Prevduo (glycopyrrolate/neostigmine methylsulfate)

Each capsule of glycopyrrolate oral inhalation powder (Seebri(R) Neohaler(R)) contains 15.6 mcg of glycopyrrolate. However, the actual amount of drug delivered to the lungs depends on factors such as the patient's inspiratory flow rate and inspiratory time. Under standardized in vitro testing at a fixed flow rate of 90 L/minute for 1.3 seconds, the Neohaler(R) device delivered 13.1 mcg from the 15.6-mcg capsule (equivalent to 12.5 mcg of glycopyrronium) from the mouthpiece.

Each capsule of glycopyrrolate/indacaterol oral inhalation powder (Utibron(R) Neohaler(R)) contains 15.6 mcg of glycopyrrolate and 27.5 mcg of indacaterol. However, the actual amount of drug delivered to the lungs depends on factors such as the patient's inspiratory flow rate and inspiratory time. Under standardized in vitro testing at a fixed flow rate of 90 L/minute for 1.3 seconds, the Neohaler(R) device delivered 12.8 mcg of glycopyrrolate (equivalent to 12.5 mcg of glycopyrronium) and 20.8 mcg of indacaterol from the mouthpiece.

Each single-dose vial of glycopyrrolate oral inhalation solution (Lonhala(R) Magnair(R)) contains 25 mcg of glycopyrrolate in 1 mL of solution. However, the actual amount of drug delivered to the lungs depends on patient factors. Under standardized in vitro testing, the Magnair(R) device delivered approximately 14.2 mcg of glycopyrrolate (equivalent to 11.4 mcg of glycopyrronium) from the mouthpiece.

After priming of the oral aerosol inhaler containing glycopyrrolate/formoterol, each actuation of the oral aerosol inhaler (Bevespi(R) Aerosphere(R)) delivers 10.4 mcg of glycopyrrolate (equivalent to 8.3 mcg of glycopyrronium) and 5.5 mcg of formoterol fumarate from the valve. Dosage is expressed in terms of drug delivered from the mouthpiece; each actuation of the inhaler delivers 9 mcg of glycopyrrolate (equivalent to 7.2 mcg of glycopyrronium) and 4.8 mcg of formoterol fumarate from the mouthpiece. The actual amount of drug delivered to the lungs depends on factors such as the patient's coordination between actuation of the device and inspiration through the delivery system. Commercially available glycopyrrolate/formoterol aerosol inhaler delivers 28 or 120 metered sprays per 5.9- or 10.7-g canister, respectively.

Neostigmine methylsulfate is administered by slow IV injection (over a period of at least 1 minute). The drug also has been administered by IM or subcutaneous injection+, but the manufacturer of the currently available injectable preparation labeled for reversal of neuromuscular blocking agents states that the injection is for IV use only.

Neostigmine methylsulfate injection should be stored at controlled room temperature (20-25degreesC) but may be exposed to temperatures ranging from 15-30degreesC; the injection should be stored in the original carton until time of use and protected from light.

Glycopyrrolate is administered orally, IM, IV, or by oral inhalation.

No dosing information is available for this tab.

No dosing information is available for this tab.

Drug interaction studies have not been conducted to date with neostigmine methylsulfate. Clinically important drug interactions are not likely to occur if neuromuscular monitoring is employed and both relaxants and reversal agents are titrated to effect.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Agents Affecting Growth Hormone/Macimorelin

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

CLINICAL EFFECTS: Concurrent use of agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of macimorelin states concurrent use with agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test. Discontinue growth hormone products at least 1 week before administering the macimorelin diagnostic test. Sufficient washout time of drugs affecting growth hormone release prior to administration of macimorelin is recommended.(1) Agents affecting growth hormone include: - Drugs that directly affect the pituitary secretion of growth hormone (e.g. somatostatin, insulin, glucocorticoids, cyclooxygenase inhibitors) - Drugs that may transiently elevate growth hormone concentrations (e.g. clonidine, levodopa, insulin) - Drugs that may blunt the growth hormone response (e.g. muscarinic antagonists, anti-thyroid medications, growth hormone products)

DISCUSSION: Concurrent use of agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Anticholinergics/Clozapine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Clozapine has potent anticholinergic properties and inhibits serotonin receptors, including 5-HT3.(1-4) Both of these properties may cause inhibition of gastrointestinal (GI) smooth muscle contraction, resulting in decreased peristalsis.(3,4) These effects may be compounded by concurrent use of anticholinergic agents.(1-6)

CLINICAL EFFECTS: Concurrent use of clozapine with other anticholinergic agents may increase the risk of constipation (common) and serious bowel complications (uncommon), including complete bowel obstruction, fecal impaction, paralytic ileus and intestinal ischemia or infarction.(1-6)

PREDISPOSING FACTORS: The risk for serious bowel complications is higher with increasing age, higher frequency of constipation, and in patients on higher doses of clozapine or multiple anticholinergic agents.(1,5)

PATIENT MANAGEMENT: Avoid the use of other anticholinergic agents with clozapine.(1-6) If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(2) Consider a prophylactic laxative in those with a history of constipation or bowel obstruction.(2) Review patient medication list for other anticholinergic agents. When possible, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. Counsel the patient about the importance of maintaining adequate hydration. Encourage regular exercise and eating a high-fiber diet.(2)

DISCUSSION: In a prospective cohort study of 26,720 schizophrenic patients in the Danish Central Psychiatric Research Registry, the odds ratio (OR) for ileus was 1.99 with clozapine and 1.48 with anticholinergics. The OR for fatal ileus was 6.73 with clozapine and 5.88 with anticholinergics. Use of anticholinergics with 1st generation antipsychotics (FGA) increased the risk of ileus compare to FGA alone, but this analysis was not done with clozapine.(5) A retrospective cohort study of 24,970 schizophrenic patients from the Taiwanese National Health Insurance Research Database found that the hazard ratio (HR) for clozapine-induced constipation increased from 1.64 when clozapine is used alone, to 2.15 when used concomitantly with anticholinergics. However, there was no significant difference in the HR for ileus when clozapine is used with and without anticholinergics (1.95 and 2.02, respectively).(6) In the French Pharmacovigilance Database, 7 of 38 cases of antipsychotic-associated ischemic colitis or intestinal necrosis involved clozapine, and 5 of these cases involved use of concomitant anticholinergic agents. Three patients died, one of whom was on concomitant anticholinergics.(3) In a case series, 4 of 9 cases of fatal clozapine-associated GI dysfunction involved concurrent anticholinergic agents.(4)

Anticholinergics/Glucagon (DIAGNOSTIC)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility.(1)

CLINICAL EFFECTS: Concurrent use of glucagon with anticholinergic agents may increase the risk of gastrointestinal hypomotility, including constipation and bowel complications.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of glucagon as a diagnotic aid is not recommended with the use of anticholinergic agents.(1) If concurrent use is necessary, evaluate the patient's bowel function. Monitor for symptoms of constipation and gastrointestinal hypomotility.

DISCUSSION: Both glucagon and anticholinergic agents may have additive effects on inhibition of gastrointestinal motility and increase the risk of gastrointestinal adverse effects.(1)

Anticholinergics; Opioids/Eluxadoline

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Eluxadoline is a mixed mu-opioid and kappa-opioid agonist and delta-opioid antagonist and may alter or slow down gastrointestinal transit.(1)

CLINICAL EFFECTS: Constipation related adverse events that sometimes required hospitalization have been reported, including the development of intestinal obstruction, intestinal perforation, and fecal impaction.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid use with other drugs that may cause constipation. If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(1) Instruct patients to stop eluxadoline and immediately contact their healthcare provider if they experience severe constipation. Loperamide may be used occasionally for acute management of severe diarrhea, but must be discontinued if constipation develops.(1)

DISCUSSION: In phase 3 clinical trials, constipation was the most commonly reported adverse reaction (8%). Approximately 50% of constipation events occurred within the first 2 weeks of treatment while the majority occurred within the first 3 months of therapy. Rates of severe constipation were less than 1% in patients receiving eluxadoline doses of 75 mg and 100 mg.(1)

Selected Anticholinesterase/Corticosteroids

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The mechanism of this interaction is unknown.

