as a guide for the initial Oxymorphone Hydrochloride Extended-Release Tablet dose.

Consider the following when using the information in the table below:

• 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.

To calculate the estimated Oxymorphone Hydrochloride Extended-Release Tablet dose using the table above:

• 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.
• For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion.

Always round the dose down, if necessary, to the appropriate Oxymorphone Hydrochloride Extended-Release Tablet 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.

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 Tablet dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, Oxymorphone Hydrochloride Extended-Release Tablet 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 Tablet 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.

Discontinuation of Oxymorphone Hydrochloride Extended-Release Tablets

When a patient no longer requires therapy with Oxymorphone Hydrochloride Extended-Release Tablets, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue Oxymorphone Hydrochloride Extended-Release Tablets [see Warnings and Precautions (5.13) , Drug Abuse and Dependence (9.3)].

Dosage Modifications in 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)].

Dosage Modifications in 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)].

Dosage Modifications in Geriatric Patients

The steady-state plasma concentrations of Oxymorphone are 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.

NDC 0115-1231-01

Twice-A-Day (every 12 hours)
Oxymorphone
Hydrochloride
Extended-Release Tablets
CII

5 mg

PHARMACIST: Dispense
the Medication Guide
provided separately to
each patient.

Rx only
100 Tablets

Impax Generics

NDC 0115-1315-01

Twice-A-Day (every 12 hours)
Oxymorphone
Hydrochloride
Extended-Release Tablets
CII

7.5 mg

PHARMACIST: Dispense
the Medication Guide
provided separately to
each patient.

Rx only
100 Tablets

 Impax Generics

NDC 0115-1317-01

Twice-A-Day (every 12 hours)
Oxymorphone
Hydrochloride
Extended-Release Tablets
CII

30 mg

PHARMACIST: Dispense
the Medication Guide
provided separately to
each patient.

Rx only
100 Tablets

Impax Generics

(oks i MOR fone)

There is an increase of 26%, 57%, and 65% in bioavailability in patients with mild, moderate, and severe renal impairment, respectively.

CrCl ≥50 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.

CrCl <50 mL/minute: Use with caution; bioavailability increased.

Oral:

Extended release:

Opioid naive: Initial: 5 mg/dose; titrate slowly with careful monitoring.

Prior opioid therapy: Initiate oxymorphone ER at 50% lower than the starting dose for patients with normal renal function on prior opioids; titrate slowly.

Immediate release: Initial: 5 mg/dose; titrate slowly with careful monitoring.

IM, IV, SubQ: Initiate with reduced dose and titrate slowly with careful monitoring.

Applies to oxymorphone: oral tablet, oral tablet extended release

Other dosage forms:

• injection solution

Along with its needed effects, oxymorphone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking oxymorphone:

• Blurred vision
• confusion
• decreased urination
• difficult or labored breathing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• fast, pounding, racing, or irregular heartbeat or pulse
• headache
• nervousness
• pounding in the ears
• rapid breathing
• sunken eyes
• sweating
• swelling of the hands, ankles, or feet
• thirst
• tightness in the chest
• unusual tiredness or weakness
• wrinkled skin

• Abdominal or stomach pain
• chest pain or discomfort
• chills
• cold sweats
• cough
• decrease in consciousness
• decrease in urine volume
• difficulty in passing urine (dribbling)
• difficulty with sleeping
• difficulty with swallowing
• disorientation
• drowsiness to profound coma
• fever
• hallucination
• hives, itching, or skin rash
• hyperventilation
• hoarseness
• irregular, slow, or shallow breathing
• irritability
• irritation
• joint pain, stiffness, or swelling
• lethargy
• painful urination
• pale or blue lips, fingernails, or skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the skin
• restlessness
• severe constipation
• severe vomiting
• shaking
• trouble in holding or releasing urine

Get emergency help immediately if any of the following symptoms of overdose occur while taking oxymorphone:

• Cold and clammy skin
• constricted, pinpoint, or small pupils (black part of the eye)
• decreased awareness or responsiveness
• low blood pressure or pulse
• muscle weakness
• severe sleepiness or unusual drowsiness
• very slow breathing

Some side effects of oxymorphone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty having a bowel movement (stool)
• feeling of constant movement of self or surroundings
• increased sweating
• nausea or vomiting
• relaxed and calm
• sensation of spinning
• sleepiness

• Acid or sour stomach
• belching
• decreased appetite
• decreased weight
• diarrhea
• discouragement
• excess air or gas in the stomach or intestines
• feeling of warmth
• feeling sad or empty
• full or bloated feeling
• heartburn
• indigestion
• lack of appetite
• loss of interest or pleasure
• passing gas
• pressure in the stomach
• redness of the face, neck, arms, and occasionally, upper chest
• stomach discomfort or upset
• swelling of the abdominal or stomach area
• tiredness
• trouble concentrating

• Blistering, crusting, irritation, itching, or reddening of the skin
• cracked, dry, scaly skin
• difficulty with thinking or concentrating
• disturbed color perception
• double vision
• false or unusual sense of well-being
• feeling jittery
• halos around lights
• loss of vision
• mental depression
• night blindness
• nightmares or unusually vivid dreams
• overbright appearance of lights
• sudden sweating
• tunnel vision
• welts

The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time; each patient should be managed individually.

