ULTIVA- remifentanil hydrochloride injection, powder, lyophilized, for solution

Kraj: Stany Zjednoczone

Język: angielski

Źródło: NLM (National Library of Medicine)

Składnik aktywny:

Remifentanil Hydrochloride (UNII: 5V444H5WIC) (Remifentanil - UNII:P10582JYYK)

Dostępny od:

Mylan Institutional LLC

Droga podania:

INTRAVENOUS

Typ recepty:

PRESCRIPTION DRUG

Wskazania:

ULTIVA is indicated for intravenous (IV) administration: ULTIVA is contraindicated: Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with remifentanil hydrochloride in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, reduced fetal rat body weight and pup weights were reported at 2.2 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min for a surgical procedure lasting 3 hours. There were no malformations noted when remifentanil was administered via bolus injection to pregnant rats or rabbits during organogenesis at doses approximately 5 times and approximately equal, respectively, to a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min for a surgical procedure lasting 3 hours [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. ULTIVA is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including ULTIVA, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. In a human clinical trial, the average maternal remifentanil concentrations were approximately twice those seen in the fetus. In some cases, however, fetal concentrations were similar to those in the mother. The umbilical arteriovenous ratio of remifentanil concentrations was approximately 30% suggesting metabolism of remifentanil in the neonate. Pregnant rats were treated from Gestation Day 6 to 15 with intravenous remifentanil doses of 0.5, 1.6, or 5 mg/kg/day (0.2, 0.7, or 2.2 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on body surface area, respectively). Reduced fetal weights were reported in the high dose group; however, no malformations were reported in surviving fetuses despite a non-dose dependent increase in maternal mortality. Pregnant rabbits were treated from Gestation Day 6 to 18 with intravenous remifentanil doses of 0.1, 0.5, or 0.8 mg/kg/day (0.09, 0.4, or 0.7 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on body surface area, respectively). No malformations were reported in surviving fetuses despite clear maternal toxicity (decreased food consumption and body weights and increased mortality in all treatment groups). Pregnant rats were treated from Gestation Day 6 to Lactation Day 21 with intravenous boluses of remifentanil 0.5, 1.6, or 5 mg/kg/day (0.2, 0.7, or 2.2 times a human intravenous infusion of an induction dose of 1 mcg/kg with a maintenance dose of 2 mcg/kg/min based on body surface area for a surgical procedure lasting 3 hours based on body surface area, respectively). Reduced birth weights were noted in the high-dose groups in the presence of maternal toxicity (increased mortality in all groups). It is not known whether remifentanil is excreted in human milk. After receiving radioactive-labeled remifentanil, the radioactivity was present in the milk of lactating rats. Because fentanyl analogs are excreted in human milk, caution should be exercised when ULTIVA is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ULTIVA and any potential adverse effects on the breastfed infant from ULTIVA or from the underlying maternal condition. Infants exposed to ULTIVA through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. The efficacy and safety of ULTIVA as an analgesic agent for use in the maintenance of general anesthesia in outpatient and inpatient pediatric surgery have been established in controlled clinical studies in pediatric patients from birth to 12 years [see Clinical Studies (14.4)] . The initial maintenance infusion regimen of ULTIVA evaluated in pediatric patients from birth to 2 months of age was 0.4 mcg/kg/min, the approved adult regimen for use with N2 O. The clearance rate observed in neonates was highly variable and on average was 2 times higher than in the young healthy adult population. Therefore, while a starting infusion rate of 0.4 mcg/kg/min may be appropriate for some neonates, an increased infusion rate may be necessary to maintain adequate surgical anesthesia, and additional bolus doses may be required. The individual dose for each patient should be carefully titrated. [See Clinical Pharmacology: Specific Populations: Pediatric Population (12.3) and Dosage and Administration, Table 2 and Maintenance of Anesthesia (2.2).] ULTIVA has not been studied in pediatric patients for use as a postoperative analgesic or as an analgesic component of monitored anesthesia care. Respiratory depression is the chief risk for elderly patients treated with opioids and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of ULTIVA slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.2)] Of the total number of subjects in clinical studies of ULTIVA, 486 were 65 and over (age range 66 to 90 years). While the effective biological half-life of remifentanil is unchanged, elderly patients have been shown to be twice as sensitive as the younger population to the pharmacodynamic effects of remifentanil. The recommended starting dose of ULTIVA should be decreased by 50% in patients over 65 years of age [see Clinical Pharmacology (12.3) and Dosage and Administration (2.2)] . Titrate the dosage of ULTIVA slowly in geriatric patients. [See Warnings and Precautions (5.5) .] The clearance of remifentanil is reduced (approximately 25%) in the elderly (> 65 years of age) compared to young adults (average 25 years of age). However, remifentanil blood concentrations fall as rapidly after termination of administration in the elderly as in young adults. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. As for all potent opioids, caution is required with use in morbidly obese patients because of alterations in cardiovascular and respiratory physiology [see Dosage and Administration (2.2)] . No data are available on the long-term (longer than 16 hours) use of ULTIVA as an analgesic in ICU patients. ULTIVA contains remifentanil, a Schedule II controlled substance. ULTIVA contains remifentanil, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions (5.1)] . Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of ULTIVA increases risk of overdosage, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of ULTIVA with alcohol and/or other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction. All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of ULTIVA abuse include those with a history of prolonged use of any opioid, including products containing remifentanil, those with a history of drug or alcohol abuse, or those who use ULTIVA in combination with other abused drugs. “Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. ULTIVA, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Abuse of ULTIVA poses a risk of overdose and death. The risk is increased with concurrent use of ULTIVA with alcohol and/or other CNS depressants. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Both tolerance and physical dependence can develop during use of opioid therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. ULTIVA should not be abruptly discontinued in a physically-dependent patient [see Dosage and Administration (2)] . If ULTIVA is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur, typically characterized by restlessness, lacrimation, rhinorrhea, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)] .

Podsumowanie produktu:

ULTIVA (remifentanil hydrochloride) for Injection, for intravenous use, is supplied as follows: 72078-034-01   3 mL Single-Dose Vial 1 mg lyophilized powder Box of 10 72078-035-02   5 mL Single-Dose Vial 2 mg lyophilized powder Box of 10 72078-036-05 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). Discard unused portion.

Status autoryzacji:

New Drug Application

Charakterystyka produktu

ULTIVA- REMIFENTANIL HYDROCHLORIDE INJECTION, POWDER, LYOPHILIZED, FOR
SOLUTION
MYLAN INSTITUTIONAL LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ULTIVA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ULTIVA.
ULTIVA (REMIFENTANIL HYDROCHLORIDE), FOR INJECTION, FOR INTRAVENOUS
USE, CII
INITIAL U.S. APPROVAL: 1996
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF ULTIVA
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
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RECENT MAJOR CHANGES
Boxed Warning 12/2023
Warnings and Precautions (5.3, 5.4) 12/2023
INDICATIONS AND USAGE
ULTIVA is an opioid agonist indicated for intravenous administration:
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
For injection: 1 mg, 2 mg, and 5 mg for intravenous administration
after reconstitution and dilution (3)
CONTRAINDICATIONS
ULTIVA is contraindicated:
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WARNINGS AND PRECAUTIONS
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®
ULTIVA EXPOSES USERS TO THE RISKS OF ADDICTION, ABUSE, AND MISUSE.
ASSESS
PATIENT’S RISK BEFORE PRESCRIBING AND REASSESS REGULARLY FOR THE
DEVELOPMENT OF
THESE BEHAVIORS AND CONDITIONS_.(5.1)_
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.
_(5.2)_
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 FOR USE
IN PATIENTS
FOR WHOM ALTERNATIVE TREATMENT OPTIONS ARE INADEQUATE. _(5.3, 7)_
As an analgesic agent for use during the induction and maintenance of
general anesthesia for
inpatient and outpatient procedures. (1)
For continuation as an analgesic into the immediate postoperative
period in adult patients under the
direct supervision of an anesthesia practitione