CLINICAL EFFECTS: Concurrent use of these agents may contribute to increased muscle weakness and decreased response to anticholinesterases shortly after onset of corticosteroid therapy in the treatment of myasthenia gravis. Deterioration in muscle strength, including severe muscular depression, has been documented in patients with myasthenia gravis while receiving corticosteroids and anticholinesterases.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, hold anticholinesterase agents at least 24 hours before initiating corticosteroid therapy. If concurrent use is necessary, close observation of the patient is indicated and life support systems should be available.

DISCUSSION: Decreased effectiveness of anticholinesterases during the period of corticosteroid-induced increased weakness probably reflects a temporary increase in the severity of the disease process itself rather than a specific, direct interaction between the two drugs. Despite the initial adverse effect, glucocorticoid (or ACTH) therapy subsequently produces improvement, beyond pre-therapy muscle strength, in most myasthenia gravis patients. In an uncontrolled study involving nine patients receiving therapeutic doses of pyridostigmine, the concurrent administration of methylprednisolone resulted in a decrease in muscle strength in 71% of treatment courses. During 57% of treatment courses, severe muscle weakness occurred, necessitating mechanical ventilation. Improvement in muscle strength and response to pyridostigmine above baseline levels occurred after methylprednisolone was discontinued. Other clinical observations have indicated that the concomitant use of these agents can affect muscle strength, although each agent alone has been used successfully in treating myasthenia gravis.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Anticholinergics/Select Antipsychotics;Select Phenothiazines

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Multiple mechanisms may be involved: 1. additive peripheral and CNS blockade of muscarinic receptors. 2. anticholinergic-induced inhibition of gastrointestinal absorption of phenothiazines. 3. antagonism of the dopamine blocking effects of selected antipsychotics and phenothiazines.

CLINICAL EFFECTS: The dopamine blocking effects of selected antipsychotic agents or phenothiazines may be decreased while anticholinergic adverse effects may be increased.

PREDISPOSING FACTORS: The risk for severe anticholinergic toxicities, e.g. delirium, hyperthermia, paralytic ileus is increased in the elderly and in patients on multiple anticholinergic agents.

PATIENT MANAGEMENT: Anticholinergic agents may be required to treat or prevent antipsychotic induced extrapyramidal symptoms. When other indications lead to co-prescribing of the combination, assess patient response to the combination. Review patient medication list for other anticholinergic agents. When needed, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly.

DISCUSSION: Although numerous studies have been published regarding a possible interaction between phenothiazines and anticholinergics, the earlier reports were not double-blind or placebo controlled and patients may have received other drugs concomitantly. These earlier investigations reported increased side effects as well as increased, decreased and no effect on the therapeutic outcome. Double-blind studies have also reported conflicting results. Anticholinergic therapy varied from having no effect on phenothiazine concentration or patient outcome, to increasing phenothiazine levels. The discrepancies reported may be due to interpatient variability including age of the patient, type and duration of illness and treatment setting.

Anticholinergics/Topiramate

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Topiramate can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2)

CLINICAL EFFECTS: Concurrent use of topiramate with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death.

PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1)

PATIENT MANAGEMENT: The manufacturer of topiramate states that caution should be used when topiramate is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered.

DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment.(1) A 64-year old woman developed non-exertional hyperthemia while taking multiple psychiatric medications with topiramate.(2)

Anticholinergics/Zonisamide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Zonisamide can cause decreased sweating and elevated body temperature. Agents with anticholinergic activity can predispose patients to heat-related disorders.(1-2)

CLINICAL EFFECTS: Concurrent use of zonisamide with agents with anticholinergic activity may increase the incidence of oligohidrosis and hyperthermia, especially in pediatric or adolescent patients.(1-2) Overheating and dehydration can lead to brain damage and death.

PREDISPOSING FACTORS: Pediatric and adolescent patients and patients with dehydration may be more likely to experience heat-related disorders.(1)

PATIENT MANAGEMENT: The UK and US manufacturers of zonisamide state that caution should be used in adults when zonisamide is prescribed with other medicinal products that predispose to heat-related disorders, such as agents with anticholinergic activity.(1-2) Pediatric and adolescent patients must not take anticholinergic agents (e.g. clomipramine, hydroxyzine, diphenhydramine, haloperidol, imipramine, and oxybutynin) concurrently with zonisamide.(1) Monitor for signs and symptoms of heat stroke: skin feels very hot with little or no sweating, confusion, muscle cramps, rapid heartbeat, or rapid breathing. Monitor for signs and symptoms of dehydration: dry mouth, urinating less than usual, dark-colored urine, dry skin, feeling tired, dizziness, or irritability. If signs or symptoms of dehydration, oligohidrosis, or elevated body temperature occur, discontinuation of zonisamide should be considered.

DISCUSSION: Case reports of decreased sweating and elevated temperature have been reported, especially in pediatric patients. Some cases resulted in heat stroke that required hospital treatment and resulted in death.(1)

Anticholinesterases/Beta-Blockers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Anticholinesterases inhibit plasma cholinesterases and increase cholinergic activity. Use of anticholinesterases may have vagotonic effects on heart rate (e.g. bradycardia). Concurrent use of anticholinesterases and beta-blockers may have additive effects on bradycardia.(1)

CLINICAL EFFECTS: Concurrent use of anticholinesterases and beta-blockers may have additive effects on bradycardia.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of anticholinesterases and beta-blockers is not recommended. Additive effects may be increased with cardioselective beta-blockers (e.g. atenolol). Monitor patients closely if concurrent use is warranted.(1)

DISCUSSION: Concurrent use of anticholinesterases and beta-blockers may have additive effects on cardiac conduction and increase the risk of bradycardia.(1) A case report of a 65 year old African American female had a witnessed a presyncopal episode followed by a true syncopal episode with concurrent use of rivastigmine and atenolol. On day 2 of the hospital stay, the patient developed bradycardia with a heart rate in the 40s and sinus pauses greater than 2 seconds. Atenolol was discontinued yet bradycardia persisted. Following discontinuation of rivastigmine, sinus pauses resolved and heart rate returned to normal.(2) A population-based cohort study in Ontario, Canada reviewed the relationship between cholinesterase inhibitor use and syncope-related outcomes over a two year period. Hospital visits for syncope were more frequent in patients receiving cholinesterase inhibitors than controls (31.5 vs 18.6 events per 1000 person-years; adjusted hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.57-1.98). Other syncope-related events were also more common in patients receiving cholinesterase inhibitors than controls: hospital visits for bradycardia (6.9 vs 4.4 events per 1000 person-years; HR 1.69; 95% CI 1.32-2.15); permanent pacemaker insertion (4.7 vs 3.3 events per 1000 person-years; HR 1.49; 95% CI 1.12-2.00); and hip fracture (22.4 vs 19.8 events per 1000 person-years; HR 1.18; 95% CI 1.04-1.34).(3) A population based case-time-control study of 1,009 patients hospitalized for bradycardia within 9 months of using a cholinesterase inhibitor were reviewed for outcomes. Of these patients, 11% required pacemaker insertion during hospitalization and 4% died prior to discharge. With adjustment for temporal changes in drug utilization, hospitalization for bradycardia was associated with recent initiation of a cholinesterase inhibitor drug (adjusted odds ratio (OR) 2.13; 95% CI 1.29-3.51). Risk was similar in patients with pre-existing cardiac disease (adjusted OR 2.25; 95% CI 1.18-4.28) and those receiving negative chronotropic drugs (adjusted OR 2.34; 95% CI 1.16-4.71).(4)

