Morphine Sulfate

⛔ FDA Black Box Warning

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF PRESERVATIVE-FREE MORPHINE SULFATE INJECTION Risks with Neuraxial Administration Single-dose neuraxial administration may result in acute or delayed respiratory depression up to 24 hours. Because of the risk of severe adverse reactions when preservative-free morphine sulfate injection is administered by the epidural or intrathecal route of administration, patients must be observed in a fully equipped and staffed environment for at least 24 hours after the initial dose [see Warnings and Precautions (5.1) ] . Addiction, Abuse, and Misuse Because the use of preservative-free morphine sulfate injection exposes 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 and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.2) ] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of preservative-free morphine sulfate injection, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of preservative-free morphine sulfate injection are essential [see Warnings and Precautions (5.3) ] . 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 preservative-free morphine sulfate injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.4) , Drug Interactions (7) ] . Neonatal Opioid Withdrawal Syndrome (NOWS) If opioid use is required for an extended period of time in a

Contraindications

4 CONTRAINDICATIONS Preservative-free morphine sulfate injection is 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 (5.9) ] • Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days [see Warnings and Precautions (5.10) , Drug Interactions (7) ] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.14) ] • Hypersensitivity to morphine (e.g., anaphylaxis) [see Adverse Reactions (6) ] Neuraxial administration of preservative-free morphine sulfate injection is contraindicated in patients with: • Infection at the injection microinfusion site [see Warnings and Precautions (5.1) ] • Concomitant anticoagulant therapy [see Warnings and Precautions (5.1) ] • Uncontrolled bleeding diathesis [see Warnings and Precautions (5.1) ] • The presence of any other concomitant therapy or medical condition which would render epidural or intrathecal administration of medication especially hazardous. Preservative-free morphine sulfate injection is contraindicated in patients with: • Significant respiratory depression ( 4 ) • Acute or severe bronchial asthma in an unmonitored setting in 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 or intolerance to morphine ( 4 ) Neuraxial administration of preservative-free morphine sulfate injection is contraindicated in patients with: • Infection at the injection microinfusion site ( 4 ) • Concomitant anticoagulant therapy ( 4 ) • Uncontrolled bleeding diathesis ( 4 ) • The presence of any other concomitant therapy or medical condition which would render epidural or intr

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5) ] . Available data with preservative-free morphine sulfate injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are adverse outcomes reported with fetal exposure to opioid analgesics (see Clinical Considerations ) . Published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see Human Data ] . In published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (HDD) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the HDD in the rabbit, growth retardation at 6 times the HDD in the rat, and axial skeletal fusion and cryptorchidism at 16 times the HDD in the mouse. Administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3-4 times the HDD; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the HDD [see Animal Data ] . Based on animal data, advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinicall