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Pyridostigmine bromide 105 mg Tablet, Extended Release — NDC 60846-0559-10 package photo

Pyridostigmine bromide 105 mg Tablet, Extended Release

by Amneal Pharmaceuticals LLC · 10 CARTON in 1 BAG (60846-559-10) / 1 BLISTER PACK in 1 CARTON (60846-559-27) / 7 TABLET, EXTENDED RELEASE in 1 BLISTER PACK
NDC 60846-0559-10
🏷️ FDA NDC (as labeled) 60846-559-10 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 60846-559-10
Product NDC 60846-559
11-digit billing NDC 60846055910
NCPDP billing unit EA — each (per item)
RxCUI 2695047
UNII KVI301NA53
UPC 0360846559279, 0360846559101
Application # NDA217604
SPL Set ID 52d6f195-165a-400b-a13b-489e94bcf0b0
Established class (EPC) Cholinesterase Inhibitor
Mechanism of action Cholinesterase Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2024-10-09
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance PYRIDOSTIGMINE BROMIDE
GCN Seq No 086594
GCN 56326
HICL code 001990
Ingredient (HICL) Pyridostigmine Bromide
HIC1 code J
Therapeutic class — broad (HIC1) Autonomic Nervous System
HIC2 code J1
Therapeutic class — intermediate (HIC2) Cholinergics
HIC3 code J1B
Therapeutic class — specific (HIC3) Cholinesterase Inhibitors
AHFS code 12:04.00.00
AHFS class Parasympathomimetic (Cholinergic Agents)
FDB label name PYRIDOSTIGMINE ER 105 MG TAB
FDB brand name Pyridostigmine Bromide Er
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 60846-559-10 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 60846-0559-10. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Cholinesterase Inhibitor class.

Pharmacologic class Cholinesterase Inhibitor
Drug family (ATC) Anticholinesterases
How it works Cholinesterase Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerAmneal Pharmaceuticals LLC
Application holderAMNEAL PHARMACEUTICALS LLC
FDA applicationNDA217604 (NDA)
Labeler code60846
First marketedOct 2024
Product typeHuman Prescription Drug
Portfolio467 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name PYRIDOSTIGMINE ER 105 MG TAB Ingredient Pyridostigmine Bromide
📖 What it is MedlinePlus · NLM

Pyridostigmine is used to treat myasthenia gravis. Pyridostigmine is in a class called cholinergic agents. It works by increasing the amount of certain natural substances in the body to improve nerve and muscle activity.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Think of it as a protective shield you put up before a threat arrives. Pyridostigmine temporarily occupies key spots on an enzyme in your body that soman would otherwise permanentl...
  • What exactly is pyridostigmine supposed to do for me — does it actually stop soman from hurting me?
  • Timing is everything with this medication. It needs to be started at least several hours before any anticipated exposure — not when an alarm goes off. If you take it immediately be...
  • Does it matter when I take it? Can I just take it right before a threat?
📖 Read our full Pyridostigmine guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 5138Q19F1X
    Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
  • UNII J2243103QO
    Ammonium methacrylate is a synthetic polymer used as a coating agent on tablets and capsules. It helps control how quickly the medication dissolves in the digestive system.
  • UNII H0G9379FGK
    Calcium carbonate is a white mineral powder used as a filler and buffering agent in medicines. It helps give tablets their bulk and size while neutralizing stomach acid in some formulations.
  • UNII 2S7830E561
    Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • UNII XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • UNII 9XZ8H6N6OH
    A plant-based cellulose derivative used as a binder to hold tablet ingredients together, a thickener in liquids, and a coating agent to control how fast the medicine dissolves.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII 3OWL53L36A
    A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 46N107B71O
    Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 8MDF5V39QO
    A white powder form of baking soda that acts as a buffer and pH regulator in medicines. It helps maintain the right acid-base balance and may aid tablet disintegration.
  • UNII AB6MNQ6J6L
    Succinic acid is an organic acid derived from natural sources or chemical synthesis. In medications, it functions as a buffer to help maintain the proper pH level and may also serve as a preservative or flavor enhancer in formulations.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
  • UNII 8Z96QXD6UM
    Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.

19 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Pyridostigmine bromide 105 mgthis 60846-0559-10 Amneal 7 tablets — — FDA listed —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2024
First FDA approval
Oct 2024
📍
2026
Currently FDA-listed
2 years listed
🛡️
2038
Latest patent/protection listed
not a guaranteed launch date
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jun 2038. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Oct 4, 2024 RLD RS ⏳ ~11.8 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 11478425 — method of use (U-4012)
US 12042559 — drug product
US 10925833 — drug product
US 12233166 — drug product
US 10987311 — drug product
US 10881617 — drug product
US 11666536 — drug product
US 11911515 — drug product
US 11229606 — drug product
2024 2026 2028 2030 2032 2034 2036 2038
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (9)
PatentTypeUse codeExpires
US 11478425 ↗ Method of use U-4012 Jun 18, 2038
US 12042559 ↗ Drug product — Jun 18, 2038
US 10925833 ↗ Drug product — Jun 18, 2038
US 12233166 ↗ Drug product — Jun 18, 2038
US 10987311 ↗ Drug product — Jun 18, 2038
US 10881617 ↗ Drug product — Jun 18, 2038
US 11666536 ↗ Drug product — Jun 18, 2038
US 11911515 ↗ Drug product — Jun 18, 2038
US 11229606 ↗ Drug product — Jun 18, 2038
Common questions
Is there a generic version of PYRIDOSTIGMINE ER 105 MG TAB?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for PYRIDOSTIGMINE ER 105 MG TAB. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Pyridostigmine Bromide — the program that covers self-administered drugs. 9 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Pyridostigmine Bromide. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$5.53M
Claims incl. refills
71.4K
Beneficiaries
45.1K
Spend / beneficiary
$122.42
Spend / claim
$77.39
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for PYRIDOSTIGMINE BROMIDE — the ingredient across all brands.

Top reported reactions

Myasthenia Gravis1,221
Fatigue915
Asthenia742
Diarrhoea681
Dyspnoea633
Headache620
Nausea587

Age at onset

Neonate14
Infant8
Child20
Adolescent21
Adult736
Elderly718

Reporter sex

10,644 reports
Male · 40%
Female · 60%
Unknown · 0%

Serious outcomes

Hospitalization3,762
Death806
Life-threatening611
Disabling242
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 781 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
60846-0559-10 You're viewing this 10 CARTON in 1 BAG (60846-559-10) / 1 BLISTER PACK in 1 CARTON (60846-559-27) / 7 TABLET, EXTENDED RELEASE in 1 BLISTER PACK 2024-10-09 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 60846-559-10, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 60846-0559-10, written without dashes as 60846055910. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 60846-0559-10, the first segment (60846) is the labeler code FDA assigned to Amneal Pharmaceuticals LLC; the middle segment (0559) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (10) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Amneal Pharmaceuticals LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Amneal Pharmaceuticals LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning ~2 min read ▾

WARNING: RISKS WITH IMPROPER USE OF PYRIDOSTIGMINE BROMIDE After Exposure to Soman, Use Atropine and Pralidoxime Pyridostigmine bromide is for use as a pretreatment for exposure to soman nerve agent. Pyridostigmine bromide alone will not protect against exposure to soman. The efficacy of pyridostigmine bromide is dependent upon the rapid use of atropine and pralidoxime (2-PAM) after soman exposure [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ].

Always Use Protective Garment(s) Primary protection against exposure to chemical nerve agents is the wearing of protective garments including masks, hoods, and overgarments designed specifically for this use. Individuals must not rely solely upon pretreatment with pyridostigmine bromide and on the antidotes atropine and pralidoxime (2-PAM) to provide complete protection from poisoning by soman nerve agent [see Dosage and Administration (2.1) ] . Pyridostigmine Bromide as Pretreatment Only If pyridostigmine bromide is taken immediately before exposure (e.g., when the gas attack alarm is given) or at the same time as poisoning by soman, it is not expected to be effective and may exacerbate the effects of a sub-lethal exposure to soman.

Do not take pyridostigmine bromide after exposure to soman [see Clinical Pharmacology (12.2) ]. FOR MILITARY MEDICAL USE ONLY WARNING: RISKS WITH IMPROPER USE OF PYRIDOSTIGMINE BROMIDE See full prescribing information for complete boxed warning. After Exposure to Soman, Use Atropine and Pralidoxime Pyridostigmine bromide is for use as a pretreatment for exposure to soman nerve agent.

Pyridostigmine bromide alone will not protect against exposure to soman. The efficacy of pyridostigmine bromide is dependent upon the rapid use of atropine and pralidoxime (2-PAM) after soman exposure. ( 2.1 , 5.1 ) Always Use Protective Garment(s) Primary protection against exposure to chemical nerve agents is the wearing of protective garments.

( 2.1 , 5.1 ) Pyridostigmine Bromide as Pretreatment Only If taken immediately before soman exposure (e.g., when the gas attack alarm is given) or at the same time as poisoning by soman, it is not expected to be effective and may exacerbate the effects of a sub-lethal exposure to soman. Do not take pyridostigmine bromide after exposure to soman. ( 2.1 , 12.2 )

🎯 Indications and Usage 138 words ▾

1 INDICATIONS AND USAGE Pyridostigmine bromide is indicated for pretreatment against the lethal effects of soman nerve agent poisoning in adults. Pyridostigmine bromide is intended for use in conjunction with protective garments, including a mask. At the first sign of nerve agent poisoning, pyridostigmine bromide should be stopped, and atropine and pralidoxime therapy started immediately.

The evidence for the effectiveness of pyridostigmine bromide as pretreatment against soman-induced toxicity was derived from animal studies alone [see Clinical Studies (14) ]. FOR MILITARY MEDICAL USE ONLY Pyridostigmine bromide is a cholinesterase inhibitor indicated for pretreatment against the lethal effects of soman nerve agent poisoning in adults. ( 1 ) Pyridostigmine bromide is for use in conjunction with Protective garments, including a gas mask, and Immediate atropine and pralidoxime therapy at the first sign of nerve agent poisoning.

( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION The recommended dosage is 105 mg orally once daily, started at least several hours prior to exposure to soman. Do not take on an empty stomach. Take with a medium-fat medium-calorie meal (e.g., meal with 650 calories, 40% fat) or a high-fat high-calorie meal (e.g., meal with 1,000 calories, 50% fat).

Do not take with a low-fat low-calorie meal (e.g., meal with 400 calories, 25% fat) ( 2.2 ) At the first sign of soman nerve agent poisoning, discontinue pyridostigmine and administer atropine and pralidoxime immediately. ( 2.2 ) Evaluate use beyond 14 consecutive days in the context of the likelihood of soman exposure. ( 2.2 )

2.1Important Administration Information For Military Medical Use Only. Treatment and Protection for Soman Exposure Pyridostigmine bromide is for use as a pretreatment for exposure to soman nerve agent (see Treatment Timing). Pyridostigmine bromide alone will not protect against exposure to soman.

Atropine and Pralidoxime The efficacy of pyridostigmine bromide is dependent upon the rapid use of atropine and pralidoxime (2-PAM) after soman exposure. Primary Protection The primary protection against exposure to chemical nerve agents consists of wearing protective garments including masks, hoods, and overgarments designed specifically for this use. Do not rely solely upon pretreatment with pyridostigmine bromide and the antidotes atropine and pralidoxime to provide complete protection from poisoning by soman nerve agent.

Treatment Timing Pyridostigmine bromide is to be administered as pretreatment before exposure to soman nerve agent [see Dosage and Administration (2.2) ]. If pyridostigmine bromide is taken immediately before exposure (e.g., when the gas attack alarm is given) or at the same time as poisoning by soman, it is not expected to be effective and may exacerbate the effects of a sublethal exposure to soman [see Clinical Pharmacology (12.2) ] . Do not take pyridostigmine bromide after exposure to soman.

Administration with Food Take pyridostigmine bromide 105 mg extended-release tablets with either a medium fat, medium calorie or high fat, high calorie meal to maintain efficacious pyridostigmine levels [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ] . Administration with Alcohol Pyridostigmine bromide 105 mg extended-release tablets should not be taken with alcohol [see Clinical Pharmacology (12.3) ] .

2.2Recommended Dosage, Administration, and Duration Dosage The recommended dosage of pyridostigmine bromide is 105 mg orally once daily with food, started at least several hours prior to exposure to soman. Do not take on an empty stomach. Take with a medium-fat medium-calorie meal (e.g., meal with 650 calories, 40% fat) or a high-fat high-calorie meal (e.g., meal with 1,000 calories, 50% fat).

Do not take with a low-fat low-calorie meal (e.g., meal with 400 calories, 25% fat) [see Clinical Pharmacology (12.3) ] . Timing and Duration of Treatment Timing Pyridostigmine bromide is a pretreatment for exposure to soman nerve agent. There is no known advantage to taking pyridostigmine bromide just prior to, or concurrent with, soman exposure.

