1 INDICATIONS AND USAGE Morphine Sulfate Oral Solution 2 mg/mL is indicated for the management of: adults with acute and chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Morphine Sulfate Oral Solution 20 mg/mL is indicated for the relief of acute and chronic pain in opioid-tolerant adult patients .

Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [ see Warnings and Precautions ( 5.2 ) ], reserve Morphine Sulfate Oral Solution 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.

Pediatric use information is approved for Hikma Pharmaceuticals USA Inc.'s morphine sulfate oral solution.

However, due to Hikma Pharmaceuticals USA Inc.'s marketing exclusivity rights, this drug product is not labeled with that informatio n.

Morphine Sulfate Oral Solution is an opioid agonist: Morphine Sulfate Oral Solution 2 mg/mL is indicated for the management of: adults with acute and chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

( 1 ) Morphine Sulfate Oral Solution 20 mg/mL is indicated for: the relief of acute and chronic pain in opioid-tolerant adult patients .

( 1 ) Limitations of Use ( 1 ): Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Morphine Sulfate Oral Solution 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.

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 ( 5.2 ) ] Life-Threatening Respiratory Depression [ see Warnings and Precautions ( 5.4 ) ] Neonatal Opioid Withdrawal Syndrome [ see Warnings and Precautions ( 5.5 ) ] Interactions with Benzodiazepine or Other CNS Depressants [ 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 use included: respiratory depression, apnea, and to a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest.

The common adverse reactions seen on initiation of therapy with morphine in adults were dose-dependent and were typical opioid-relatedadverse reactions.

The most frequent of these included constipation, nausea, and somnolence.

Other commonly observed adverse reactions included: lightheadedness, dizziness, sedation, vomiting, and sweating.

The frequency of these events depended upon several factors including clinical setting, the patient’s level of opioid tolerance, and host factors specific to the individual.

Other less frequently observed adverse reactions from opioid analgesics, including morphine sulfate included: Body as a Whole: malaise, withdrawal syndrome Cardiovascular System: bradycardia, hypertension, hypotension, palpitations, syncope, tachycardia Digestive System: anorexia, biliary pain, dyspepsia, dysphagia, gastroenteritis, abnormal liver function tests, rectal disorder, thirst Endocrine: hypogonadism Hemic and Lymphatic System: anemia, thrombocytopenia Metabolic and Nutritional Disorders: edema, weight loss Musculoskeletal: skeletal muscle rigidity, decreased bone mineral density Nervous System: abnormal dreams, abnormal gait, agitation, amnesia, anxiety, ataxia, confusion, convulsions, coma, delirium, depression, dry mouth, euphoria, hallucinations, lethargy, nervousness, abnormal thinking, tremor, vasodilation, vertigo, headache Respiratory System: hiccup, hypoventilation, voice alteration Skin and Appendages: dry skin, urticaria, pruritus Special Senses: amblyopia, eye pain, taste perversion Urogenital System: abnormal ejaculation, dysuria, impotence, decreased libido, oliguria, urinary retention or hesitancy, anti-diuretic effect, amenorrhea 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 Oral Solution.

Androgen Deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [ see Clinical Pharmacology ( 12.2 ) ].

Pediatric use information is approved for Hikma Pharmaceuticals USA Inc.'s morphine sulfate oral solution.

However, due to Hikma Pharmaceuticals USA Inc.'s marketing exclusivity rights, this drug product is not labeled with that informatio n.

Most common adverse reactions on initiation of therapy are: Adults: constipation, nausea, somnolence, lightheadedness, dizziness, sedation, vomiting, and sweating.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Tris Pharma, Inc., at (732) 940-0358 or FDA at 1-800-FDA-1088 or WWW.FDA.GOV/MEDWATCH .