FDA label 54db2d37-d4f4-464e-be5d-95618a9a2f3a

WARNING: AVINZA capsules are a modified-release formulation of morphine sulfate indicated for once daily administration for the relief of moderate to severe pain requiring continuous, around-the-clock opioid therapy for an extended period of time. AVINZA CAPSULES ARE TO BE SWALLOWED WHOLE OR THE CONTENTS OF THE CAPSULES SPRINKLED ON APPLESAUCE. THE CAPSULE BEADS ARE NOT TO BE CHEWED, CRUSHED, OR DISSOLVED DUE TO THE RISK OF RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE . PATIENTS MUST NOT CONSUME ALCOHOLIC BEVERAGES WHILE ON AVINZA THERAPY. ADDITIONALLY, PATIENTS MUST NOT USE PRESCRIPTION OR NON-PRESCRIPTION MEDICATIONS CONTAINING ALCOHOL WHILE ON AVINZA THERAPY. CONSUMPTION OF ALCOHOL WHILE TAKING AVINZA MAY RESULT IN THE RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE.

WARNINGS AVINZA must be swallowed whole (not chewed, crushed, or dissolved) or AVINZA may be opened and the entire bead contents sprinkled on a small amount of applesauce immediately prior to ingestion. THE CAPSULES MUST NOT BE CHEWED, CRUSHED, OR DISSOLVED DUE TO THE RISK OF RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE. (see BOX WARNING , CLINICAL PHARMACOLOGY ) Patients must not consume alcoholic beverages while on AVINZA therapy. Additionally, patients must not use prescription or non-prescription medications containing alcohol while on AVINZA therapy. Consumption of alcohol while taking AVINZA may result in the rapid release and absorption of a potentially fatal dose of morphine. THE DAILY DOSE OF AVINZA MUST BE LIMITED TO A MAXIMUM OF 1600 MG/DAY. AVINZA DOSES OF OVER 1600 MG/DAY CONTAIN A QUANTITY OF FUMARIC ACID THAT HAS NOT BEEN DEMONSTRATED TO BE SAFE, AND WHICH MAY RESULT IN SERIOUS RENAL TOXICITY. Misuse, Abuse and Diversion of Opioids Morphine 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 can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing AVINZA in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Abuse of AVINZA by crushing, chewing, snorting, or injecting the dissolved product will result in the immediate release of the entire daily dose of the opioid and pose a significant risk to the abuser that could result in overdose and death. Intravenous abuse of a water extract of AVINZA may lead to serious pulmonary complications due to the extraction of talc along with morphine sulfate. (see DRUG ABUSE AND ADDICTION ) 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 may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression. In vitro studies performed by the FDA demonstrated that when AVINZA 30 mg was mixed with 900 mL of buffer solutions containing ethanol (20% and 40%), the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine. While the relevance of in vitro lab tests regarding AVINZA to the clinical setting remains to be determined, this acceleration of release may correlate with in vivo rapid release of the total morphine dose, which could result in the absorption of a potentially fatal dose of morphine. Impaired Respiration Respiratory depression is the chief hazard of all morphine preparations. 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. Morphine 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. 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 produces effects which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries. Morphine should only be administered under such circumstances when considered essential and then with extreme care. Hypotensive Effect AVINZA, like all morphine products, 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. (see also PRECAUTIONS, Drug Interactions ) AVINZA may produce orthostatic hypotension and syncope in ambulatory patients. AVINZA is an opioid analgesic which should be administered with caution to patients in circulatory shock, as vasodilation produced by the drug may further reduce cardiac output and blood pressure. Gastrointestinal Obstruction AVINZA should not be administered to patients with gastrointestinal obstruction, especially paralytic ileus because AVINZA, like all morphine preparations, diminishes propulsive peristaltic waves in the gastrointestinal tract and may prolong the obstruction.

ADVERSE REACTIONS In controlled and open label clinical studies, 560 patients with chronic malignant or non-malignant pain were treated with AVINZA. The most common serious adverse events reported with administration of AVINZA were vomiting, nausea, death, dehydration, dyspnea, and sepsis. (Deaths occurred in patients treated for pain due to underlying malignancy.) Serious adverse events caused by morphine include respiratory depression, apnea, and to a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest. Adverse Events The common adverse events seen on initiation of therapy with morphine are dose-dependent and are typical opioid‑related side effects. The most frequent of these include constipation, nausea and somnolence. The frequency of these events depends upon several factors including the clinical setting, the patient’s level of opioid tolerance, and host factors specific to the individual. These events should be anticipated and managed as part of opioid analgesia therapy. The most common adverse events (seen in greater than 10%) reported by patients treated with AVINZA during the clinical trials at least once during therapy were constipation, nausea, somnolence, vomiting, and headache. Adverse events occurring in 5‑10% of study patients were peripheral edema, diarrhea, abdominal pain, infection, urinary tract infection, accidental injury, flu syndrome, back pain, rash, sweating, fever, insomnia, depression, paresthesia, anorexia, dry mouth, asthenia and dyspnea. Other less common side effects expected from opioid analgesics, including morphine, or seen in fewer than 5% of patients taking AVINZA in the clinical trials were: 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, euphoria, hallucinations, lethargy, nervousness, abnormal thinking, tremor, vasodilation, vertigo . Respiratory System: hiccup, hypoventilation, voice alteration. Skin and Appendages: dry skin, urticaria. Special Senses: amblyopia, eye pain, taste perversion. Urogenital System: abnormal ejaculation, dysuria, impotence, decreased libido, oliguria, urinary retention.