Use as the First Opioid Analgesic or for those who are NOT Opioid Tolerant:
Initial dose: Extended-release tablets: 5 mg orally every 12 hours

CONVERSION DOSES:
Immediate-Release Oxymorphone to Extended-Release Oxymorphone Tablets:
-Administer one-half the patient's total daily immediate-release requirement as extended-release tablet taken orally every 12 hours

Parenteral Oxymorphone to Extended-Release Oxymorphone:
-Give 10 times the patient's total daily parenteral oxymorphone dose as extended-release tablet taken in 2 equally divided doses orally every 12 hours.

From Other Oral Opioids to Oxymorphone Extended-Release Tablets:
-Discontinue all other around-the-clock opioid drugs when oxymorphone extended-release therapy is initiated.
-Published potency tables can be used to estimate a patient's 24-hour oral oxymorphone requirement; however, due to substantial inter-patient variability, the conversion should then underestimate a patient's 24-hour requirement and provide rescue medication as the dose is titrated.
-Alternatively, the following conversion factors (CF) may be used to convert selected oral opioids to the extended-release oxymorphone tablet: Oxymorphone, CF=1; Hydrocodone, CF=0.5; Oxycodone, CF=0.5; Methadone, CF= 0.5, Morphine, CF=0.333
-As an example: Sum the total daily dose of prior oral opioid; multiply that sum by the CF to obtain 24-hour oral oxymorphone requirement; divide by 2 to calculate approximate starting dose to be given every 12 hours, round down, if necessary.
-These CFs cannot be used to convert from oxymorphone extended-release tablets to the selected oral opioid as doing so will result in overestimation of the oral opioid dose and may result in fatal respiratory depression

TITRATION AND MAINTENANCE:
Maintenance Dose: Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; dose adjustments may be made in 5 to 10 mg increments every 12 hours, every 3 to 7 days.
Breakthrough Pain: If the level of pain increases after dose stabilization, attempt to identify the source before increasing dose; rescue medication with appropriate immediate-release analgesia may be helpful

Comments:
-An opioid tolerant patient is one who has been receiving for 1-week or longer at least: oral morphine 60 mg/day, fentanyl transdermal patch 25 mcg per hour, oral oxycodone 30 mg/day, oral hydromorphone 8 mg/day, oral oxymorphone 25 mg/day, or an equianalgesic dose of another opioid
-When converting from methadone, close monitoring is of particular importance due to methadone's long half-life.
-Dose conversion should be done carefully and with close monitoring due to large patient variability in regards to opioid analgesic response.
-Upon cessation of therapy, taper gradually in physically dependent patient.

Use: 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.

Moderate to severe renal impairment: Use with caution starting at the lowest dose and titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Extended-release tablets:
Opioid-naive with CrCl less than 50 mL/min: Initial dose: 5 mg orally every 12 hours
Opioid-experienced with CrCl less than 50 mL/min: Initial dose: 50% lower than starting dose for patients with normal function, titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Moderate to severe hepatic impairment: Use is contraindicated
Mild hepatic impairment: titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

Extended-release tablets:
Opioid-naive with mild hepatic impairment: Initial dose: 5 mg orally every 12 hours
Opioid-experienced with mild hepatic impairment: Initial dose: 50% lower than starting dose for patients with normal function, titrate slowly while monitoring for signs and symptoms of respiratory and CNS depression.

• Swallow tablets on an empty stomach with a large glass of water at least one hour before or two hours after food.
• Swallow oxymorphone extended-release tablets whole; never crush, chew or attempt to dissolve, as this could lead to a potentially fatal dose of oxymorphone.
• Never use oxymorphone extended-release tablets on an "as needed" basis.
• Oxymorphone is a very potent medication that can cause addiction. Only take as prescribed by your doctor; never increase the dosage without his or her advice. Avoid taking oxymorphone during pregnancy and when breastfeeding. Taper off dosage under medical supervision after extended administration because withdrawal symptoms may result.
• Avoid alcohol while taking oxymorphone because it may increase the risk of sedation and potentially fatal side effects.
• Initial dosages should be low especially in the elderly or with certain preexisting conditions (such as liver or kidney disease).
• Should not be used by people with alcohol-dependence or previous drug dependence. Monitor regularly for the development of dependence and addiction and do not misuse or overuse.
• Report any breathing difficulties to your doctor immediately.
• Laxatives may be needed to treat constipation and antiemetics may be used to relieve nausea
• Oxymorphone is available as both immediate and extended-release tablets. Ensure you have been dispensed the correct formulation before taking. Oxymorphone injection is also available; this is ten times more potent than oxymorphone tablets.
• May impair reaction times and affect your ability to drive or operate machinery.
• May lower blood pressure on standing; take your time when going from a lying down to a standing up position.
• The need for continued treatment with oxymorphone should be assessed at regular intervals.
• Keep well out of reach of children and pets. Even one accidental dose can be fatal.