HYDROMORPHONE HYDROCHLORIDE tablet, extended release

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

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Active ingredient:
HYDROMORPHONE HYDROCHLORIDE (UNII: L960UP2KRW) (HYDROMORPHONE - UNII:Q812464R06)
Available from:
Paddock Laboratories, LLC.
INN (International Name):
HYDROMORPHONE HYDROCHLORIDE
Composition:
HYDROMORPHONE HYDROCHLORIDE 8 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Hydromorphone hydrochloride extended-release tablets are indicated for the management of pain in opioid-tolerant patients severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Patients considered opioid tolerant are those who are 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, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Limitations of Use Hydromorphone hydrochloride extended-release tablets are contraindicated in: Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4) ]. There are no adequate and well-controlled studies in pregnant women. Based on animal data, advise pregnant women of the potential risk to a fetus. In animal reproduction studies, r
Product summary:
Hydromorphone Hydrochloride Extended-Release Tablet Strengths Strength Color Tablet Description Bottle Count NDC 8 mg Dark Beige Round, biconvex, imprinted with “P293” over “8” on one side 100 0574-0293-01 12 mg White Round, biconvex, imprinted with “P294” over “12” on one side 100 0574-0294-01 16 mg Light Beige Round, biconvex, imprinted with “P295” over “16” on one side 100 0574-0295-01 32 mg Pink Round, biconvex, imprinted with “P297” over “32” on one side 100 0574-0297-01 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Store hydromorphone hydrochloride extended-release tablets securely and dispose of properly [see Patient Counseling Information (17)] .
Authorization status:
Abbreviated New Drug Application
Authorization number:
0574-0293-01, 0574-0294-01, 0574-0295-01, 0574-0297-01

Paddock Laboratories, LLC.

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Medication Guide

Hydromorphone Hydrochloride (hy-druh-mor-fon hy-druh-klawr-ahyd) Extended-Release Tablets, CII

Hydromorphone 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 hydromorphone hydrochloride extended-release tablets:

Get emergency help or call 911 right away if you take too many hydromorphone hydrochloride

extended-release tablets (overdose). When you first start taking hydromorphone 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. Talk to your healthcare

provider about naloxone, a medicine for the emergency treatment of an opioid overdose.

Taking hydromorphone 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 else your hydromorphone hydrochloride extended-release tablets. They could

die from taking it. Store hydromorphone hydrochloride extended-release tablets away from

children and in a safe place to prevent stealing or abuse. Selling or giving away hydromorphone

hydrochloride extended-release tablets is against the law.

Do not take hydromorphone 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 hydromorphone hydrochloride extended-release tablets, tell your healthcare provider if you

have a history of:

head injury, seizures

liver, kidney, thyroid problems

allergy to sulfites

problems urinating

pancreas or gallbladder problems

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

Tell your healthcare provider if you are:

pregnant or planning to become pregnant. Prolonged use of hydromorphone 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. Not recommended during treatment with hydromorphone hydrochloride extended-

release tablets. It may harm your baby.

living in a household where there are small children or someone who has abused street or

prescription drugs

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

hydromorphone hydrochloride extended-release tablets with certain other medicines can cause

serious side effects.

When taking hydromorphone hydrochloride extended-release tablets:

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

prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.

Take your prescribed dose every 24 hours, at the same time every day. Do not take more than

your prescribed dose in 24 hours. If you miss a dose, take your next dose at your usual time the

next day.

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

crush, dissolve, snort, or inject hydromorphone 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 hydromorphone hydrochloride extended-release tablets without talking to your

healthcare provider.

Hydromorphone hydrochloride extended-release tablets are contained in a hard tablet shell that

you may see in your bowel movement; this is normal.

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

tablets down the toilet.

While taking hydromorphone hydrochloride extended-release tablets, DO NOT:

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

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

sleepy, dizzy, or lightheaded.

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

products containing alcohol during treatment with hydromorphone hydrochloride extended-

release tablets may cause you to overdose and die.

The possible side effects of hydromorphone hydrochloride extended-release tablets are:

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 or call 911 right away if you have:

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

throat, 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 hydromorphone 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

Manufactured By

Perrigo®

Minneapolis, MN 55427

2203068 1B500 RC IC5 Rev 08-20 E

www.perrigorx.com or call 1-866-634-9120

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

Revised August 2020

Revised: 8/2020

Document Id: bfa6b12f-e066-45fb-ac99-10e8f0e35fb9

34391-3

Set id: 780a2616-0392-4715-bc50-71799bea1957

Version: 11

Effective Time: 20200814

Paddock Laboratories, LLC.

