Neostigmine and glycopyrrolate
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
Renal Impairment Elimination half-life of neostigmine methylsulfate was prolonged in anephric patients compared to normal subjects. In one study glycopyrrolate was administered IV in uremic patients undergoing renal transplantation. The mean elimination half-life was significantly longer (46.8 minutes) than in healthy patients (18.6 minutes).
The mean area-under-the-concentration-time curve (10.6 hr-μg/L), mean plasma clearance (
Dosing in liver impairment
Hepatic Impairment The pharmacokinetics of neostigmine methylsulfate in patients with hepatic impairment have not been studied. Neostigmine methylsulfate is metabolized by microsomal enzymes in the liver, while glycopyrrolate is mostly eliminated unchanged by the kidney. No adjustments to the dosing of PREVDUO @ appear to be warranted in patients with hepatic insufficiency.
However, patients should be carefully monitored if hepatically cleared neuromuscular blocking agents were used during their surgical procedure as their duration of action may be prolonged by hepatic insufficiency. This could result in the effects of the neuromuscular blocking agent outlasting those of neostigmine methylsulfate.
This same situation may arise if the neuromuscular blocking agent has active metabolites. 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.
Preparation and administration
Prepare this dose
Your numbers for neostigmine and glycopyrrolate. Take vial strength, diluent, and limits from the label below.
Enter a dose to see draw volume, final concentration, and rates.
Important Dosage and Administration Information
PREVDUO ® should be administered by trained healthcare providers familiar with the use, actions, characteristics, and complications of neuromuscular blocking agents (NMBA) and neuromuscular block reversal agents. Doses of PREVDUO ® should be individualized, and a peripheral nerve stimulator should be used to determine the time of initiation of PREVDUO ® and should be used to determine the need for additional doses.
PREVDUO ® is for intravenous use only and should be injected slowly over a period of at least 1 minute. The PREVDUO ® dosage is weight-based [ see Dosage and Administration ].
Prior to PREVDUO ® administration and until complete recovery of normal ventilation, the patient should be well ventilated and a patent airway maintained. Satisfactory recovery should be judged by adequacy of skeletal muscle tone and respiratory measurements in addition to the response to peripheral nerve stimulation.
Peripheral nerve stimulation devices capable of delivering a train-of-four (TOF) stimulus are essential to effectively using PREVDUO ® .
There must be a twitch response to the first stimulus in the TOF of at least 10% of its baseline level, i.e., the response prior to NMBA administration, prior to the administration of PREVDUO ® .
Prior to administration, visually inspect PREVDUO ® for particulate matter and discoloration.
TOF monitoring should continue to be used to evaluate the extent of recovery of neuromuscular function and the possible need for an additional dose of PREVDUO ® .
TOF monitoring alone should not be relied upon to determine the adequacy of reversal of neuromuscular blockade as related to a patient’s ability to adequately ventilate and maintain a patent airway following tracheal extubation.
Patients should continue to be monitored for adequacy of reversal from NMBAs for a period of time that would assure full recovery based on the patient’s medical condition and the pharmacokinetics of neostigmine and the NMBA used.
Instructions for Use (Administration Technique) a) Inspect the outer carton for: - absence of external particles - drug product name - dosage form - drug strength - fill volume - route of administration - expiration date b) Take out the plastic tray from the outer carton and remove the prefilled syringe from tray. c) Perform visual inspection of the prefilled syringe for: - absence of physical damage to syringe - absence of external particles - absence of internal particles (particulate matter) - discoloration - drug product name - drug strength - fill volume - expiration date d) Remove tip cap by twisting off e) Discard the tip cap. f) Expel the air bubble by pushing the plunger rod.
Adjust the dose (if applicable). g) Connect the prefilled syringe to an appropriate intravenous connection. Ensure that the prefilled syringe is securely attached to the needle or needleless luer access device (NLAD). h) Press the plunger rod slowly to deliver the medication through needle or needleless luer access device (NLAD) over a period of at least 1 minute.
Ensure that appropriate pressure is maintained on the plunger rod during the entire administration. i) Remove the prefilled syringe from needle or needleless luer access device (NLAD) and discard into appropriate receptacle. When needle is connected to syringe, to prevent needle-stick injuries, needles should not be recapped.
NOTES: - All steps given in the ‘instructions for use’ must be performed sequentially - Do not re-sterilize the syringe - Do not use this product on a sterile field - Do not introduce any other fluid into the syringe at any time - This product is for single use only ifu-1 IFU-2 IFU-3
Drug interactions
Check neostigmine and glycopyrrolate against a medication listLabel text (2 paragraphs)
Neostigmine Methylsulfate The pharmacokinetic interaction between neostigmine methylsulfate and other drugs has not been studied. Neostigmine methylsulfate is metabolized by microsomal enzymes in the liver. Use with caution when using neostigmine methylsulfate with other drugs which may alter the activity of metabolizing enzymes or transporters. Glycopyrrolate The concurrent use of glycopyrrolate with other anticholinergics or medications with anticholinergic activity, such as phenothiazines, antiparkinson drugs, or tricyclic antidepressants, may intensify the antimuscarinic effects and may result in an increase in anticholinergic side effects.
The concurrent use of glycopyrrolate with other anticholinergics or medications with anticholinergic activity may intensify the antimuscarinic effects and may result in an increase in anticholinergic side effects. ( 7 )
Contraindications
4 CONTRAINDICATIONS PREVDUO ® 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) and glycopyrrolate or any inactive ingredients [ see Warnings and Precautions ( 5.3 ) ]. • peritonitis or mechanical obstruction of the intestinal or urinary tract.
• Glaucoma; obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis, etc.); 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.
• Hypersensitivity to neostigmine, glycopyrrolate, or nonactive ingredients ( 4 ) • Peritonitis or mechanical obstruction of the intestinal or urinary tract ( 4 ) • Patients with glaucoma; obstructive uropathy; obstructive disease of the gastrointestinal tract; 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 ( 4 ).
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Neostigmine Methylsulfate There are no adequate or well-controlled studies of neostigmine in pregnant women. It is not known whether neostigmine 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. 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.
Most of the available data are based on studies with exposures that occurred at the time of Cesarean-section delivery, and these studies have not identified an adverse effect on maternal outcomes or infant Apgar scores (see Data). In animal reproduction studies in pregnant rats and rabbits administered glycopyrrolate orally (rats) and intramuscularly (rabbits) during the period of organogenesis, no teratogenic effects were seen at 640-times and 10-times the maximum recommended human dose (MRHD) of 1 mg (on a mg/m 2 basis), respectively (see Data). The estimated background risk for major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2-4% and 15-20%, respectively. PREVDUO @ should be only given to a pregnant woman if the benefit outweighs the risk. Data Human Data Neostigmine Methylsulfate: There are no adequate or well-controlled studies of neostigmine methylsulfate in pregnant women.
Glycopyrrolate: Published, randomized, controlled trials over several decades, which compared the use of glycopyrrolate to another antimuscarinic agent in pregnant women during Cesarean section, have not identified adverse…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.