NEOSTIGMINE METHYLSULFATE- neostigmine methylsulfate injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Fresenius Kabi USA, LLC

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Neostigmine Methylsulfate Injection, a cholinesterase inhibitor, is indicated for reversal of the effects of nondepolarizing neuromuscular blocking agents (NMBA) after surgery. Neostigmine is contraindicated in patients with: - known hypersensitivity to neostigmine methylsulfate (known hypersensitivity reactions have included urticaria, angioedema, erythema multiforme, generalized rash, facial swelling, peripheral edema, pyrexia, flushing, hypotension, bronchospasm, bradycardia and anaphylaxis). - peritonitis or mechanical obstruction of the urinary or intestinal tracts. Risk Summary There are no adequate or well-controlled studies of Neostigmine Methylsulfate Injection in pregnant women. It is not known whether Neostigmine Methylsulfate Injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. The incidence of malformations in human pregnancies has not been established for neostigmine as the data are limited. All pregnancies, regardless of drug exposure, have a background risk of 2 to 4% for major birth defects, and 15 to 20% for pregnancy loss. No adverse effects were noted in rats or rabbits treated with human equivalent doses of neostigmine methylsulfate doses up to 8.1 and 13 mcg/kg/day, respectively, during organogenesis (0.1 to 0.2-times the maximum recommended human dose of 5 mg/60 kg person/day based on body surface area comparisons). Anticholinesterase drugs, including neostigmine may cause uterine irritability and induce premature labor when administered to pregnant women near term. Neostigmine Methylsulfate Injection should be given to a pregnant woman only if clearly needed. Data Animal Data It is not known whether Neostigmine Methylsulfate Injection is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Neostigmine Methylsulfate Injection in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Data from published literature support the intravenous use of neostigmine methylsulfate for reversal of nondepolarizing neuromuscular blocking agents in all pediatric age groups. 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 Neostigmine Methylsulfate (up to 0.07 mg/kg or up to a total of 5 mg, whichever is lower). The dose of Neostigmine Methylsulfate required to reverse neuromuscular blockade in children varies between 0.03 mg to 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. Elderly patients are likely to have decreased renal function, which may prolong the duration of action of neostigmine methylsulfate. However, elderly patients also experience slower spontaneous recovery from neuromuscular blocking agents. Therefore, dosage adjustments are generally not needed in geriatric patients; however, they should be monitored for longer periods than younger adults to assure additional doses of Neostigmine Methylsulfate Injection are not required. The duration of monitoring should be predicated on the anticipated duration of action for the neuromuscular blocking agents used on the patient. Elimination half-life of neostigmine was prolonged in anephric patients compared to normal subjects, so neostigmine concentration may increase in patients with impaired renal functions. Although no adjustments to Neostigmine Methylsulfate Injection dosing appear to be warranted in patients with impaired renal function, they should be closely monitored for a longer period of time. To assure the effects of the neuromuscular blocking agent, particularly one cleared by the kidneys, do not persist beyond those of Neostigmine Methylsulfate Injection, 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 is metabolized by microsomal enzymes in the liver so neostigmine concentration may increase in patients with impaired hepatic functions. Although no adjustments to the dosing of Neostigmine Methylsulfate Injection appear to be warranted in patients with hepatic insufficiency, patients should be carefully monitored for a longer period of time. If hepatically cleared neuromuscular blocking agents were used during the surgical procedure, their duration of action may also be prolonged by hepatic insufficiency. This could result in the effects of the neuromuscular blocking agent outlasting those of Neostigmine Methylsulfate Injection. 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. INSTRUCTIONS FOR USE Figure 1: Outer Packaging and Prefilled Syringe NOTES: - Inspect the outer packaging (blister pack) to confirm the integrity of the packaging. Do not use if the blister pack or the prefilled syringe has been damaged. - Remove the syringe from the outer packaging. (See Figure 2) Figure 2 Remove the syringe from the outer packaging. (See Figure 2) Figure 2 - Visually inspect the syringe. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Visually inspect the syringe. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. - Twist off the syringe tip cap. Do not remove the label around the luer lock collar. (See Figure 3) Figure 3 Twist off the syringe tip cap. Do not remove the label around the luer lock collar. (See Figure 3) Figure 3 - Expel air bubble(s). Adjust the dose (if applicable). - Administer the dose ensuring that pressure is maintained on the plunger rod during the entire administration. - Discard the used syringe into an appropriate receptacle. For more information concerning this drug, please call Fresenius Kabi USA, LLC at 1-800-551-7176. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. U.S. Patents 9,731,082 and 10,661,018 Lake Zurich, IL 60047 www.fresenius-kabi.com/us 451585B

Product summary:

Neostigmine Methylsulfate Injection, USP is supplied as a colorless liquid in a prefilled syringe as follows: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Authorization status:

New Drug Application

Summary of Product characteristics

NEOSTIGMINE METHYLSULFATE - NEOSTIGMINE METHYLSULFATE INJECTION,
SOLUTION
FRESENIUS KABI USA, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
NEOSTIGMINE
METHYLSULFATE INJECTION SAFELY AND EFFECTIVELY.
SEE FULL PRESCRIBING INFORMATION FOR NEOSTIGMINE METHYLSULFATE
INJECTION.
NEOSTIGMINE METHYLSULFATE INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1939
INDICATIONS AND USAGE
Neostigmine Methylsulfate, a cholinesterase inhibitor, is indicated
for reversal of the effects of
nondepolarizing neuromuscular blocking agents (NMBA) after surgery
(1).
DOSAGE AND ADMINISTRATION
Dosage
Should be administered by trained healthcare providers (2.1)
Recommend use of a peripheral nerve stimulator to determine whether
neostigmine methylsulfate
should be administered and to monitor recovery from neuromuscular
blockade (2.1).
Recommended dosage range is 0.03 mg/kg to 0.07mg/kg for reversing
non-depolarizing neuromuscular
block when administered with an anticholinergic agent (atropine or
glycopyrrolate) (2.2, 2.3, 2.4)
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 neostigmine methylsulfate (2.4)
Dose of Anticholinergic Agent (atropine or glycopyrrolate)
Administer atropine sulfate (~15 mcg/kg) or glycopyrrolate (~10
mcg/kg) intravenously either several
minutes before or concomitantly with neostigmine methylsulfate (using
separate syringes) (2.4)
DOSAGE FORMS AND STRENGTHS
Injection: 3 mg per 3 mL (1 mg per mL) solution in 3 mL single-dose
prefilled syringe (3)
CONTRAIN