Version May 2024
Note: Product formulation (Prevduo) contains neostigmine 1 mg and glycopyrrolate 0.2 mg per mL; dosing based on neostigmine component.
Reversal of nondepolarizing neuromuscular blockade after surgery:
Note: Peripheral nerve stimulation delivering train-of-four (TOF) stimulus must be used to determine time of neostigmine initiation, monitoring of recovery of neuromuscular function, and possible need for additional doses. Dose necessary varies with neuromuscular blockade being reversed.
Children ≥2 years and Adolescents:
Usual dose: IV: Neostigmine: 0.03 to 0.07 mg/kg and glycopyrrolate 0.006 to 0.014 mg/kg generally achieves a TOF twitch ratio of 90% within 10 to 20 minutes of administration; maximum total dose: Neostigmine: 0.07 mg/kg or 5 mg (whichever is less).
Dose selection guide: IV:
Neostigmine 0.03 mg/kg dose is recommended for reversal of neuromuscular blocking agents (NMBAs) with shorter half-lives (eg, rocuronium), when the first twitch response to the TOF stimulus is substantially >10% of baseline, or when a second twitch is present.
Neostigmine 0.07 mg/kg dose is recommended for reversal of NMBAs with longer half-lives (eg, vecuronium, pancuronium), when the first twitch response is relatively weak (ie, not substantially >10% of baseline), or rapid recovery is needed.
There are no dosage adjustments provided in manufacturer's labeling; elimination of glycopyrrolate is severely impaired in kidney failure and neostigmine half-life is prolonged in anephric patients; use with caution and closely monitor.
There are no dosage adjustments provided in manufacturer's labeling; however, neostigmine is metabolized by the liver, use with caution and monitor closely.
(For additional information see "Neostigmine and glycopyrrolate: Drug information")
Reversal of nondepolarizing neuromuscular-blocking agents:
Note: Product formulation (Prevduo) contains neostigmine 1 mg and glycopyrrolate 0.2 mg per mL; dosing based on neostigmine component. Avoid use or use with caution in patients with certain neuromuscular diseases (eg, myasthenia gravis, muscular dystrophy); other agents may be preferred (eg, sugammadex); if neostigmine is used, reduced dosing may be required with titration based on train-of-four (TOF) monitoring (Ref). TOF monitoring should be used to determine time of neostigmine initiation and need for additional doses. Dosing may vary depending on patient-specific factors (eg, depth of paralysis, type of neuromuscular-blocking agent [NMBA] used, type of anesthesia, organ dysfunction, age, acid-base status) (Ref). Refer to institutional protocols and policies.
Usual dose: IV: Neostigmine 0.03 to 0.07 mg/kg (and glycopyrrolate 0.006 to 0.014 mg/kg); generally achieves a TOF twitch ratio of 90% within 10 to 20 minutes of administration; maximum total dose: neostigmine 0.07 mg/kg or 5 mg (whichever is less).
Dose selection based on neuromuscular-blocking agents administered or train-of-four monitoring:
Neostigmine 0.03 mg/kg: IV: Neostigmine 0.03 mg/kg dose is recommended for reversal of NMBAs with shorter half-lives (eg, rocuronium); or when the first twitch response to the TOF stimulus is substantially >10% of baseline or when a second twitch is present.
Neostigmine 0.07 mg/kg: IV: Neostigmine 0.07 mg/kg dose is recommended for reversal of NMBAs with longer half-lives (eg, vecuronium, pancuronium), when the first twitch response is relatively weak (ie, not substantially >10% of baseline), or when rapid recovery is needed.
There are no dosage adjustments provided in manufacturer's labeling; elimination of glycopyrrolate is severely impaired in kidney failure and neostigmine half-life is prolonged in anephric patients; use with caution and closely monitor.
There are no dosage adjustments provided in manufacturer's labeling; however, neostigmine and some neuromuscular-blocking agents are metabolized by the liver; use with caution and monitor closely.
See individual agents.
Hypersensitivity to neostigmine methylsulfate, glycopyrrolate, or any component of the formulation; peritonitis or mechanical obstruction of the intestinal or urinary tract; glaucoma; obstructive uropathy (eg, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the GI tract (eg, achalasia, pyloroduodenal stenosis); paralytic ileus, intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis.
Concerns related to adverse effects:
• Cardiovascular effects: Bradycardia, hypotension, and dysrhythmias may occur with neostigmine use; risk may be increased in patients with certain cardiovascular conditions (eg, coronary artery disease, cardiac arrhythmias, recent acute coronary syndrome). Risk may also be increased in patients with myasthenia gravis.