HYDROMORPHONE HYDROCHLORIDE- hydromorphone hydrochloride tablet, extended

release

Paddock Laboratories, LLC.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use HYDROMORPHONE HYDROCHLORIDE

EXTENDED-RELEASE TABLETS safely and effectively. See full prescribing information for

HYDROMORPHONE HYDROCHLORIDE EXTENDED-RELEASE TABLETS.

HYDROMORPHONE HYDROCHLORIDE extended-release tablets, for oral use, CII

Initial U.S. Approval: 1984

WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY

(REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL

OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH

BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

See full prescribing information for complete boxed warning.

RECENT MAJOR CHANGES

Dosage and Administration (2.2) 08/2020

Dosage and Administration (2.5) 10/2019

Warnings and Precautions (5.3, 5.12) 10/2019

INDICATIONS AND USAGE

Hydromorphone hydrochloride extended-release tablets are an opioid agonist indicated in opioid-tolerant patients 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)

Patients considered opioid tolerant are those who are 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, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. (1)

Limitations of Use (1)

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

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

monitor regularly for these behaviors and conditions. (5.1)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse,

the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy

(REMS) for these products. (5.2)

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

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

extended-release tablets whole to avoid exposure to a potentially fatal dose of hydromorphone. (5.3)

Accidental ingestion of hydromorphone hydrochloride extended-release tablets, especially by

children, can result in fatal overdose of hydromorphone. (5.3)

Prolonged use of hydromorphone 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. (5.4)

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. Reserve concomitant prescribing for use in patients for whom alternative treatment options

are inadequate; limit dosages and durations to the minimum required; and follow patients for signs

and symptoms of respiratory depression and sedation. (5.5, 7)

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 hydromorphone

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)

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

DOSAGE AND ADMINISTRATION

DOSAGE FORMS AND STRENGTHS

Extended-release tablets: 8 mg, 12 mg, 16 mg, 32 mg (3)

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

Most common adverse reactions (incidence >10%) are: constipation, nausea, vomiting, somnolence, headache, and

dizziness. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-866-634-9120 or FDA at 1-800-FDA-1088

or www.fda.gov/medwatch.

DRUG INTERACTIONS

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

To be prescribed only by healthcare providers knowledgeable in use of potent opioids for management of chronic

pain.

For once daily administration IN OPIOID-TOLERANT PATIENTS. (2.1)

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. (2.1)

Individualize dosing based on the severity of pain, patients response, prior analgesic experience, and risk factors for

addiction, abuse and misuse. (2.4)

Instruct patients to swallow hydromorphone hydrochloride extended-release tablets intact, and not to cut, break,

chew, crush, or dissolve the tablets (risk of potentially fatal overdose). (2.1, 5.1)

Discuss the availability of naloxone with the patient and caregiver and assess each patient’s need for access to

naloxone, both when initiating and renewing treatment with hydromorphone hydrochloride extended-release tablets.

Consider prescribing naloxone based on the patient’s risk factors for overdose. (2.2, 5.1, 5.3, 5.5)

Dose may be increased using increments of 4 to 8 mg every 3 to 4 days as needed to achieve adequate analgesia.

(2.4)

Do not abruptly discontinue hydromorphone hydrochloride extended-release tablets in a physically-dependent

patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled

pain, and suicide. (2.5, 5.12)

Moderate Hepatic Impairment: Initiate treatment with 25% of the dose that would be prescribed for patients with

normal hepatic function. Monitor closely for respiratory and central nervous system depression. (2.6)

Moderate and Severe Renal Impairment: Initiate treatment in patients with moderate renal impairment with 50% and

patients with severe renal impairment with 25% of the hydromorphone hydrochloride extended-release dose that

would be prescribed for patients with normal renal function. Monitor closely for respiratory and central nervous

system depression. (2.7)

Opioid non-tolerant patients (4)

Significant respiratory depression (4)

Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment (4)

Known or suspected gastrointestinal obstruction, including paralytic ileus (4)

Narrowed or obstructed gastrointestinal tract (4)

Known hypersensitivity to any components including hydromorphone hydrochloride and sulfites (4, 5.13)

Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or Elderly Cachectic Debilitated

Patients: Monitor closely, particularly during initiation and titration. (5.6)