Anticholinesterases/Succinylcholine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Anticholinesterases inhibit plasma cholinesterases, delaying succinylcholine hydrolysis and prolonging its duration of action.

CLINICAL EFFECTS: May see an increase in the neuromuscular blocking effects of succinylcholine, producing profound sedation, respiratory depression, coma, and/or death.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concurrent administration of anticholinesterases and succinylcholine in patients with depolarizing type (phase I) neuromuscular blockade. In addition, use with caution in the presence of a nondepolarizing type (phase II) blockade. If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

DISCUSSION: Concomitant administration of anticholinesterases and succinylcholine has been associated with prolonged respiratory depression and apnea.

Beta-Agonists; Anticholinergics; Theophylline/Methacholine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway.(1)

CLINICAL EFFECTS: The result of the methacholine challenge test may not be accurate.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The following drugs should be held before a methacholine challenge for the the duration indicated:(1) - short-acting beta-agonists: 6 hours - long-acting beta-agonists: 36 hours - short-acting anti-cholinergics: 12 hours - long-acting anti-cholinergics: at least 168 hours (7 days) - oral theophylline: 12-48 hours

DISCUSSION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway and cause inaccurate test results.

Cholinergics/Quinidine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The anticholinergic properties of quinidine may oppose cholinergic drug effects.

CLINICAL EFFECTS: Quinidine may antagonize the effects of cholinergic drugs in the treatment of myasthenia gravis. Cardiac slowing secondary to cholinergic drugs would tend to be prevented by quinidine.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If both drugs are administered, observe the myasthenic patient for signs and symptoms of the disease.

DISCUSSION: Caution is warranted in co-administration of these drugs due to their opposing pharmacologic properties.

*Known hypersensitivity to neostigmine.

*Mechanical obstruction of the intestinal or urinary tract.

*Peritonitis.

• Colonic necrosis
• Glaucoma
• Hemorrhagic shock
• Mechanical intestinal obstruction
• Paralytic ileus
• Peritonitis
• Pyloroduodenal obstruction
• Toxic megacolon
• Urinary tract obstructive uropathy

• Benign prostatic hyperplasia
• Gastrointestinal obstruction
• Hypotension
• Myasthenia gravis
• Sinus bradycardia
• Toxin-mediated diarrhea
• Ulcerative colitis
• Urinary tract obstructive uropathy

• Asthma
• Autonomic neuropathy
• Cardiac arrhythmia
• Chronic heart failure
• Coronary artery disease
• Hiatal hernia
• Hyperthyroidism
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Parkinsonism
• Peptic ulcer
• Seizure disorder
• Tachyarrhythmia

The most common adverse effects of neostigmine include bradycardia, nausea, and vomiting. Adverse effects of neostigmine methylsulfate generally are due to exaggerated pharmacologic effects of the drug, particularly at muscarinic-cholinergic receptors.

Less Frequent

• Bradycardia

Rare or Very Rare

• Abdominal distension
• Acute cognitive impairment
• Acute respiratory failure
• Anaphylaxis
• Bradycardia
• Cardiac arrest
• Cardiac arrhythmia
• Cardiac arrhythmia
• Dehydration
• Heart block
• Heat stroke
• Hypersensitivity drug reaction
• Hypertension
• Hypotension
• Hypotension
• Ileus
• Injection site sequelae
• Ocular hypertension
• Pneumonia
• Seizure disorder
• Skin rash
• Tachycardia
• Urticaria

