FDA-filed SPL labeling · retrieved through openFDA

Neostigmine Methylsulfate

Neostigmine methylsulfate is a cholinesterase inhibitor given intravenously after surgery to reverse the muscle-paralyzing effects of non-depolarizing neuromuscular blocking agents.

Brand name Bloxiverz
Drug class ⓘ Cholinesterase Inhibitor
Rx Form 1 Route Intravenous
Dr. Brian Staiger, PharmD, BCPS
Reviewed by Last reviewed Jul 10, 2026
🧬 Where this information comes from Click to expand

The clinical label records used on this page are FDA-filed Structured Product Labeling (SPL) retrieved through openFDA. We identified 33 clinical label sets within the page’s selected clinical scope after exact ingredient or ingredient-combination matching and applicable route/form matching. Forms, routes, brands, labelers, strengths, and NDC product-record counts are built separately from matching FDA National Drug Code Directory records. The linked DailyMed document is a representative official source for verification, not the page’s only clinical source. View the linked label on DailyMed →

At a glance
Linked label effectiveOct 15, 2024
Clinical labels in scope ⓘ33
AvailabilityRx
Earliest approval/marketing year ⓘ2011
FDA-listed product records ⓘ114
Boxed warningNone found in compared labels
How we combine label and product data →
⭐ Neostigmine Methylsulfate at a glance The quick version — the full detail is in the Patient Information Guide below.
💊
HelloPharmacist Editorial Team Bottom Line
Neostigmine methylsulfate is a short-acting IV medication given by anesthesia teams right after surgery to wake up the muscles that were intentionally paralyzed during the procedure. It works quickly but requires careful monitoring and must always be paired with an anticholinergic drug to protect the heart. Patients with heart disease, kidney problems, or liver issues need extra observation time after it is given.
How we write & review this content — our editorial policy →

📖 Neostigmine Methylsulfate: Patient Information Guide

A plain-language walkthrough of Neostigmine Methylsulfate — what it treats, how it works, how it’s taken, side effects, warnings and interactions. Tap any section to expand it.

🎯What it's used for▾

Neostigmine methylsulfate injection is used in surgical settings to reverse muscle paralysis caused by non-depolarizing neuromuscular blocking agents.

  • Bloxiverz (intravenous injection) is FDA-approved to reverse the effects of non-depolarizing neuromuscular blocking agents (NMBAs) after surgery.
  • Neostigmine Methylsulfate injection (including the USP and solution formulations) is also approved for the same indication — reversing non-depolarizing NMBA effects after surgery — given intravenously.
⚙️How it works▾

Neostigmine methylsulfate is a cholinesterase inhibitor — it blocks an enzyme that normally destroys acetylcholine, a chemical that nerves use to signal muscles. With more acetylcholine available at the nerve-muscle junction, it outcompetes the neuromuscular blocking drug for the same binding site, restoring normal muscle contraction. Because it does not easily cross the blood-brain barrier, its effects are focused on the muscles and peripheral nervous system rather than the brain.

The rise in acetylcholine also activates muscarinic receptors — the ones that slow the heart and increase secretions — which is why an anticholinergic drug is always given alongside neostigmine to counterbalance those effects.

💊How it's taken▾

Neostigmine methylsulfate is given only by intravenous injection in a hospital or surgical setting by trained providers — it is not taken at home. The dose is based on body weight and on how much muscle recovery has already occurred, as measured by a peripheral nerve stimulator. It is injected slowly over at least one minute, and additional doses may be given based on the patient's ongoing response.

  • Always given with an anticholinergic drug (atropine or glycopyrrolate) to protect the heart
  • Monitoring continues until full breathing and muscle recovery is confirmed
  • Older adults, and those with kidney or liver problems, are monitored for longer periods
🤒Side effects — in detail▾

The most common side effects are related to neostigmine's effect on the body's cholinergic system. Common reactions include:

  • Slow heart rate (bradycardia)
  • Nausea and vomiting
  • Dizziness or fainting
  • Increased saliva, mucus, or airway secretions
  • Sweating and flushing
  • Muscle cramps or spasms
  • Low blood pressure
  • Rash or hives

Serious reactions — including cardiac arrest, severe irregular heartbeat, respiratory arrest, anaphylaxis (severe allergic reaction), seizures, or loss of consciousness — require immediate medical attention from the care team.

