Neostigmine-Glycopyrrolate

Neostigmine-Glycopyrrolate is a combination medication used for nondepolarizing neuromuscular blockade reversal.

• Neostigmine-Glycopyrrolate is available under the following different brand names: Prevduo

Common side effects of Neostigmine-Glycopyrrolate include:

• nausea,
• bloating,
• headache,
• dizziness,
• drowsiness,
• tiredness,
• back pain,
• joint or muscle pain,
• swelling in your hands or feet,
• flushing (warmth, redness, or tingly feeling),
• stuffy nose,
• sneezing,
• sore throat,
• cough, and
• mild itching

Serious side effects of Neostigmine-Glycopyrrolate include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• wheezing,
• lightheadedness,
• fever,
• chills,
• body aches,
• flu symptoms,
• sores in the mouth and throat,
• pain or burning when you urinate,
• chest pain or tightness, and
• vision changes

Rare side effects of Neostigmine-Glycopyrrolate include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injectable solution

• (3 mg/0.6 mg)/3 mL (single-dose prefilled syringe)
• Nondepolarizing Neuromuscular Blockade Reversal

Adult dosage

• 0.03-0.07 mg/kg neostigmine (0.006-0.014 mg/kg of glycopyrrolate) IV will achieve a train-of-four (TOF) twitch ratio of 90% (TOF0.9) within 10-20 min of administration
• Neostigmine-induced bradycardia is minimized due to the included 0.2 mg of glycopyrrolate per 1 mg neostigmine
• Select a dose based on the extent of spontaneous recovery that has occurred at the time of administration, the half-life of NMBA being reversed, and whether there is a need to rapidly reverse the NMBA
• Use 0.03 mg/kg dose of neostigmine (0.006 mg/kg of glycopyrrolate) for:
  • Reversal of NMBAs with shorter half-lives (e.g., rocuronium) or
    • When the first twitch response to TOF stimulus is more than 10% of baseline or
    • When a second twitch is present
• Use 0.07 mg/kg dose of neostigmine (0.014 mg/kg of glycopyrrolate) for:
  • Reversal of NMBAs with longer half-lives (e.g., vecuronium, pancuronium) or
  • When the first twitch response is relatively weak (ie, not substantially more than 10% of baseline) or
    • There is a need for more rapid recovery
• Recommended maximum total dose is 0.07 mg/kg of neostigmine or up to a total of 5 mg of neostigmine, whichever is less

Pediatric dosage

• Aged above 2 years: Not recommended as blood pressure in these patients is sensitive to changes in heart rate.
• Aged above 2 years
  • 0.03-0.07 mg/kg neostigmine (0.006-0.014 mg/kg of glycopyrrolate) IV will achieve a train-of-four (TOF) twitch ratio of 90% (TOF0.9) within 10-20 min of administration
  • Neostigmine-induced bradycardia is minimized due to the included 0.2 mg of glycopyrrolate per 1 mg neostigmine
  • Select a dose based on the extent of spontaneous recovery that has occurred at the time of administration, the half-life of NMBA being reversed, and whether there is a need to rapidly reverse the NMBA
  • Use 0.03 mg/kg dose of neostigmine (0.006 mg/kg of glycopyrrolate) for:
    • Reversal of NMBAs with shorter half-lives (e.g., rocuronium) or
    • When the first twitch response to TOF stimulus is more than 10% of baseline or
    • When a second twitch is present
      • Use 0.07 mg/kg dose of neostigmine (0.014 mg/kg of glycopyrrolate) for:
      • Reversal of NMBAs with longer half-lives (e.g., vecuronium, pancuronium) or
      • When the first twitch response is relatively weak (ie, not substantially more than 10% of baseline) or
      • There is a need for more rapid recovery
  • Recommended maximum total dose is 0.07 mg/kg of neostigmine or up to a total of 5 mg of neostigmine, whichever is less

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Neostigmine-Glycopyrrolate has severe interactions with no other drugs.
• Neostigmine-Glycopyrrolate has serious interactions with no other drugs.
• Neostigmine-Glycopyrrolate has moderate interactions with no other drugs.
• Neostigmine-Glycopyrrolate has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

Hypersensitivity to neostigmine

• Peritonitis or mechanical obstruction of the intestinal or urinary tract
• Glaucoma; obstructive uropathy (e.g., bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (eg, achalasia, pyloroduodenal stenosis); paralytic ileus, intestinal atony of elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Neostigmine-Glycopyrrolate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Neostigmine-Glycopyrrolate?”

