FDA label 1e83e2cb-fb53-48cd-8049-7d2672aa0f03

5 WARNINGS AND PRECAUTIONS Respiratory depression: Increased risk in elderly, debilitated patients, those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction. ( 5.1 ) Controlled substance: Morphine sulfate is a Schedule II controlled substance with an abuse liability similar to other opioids. ( 5.2 ) CNS effects: Additive CNS depressive effects when used in conjunction with alcohol, other opioids, or illicit drugs. ( 5.3 ) Elevation of intracranial pressure: May be markedly exaggerated in the presence of head injury, other intracranial lesions. ( 5.4 ) Hypotensive effect: Increased risk with compromised ability to maintain blood pressure. ( 5.5 ) Prolonged gastric obstruction: In patients with gastrointestinal obstruction, especially paralytic ileus. ( 5.6 ) Sphincter of Oddi spasm and diminished biliary/pancreatic secretions. Increased risk with biliary tract disease. ( 5.7 ) Special Risk Groups: Use with caution and in reduced dosages in patients with severe renal or hepatic impairment, Addison's disease, hypothyroidism, prostatic hypertrophy, or urethral stricture, elderly, CNS depression, toxic psychosis, acute alcoholism and delirium tremens, may aggravate or induce seizures. (5.8) Impaired mental/physical abilities: Caution must be used with potentially hazardous activities. ( 5.9 ) 5.1 Respiratory Depression Respiratory depression is the primary risk of morphine sulfate. Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation. Use morphine sulfate with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale and in patients having a substantially decreased respiratory reserve (e.g., severe kyphoscoliosis), hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of morphine sulfate may increase airway resistance and decrease respiratory drive to the point of apnea. Consider alternative non-opioid analgesics, and use morphine sulfate only under careful medical supervision at the lowest effective dose in such patients. 5.2 Misuse, Abuse and Diversion of Opioids Morphine sulfate is an opioid agonist and a Schedule II controlled substance. Such drugs are sought by drug abusers and people with addiction disorders. Diversion of Schedule II products is an act subject to criminal penalty. Morphine sulfate can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing morphine sulfate in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Morphine sulfate may be abused by crushing, chewing, snorting or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death. [See DRUG ABUSE AND DEPENDENCE (9) ] Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product. 5.3 Interactions with Alcohol and Drugs of Abuse Morphine sulfate may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, profound sedation, coma or death may result. 5.4 Use In Head Injury and Increased Intracranial Pressure In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the possible respiratory depressant effects of morphine sulfate and its potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO 2 retention) may be markedly exaggerated. Furthermore, morphine sulfate can produce effects on pupillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries. 5.5 Hypotensive Effect Morphine sulfate may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume or concurrent administration of drugs such as phenothiazines or general anesthetics. Morphine sulfate may produce orthostatic hypotension and syncope in ambulatory patients. Administer morphine sulfate with caution to patients in circulatory shock, as vasodilation produced by the drug may further reduce cardiac output and blood pressure. 5.6 Gastrointestinal Effects Do not administer morphine sulfate to patients with gastrointestinal obstruction, especially paralytic ileus because morphine sulfate diminishes propulsive peristaltic waves in the gastrointestinal tract and may prolong the obstruction. The administration of morphine sulfate may obscure the diagnosis or clinical course in patients with acute abdominal condition. 5.7 Use in Pancreatic/Biliary Tract Disease Use morphine sulfate with caution in patients with biliary tract disease, including acute pancreatitis, as morphine sulfate may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions. 5.8 Special Risk Groups Use morphine sulfate with caution and in reduced dosages in patients with severe renal or hepatic impairment, Addison’s disease, hypothyroidism, prostatic hypertrophy, or urethral stricture, and in elderly or debilitated patients. [See USE IN SPECIFIC POPULATIONS (8.5) ] Exercise caution in the administration of morphine sulfate to patients with CNS depression, toxic psychosis, acute alcoholism and delirium tremens. All opioids may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings. Keep Morphine Sulfate Tablets out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately. 5.9 Driving and Operating Machinery Caution patients that morphine sulfate could impair the mental and/or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Caution patients about the potential combined effects of morphine sulfate with other CNS depressants, including other opioids, phenothiazines, sedative/hypnotics and alcohol. [See DRUG INTERACTIONS (7) ]

6 ADVERSE REACTIONS Serious adverse reactions associated with morphine sulfate use include: 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 sulfate are dose-dependent and are typical opioid-related side effects. The most frequent of these include constipation, nausea, and somnolence. Other commonly observed adverse reactions include: lightheadedness, dizziness, sedation, vomiting, and sweating. The frequency of these events depends upon several factors including clinical setting, the patient’s level of opioid tolerance, and host factors specific to the individual. Anticipate and manage these events as part of opioid analgesia therapy. Other less frequently observed adverse reactions expected from opioid analgesics, including morphine sulfate include: Body as a Whole : malaise, withdrawal syndrome Cardiovascular System : bradycardia, hypertension, hypotension, palpitations, syncope, tachycardia Digestive System : biliary pain, dyspepsia, dysphagia, gastroenteritis, abnormal liver function tests, rectal disorder, thirst Hemic and Lymphatic System : anemia, thrombocytopenia Metabolic and Nutritional Disorders: edema, weight loss Musculoskeletal: skeletal muscle rigidity Nervous System : abnormal dreams, abnormal gait, agitation, amnesia, anxiety, ataxia, confusion, convulsions, coma, delirium, 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, anti-diuretic effect Most common adverse reactions seen on initiation of therapy are: constipation, nausea, somnolence, lightheadedness, dizziness, nausea, vomiting, sweating, dysphoria, and euphoria. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Roxane Laboratories, Inc. at (614) 276-4000 or Technical Product Information (800) 962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.