Version July 2025
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.
Refer to adult dosing; use with caution.
(For additional information see "Neostigmine and glycopyrrolate: Pediatric drug information")
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.
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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IV: For IV use only; administer by slow IV injection over at least 1 minute.
Parenteral: IV: Administer over at least 1 minute.
Reversal of nondepolarizing neuromuscular-blocking agents: 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 in adults and pediatric patients ≥2 years of age.
Refer to individual components.
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Agents with Clinically Relevant Anticholinergic Effects: May increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Amantadine: May increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Amifampridine: Acetylcholinesterase Inhibitors may increase therapeutic effects of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may increase therapeutic effects of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Risk C: Monitor
Atenolol: Glycopyrrolate (Systemic) may increase serum concentration of Atenolol. Risk C: Monitor
Benoxinate: Acetylcholinesterase Inhibitors may increase therapeutic effects of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Risk C: Monitor
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor
Beta-Blockers: Acetylcholinesterase Inhibitors may increase bradycardic effects of Beta-Blockers. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor
Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Bromperidol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bromperidol. Risk C: Monitor
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects 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
Chlorprothixene: Acetylcholinesterase Inhibitors may increase adverse/toxic effects of Chlorprothixene. Acetylcholinesterase Inhibitors may increase therapeutic effects of Chlorprothixene. Risk C: Monitor
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Chlorprothixene. Risk C: Monitor
Cholinergic Agonists: Acetylcholinesterase Inhibitors may increase adverse/toxic effects of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Risk C: Monitor
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects 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 increase adverse/toxic effects of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor
Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor
Digoxin: Glycopyrrolate (Systemic) may increase serum concentration of Digoxin. Risk C: Monitor
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor
Dipyridamole: May decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid
Etrasimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor
Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of Fexinidazole. Risk X: Avoid
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects 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
FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Gepotidacin: May increase therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Haloperidol: Glycopyrrolate (Systemic) may decrease 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 (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor
Ivabradine: Bradycardia-Causing Agents may increase bradycardic effects of Ivabradine. Risk C: Monitor
Kanamycin: Neostigmine (Systemic) may decrease therapeutic effects of Kanamycin. Risk C: Monitor
Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of Lacosamide. Risk C: Monitor
Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of Landiolol. Risk X: Avoid
Levodopa-Foslevodopa: Glycopyrrolate (Systemic) may decrease serum concentration of Levodopa-Foslevodopa. Risk C: Monitor
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
MetFORMIN: Glycopyrrolate (Systemic) may increase serum concentration of MetFORMIN. Risk C: Monitor
Methotrimeprazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methotrimeprazine. Risk C: Monitor
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor
Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may decrease neuromuscular-blocking effects of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor
Opioid Agonists: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor
Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk C: Monitor
Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
Ponesimod: Bradycardia-Causing Agents may increase bradycardic effects 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: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. 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
Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects 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 increase bradycardic effects 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
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
Succinylcholine: Acetylcholinesterase Inhibitors may increase neuromuscular-blocking effects of Succinylcholine. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor
Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor
Refer to individual monographs.
It is not known if glycopyrrolate or neostigmine is present in breast milk.
According to the manufacturer, the decision to breastfeed should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Refer to individual monographs for additional information.
BP, heart rate, respiratory status, ECG (as clinically indicated); anticholinergic effects; train-of-four monitoring; kidney and hepatic function; consult individual institutional policies and procedures.
See individual agents.
See individual agents.
