Morphine: uses, appearance and warnings

Morphine sulfate extended-release tablets are indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. 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 morphine sulfate extended-release 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. Morphine sulfate extended-release tablets are not indicated as an as-needed (prn) analgesic. Morphine sulfate extended-release tablets are an opioid agonist indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. ( 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 morphine sulfate extended-release 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 , 5.1 ) Morphine sulfate extended-release tablets are not indicated as an as-needed (prn) analgesic. ( 1 )

Morphine Sulfate Extended-Release Tablets 15 mg Round, blue convex tablets, with one side debossed and the other side debossed “15” Morphine Sulfate Extended-Release Tablets 30 mg Round, purple convex tablets, with one side debossed and the other side debossed “30” Morphine Sulfate Extended-Release Tablets 60 mg Round, orange convex tablets, with one side debossed and the other side debossed “60” Morphine Sulfate Extended-Release Tablets 100 mg Round, gray convex tablets, with one side debossed and the other side debossed “100” Morphine Sulfate Extended-Release Tablets 200 mg Capsule-shaped, green convex tablets, with one side debossed and the other side debossed “200” Extended-release tablets: 15 mg, 30 mg, 60 mg, 100 mg, 200 mg ( 3 ) Boxed M Boxed M Boxed M Boxed M Boxed M

Morphine Sulfate Extended-Release Tablets are supplied as follows: 15 mg - round, blue convex tablet, debossed on one side and debossed “15” on the other. Bottles of 100 ................................. NDC 0406-8315-01 Unit Dose (10 x 10)......................... NDC 0406-8315-62 30 mg - round, purple convex tablet, debossed on one side and debossed “30” on the other. Bottles of 100 ................................. NDC 0406-8330-01 Unit Dose (10 x 10)......................... NDC 0406-8330-62 60 mg - round, orange convex tablet, debossed on one side and debossed “60” on the other. Bottles of 100 ................................. NDC 0406-8380-01 Unit Dose (10 x 10)......................... NDC 0406-8380-62 100 mg - round, gray convex tablet, debossed on one side and debossed “100” on the other. Bottles of 100 ................................. NDC 0406-8390-01 Unit Dose (10 x 10)......................... NDC 0406-8390-62 200 mg - capsule-shaped, green convex tablet, debossed on one side and debossed “200” on the other. Bottles of 100 ................................. NDC 0406-8320-01 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Store morphine sulfate extended-release tablets securely and dispose of properly [see Patient Counseling Information (17) ] . Dispense in a tight, light-resistant container. Boxed M Boxed M Boxed M Boxed M Boxed M

Morphine sulfate extended-release tablets are contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.2 )] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.7 )] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Warnings and Precautions ( 5.8 ), Drug Interactions ( 7 )] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.12 )] Hypersensitivity (e.g., anaphylaxis) to morphine [see Adverse Reactions ( 6.2 )] Significant respiratory depression ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment ( 4 ) Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 ) Hypersensitivity to morphine ( 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. ( 5.6 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Regularly evaluate, particularly during initiation and titration. ( 5.7 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.9 ) Severe Hypotension : Regularly evaluate during dosage initiation and titration. Avoid use in patients with circulatory shock. ( 5.10 ) 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 morphine sulfate extended-release tablets in patients with impaired consciousness or coma. ( 5.11 ) 5.1 Addiction, Abuse, and Misuse Morphine sulfate extended-release tablets contain morphine, a Schedule II controlled substance. As an opioid, morphine sulfate extended-release tablets expose its users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed morphine sulfate extended-release 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 morphine sulfate extended-release tablets, and reassess all patients receiving morphine sulfate extended-release tablets for 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 morphine sulfate extended-release tablets, but use in such patients necessitates intensive counseling about the risks of proper use of morphine sulfate extended-release 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 ( 5.2 )] . Abuse or misuse of morphine sulfate extended-release tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of morphine and can result in overdose and death [see Overdosage ( 10 )] . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing morphine sulfate extended-release 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 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. 5.2 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 , 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 morphine sulfate extended-release 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 morphine sulfate extended-release tablets are essential [see Dosage and Administration ( 2 )] . Overestimating the morphine sulfate extended-release 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 morphine sulfate extended-release tablets, especially by children, can result in respiratory depression and death due to an overdose of morphine. 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 ( 2.6 )] . 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 ( 5.1 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Interactions with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions ( 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.6 )] 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 (>10%): constipation, nausea, and sedation. …

Table 1 includes clinically significant drug interactions with morphine sulfate extended-release tablets. Table 1: Clinically Significant Drug Interactions with Morphine Sulfate Extended-Release 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 ( 5.3 )] . 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). …