Remifentanil Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- REMIFENTANIL HYDROCHLORIDE
- ULTIVA
Boxed Warning
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 [see Warnings and Precautions (5.1)]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of ULTIVA, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of ULTIVA are essential [see Warnings and Precautions (5.2)]. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of ULTIVA and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3), Drug Interactions (7)].
Indications and Usage
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.
Contraindications
ULTIVA is contraindicated: •For epidural or intrathecal administration due to the presence of glycine in the formulation [see Nonclinical Toxicology (13)]. •In patients with hypersensitivity to remifentanil (e.g., anaphylaxis) [see Adverse Reactions (6.2)].
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 or other CNS Depressants [see Warnings and Precautions (5.3)] •Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.4)] •Serotonin Syndrome [see Warnings and Precautions (5.5) ] •Skeletal Muscle Rigidity [see Warnings and Precautions (5.6)] •Bradycardia [see Warnings and Precautions (5.8)] •Hypotension [see Warnings and Precautions (5.9)] •Biliary Tract Disease [see Warnings and Precautions (5.12)] •Seizures [see Warnings and Precautions (5.13)]
Drug Interactions
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 [see Warnings and Precautions (5.3)]. 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 [see Warnings and Precautions (5.3)]. Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings and Precautions (5.5) ]. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue ULTIVA if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome [see Warnings and Precautions (5.5) ] or opioi
Mechanism of Action
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.
Overdosage
Clinical Presentation Acute overdose with remifentanil can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2)]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures. For clinically significant respiratory or circulatory depression secondary to remifentanil overdose, stop the infusion or administer an opioid overdose reversal agent such as naloxone or nalmefene. Opioid overdose reversal agents should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to remifentanil overdose. In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the reversal agent should be begun with care and by titration with smaller than usual doses of the reversal agent.