⚠️Warnings & precautions▾
  • Slow heart rate (bradycardia): Neostigmine commonly slows the heart. An anticholinergic drug must be given first or at the same time to reduce this risk.
  • Cardiovascular complications: Patients with heart disease, arrhythmias, or a recent heart attack are at higher risk for blood pressure and heart rate problems. Continuous cardiac monitoring is required for these patients.
  • Cholinergic crisis (too much neostigmine): Overdose can cause extreme muscle weakness and breathing failure. Treatment requires stopping all anticholinergic drugs immediately and giving atropine — the opposite of what is done for a myasthenic crisis.
  • Neuromuscular dysfunction: Giving too large a dose when the muscle block is nearly gone can paradoxically cause muscle weakness. The care team adjusts dosing based on nerve stimulator readings.
  • Severe allergic reactions (anaphylaxis): Emergency resuscitation equipment and medications must be on hand whenever neostigmine is given.
🔀What it interacts with▾

Neostigmine methylsulfate can interact with certain other drugs used in surgical and anesthetic settings:

  • Depolarizing muscle relaxants (e.g., succinylcholine): Neostigmine should not be used to reverse these drugs — it can prolong the paralysis rather than reverse it.
  • Certain antibiotics (neomycin, streptomycin, kanamycin): These antibiotics have their own mild muscle-blocking effect, so the neostigmine dose may need adjustment in patients taking them.
  • Drugs that affect liver enzymes: Since neostigmine is processed by the liver, drugs that inhibit or stimulate liver enzymes could raise or lower neostigmine levels in the body, requiring closer monitoring.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

📋Before taking it▾
  • Known allergy to neostigmine: This drug is contraindicated — do not use it if you have had a hypersensitivity reaction (including hives, swelling, difficulty breathing, or anaphylaxis) to neostigmine.
  • Peritonitis or bowel/urinary obstruction: Neostigmine is contraindicated in these conditions.
  • Heart disease, arrhythmias, or recent heart attack: Higher risk of cardiovascular complications; requires continuous monitoring.
  • Myasthenia gravis: May increase the risk of cardiovascular complications.
  • Pregnancy: Use only if clearly needed; near the end of pregnancy it may cause uterine contractions and trigger early labor.
  • Breastfeeding: It is unknown whether neostigmine passes into breast milk; discuss the risks and benefits with your provider.
  • Infants and young children: Can be used in all pediatric age groups, but infants are especially vulnerable if reversal is incomplete, because they have less breathing reserve. An anticholinergic drug should be confirmed effective before neostigmine is given.
  • Older adults: The drug lasts longer due to reduced kidney function; extended monitoring is needed.
  • Kidney impairment: Neostigmine is cleared more slowly; monitoring should be extended after dosing.
  • Liver impairment: Neostigmine is metabolized in the liver; levels may be higher in patients with liver problems, warranting closer observation.
🚑If you take too much▾

Too much neostigmine can cause a cholinergic crisis — signs include extreme muscle weakness, heavy sweating, increased secretions, slow heart rate, nausea, vomiting, diarrhea, and difficulty breathing. If breathing is severely affected, it can be life-threatening. Treatment involves stopping all anticholinergic medications immediately, giving atropine, and supporting breathing artificially if needed. It is critical to distinguish a cholinergic crisis from a myasthenic crisis, as the treatments are completely different — the care team may use a test drug called edrophonium to help tell them apart.

📡Pharmacodynamics — effects in the body▾

By increasing acetylcholine levels at the nerve-muscle junction, neostigmine methylsulfate boosts both muscarinic and nicotinic cholinergic activity throughout the body. At the muscle, this elevated acetylcholine competes with the neuromuscular blocking drug and restores the ability of muscles to contract. Because it does not readily cross the blood-brain barrier, it does not significantly affect cholinergic signaling in the central nervous system. The increase in muscarinic activity — effects like slower heart rate and more secretions — is managed clinically by giving atropine or glycopyrrolate at the same time.

🔬Pharmacokinetics — how your body processes it▾

After intravenous injection, neostigmine binds modestly to proteins in the blood (15–25%) and is distributed throughout the body. It is broken down by enzymes in the liver, and the time it takes to clear the body (elimination half-life) ranges roughly from 24 to 113 minutes in adults, though this is prolonged in people with little or no kidney function. In infants and young children, the half-life is shorter (around 39–48 minutes), while in patients without functioning kidneys it can extend to about 3 hours. Because other drugs can either speed up or slow down the liver enzymes that process neostigmine, levels in the blood may vary when it is used alongside those medications.

📦How to store it▾

Neostigmine Methylsulfate Injection, USP should be stored at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). Protect from light. Store in carton until time of use.

📄 Written from Neostigmine Methylsulfate’s FDA-approved label information, summarized in plain language with AI, and reviewed by our pharmacy team before publication. Every point is grounded in that labeling — nothing is invented. How we use AI →

🩺 Pharmacist Counseling Corner

Quick, plain-English answers to the questions patients ask most about Neostigmine Methylsulfate — the kind of thing our pharmacy team would talk through with you at the counter.

What exactly does neostigmine methylsulfate do during or after surgery? ▾
During surgery, you may be given a muscle relaxant to keep your muscles completely still — including your breathing muscles. When the procedure is over, the care team needs those muscles to work again. Neostigmine is given at that point to reverse the paralysis and help your body regain normal muscle control, including the ability to breathe on your own. Think of it as the 'antidote' to the muscle relaxant.
Will I feel anything when it's given? ▾
Neostigmine is given directly into a vein by the anesthesia team, so you won't feel a needle stick in the usual sense. Some people experience nausea, increased saliva, or a slow or irregular heartbeat afterward. To reduce that slow heart rate effect, the team always gives another medication — atropine or glycopyrrolate — at the same time. Most of these effects are managed right there in the operating or recovery room.
Is there anything about my health history the team needs to know before I get this? ▾
Yes — it's important to tell your anesthesia team if you have heart disease, irregular heart rhythms, or had a recent heart attack, because neostigmine can affect your heart rate and blood pressure. Also mention any history of a severe allergic reaction to neostigmine. And if you have any blockage in your bowels or urinary tract, or an infection in your abdomen called peritonitis, neostigmine cannot be used. Being upfront about all medications and health conditions helps the team plan the safest approach for you.
I'm pregnant — is this drug safe for my baby? ▾
There isn't much human data on neostigmine use in pregnancy, so the guidance is to use it only if it's clearly necessary. One important thing to know is that near the end of pregnancy, it can cause uterine contractions, which might trigger early labor. The care team will weigh the benefit of reversing muscle paralysis after surgery against those risks and discuss it with you. Animal studies at doses well below those used in humans did not show birth defects.
What happens if too much neostigmine is given? ▾
Too much neostigmine can actually cause something called a cholinergic crisis — which, confusingly, looks like the opposite of what you'd expect: instead of your muscles recovering, you get extreme weakness, trouble breathing, a very slow heart rate, heavy sweating, and nausea. The care team is trained to watch for this and can treat it right away with atropine. That's one reason your muscle responses are continuously monitored with a nerve stimulator throughout the process — it helps prevent overdose from happening in the first place.
My elderly parent is having surgery — should I be concerned about this drug? ▾
It's a fair question. Older adults tend to clear neostigmine from their bodies more slowly because kidney function naturally decreases with age. That means the drug may stay active a bit longer. The care team accounts for this by monitoring your parent closely for a longer period after it's given to make sure the muscle relaxant effects don't outlast the reversal. Generally, no special dose adjustment is needed — just extended observation and care.
Is Neostigmine Methylsulfate available over the counter? ▾
Neostigmine Methylsulfate is dispensed by prescription according to its FDA labeling, so it isn't sold over the counter. Your prescriber and pharmacist will determine if it's appropriate for you.
When was Neostigmine Methylsulfate first available? ▾
Neostigmine Methylsulfate has been available in the United States since at least 2011, based on FDA approval history (Drugs@FDA) and product marketing records.
Who makes Neostigmine Methylsulfate? ▾
Neostigmine Methylsulfate is supplied by 37 manufacturers listed in the FDA NDC Directory, including Fresenius Kabi USA, LLC, Hikma Pharmaceuticals USA Inc., Medical Purchasing Solutions, LLC.

💬 Answers drafted from Neostigmine Methylsulfate’s FDA-approved label information, summarized in plain language with AI, and reviewed by our pharmacy team before publication. Grounded in that labeling — nothing is made up. How we use AI →

🧰 Keep exploring

🌿Drug & Supplement CheckerNeostigmine Methylsulfate vs. vitamins & herbs 💬Ask a PharmacistFree answer, usually < 24h 🔎NDC & pricing lookupFind Neostigmine Methylsulfate NDCs & costs 🅰️Browse Drugs A–ZLook up any medication

💊 How Neostigmine Methylsulfate comes

Neostigmine Methylsulfate is available in 1 form. Different forms and brands can have different approved uses, doses, schedules, and directions. Follow the instructions for your exact product, and do not switch forms without guidance from your prescriber or pharmacist.

