1 INDICATIONS AND USAGE Morphine Sulfate Injection is 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, and misuse with opioids, which can occur at any dosage or duration [see Warnings and Precautions (5.1) ] , reserve Morphine Sulfate Injection for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated, or are not expected to be tolerated, Have not provided adequate analgesia or are not expected to provide adequate analgesia.

Morphine Sulfate Injection should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

Morphine Sulfate Injection is an opioid agonist indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

( 1 ) Limitations of Use ( 1 ) Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration ( 5.1 ), reserve Morphine Sulfate Injection for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated or are not expected to be tolerated Have not provided adequate analgesia or are not expected to provide adequate analgesia Morphine Sulfate Injection should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

6 ADVERSE REACTIONS 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 Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.3) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4) ] Cardiovascular Instability [see Warnings and Precautions (5.5) ] 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) ] 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.

Serious adverse reactions associated with Morphine Sulfate Injection included respiratory depression, apnea, and to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest.

Rarely, anaphylactoid reactions have been reported when morphine or other phenanthrene alkaloids of opium are administered intravenously.

The most frequently observed adverse reactions included sedation, lightheadedness, dizziness, nausea, vomiting, constipation, and diaphoresis.

Other possible adverse reactions included: Central Nervous System– Euphoria, dysphoria, weakness, headache, agitation, tremor, uncoordinated muscle movements, visual disturbances, transient hallucinations and disorientation.

Gastrointestinal– Constipation, biliary tract spasm.

Cardiovascular– Tachycardia, bradycardia, palpitation, faintness, syncope, and orthostatic hypotension.

Genitourinary– Oliguria and urinary retention; an antidiuretic effect has been reported.

Allergic– Pruritus, urticaria, and skin rashes.

Anaphylactoid reactions have been reported following intravenous administration.

Other– Opioid-induced histamine release may be responsible for the flushing of the face, diaphoresis, and pruritus often seen with these drugs.

Wheals and urticaria at the site of injection are probably related to histamine release.

Local tissue irritation, pain and induration have been reported following repeated subcutaneous injection.

Morphine may alter temperature regulation in susceptible individuals and will depress the cough reflex.

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Morphine Sulfate Injection.

Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology (12.2) ] .

Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions (5.6) ] .

Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids.

Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

The most serious adverse reactions encountered are respiratory depression, apnea, circulatory depression, respiratory arrest, shock, and cardiac arrest.

Other common frequently observed adverse reactions include: sedation, lightheadedness, dizziness, nausea, vomiting, and constipation.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc.

at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .