FDA label f7f75d02-ed35-4066-9f81-6c30d5cdedca

WARNING: Morphine sulfate extended-release capsules contains morphine sulfate, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. Morphine sulfate extended-release capsules can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing morphine sulfate extended-release capsules in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Morphine sulfate extended-release capsules are an extended-release oral formulation of morphine sulfate indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. Morphine sulfate extended-release capsules are NOT for use as a prn analgesic. Morphine sulfate extended-release capsules 100 mg ARE FOR USE IN OPIOID-TOLERANT PATIENTS ONLY. Ingestion of these capsules or of the pellets within the capsules may cause fatal respiratory depression when administered to patients not already tolerant to high doses of opioids. MORPHINE SULFATE EXTENDED-RELEASE CAPSULES ARE TO BE SWALLOWED WHOLE OR THE CONTENTS OF THE CAPSULES SPRINKLED ON APPLE SAUCE. THE PELLETS IN THE CAPSULES ARE NOT TO BE CHEWED, CRUSHED, OR DISSOLVED DUE TO THE RISK OF RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE.

WARNINGS Morphine sulfate extended-release capsules are to be swallowed whole and are not to be chewed, crushed, or dissolved. Taking chewed, crushed, or dissolved morphine sulfate extended-release capsules, USP leads to rapid release and absorption of a potentially fatal dose of morphine. Morphine sulfate extended-releasecapsules 100 mg ARE FOR USE IN OPIOID-TOLERANT PATIENTS ONLY. This capsule strength may cause fatal respiratory depression when ingested or administered to patients who are not previously exposed to opioids. Care should be taken in the prescribing of this capsule strength. Patients should be instructed against use by individuals other than the patient for whom it was prescribed, as such inappropriate use may have severe medical consequences, including death. Misuse, Abuse and Diversion of Opioids Morphine sulfate extended-release contains morphine an opioid agonist and a Schedule II controlled substance. Opioid agonists have the potential for being abused and are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Morphine can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing morphine sulfate extended-release in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Abuse of morphine sulfate extended-release by crushing, chewing, snorting or injecting the dissolved product will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see WARNINGS and DRUG ABUSE AND DEPENDENCE ) 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. Interactions with Alcohol and Drugs of Abuse Morphine sulfate extended-release 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, and profound sedation or coma may result. Impaired Respiration Respiratory depression is the chief hazard of all morphine preparations. Respiratory depression occurs more frequently in elderly and debilitated patients, and those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction (when even moderate therapeutic doses may significantly decrease pulmonary ventilation). Morphine sulfate extended-release should be used 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 may increase airway resistance and decrease respiratory drive to the point of apnea. In these patients, alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose. Head Injury and Increased Intracranial Pressure The respiratory depressant effects of morphine with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a pre-existing increase in intracranial pressure. Morphine sulfate extended-release produces effects which may obscure neurologic signs of further increases in pressure in patients with head injuries. Morphine should only be administered under such circumstances when considered essential and then with extreme care. Hypotensive Effect Morphine sulfate extended-release may cause severe hypotension. There is an added risk to individuals whose ability to maintain blood pressure has already been compromised by a reduced blood volume, or a concurrent administration of drugs such as phenothiazines or general anesthetics. (See also PRECAUTIONS - Drug Interactions . ) Morphine sulfate extended-release may produce orthostatic hypotension and syncope in ambulatory patients. Morphine sulfate extended-release, like all opioid analgesics, should be administered with caution to patients in circulatory shock, as vasodilation produced by the drug may further reduce cardiac output and blood pressure. Interactions with other CNS Depressants Morphine sulfate extended-release should be used with great caution and in reduced dosage in patients who are concurrently receiving other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, other tranquilizers, and alcohol because respiratory depression, hypotension, and profound sedation or coma may result. Gastrointestinal Obstruction Morphine sulfate extended-release should not be given to patients with gastrointestinal obstruction, particularly paralytic ileus, as there is a risk of the product remaining in the stomach for an extended period and the subsequent release of a bolus of morphine when normal gut motility is restored. As with other solid morphine formulations diarrhea may reduce morphine absorption. Other Although extremely rare, cases of anaphylaxis have been reported.

