1 INDICATIONS AND USAGE DILAUDID INJECTION is an opioid agonist indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate.

( 1 ) Limitations of Use: ( 1 ) Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, reserve Hydromorphone Hydrochloride Injection 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 DILAUDID INJECTION should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

DILAUDID INJECTION is indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate.

Limitations of Use: Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see Warnings and Precautions ( 5.1 )] , reserve DILAUDID INJECTION 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.

DILAUDID INJECTION should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

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 ( 5.1 )] • Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] • Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions ( 5.3 )] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] • Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.5 )] • Adrenal Insufficiency [see Warnings and Precautions ( 5.7 )] • Severe Hypotension [see Warnings and Precautions ( 5.8 )] • Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.10 )] • Seizures [see Warnings and Precautions ( 5.11 )] • Withdrawal [see Warnings and Precautions ( 5.12 )] The following adverse reactions associated with the use of hydromorphone 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 DILAUDID INJECTION include respiratory depression and apnea and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest.

The most common adverse effects are lightheadedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus.

These effects seem to be more prominent in ambulatory patients and in those not experiencing severe pain.

Most common adverse reactions are lightheadedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Less Frequently Observed Adverse Reactions Cardiac disorders: tachycardia, bradycardia, palpitations Eye disorders: vision blurred, diplopia, miosis, visual impairment Gastrointestinal disorders: constipation, ileus, diarrhea, abdominal pain General disorders and administration site conditions: weakness, feeling abnormal, chills, injection site urticaria, fatigue, injection site reactions, peripheral edema Hepatobiliary disorders: biliary colic Immune system disorders: anaphylactic reactions, hypersensitivity reactions Investigations: hepatic enzymes increased Metabolism and nutrition disorders: decreased appetite Musculoskeletal and connective tissue disorders: muscle rigidity Nervous system disorders: headache, tremor, paraesthesia, nystagmus, increased intracranial pressure, syncope, taste alteration , involuntary muscle contractions, presyncope, convulsion, drowsiness, dyskinesia, hyperalgesia, lethargy, myoclonus, somnolence Psychiatric disorders: agitation, mood altered, nervousness, anxiety , depression, hallucination, disorientation, insomnia, abnormal dreams Renal and urinary disorders: urinary retention, urinary hesitation, antidiuretic effects Reproductive system and breast disorders: erectile dysfunction Respiratory, thoracic, and mediastinal disorders: bronchospasm, laryngospasm, dyspnea, oropharyngeal swelling Skin and subcutaneous tissue disorders: injection site pain, urticaria, rash, hyperhidrosis Vascular disorders: flushing, hypotension, hypertension 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 DILAUDID INJECTION.

Androgen deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology ( 12.2 )] .

Hyperalgesia and Allodynia : Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions ( 5.5 )] Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids .

Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).