Overview
11 DESCRIPTION ULTIVA (remifentanil hydrochloride) for injection is an opioid agonist. The chemical name is 3-[4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidine]propanoic acid methyl ester, hydrochloride salt. The molecular weight is 412.91. Its molecular formula is C 20 H 28 N 2 O 5 •HCl, and it has the following chemical structure.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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 such as naloxone. 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. 12.2 Pharmacodynamics The analgesic effects of ULTIVA are rapid in onset and offset. Its effects and side effects are dose dependent and similar to other µ-opioids.
Indications
- 1 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.
Common Doses
- 1 mcg
- 200 mcg
- 0.1 mcg
- 0.025 mcg
Dosage
2 DOSAGE AND ADMINISTRATION • Monitor patients closely for respiratory depression when initiating therapy and following dosage increases and adjust the dosage accordingly. ( 2.1 ) • Initial Dosage in Adults : See full prescribing information for recommended doses in adult patients. ( 2.2 , 2.3 ) • Initial Dosage in Pediatric Patients : See full prescribing information for recommended doses in pediatric patients. ( 2.2 ) • Geriatric Patients : The starting doses should be decreased by 50% in elderly patients (> 65 years). ( 2.6 ) 2.
Black Box Warning
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 [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...
Contraindications
- 4 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) ] . ULTIVA is contraindicated: • For epidural or intrathecal administration due to the presence of glycine in the formulation. ( 4 ) • In patients with hypersensitivity to remifentanil (e.g., anaphylaxis). ( 4 )
Side Effects
- 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 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.
Interactions
- 7 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. Intervention: Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation.