BLOXIVERZ- neostigmine methylsulfate injection

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

NEOSTIGMINE METHYLSULFATE (UNII: 98IMH7M386) (NEOSTIGMINE - UNII:3982TWQ96G)

Tilgjengelig fra:

Exela Pharma Sciences, LLC

Administreringsrute:

INTRAVENOUS

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

BLOXIVERZ, is a cholinesterase inhibitor, indicated for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery. BLOXIVERZ is contraindicated in patients with: Risk Summary Published studies and case reports over several decades about the use of neostigmine products, including neostigmine methylsulfate, in pregnant women have not identified any drug-associated risk for major birth defects and miscarriage. However, most of the available data are based on studies with exposure that occurred at the time of caesarean section or labor and delivery. These studies have not identified an adverse effect on maternal or infant outcomes. In animal reproduction studies, no adverse developmental effects were observed after administration of neostigmine methylsulfate to pregnant rats and rabbits during organogenesis with doses up to 0.1 and 0.2 times, respectively, the maximum recommended human dose (MRHD) of 5mg/60kg/person/day based on body surface area (mg/m2 ). The 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 the clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively. Data Animal Data In embryofetal development studies, rats and rabbits were administered neostigmine methylsulfate at human equivalent doses (HED, on a mg/m2 basis) of 1.6, 4 and 8.1 mcg/kg/day and 3.2, 8.1, and 13 mcg/kg/day, respectively, during the period of organogenesis (Gestation Days 6 through 17 for rats and Gestation Days 6 through 18 for rabbits). There was no evidence for a teratogenic effect in rats and rabbits up to HED 8.1 and 13 mcg/kg/day, which are approximately 0.097 times and 0.16 times the MRHD of 5 mg/60 kg, respectively in the presence of minimal maternal toxicity (tremors, ataxia, and prostration). The studies resulted in exposures in the animals well below predicted exposures in humans. In a pre- and postnatal development study in rats, neostigmine methylsulfate was administered to pregnant female rats at human equivalent doses (HED) of 1.6, 4 and 8.1 mcg/kg/day from Day 6 of gestation through Day 20 of lactation, with weaning on Day 21. There were no adverse effects on physical development, behavior, learning ability, or fertility in the offspring at HED doses up to 8.1 mcg/kg/day which is 0.097 times the MRHD of 5 mg/60 kg on a mg/m2 basis in the presence of minimal maternal toxicity (tremors, ataxia, and prostration). The studies resulted in exposures in the animals well below predicted exposures in humans. Risk Summary Published data from case reports are insufficient to determine the presence of neostigmine methylsulfate in human milk or the effects on the breastfed infant. There is no information on the effects of neostigmine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BLOXIVERZ and any potential adverse effects on the breastfed infant from BLOXIVERZ or from the underlying maternal condition. BLOXIVERZ is approved for the reversal of the effects of non-depolarizing neuromuscular blocking agents after surgery in pediatric patients of all ages. Recovery of neuromuscular activity occurs more rapidly with smaller doses of cholinesterase inhibitors in infants and children than in adults. However, infants and small children may be at greater risk of complications from incomplete reversal of neuromuscular blockade due to decreased respiratory reserve. The risks associated with incomplete reversal outweigh any risk from giving higher doses of BLOXIVERZ (up to 0.07 mg/kg or up to a total of 5 mg, whichever is less). The dose of BLOXIVERZ required to reverse neuromuscular blockade in children varies between 0.03 mg - 0.07 mg/kg, the same dose range shown to be effective in adults, and should be selected using the same criteria as used for adult patients [see Clinical Pharmacology (12.3)] . Since the blood pressure in pediatric patients, particularly infants and neonates, is sensitive to changes in heart rate, the effects of an anticholinergic agent (e.g., atropine) should be observed prior to administration of neostigmine to lessen the probability of bradycardia and hypotension. Because elderly patients are more likely to have decreased renal function, BLOXIVERZ should be used with caution and monitored for a longer period in elderly patients. The duration of action of neostigmine methylsulfate is prolonged in the elderly; however, elderly patients also experience slower spontaneous recovery from neuromuscular blocking agents. Therefore, dosage adjustments are not generally needed in geriatric patients; however, they should be monitored for longer periods than younger adults to assure additional doses of BLOXIVERZ are not required. The duration of monitoring should be predicated on the anticipated duration of action for the NMBA used on the patient [see Dosage and Administration (2.3)] . Elimination half-life of neostigmine methylsulfate was prolonged in anephric patients compared to normal subjects. Although no adjustments to BLOXIVERZ dosing appear to be warranted in patients with impaired renal function, they should be closely monitored to assure the effects of the neuromuscular blocking agent, particularly one cleared by the kidneys, do not persist beyond those of BLOXIVERZ. In this regard, the interval for re-dosing the neuromuscular blocking agent during the surgical procedure may be useful in determining whether, and to what extent, post-operative monitoring needs to be extended. The pharmacokinetics of neostigmine methylsulfate in patients with hepatic impairment have not been studied. Neostigmine methylsulfate is metabolized by microsomal enzymes in the liver. No adjustments to the dosing of BLOXIVERZ appear to be warranted in patients with hepatic insufficiency. However, patients should be carefully monitored if hepatically cleared neuromuscular blocking agents were used during their surgical procedure as their duration of action may be prolonged by hepatic insufficiency whereas BLOXIVERZ, which undergoes renal elimination, will not likely be affected. This could result in the effects of the neuromuscular blocking agent outlasting those of BLOXIVERZ. This same situation may arise if the neuromuscular blocking agent has active metabolites. In this regard, the interval for re-dosing the neuromuscular blocking agent during the surgical procedure may be useful in determining whether, and to what extent, post-operative monitoring needs to be extended.

Produkt oppsummering:

BLOXIVERZ (Neostigmine Methylsulfate Injection, USP) is available in the following: NDC No. Strength Vial Size 51754-1210-3 0.5 mg/mL 10 mL multiple-dose vials (supplied in packages of 10) 51754-1220-3 1 mg/mL 10 mL multiple-dose vials (supplied in packages of 10) 51754-1200-3 1 mg/mL 5 mL single-dose prefilled syringe (supplied in packages of 10) The vial stopper is not made with natural rubber latex. BLOXIVERZ should be stored at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature). Protect from light. Store in carton until time of use. Manufactured for: Exela Pharma Sciences, LLC Lenoir, NC 28645

Autorisasjon status:

New Drug Application

Preparatomtale

BLOXIVERZ- NEOSTIGMINE METHYLSULFATE INJECTION
EXELA PHARMA SCIENCES, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
BLOXIVERZ SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR BLOXIVERZ.
BLOXIVERZ (NEOSTIGMINE METHYLSULFATE INJECTION), FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1939
INDICATIONS AND USAGE
BLOXIVERZ, is a cholinesterase inhibitor, indicated for the reversal
of the effects of non-depolarizing
neuromuscular blocking agents after surgery (1).
DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
Injection: 0.5 mg/mL and 1 mg/mL in 10 mL multiple-dose vials and 1
mg/mL in 5 mL single-dose prefilled
syringe (3)
CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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ADVERSE REACTIONS
Most common adverse reactions during treatment: bradycardia, nausea
and vomiting. (6)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT EXELA PHARMA SCIENCES,
LLC AT 1-888-
451-4321 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
REVISED: 12/2023
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
®
Should be administered by trained healthcare providers (2.1)
Peripheral nerve stimulator and monitoring for twitch responses should
be used to determine when
BLOXIVERZ should be initiated and if additional doses are needed (2.2)
o
o
For reversal of NMBAs with shorter half-lives, when first twitch
response is substantially greater
than 10% of baseline, or when a second twitch is present: 0.03 mg/kg
by intravenous route (2.2)
For reversal of NMBAs with longer half-lives or when first twitch
response is close to 10% of
baseline: 0.07 mg/kg by intravenous route (2.2)
Maximum total dosage is 0.07 mg/kg or up to a total of 5 mg (whichever
is less) (2.2)
An anticholinergic agent, e.g., atropine sulfate or glycopyrrolate,
should be administered prior to or
concomitantly with BLOXIVERZ (2.4)
Hypersensitivity to neostigmine (4)
Peritonitis or mechanical obstruction of the intestinal or urinary
tract (4)
Bradycardia: Atropi