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

opioid. (5.7)

Severe Hypotension: Monitor during dose initiation and titration. Avoid use of hydromorphone hydrochloride

extended-release tablets in patients with circulatory shock. (5.8)

Risks of Use in Patients with Increased Intracranial Pressure, Brain, Tumors, Head Injury, or Impaired

Consciousness: Monitor for sedation and respiratory depression. Avoid use of hydromorphone hydrochloride

extended-release tablets in patients with impaired consciousness or coma. (5.9)

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

extended-release tablets if serotonin syndrome is suspected. (7)

Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects of hydromorphone. Avoid concomitant use in

patients receiving MAOIs or within 14 days of stopping treatment with an MAOI. (7)

Mixed agonist/antagonist and partial agonist opioid analgesics: Avoid use with hydromorphone hydrochloride

USE IN SPECIFIC POPULATIONS

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 8/2020

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION

STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION;

ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and

RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS

DEPRESSANTS

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosage and Administration Information

2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

2.3 Initial Dosage

2.4 Titration and Maintenance of Therapy

2.5 Safe Reduction or Discontinuation of Hydromorphone Hydrochloride Extended-Release

Tablets

2.6 Dosage Modifications in Patients with Moderate Hepatic Impairment

2.7 Dosage Modifications in Patients with Renal Impairment

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Addiction, Abuse, and Misuse

5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

5.3 Life-Threatening Respiratory Depression

5.4 Neonatal Opioid Withdrawal Syndrome

5.5 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

5.6 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in

Elderly, Cachectic, or Debilitated Patients

5.7 Adrenal Insufficiency

5.8 Severe Hypotension

5.9 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or

Impaired Consciousness

5.10 Risks of Use in Patients with Gastrointestinal Conditions

5.11 Increased Risk of Seizures in Patients with Seizure Disorders

5.12 Withdrawal

5.13 Sulfites

5.14 Risks of Driving and Operating Machinery

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience

6.2 Postmarketing Experience

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

release tablets or precipitate withdrawal symptoms. (5.12, 7)

Pregnancy: May cause fetal harm. (8.1)

Lactation: Not recommended. (8.2)

Severe Hepatic Impairment: Use not recommended. (8.6)

Severe Renal Impairment: Consider an alternate analgesic. (8.7)

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Renal Impairment

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; RISK EVALUATION AND

MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY

DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL

SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR

OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse

Hydromorphone 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 hydromorphone hydrochloride extended-

release tablets, and monitor all patients regularly for the development of these behaviors

and conditions [see Warnings and Precautions (5.1)].

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS):

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and

misuse, the Food and Drug Administration (FDA) has required a REMS for these products

[see Warnings and Precautions (5.2)]. Under the requirements of the REMS, drug companies

with approved opioid analgesic products must make REMS-compliant education programs

available to healthcare providers. Healthcare providers are strongly encouraged to

Life-Threatening Respiratory Depression

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

hydromorphone hydrochloride extended-release tablets. Monitor for respiratory

depression, especially during initiation of hydromorphone hydrochloride extended-release

tablets or following a dose increase. Instruct patients to swallow hydromorphone

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

hydromorphone hydrochloride extended-release tablets can cause rapid release and

absorption of a potentially fatal dose of hydromorphone [see Warnings and Precautions (5.3)].

Accidental Ingestion

Accidental ingestion of even one dose of hydromorphone hydrochloride extended-release

tablets, especially by children, can result in a fatal overdose of hydromorphone [see

Warnings and Precautions (5.3)].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of hydromorphone 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 (5.4)].

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,

complete a REMS-compliant education program,

counsel patients and/or their caregivers, with every prescription, on safe use, serious

risks, storage, and disposal of these products,

emphasize to patients and their caregivers the importance of reading the Medication

Guide every time it is provided by their pharmacist, and

consider other tools to improve patient, household, and community safety.

coma, and death [see Warnings and Precautions (5.5), Drug Interactions (7)].

1 INDICATIONS AND USAGE

Hydromorphone hydrochloride extended-release tablets are indicated for the management of pain in

opioid-tolerant patients severe enough to require daily, around-the-clock, long-term opioid treatment

and for which alternative treatment options are inadequate.

Patients considered opioid tolerant are those who are 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, 60 mg oral hydrocodone per day, or an

equianalgesic dose of another opioid.

Limitations of Use

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosage and Administration Information

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

as both immediate-release 8 mg tablets and extended-release 8 mg tablets.

