Remifentanil

ULTIVA is indicated for intravenous (IV) administration: • As an analgesic agent for use during the induction and maintenance of general anesthesia for inpatient and outpatient procedures. • For continuation as an analgesic into the immediate postoperative period in adult patients under the direct supervision of an anesthesia practitioner in a postoperative anesthesia care unit or intensive care setting. • As an analgesic component of monitored anesthesia care in adult patients. ULTIVA is an opioid agonist indicated for intravenous administration: • As an analgesic agent for use during the induction and maintenance of general anesthesia for inpatient and outpatient procedures.

ULTIVA is a µ-opioid agonist with rapid onset and peak effect, and short duration of action. The µ-opioid activity of ULTIVA is antagonized by opioid antagonists, including overdose reversal agents such as naloxone or nalmefene. Unlike other opioids, ULTIVA is rapidly metabolized by hydrolysis of the propanoic acid-methyl ester linkage by nonspecific blood and tissue esterases. ULTIVA is not a substrate for plasma cholinesterase (pseudocholinesterase) and, therefore, patients with atypical cholinesterase are expected to have a normal duration of action.

• Monitor patients closely for respiratory depression when initiating therapy and following dosage increases and adjust the dosage accordingly. • Administration: Continuous infusions of ULTIVA should be administered only by an infusion device. • Initial Dosage in Adults: See full prescribing information for recommended doses in adult patients. • Initial Dosage in Pediatric Patients: See full prescribing information for recommended doses in pediatric patients. • Geriatric Patients: The starting doses should be decreased by 50% in elderly patients (> 65 years).

ULTIVA is contraindicated: • For epidural or intrathecal administration due to the presence of glycine in the formulation. • In patients with hypersensitivity to remifentanil (e.g., anaphylaxis).

Boxed warning (serious and life-threatening risks from use of ultiva): Addiction, Abuse, and Misuse Because the use of ULTIVA exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions. • Life-Threatening Respiratory Depression: Monitor closely, particularly during initiation and titration. • Risks from Use as Postoperative Analgesia with Concomitant Benzodiazepines or other CNS Depressants: Hypotension, profound sedation, respiratory depression, coma, and death may result from the concomitant use of ULTIVA with benzodiazepines or other CNS depressants.

The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse • Life-Threatening Respiratory Depression • Interactions with Benzodiazepines or other CNS Depressants • Opioid-Induced Hyperalgesia and Allodynia • Serotonin Syndrome • Skeletal Muscle Rigidity • Bradycardia • Hypotension • Biliary Tract Disease • Seizures Most common adverse reactions (incidence ≥ 1%) were respiratory depression, bradycardia, hypotension, and skeletal muscle rigidity.

Table 18 includes clinically significant drug interactions with ULTIVA. Table 18: Clinically Significant Drug Interactions with ULTIVA Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, increases the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. Patients should be advised to avoid alcohol for 24 hours after surgery. Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol.

ULTIVA (remifentanil hydrochloride) for Injection, for intravenous use, is supplied as follows: NDC Number Container Concentration Quantity 67457-912-01 3 mL Single-Dose Vial 1 mg lyophilized powder Box of 10 67457-913-02 5 mL Single-Dose Vial 2 mg lyophilized powder Box of 10 67457-914-05 10 mL Single-Dose Vial 5 mg lyophilized powder Box of 10 ULTIVA should be stored at 2° to 25°C (36° to 77°F).