• Cholinergic crisis: Overdosage may result in cholinergic crisis, characterized by extreme muscle weakness and potentially fatal respiratory paralysis. Cholinergic crisis should be distinguished from myasthenic crisis, which is also characterized by extreme muscle weakness, but would require radically different treatment.
• CNS effects: Glycopyrrolate may cause drowsiness and/or blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Heat prostration: Glycopyrrolate may cause heat prostration in the presence of fever, increased environmental temperature, and/or during physical exercise, particularly in children and older adults; use caution in hot weather and/or exercise. Avoid exertion and high environmental temperature after administration.
• Hypersensitivity reactions: Symptoms of hypersensitivity have included anaphylaxis, angioedema, bradycardia, bronchospasm, erythema multiforme, facial swelling, flushing, generalized rash, hypotension, peripheral edema, pyrexia, and urticaria. Have epinephrine and atropine ready to treat hypersensitivity reactions.
• Intestinal obstruction (incomplete): Diarrhea may be an early sign of incomplete intestinal obstruction, especially in patients with an ileostomy or colostomy; avoid use in these patients.
• Neuromuscular effects: Large doses of IV neostigmine administered for the reversal of nondepolarizing neuromuscular-blocking agents, when neuromuscular blockade is minimal, can result in neuromuscular dysfunction. Reduce dose if recovery from neuromuscular blockade is nearly complete.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with bradycardia, cardiac arrhythmias, coronary artery disease, heart failure, hypertension, recent acute coronary syndrome, or tachycardia; evaluate tachycardia before administration.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism.
• Kidney impairment: Use with caution in patients with kidney impairment; elimination of glycopyrrolate is severely impaired in kidney failure and neostigmine half-life is prolonged in anephric patients.
• Neuromuscular diseases: For reversal of nondepolarizing neuromuscular blockade, avoid use or use with caution in patients with certain neuromuscular diseases (eg, myasthenia gravis, muscular dystrophy); other agents may be preferred (eg, sugammadex); if used, reduced dosing may be required with titration based on train-of-four monitoring (Balaka 2011; Briggs 2003; Buzello 1982). Adequate facilities should be available for cardiopulmonary resuscitation when testing and adjusting dose for myasthenia gravis.
• Vagotonia: Use with caution in patients with vagotonia.
Special populations:
• Older adult: Use with caution and monitor for a longer period.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Intravenous:
Prevduo: Neostigmine methylsulfate 3 mg and glycopyrrolate 0.6 mg/3 mL (3 mL) [contains edetate (edta) disodium dihydrate]
No
Solution Prefilled Syringe (Prevduo Intravenous)
3-0.6 mg/3 mL (per mL): $8.50
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Parenteral: IV: Administer over at least 1 minute.
IV: For IV use only; administer by slow IV injection over at least 1 minute.
Store intact vial at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Store in carton until time of use.
For the reversal of the effects of nondepolarizing neuromuscular blocking agents (NMBAs) after surgery, while decreasing the peripheral muscarinic effects (eg, bradycardia, excessive secretions) associated with cholinesterase inhibition following NMBA reversal administration (FDA approved in ages ≥2 years and adults).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Amantadine: May enhance the anticholinergic effect of Glycopyrrolate (Systemic). Risk C: Monitor therapy
Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Atenolol: Glycopyrrolate (Systemic) may increase the serum concentration of Atenolol. Risk C: Monitor therapy
Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Risk C: Monitor therapy
Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Chlorprothixene: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Chlorprothixene. Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy
Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Digoxin: Glycopyrrolate (Systemic) may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Haloperidol: Glycopyrrolate (Systemic) may decrease the serum concentration of Haloperidol. Management: Consider avoiding concurrent use of glycopyrrolate and haloperidol.Monitor patients closely for signs/symptoms of reduced clinical response to haloperidol if concurrent use with glycopyrrolate is required. Risk D: Consider therapy modification
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Kanamycin: Neostigmine may diminish the therapeutic effect of Kanamycin. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Levodopa-Foslevodopa: Glycopyrrolate (Systemic) may decrease the serum concentration of Levodopa-Foslevodopa. Risk C: Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
MetFORMIN: Glycopyrrolate (Systemic) may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Refer to individual monographs.
BP, heart rate, neuromuscular dysfunction.
See individual agents.
See individual agents.
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