More Frequent

• Abdominal pain with cramps
• Blurred vision
• Constipation
• Decreased sweating
• Diarrhea
• Drowsy
• Flushing
• Hyperhidrosis
• Mydriasis
• Nasal congestion
• Nausea
• Palpitations
• Photophobia
• Sialorrhea
• Vomiting
• Vomiting
• Xerostomia

Less Frequent

• Abdominal distension
• Acute cognitive impairment
• Alopecia
• Breast milk flow decreased
• Dizziness
• Dry skin
• Dysmenorrhea
• Dyspnea
• Epistaxis
• Eye tearing
• Flatulence
• Hypertonia
• Hypoesthesia
• Increased bronchial secretions
• Increased urinary frequency
• Miosis
• Myalgia
• Neck pain
• Ocular pain
• Rhinorrhea
• Tingling sensation of hands or feet
• Toxic amblyopia
• Urinary hesitancy
• Urinary retention
• Urinary tract infection
• Urinary urgency

Rare or Very Rare

• Acute abdominal pain
• Agitation
• Anticholinergic toxicity
• Cheilosis
• Cramps
• Cycloplegia
• Dizziness
• Dry nose
• Dry skin
• Dysgeusia
• Erectile dysfunction
• Fever
• Flatulence
• General weakness
• General weakness
• Headache disorder
• Headache disorder
• Impulse control disorder
• Injection site erythema
• Injection site pain
• Insomnia
• Irritability
• Loss of taste
• Malaise
• Mood changes
• Muscle fasciculation
• Nausea
• Nervousness
• Nystagmus
• Pallor
• Pruritus of skin
• Sinusitis
• Skin rash
• Sore throat
• Thick bronchial secretions
• Upper respiratory infection
• Vertigo

No enhanced messaging available.

Neostigmine may be used in pediatric patients of all ages to reverse the effects of nondepolarizing neuromuscular blocking agents after surgery. The available data indicate that efficacy and pharmacokinetics of neostigmine are similar across all pediatric age groups and also similar to those in adults when the same dosing guidelines are applied.

Based on limited data, neostigmine dosing requirements for reversal of neuromuscular blockade may be lower in infants and neonates than in older pediatric patients and adults; however, pediatric patients have a greater risk of incomplete reversal of neuromuscular blockade because of their decreased respiratory reserve. Therefore, the risks of administering higher doses of neostigmine (up to maximum recommended dosage) should not outweigh the risks associated with incomplete reversal in this age group.

Because pediatric patients, particularly neonates and infants, may be more sensitive to changes in heart rate, the effects of anticholinergic agents should be observed prior to administration of neostigmine to lessen the probability of bradycardia and hypotension.

It is not known whether neostigmine can cause fetal harm when administered to pregnant women or affect reproductive capacity; the drug should be used during pregnancy only when clearly indicated as no adequate or well-controlled studies of the drug have been conducted in pregnant women. Administration of anticholinesterase drugs such as neostigmine to pregnant women near term may cause uterine irritability and induce premature labor.

There are limited data from animal reproduction studies; in such studies, no teratogenic or other adverse effects were identified; however, drug exposure was well below the predicted exposures in humans.

It is not known whether neostigmine is distributed into human milk. Caution should be exercised when the drug is used in nursing women.

Although dosage adjustments are not required in geriatric patients undergoing reversal of neuromuscular blockade, a longer period of monitoring is recommended in such patients to ensure that additional doses of neostigmine are not necessary to adequately reverse neuromuscular blockade.

Because geriatric patients may have decreased renal function, neostigmine should be used with caution and increased monitoring in this age group. The duration of action of neostigmine is prolonged in geriatric patients; however, such patients also experience slower spontaneous recovery from neuromuscular blocking agents. Geriatric patients should be monitored for longer periods of time to ensure that additional doses of neostigmine are not necessary to adequately reverse neuromuscular blockade.