Injection

Into a vein
Brands Bloxiverz
How this form is used
What it may be used for
  • Bloxiverz (intravenous injection) is indicated to reverse the effects of non-depolarizing neuromuscular blocking agents after surgery
  • Neostigmine Methylsulfate injection is indicated to reverse the effects of non-depolarizing neuromuscular blocking agents after surgery
Important instructions
  • Bloxiverz must be given slowly by intravenous route over at least 1 minute by trained healthcare providers, with a peripheral nerve stimulator used to guide dosing
  • Neostigmine Methylsulfate injection is administered by intravenous bolus injection, slowly, with additional doses given based on the patient's nerve stimulator response
  • An anticholinergic agent (atropine or glycopyrrolate) must be given before or at the same time as either product to reduce the risk of slow heart rate
  • Patients must be monitored for full recovery of breathing and muscle function after administration of either product
Available strengths 4 strengths
0.5 mg/mL 0.51 mg/mL 1 mg/mL 1.02 mg/mL
105 FDA-listed product records ⓘ

📊 Neostigmine Methylsulfate across the U.S. market

How Neostigmine Methylsulfate appears in the FDA’s National Drug Code Directory — including its dosage forms, strengths, brand names, manufacturers, and FDA-listed product records. These are directory records, not sales or prescription volume.

1
Dose forms ⓘ
37
Manufacturers
2
Brand names
114
FDA-listed product records ⓘ
2011
First marketed ⓘ

Also listed with the FDA, not a patient dose form: Powder (9) — bulk drug substance sold to compounders/manufacturers and multi-item kits. These aren’t counted in the dose-form total above.

Fresenius Kabi USA, LLC12%
Hikma Pharmaceuticals USA Inc.11%
Medical Purchasing Solutions, LLC6%
Exela Pharma Sciences, LLC6%
Amneal Pharmaceuticals LLC5%
Indoco Remedies Limited4%
Other makers55%

Share of FDA-listed product records by manufacturer — FDA National Drug Code Directory. Record counts are not sales or prescription volume.

📈 How widely Neostigmine Methylsulfate is used

A general measure of how commonly Neostigmine Methylsulfate is prescribed, based on Medicaid — one of the largest public drug programs. The figure below is prescriptions filled in Q1 2025 – Q1 2026, summed across every form and brand of the drug.

Think of this as a proxy for how widely Neostigmine Methylsulfate is used, drawn from freely available public data. Medicaid is just one program — these numbers don’t include Medicare, other government coverage, or commercial and cash-pay prescriptions, so real-world use is higher than what’s shown here.

6,840
Medicaid prescriptions filled (Q1 2025 – Q1 2026)
$663,182 gross Medicaid reimbursement (before mandatory rebates — net cost is lower)

How commonly is Neostigmine Methylsulfate prescribed? Of the 1,596 medications we measure, Neostigmine Methylsulfate ranks #995 by Medicaid prescriptions — more than 38% of them.

Where Neostigmine Methylsulfate ranks among the drugs we measure · Q1 2025 – Q1 2026 · neighbors ±5
Total prescriptions — #995 of 1,596
#990 Fingolimod 6,946 Rx #991 Canakinumab Injection 6,924 Rx #992 Vericiguat 6,901 Rx #993 Octreotide 6,900 Rx #994 Silodosin 6,899 Rx #995 Neostigmine Methylsulf... 6,840 Rx #996 Diroximel Fumarate 6,829 Rx #997 Octreotide Injection 6,763 Rx #998 Olaparib 6,734 Rx #999 Blinatumomab Injection 6,717 Rx #1,000 Relugolix 6,636 Rx

Source: Medicaid State Drug Utilization Data (CMS), aggregated by generic ingredient — summed across every NDC (all brands, strengths, salt forms and dosage forms) of Neostigmine Methylsulfate, and across all states and both fee-for-service and managed-care claims. A general popularity signal; it excludes Medicare, commercial insurance and cash prescriptions, so it is not total U.S. use. Based on the 22 of 91 listed Neostigmine Methylsulfate NDCs with Medicaid activity.

🔍 Compare Neostigmine Methylsulfate products

A representative set of FDA-listed product records for Neostigmine Methylsulfate — across manufacturers, strengths, and dosage forms, grouped by form with each product’s manufacturer and how the FDA approved it. The same medicine may be made and packaged by different companies, so a single drug can have many directory entries. (It’s also why a refill can look different — a new shape, color, or box — even though it contains the same medication.)

