Hydromorphone: uses, appearance and warnings

Hydromorphone hydrochloride tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions ( 5.2 )] , reserve opioid analgesics, including hydromorphone hydrochloride tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Hydromorphone hydrochloride tablets contain hydromorphone, an opioid agonist, and are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. ( 1 ) Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including hydromorphone hydrochloride tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. ( 1 , 5.2 )

2 mg tablets (flat faced beveled or radius edge white to off-white tablet with one side debossed “M”; other side debossed “2”) 4 mg tablets (flat faced beveled edge white to off-white tablet with one side debossed “M”; other side debossed “4”) 8 mg tablets (white to off-white arc triangle shaped tablet debossed with a bisected “M” on one side and a split “8” on the other side) Hydromorphone hydrochloride tablets: 2 mg, 4 mg, 8 mg ( 3 )

Hydromorphone Hydrochloride Tablets USP, 2 mg are available as a flat faced beveled or radius edge white to off-white tablet with one side debossed “M”; other side debossed “2”. Bottles of 100................................... NDC 0406-3243-01 Hydromorphone Hydrochloride Tablets USP, 4 mg are available as a flat faced beveled edge white to off-white tablet with one side debossed “M”; other side debossed “4”. Bottles of 100................................... NDC 0406-3244-01 Hydromorphone Hydrochloride Tablets USP, 8 mg are available as a white to off-white arc triangle shaped tablet debossed with a bisected “M” on one side and a split “8” on the other side. Bottles of 100................................... NDC 0406-3249-01 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Store hydromorphone hydrochloride tablets securely and dispose of properly.

Hydromorphone hydrochloride tablets are contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.3 )] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.8 )] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.12 )] Hypersensitivity to hydromorphone, hydromorphone salts, any other components of the product, or sulfite-containing medications (e.g., anaphylaxis) [see Warnings and Precautions ( 5.16 ), Adverse Reactions ( 6.1 )] 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 ) Known hypersensitivity to hydromorphone, hydromorphone salts, or sulfite-containing medications. ( 4 )

Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation. ( 5.7 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Regularly evaluate patients, particularly during initiation and titration. ( 5.8 ) Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.9 ) Severe Hypotension: Regularly evaluate patients during dosage initiation and titration. Avoid use of hydromorphone hydrochloride tablets in patients with circulatory shock. ( 5.10 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor patients for sedation and respiratory depression. Avoid use of hydromorphone hydrochloride tablets in patients with impaired consciousness or coma. ( 5.11 ) 5.1 Risk of Accidental Overdose and Death Due to Medication Errors Dosing errors can result in accidental overdose and death. Ensure that the dose is communicated clearly and dispensed accurately. 5.2 Addiction, Abuse, and Misuse Hydromorphone hydrochloride tablets contain hydromorphone, a Schedule II controlled substance. As an opioid, hydromorphone hydrochloride tablets expose users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ( 9 )] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed hydromorphone hydrochloride tablets. Addiction can occur at recommended doses and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions ( 6.2 )] . Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing hydromorphone hydrochloride tablets, and reassess all patients receiving hydromorphone hydrochloride tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as hydromorphone hydrochloride tablets, but use in such patients necessitates intensive counseling about the risks and proper use of hydromorphone hydrochloride tablets along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.3 )] . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing hydromorphone hydrochloride tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and the proper disposal of unused drug. 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. 5.3 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, 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 overdose reversal agents (e.g., naloxone, nalmefene), depending on the patient’s clinical status [see Overdosage ( 10 )] . Carbon dioxide (CO 2 ) 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 hydromorphone hydrochloride tablets, the risk is greatest during the initiation of therapy or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of hydromorphone hydrochloride tablets are essential [see Dosage and Administration ( 2 )] . Overestimating the hydromorphone hydrochloride tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of even one dose of hydromorphone hydrochloride tablets, especially by children, can result in respiratory depression and death due to an overdose of hydromorphone. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. 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 [see Dosage and Administration ( 2.7 )] . Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). …

The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.2 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.3 )] Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions ( 5.4 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.7 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.9 )] Severe Hypotension [see Warnings and Precautions ( 5.10 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.12 )] Seizures [see Warnings and Precautions ( 5.13 )] Withdrawal [see Warnings and Precautions ( 5.14 )] Most common adverse reactions are lightheadedness, dizziness, sedation, nausea, vomiting, sweating …

Table 1 includes clinically significant drug interactions with hydromorphone hydrochloride tablets. Table 1: Clinically Significant Drug Interactions with Hydromorphone Hydrochloride Tablets 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, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death [see Warnings and Precautions ( 5.4 )] . 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. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). …