EXALGO^® (hydromorphone HCl) extended-release tablets, CII 32 mg

IMPORTANT RISK INFORMATION

WARNINGS AND PRECAUTIONS

• EXALGO contains hydromorphone, a Schedule II controlled substance. As an opioid, EXALGO exposes users to the risks of addiction, abuse, and misuse.  As modified-release products such as EXALGO deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of hydromorphone present. With intravenous abuse, the tablet excipients, especially polyethylene oxide, can be expected to result in necrosis and inflammation of cardiac tissues. In addition, parenteral drug abuse is commonly associated with transmission of infectious disease such as hepatitis and HIV. 
• While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of EXALGO, the risk is greatest during the initiation of therapy or following a dose increase.  Overestimating the EXALGO dose when converting patients from another opioid product can result in fatal overdose with the first dose.  Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients. In patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression, EXALGO may decrease respiratory drive to the point of apnea, particularly when initiating therapy and titrating with EXALGO, even at usual therapeutic doses. 
• Hypotension, profound sedation, coma, respiratory depression, and death may result if EXALGO is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). 
• EXALGO may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised.
• In patients with head injury or increased intracranial pressure, EXALGO may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury.
• EXALGO may cause spasm of the sphincter of Oddi.
• May aggravate convulsions in patients with convulsive disorders; may induce or aggravate seizures in some clinical settings.
• Do not abruptly discontinue EXALGO.  The use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (buprenorphine) analgesics in patients who have received or are receiving EXALGO may reduce the analgesic effect and/or may precipitate withdrawal symptoms.
• EXALGO may impair the ability to drive a car or operate machinery. 

ADVERSE REACTIONS

• Serious adverse events include respiratory depression, overdose, and death. Hypersensitivity reactions, angioedema, and urticaria have been identified during post-approval use of EXALGO. 
• The most common adverse events (>10%) seen in clinical studies (N=2474) were: constipation, nausea, vomiting, somnolence, headache, asthenia/fatigue, and dizziness.

USE IN SPECIFIC POPULATIONS

• Pregnancy: Opioids cross the placenta and may produce respiratory depression in neonates. Prolonged use of EXALGO during pregnancy can result in withdrawal syndrome in the neonate, which can be life threatening.
• Breastfeeding: Nursing should not be undertaken while a patient is receiving EXALGO since hydromorphone is excreted in the milk.
• Pediatrics: The safety and effectiveness of EXALGO in patients 17 years of age and younger have not been established.
• Patients with moderate renal or hepatic impairment have been shown to have increased plasma concentrations of hydromorphone.  These patients should be closely monitored for respiratory and central nervous system depression.  Use of alternate analgesics is recommended in patients with severe hepatic impairment and alternate analgesics which permit greater dosing flexibility should be considered in patients with severe renal impairment.

For additional information on EXALGO^® (hydromorphone HCl) extended-release tablets, CII 32 mg, call Customer Service at 1.800.325.8888 or Medical Information at 1.800.778.7898.