Cautions

• Medications to treat anaphylaxis should be readily available
• Large doses of Neostigmine-Glycopyrrolate administered when the neuromuscular blockade is minimal can produce neuromuscular dysfunction; reduce dose if recovery from neuromuscular blockade is nearly complete
• It is important to differentiate between myasthenic crisis and cholinergic crisis caused by overdosage of neostigmine; both conditions result in extreme muscle weakness but require radically different treatment
• Glycopyrrolate may cause drowsiness or blurred vision; advise patients not to participate in activities requiring mental alertness, such as operating a motor vehicle or other machinery or performing hazardous work, until these issues resolve
• Glycopyrrolate, may cause heat prostration (due to decreased sweating) in presence of fever, high environmental temperature, and/or during physical exercise, particularly in children and the elderly; advise patients to avoid exertion and high environmental temperature after receiving therapy
• Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy; avoid use with these conditions
• Cardiovascular cautions
  • Neostigmine is associated with bradycardia; consider administering glycopyrrolate before neostigmine (eg, as separate products) in patients with bradycardia or in patients in whom bradycardia, a known risk of neostigmine, may cause hemodynamic instability
  • Caution with coronary artery disease, congestive heart failure, cardiac arrhythmias, recent acute coronary syndrome, or hypertension
  • Patients with acute cardiovascular conditions (eg, coronary artery disease, cardiac arrhythmias or recent acute coronary syndrome) may be at an increased risk of blood pressure and heart rate complications
  • Owing to the pharmacology of neostigmine as an acetylcholinesterase inhibitor, cardiovascular effects (eg, bradycardia, hypotension, dysrhythmia) would be anticipated
  • Investigate any tachycardia before giving glycopyrrolate because an increase in heart rate may occur
• Myasthenia gravis and hyperthyroidism
  • Caution with myasthenia gravis and hyperthyroidism
  • Patients with myasthenia gravis may be at an increased risk of blood pressure and heart rate complications
• Ophthalmic cautions
  • Advise patients with glaucoma to promptly seek medical care if they experience symptoms of acute angle closure glaucoma (pain and reddening of the eyes, accompanied by dilated pupils)
  • Glycopyrrolate may cause drowsiness or blurred vision; advise patients not to participate in activities requiring mental alertness, such as operating a motor vehicle or other machinery or performing hazardous work until these issues resolve
• Drug interactions overview
  • Neostigmine
    • Pharmacokinetic interaction between neostigmine and other drugs not studied
    • Caution when coadministered with other drugs which may alter the activity of metabolizing enzymes or transporters
  • Glycopyrrolate
    • Coadministration with other anticholinergics or medications with anticholinergic activity (e.g., phenothiazines, antiparkinson drugs, tricyclic antidepressants) may intensify antimuscarinic effects and result in increased anticholinergic side effects

Pregnancy and Lactation

• Neostigmine
  • There are no adequate or well-controlled studies of neostigmine in pregnant females
  • Unknown whether neostigmine can cause fetal harm when administered to pregnant females or can affect reproductive capacity
  • Anticholinesterase drugs, including neostigmine, may cause uterine irritability and induce premature labor when administered to pregnant females near term
• Glycopyrrolate
  • Limited data available with glycopyrrolate use during pregnancy have not identified a drug-associated risk of birth defects and miscarriage, however, most of the reported exposures occurred after the first trimester
• Lactation
  • Unknown whether neostigmine and glycopyrrolate are excreted in human milk
  • As with other anticholinergics, glycopyrrolate may suppress lactation