Addiction, Abuse, And Misuse; Life-Threatening Respiratory Depression; Accidental Ingestion; Neonatal Opioid Withdrawal Syndrome; And Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants; Risk Evaluation And Mitigation Strategy (REMS)

Proper Patient Selection: For Use in Opiod Tolerant Patients Only

• Hydromorphone HCl extended release  are indicated for the management of persistent, moderate to severe pain in patients requiring continuous, around-the-clock analgesia with a high potency opioid for an extended period of time (weeks to months) or longer.  [Palladone, Exalgo]
• For use in opioid tolerant patients only. [Palladone, Exalgo]
• This product should only be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a minimum total daily dose of opiate medication equivalent to 12 mg of oral hydromorphone. [Palladone]
• Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, or at least 30 mg of oral oxycodone/day, or at least 8 mg oral hydromorphone/day, or an equianalgesic dose of another opioid, for a week or longer. [Palladone]
• Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, 25 mcg transdemral fentanyl/hour, 30 mg of oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg of oral oxymorhpone/day, or an equianalgesic dose of another opioid, for a week or longer [Exalgo]
• Appropriate patients for treatment with Palladone Capsules include patients who require high doses of potent opioids on an around-the clock basis to improve pain control and patients who have difficulty attaining adequate analgesia with immediate-release opioid formulations. [Palladone]

Limitations of Use

• Contraindicated for use on an as needed basis (i.e., prn). [Palladone, Exalgo]
• NOT intended to be used as the first opioid product prescribed for a patient, or in patients who require opioid analgesia for a short period of time. [Palladone]
• Not indicated for the management of acute or postoperative pain. [Exalgo]

Opioid Tolerant Patients

• For use in OPIOID-TOLERANT patients ONLY. Use in non-opioid-tolerant patients may lead to FATAL RESPIRATORY DEPRESSION. [Palladone, Exalgo]
• Overestimating the Palladone dose when converting patients from another opioid medication can result in fatal overdose with the first dose. Due to the mean apparent 18-hour elimination half-life of Palladone, patients who receive an overdose will require an extended period of monitoring and treatment that may go beyond 18 hours. Even in the face of improvement, continued medical monitoring is required because of the possibility of extended effects. [Palladone]

Risk of Overdose

• Schedule II opioid agonists (which include hydromorphone, fentanyl, methadone, morphine, oxycodone, and oxymorphone), have the highest risk of fatal overdoses due to respiratory depression, as well as the highest potential for abuse. [Palladone, Exalgo]
• Accidental consumption, especially in children, can result in a fatal overdose of hydromorphone. [Exalgo]

Life-Threatening Respiratory Depression

• Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

 Addition, Abuse, and Misuse 

• Hydromorphone, an opioid agonist, and a Schedule II controlled substance can be abused in a manner similar to other opioid agonists, legal or illicit. These risks should be considered when administering, prescribing, or dispensing hydromorphine in situations where the healthcare professional is concerned about increased risk of misuse, abuse, or diversion. [Palladone, Exalgo]
• Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. [Palladone]
• All patients receiving opioids should be routinely monitored for signs of misuse, abuse and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction. [Palladone]
• Patients at increased risk may be prescribed opioids, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose. 
• Patients at increased risk may be prescribed opioids, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose. 

Administration Instructions

• Palladone Capsules should be administered once every 24 hours. [Palladone]
• Extended release hydromorphone products are to be swallowed WHOLE and are not to be broken, chewed, opened, dissolved or crushed. Taking broken, chewed, dissolved, or crushed product or its contents can lead to the rapid release and absorption of a potentially fatal dose of hydromorphone. [Palladone, Exalgo]
• Consuming alcohol while taking Palladone Capsules or can lead to the rapid release and absorption of a potentially fatal dose of hydromorphone. [Palladone]
• Overestimating the Palladone dose when converting the patient from another opioid medication can result in fatal overdose with the first dose. With the long half-life of Palladone (18 hours), patients who receive the wrong dose will require an extended period of monitoring and treatment that may go beyond 18 hours. Even in the face of improvement, continued medical monitoring is required because of the possibility of extended effects. [Palladone]

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 

• Reserve concomitant prescribing of opioids 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.

Life-Threatening Respiratory Depression

• Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.
• Do not abruptly discontinue DILAUDID ORAL SOLUTION OR DILAUDID TABLETS in a patient physically dependent on opioids. When discontinuing DILAUDID Oral Solution or DILAUDID Tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of hydromorphone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.

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. 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:

• 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.

THESE ARE EXAMPLES OF VARIATIONS IN BOX WARNING DATA FOR HYDROMORPHONE ER  PRODUCTS. REFER TO SPECIFIC PRODUCT PACKAGE INSERT FOR DETAILS