Showing 114 of 114 products — FDA National Drug Code Directory. See every product, package size and price: browse all 114 Neostigmine Methylsulfate NDCs →

🏷️ Sold under these brand names

Bloxiverz

🏭 Manufacturers & labelers

Fresenius Kabi USA, LLC 14 Hikma Pharmaceuticals USA Inc. 12 Medical Purchasing Solutions, LLC 7 Exela Pharma Sciences, LLC 7 Amneal Pharmaceuticals LLC 6 Indoco Remedies Limited 5 Xiromed LLC 4 Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. 4 Gland Pharma Limited 4 Eugia US LLC 4 Civica, Inc. 3 HF Acquisition Co LLC, DBA HealthFirst 2 Par Pharmaceutical, Inc. 2 Par Health USA, LLC 2 Nivagen Pharmaceuticals, Inc. 2 Meitheal Pharmaceuticals Inc. 2 Sagent Pharmaceuticals 2 Amphastar Pharmaceuticals, Inc. 2 Dr.Reddys Laboratories Inc 2 Somerset Therapeutics, LLC 2 Avadel Legacy Pharmaceuticals, LLC 2 BE Pharmaceuticals Inc. 2 Henry Schein, Inc. 2 Harman finochem Limited 2

…and 13 more on the FDA NDC directory.

RxNorm drug class

Neostigmine Methylsulfate belongs to the Cholinesterase Inhibitor class.

Pharmacologic class Cholinesterase Inhibitor
Drug family (ATC) Anticholinesterases, Parasympathomimetics
How it works Cholinesterase Inhibitors

Classified by RxNorm RxClass — the U.S. National Library of Medicine's standardized drug-classification service (Established Pharmacologic Class from the FDA, the ATC drug family from the WHO, and mechanism of action). Reference only, not medical advice.

🔬 Where this comes from

Core label, product, RxNorm, safety, and utilization data on this page come from the sources identified below. AI-written, editorial, and licensed sections are labeled separately.

📄
FDA-filed drug labels (SPL) Uses, dosing, warnings & side effects from SPL records retrieved through openFDA; the linked representative set can be verified on DailyMed. ✓ Linked label effective Oct 15, 2024
🏭
Forms, brands & labelersAggregated from ingredient-matched FDA National Drug Code Directory product records for Neostigmine Methylsulfate.
📈
Real-world reportsThe FDA Adverse Event Reporting System (FAERS), served through openFDA.
🚨
Recalls & shortagesopenFDA drug-enforcement reports and the FDA drug-shortage database.
🧾 Clinical label set — FDA-filed SPL labels retained for Neostigmine Methylsulfate after exact ingredient or ingredient-combination matching and applicable route/form matching
Clinical labels in scope
33
NDC products indexed
114
Distinct labelers/manufacturers represented
37
Linked representative label ⓘ
Fresenius Kabi USA, LLC
Linked label effective
Oct 15, 2024
Composite sections available
22
Linked SPL Set ID
d0e11e4c-41c3-4874-b567-579db655fba3
Linked SPL Document ID
1efedce1-b2c3-4652-a289-6ea596b039e2
Open the linked representative label on DailyMed ↗

How we combine label and product data

HelloPharmacist combines public FDA and NLM records; we don’t author the underlying clinical facts. We identified 33 FDA-filed SPL label sets within the page’s selected clinical scope after exact ingredient or ingredient-combination matching and applicable route/form matching. The representative label is the starting point for the displayed reference monograph; the 12 largest stored in-scope SPL records, which may include that representative, are compared section by section, and the longest available version of each section is retained. Forms, routes, brands, labelers, product-listed strengths, and product-record counts are aggregated separately from ingredient-matched FDA NDC Directory records; package records listed above are associated with the linked SPL; and the normalized concept hierarchy comes from NLM RxNorm.

For canonical ingredient pages, bounded product-attributed indication and administration excerpts may be added to the AI evidence, and the generator is instructed to preserve available product, brand, route, and form qualifiers instead of treating one label as universal. Where a section is identified as AI-written, its plain-language text is generated from bounded label evidence. New draft drug pages remain in the admin review queue before first publication. Fresenius Kabi USA, LLC is the representative DailyMed label linked for verification and dates; it is not the sole source used for the page.

This is general education, not medical advice — always consult your doctor or pharmacist about your medications and any medical condition. For the exact wording of the linked representative label, view that label on DailyMed; some displayed composite sections may come from other in-scope SPL labels. Learn how we use AI and our data sources & update cadence.