Hydromorphone 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.

Due to the risk of respiratory depression, hydromorphone hydrochloride extended-release tablets are

only indicated for use in patients who are already opioid-tolerant. Discontinue or taper all other

extended-release opioids when beginning hydromorphone hydrochloride extended-release tablet

therapy. As hydromorphone hydrochloride extended-release tablets are only for use in opioid-tolerant

patients, do not begin any patient on hydromorphone hydrochloride extended-release tablets as the first

opioid.

Patients who are opioid-tolerant are those receiving, for one week or longer, at least 60 mg of oral

morphine per day, at least 25 mcg transdermal fentanyl per hour, at least 30 mg of oral oxycodone per

day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60

mg oral hydrocodone per day, or an equianalgesic dose of another opioid.

Reserve concomitant prescribing of hydromorphone hydrochloride extended-release

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

alternative treatment options are inadequate.

Limit dosages and durations to the minimum required.

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

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 hydromorphone 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.

Hydromorphone hydrochloride extended-release tablets are not indicated as an as-needed (prn)

analgesic.

Use the lowest effective dosage for the shortest duration consistent with individual patient

treatment goals [see Warnings and Precautions (5)].

Instruct patients to swallow hydromorphone hydrochloride extended-release tablets whole [see Patient

Counseling Information (17)]. Crushing, chewing, or dissolving hydromorphone hydrochloride

extended-release tablets will result in uncontrolled delivery of hydromorphone and can lead to

overdose or death [see Warnings and Precautions (5.1)].

2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient

and caregiver and assess the potential need for access to naloxone, both when initiating and renewing

treatment with hydromorphone hydrochloride extended-release tablets [see Warnings and Precautions

(5.3), Patient Counseling Information (17)].

Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state

naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a

pharmacist, or as part of a community-based program).

Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant

use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of

risk factors for overdose should not prevent the proper management of pain in any given patient [see

Warnings and Precautions (5.1, 5.3, 5.5)].

Consider prescribing naloxone if the patient has household members (including children) or other close

contacts at risk for accidental ingestion or overdose.

2.3 Initial Dosage

Conversion from Other Oral Hydromorphone Formulations to Hydromorphone Hydrochloride

Extended-Release Tablets

Patients receiving oral immediate-release hydromorphone may be converted to hydromorphone

hydrochloride extended-release tablets by administering a starting dose equivalent to the patient’s total

daily oral hydromorphone dose, taken once daily.

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

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

release tablet therapy is initiated.

There is substantial inter-patient variability in the relative potency of different opioid drugs and opioid

formulations. Therefore, a conservative approach is advised when determining the total daily dosage of

hydromorphone hydrochloride extended-release tablets. It is safer to underestimate a patient's 24-hour

oral hydromorphone dosage and provide rescue medication (e.g., immediate-release opioid) than to

overestimate the 24-hour oral hydromorphone dosage and manage an adverse reaction due to overdose.

In a hydromorphone hydrochloride extended-release tablet clinical trial with an open-label titration

period, patients were converted from their prior opioid to hydromorphone hydrochloride extended-

release tablets using the Table 1 as a guide for the initial hydromorphone hydrochloride extended-

release tablets dose. The recommended starting dose of hydromorphone hydrochloride extended-

release tablets is 50% of the calculated estimate of daily hydromorphone requirement. Calculate the

estimated daily hydromorphone requirement using Table 1.

Consider the following when using the information in Table 1:

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 and following dosage increases with hydromorphone hydrochloride extended-

release tablets and adjust the dosage accordingly [see Warnings and Precautions (5.3)].

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 hydromorphone hydrochloride extended-release tablets.

The table cannot be used to convert from hydromorphone hydrochloride extended-release tablets to

another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in

fatal overdose.

Table 1.

Conversion Factors to Hydromorphone Hydrochloride Extended-Release Tablets

Prior Oral Opioid

Approximate Oral Conversion Factor

Hydromorphone

Codeine

0.06

Hydrocodone

Methadone

Morphine

Oxycodone

Oxymorphone

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

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

release tablet strength(s) available.

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

Step 1: Sum the total daily dose of the opioid

Close observation and frequent titration are warranted until pain management is stable on the new opioid.

Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-sedation/toxicity

after converting patients to hydromorphone hydrochloride extended-release tablets.

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 hydromorphone daily

dose.