ADVERSE REACTIONS Serious adverse reactions that may be associated with morphine sulfate extended-release therapy in clinical use are those observed with other opioid analgesics and include: respiratory depression, respiratory arrest, apnea, circulatory depression, cardiac arrest, hypotension, and/or shock (see OVERDOSAGE , WARNINGS ). The less severe adverse events seen on initiation of therapy with morphine sulfate extended-release are also typical opioid side effects. These events are dose dependent, and their frequency depends on the clinical setting, the patient's level of opioid tolerance, and host factors specific to the individual. They should be expected and managed as a part of opioid analgesia. The most frequent of these include drowsiness, dizziness, constipation and nausea. In many cases, the frequency of these events during initiation of therapy may be minimized by careful individualization of starting dosage, slow titration, and the avoidance of large rapid swings in plasma concentrations of the opioid. Many of these adverse events, will cease or decrease as morphine sulfate extended-release therapy is continued and some degree of tolerance is developed, but others may be expected to remain troublesome throughout therapy. Management of Excessive Drowsiness Most patients receiving morphine sulfate extended-release will experience initial drowsiness. This usually disappears within 3 to 5 days and is not a cause of concern unless it is excessive, or accompanied by unsteadiness or confusion. Dizziness and unsteadiness may be associated with postural hypotension, particularly in elderly or debilitated patients, and has been associated with syncope and falls in non-tolerant patients started on opioids. Excessive or persistent sedation should be investigated. Factors to be considered should include: concurrent sedative medications, the presence of hepatic or renal insufficiency, hypoxia or hypercapnia due to exacerbated respiratory failure, intolerance to the dose used (especially in older patients), disease severity and the patient's general condition. The dosage should be adjusted according to individual needs, but additional care should be used in the selection of initial doses for the elderly patient, the cachectic or gravely ill patient, or in patients not already familiar with opioid analgesic medications to prevent excessive sedation at the onset of treatment. Management of Nausea and Vomiting Nausea and vomiting are common after single doses of morphine sulfate extended-release or as an early undesirable effect of chronic opioid therapy. The prescription of a suitable antiemetic should be considered, with the awareness that sedation may result (see Drug Interactions ). The frequency of nausea and vomiting usually decreases within a week or so but may persist due to opioid-induced gastric stasis. Metoclopramide is often useful in such patients. Management of Constipation Virtually all patients suffer from constipation while taking opioids, such as morphine sulfate extended-release, on a chronic basis. Some patients, particularly elderly, debilitated or bedridden patients may become impacted. Tolerance does not usually develop for the constipating effects of opioids. Patients must be cautioned accordingly and laxatives, softeners and other appropriate treatments should be used prophylactically from the beginning of opioid therapy. Adverse Events Probably Related to morphine sulfate extended-release Administration In clinical studies in patients with chronic cancer pain the most common adverse events reported by patients at least once during therapy were drowsiness (9%), constipation (9%), nausea (7%), dizziness (6%), and anxiety (6%). Other less common side effects expected from morphine sulfate extended-release or seen in less than 3% of patients in the clinical studies were: Body as a Whole: Asthenia, accidental injury, fever, pain, chest pain, headache, diaphoresis, chills, flu syndrome, back pain, malaise, withdrawal syndrome Cardiovascular: Tachycardia, atrial fibrillation, hypotension, hypertension, pallor, facial flushing, palpitations, bradycardia, syncope Central Nervous System: Confusion, dry mouth, anxiety, abnormal thinking, abnormal dreams, lethargy, depression, tremor, loss of concentration, insomnia, amnesia, paresthesia, agitation, vertigo, foot drop, ataxia, hypesthesia, slurred speech, hallucinations, vasodilation, euphoria, apathy, seizures, myoclonus Endocrine: Hyponatremia due to inappropriate ADH secretion, gynecomastia Gastrointestinal: Vomiting, anorexia, dysphagia, dyspepsia, diarrhea, abdominal pain, stomach atony disorder, gastro-esophageal reflux, delayed gastric emptying, biliary colic Hemic & Lymphatic: Anemia, leukopenia, thrombocytopenia Metabolic & Nutritional: Peripheral edema, hyponatremia, edema Musculoskeletal: Back pain, bone pain, arthralgia Respiratory: Hiccup, rhinitis, atelectasis, asthma, hypoxia, dyspnea, respiratory insufficiency, voice alteration, depressed cough reflex, non-cardiogenic pulmonary edema Skin and Appendages: Rash, decubitus ulcer, pruritus, skin flush Special Senses: Amblyopia, conjunctivitis, miosis, blurred vision, nystagmus, diplopia Urogenital: Urinary abnormality, amenorrhea, urinary retention, urinary hesitancy, reduced libido, reduced potency, prolonged labor Post-marketing Adverse Events Probably Related to Morphine Sulfate Extended-Release The safety of morphine sulfate extended-release has been evaluated in a randomized, prospective, open-label, 4-week treatment period, post-marketing study consisting of 1418 patients ages 18 to 85 with chronic, non-malignant pain (e.g., back pain, osteoarthritis, neuropathic pain). No control arm was included in this study. The most common adverse events reported at least once during therapy were constipation (12%), nausea (9%) and somnolence (3%). Other less common side effects occurring in less than 3% of patients were vomiting, pruritus, dizziness, sedation, dry mouth, headache, fatigue and rash.