Morphine

INFUMORPH is for use in continuous microinfusion devices and indicated only for intrathecal or epidural infusion in the management of intractable chronic pain severe enough to require an opioid analgesic and for which less invasive means of controlling pain are inadequate. Limitations of Use Not for single-dose intravenous, intramuscular, or subcutaneous administration due to the risk of overdose. Not for single-dose neuraxial injection because INFUMORPH is too concentrated for accurate delivery of the smaller doses used in this setting. INFUMORPH is an opioid agonist, for use in continuous microinfusion devices and indicated only for intrathecal or epidural infusion in the management of intractable chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Morphine is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of morphine is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

INFUMORPH should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Should be administered by or under the direction of a physician experienced in the techniques of epidural or intrathecal administration. Patients should be observed in a fully equipped and staffed environmentforatleast24hoursaftereachtestdoseand,as indicated, for the first several days after surgery. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of INFUMORPH for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.

INFUMORPH is contraindicated in patients with: Significant respiratory depression Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days Known or suspected gastrointestinal obstruction, including paralytic ileus Hypersensitivity to morphine (e.g., anaphylaxis) Neuraxial administration of INFUMORPH is contraindicated in patients with: Infection at the injection microinfusion site Concomitant anticoagulant therapy Uncontrolled bleeding diathesis The presence of any other concomitant therapy or medical condition which would render epidural or intrathecal administration of medication especially hazardous.

Boxed warning (serious and life-threatening risks from use of infumorph): Risks with Neuraxial Administration Single-dose neuraxial administration may result in acute or delayed respiratory depression up to 24 hours. Risk of Inflammatory Masses: Monitor patients receiving continuous infusion of INFUMORPH via indwelling intrathecal catheter for new signs or symptoms of neurologic impairment. Risk of Tolerance and Myoclonic Activity: Monitor patients for unusual acceleration of neuraxial morphine, which may cause myoclonic-like spasm of lower extremities. Detoxification may be required. 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.

The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse Life-Threatening Respiratory Depression Interactions with CNS Benzodiazepines or Other Depressants Neonatal Opioid Withdrawal Syndrome Inflammatory Masses Myoclonic Activity Opioid-Induced Hyperalgesia and Allodynia Adrenal Insufficiency Severe Hypotension Gastrointestinal Adverse Reactions Seizures Withdrawal Urinary Retention Orthostatic Hypotension The following adverse reactions associated with the use of morphine were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Table 1 includes clinically significant drug interactions with INFUMORPH. Table 1. Clinically Significant Drug Interactions with INFUMORPH 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. The depressant effects of morphine are potentiated by the presence of other CNS depressants. Use of neuroleptics in conjunction with neuraxial morphine may increase the risk of respiratory depression. 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.

DO NOT FREEZE. Store at 20˚‑25˚C (68˚‑77˚F), excursions permitted to 15˚‑30˚C (59˚‑86˚F).