For patients on a regimen of more than one opioid, calculate the approximate oral hydromorphone

dose for each opioid and sum the totals to obtain the approximate total hydromorphone 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.

30 mg of oxycodone 2 times daily = 60 mg total daily dose of oxycodone

Step 2: Calculate the approximate equivalent dose of oral hydromorphone based on the total daily

dose of the current opioid using Table 1

60 mg total daily dose of oxycodone x Conversion Factor of 0.4 = 24 mg of oral hydromorphone

daily

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

release tablets to be given every 24 hours, which is 50% of the calculated oral hydromorphone

dose. Round down, if necessary, to the appropriate hydromorphone hydrochloride extended-

release tablet strengths available.

50% of 24 mg results in an initial dose of 12 mg of hydromorphone hydrochloride extended-

release tablets once daily

Adjust individually for each patient

Conversion from Transdermal Fentanyl to Hydromorphone Hydrochloride Extended-Release Tablets

Eighteen hours following the removal of the transdermal fentanyl patch, hydromorphone hydrochloride

extended-release tablets treatment can be initiated. To calculate the 24-hour hydromorphone

hydrochloride extended-release tablets dose, use a conversion factor of 25 mcg/hr fentanyl transdermal

patch to 12 mg of hydromorphone hydrochloride extended-release tablets. Then reduce the

hydromorphone hydrochloride extended-release tablets dose by 50%.

For example:

Conversion from Methadone to Hydromorphone 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.

2.4 Titration and Maintenance of Therapy

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

adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving

hydromorphone 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, or 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 opioid analgesics.

Plasma levels of hydromorphone hydrochloride extended-release tablets are sustained for 18 to 24

hours. Dosage adjustments of hydromorphone hydrochloride extended-release tablets may be made in

increments of 4 to 8 mg every 3 to 4 days as needed to achieve adequate analgesia.

Patients who experience breakthrough pain may require a dose increase of hydromorphone

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 the hydromorphone hydrochloride extended-release

tablets dose.

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

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

reactions.

2.5 Safe Reduction or Discontinuation of Hydromorphone Hydrochloride Extended-Release

Step 1: Identify the dose of transdermal fentanyl.

75 mg of transdermal fentanyl

Step 2: Use the conversion factor of 25 mcg/hr fentanyl transdermal patch to 12 mg of

hydromorphone hydrochloride extended-release tablets.

75 mg of transdermal fentanyl: 36 mg total daily dose of hydromorphone hydrochloride extended-

release tablets

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

release tablets to be given every 24 hours, which is 50% of the converted dose. Round down, if

necessary, to the appropriate hydromorphone hydrochloride extended-release tablet strengths

available.

50% of 36 mg results in an initial dose of 18 mg, which would be rounded down to 16 mg of

hydromorphone hydrochloride extended-release tablets once daily

Adjust individually for each patient

Tablets

Do not abruptly discontinue hydromorphone hydrochloride extended-release tablets in patients who may

be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are

physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and

suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid

analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their

pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent

patient taking hydromorphone hydrochloride extended-release tablets, there are a variety of factors that

should be considered, including the dose of hydromorphone hydrochloride extended-release tablets the

patient has been taking, the duration of treatment, the type of pain being treated, and the physical and

psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree

on an appropriate tapering schedule and follow-up plan so that patient and provider goals and

expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected

substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the

substance use disorder. Treatment should include evidence-based approaches, such as medication

assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use

disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice

dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on hydromorphone

hydrochloride extended-release tablets who are physically opioid-dependent, initiate the taper by a

small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal

symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been

taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper.

Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common

withdrawal symptoms include 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. If withdrawal symptoms arise, it may be

necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the

previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in

mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for a long

duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management,

including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A

multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist

with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.12), Drug Abuse

and Dependence (9.3)].

2.6 Dosage Modifications in Patients with Moderate Hepatic Impairment

Start patients with moderate hepatic impairment on 25% of the hydromorphone hydrochloride extended-

release tablets dose that would be prescribed for patients with normal hepatic function. Closely monitor

patients with moderate hepatic impairment for respiratory and central nervous system depression during

initiation of therapy with hydromorphone hydrochloride extended-release tablets and during dose

titration. Use of alternate analgesics is recommended for patients with severe hepatic impairment [see

Use in Specific Populations (8.6)].

2.7 Dosage Modifications in Patients with Renal Impairment

Start patients with moderate renal impairment on 50% of the hydromorphone hydrochloride extended-

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