According to the mechanism of action of pyridostigmine bromide [see Clinical Pharmacology (12.1 , 12.2) ] , pyridostigmine bromide is effective when it is given sufficiently in advance of soman poisoning to provide a pool of protected enzyme. Therefore, it is expected that pyridostigmine bromide will not be effective if administered just prior to or during exposure to soman. Duration At the first sign of nerve agent poisoning, discontinue pyridostigmine bromide and administer pretreatment with atropine and pralidoxime immediately [see Warnings and Precautions (5.1) ] .

The benefits and risks of use beyond 14 consecutive days have not been definitively established; therefore, evaluate continued use beyond 14 consecutive days in the context of the likelihood of exposure to soman nerve agent. Missed Dose If a dose is miss…

💊 Dosage Forms and Strengths 46 words ▾

3 DOSAGE FORMS AND STRENGTHS Extended-Release Tablets: 105 mg, peach, oval, coated, unscored, biconvex tablets imprinted with “A2 463” on one side and plain on the other side. A hole may be visible on one side of the tablet. Extended-release tablets: 105 mg ( 3 )

⛔ Contraindications 43 words ▾

4 CONTRAINDICATIONS Pyridostigmine bromide extended-release tablets are contraindicated in patients with: Mechanical intestinal or urinary obstruction Known hypersensitivity to pyridostigmine or other anticholinesterase agents Mechanical intestinal or urinary obstruction. ( 4 ) Known hypersensitivity to pyridostigmine or other anticholinesterase agents. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS At the first sign of soman poisoning pyridostigmine must be stopped, and atropine and 2-PAM must be administered immediately. ( 5.1 ) Use with caution in persons with increased risk of anticholinergic reactions, such as persons with bronchial asthma, chronic obstructive pulmonary disease, bradycardia, cardiac arrhythmias, beta blocker treatment (increased risk of anticholinergic reactions). ( 5.2 ) Use with caution in persons with bromide sensitivity.

( 5.3 ) In case of serious adverse reactions, advise personnel to temporarily discontinue pyridostigmine and seek immediate medical attention. ( 5.4 )

5.1Risk of Improper Use of Pyridostigmine Bromide Risk of Not Stopping Pyridostigmine Bromide and Using Atropine and Pralidoxime in the Event of Soman Exposure Pyridostigmine bromide is for use as pretreatment for exposure to soman nerve agent and must not be taken after exposure to soman nerve agent [see Dosage and Administration (2.1 , 2.2) ]. Pyridostigmine bromide pretreatment offers no benefit against the nerve agent soman unless the nerve agent antidotes, atropine and pralidoxime (2-PAM), are administered once symptoms of poisoning appear.

Discontinue pyridostigmine at the first sign of nerve agent poisoning because it may exacerbate the effects of a sublethal exposure to soman if taken immediately before exposure (e.g., when the gas attack alarm is given) or at the same time as poisoning by soman [see Clinical Pharmacology (12.2) ]. Signs of nerve agent poisoning can include runny nose; watery eyes; small, pinpoint pupils; eye pain; blurred vision; drooling and excessive sweating; cough; chest tightness; rapid breathing; diarrhea; increased urination; confusion; drowsiness; weakness; headache; nausea, vomiting, and/or abdominal pain; slow or fast heart rate; and/or abnormally low or high blood pressure.

Risk of Not Wearing Protective Garments Pyridostigmine bromide is not the primary protection against exposure to soman nerve agent. The primary protection against exposure to chemical nerve agents is the wearing of protective garments including masks, hoods, and overgarments designed specifically for this use. Individuals must not rely solely upon pretreatment with pyridostigmine bromide and on the antidotes, atropine and pralidoxime (2-PAM), to provide complete protection from poisoning by soman nerve agent.

5.2Increased Risk of Anticholinergic Adverse Reactions in Individuals with Certain Conditions Pulmonary Conditions Drugs that increase cholinergic activity, including pyridostigmine bromide, should be used with caution in persons with bronchial asthma or chronic obstructive pulmonary disease. Cardiovascular Conditions Because pyridostigmine bromide increases cholinergic activity, it may have vagotonic effects on heart rate, which can lead to bradycardia or cardiac arrhythmias. Genitourinary Tract or Gastrointestinal Tract Obstruction Drugs that increase cholinergic agents, including pyridostigmine bromide, could cause symptoms in persons susceptible to genitourinary tract or gastrointestinal tract obstruction.

Conditions Treated with Beta Adrenergic Receptor Blockers Pyridostigmine bromide should be used with caution in people being treated for hypertension or glaucoma with beta adrenergic receptor blockers [see Drug Interactions (7.2) ].

5.3Use in Bromide-Sensitive Individuals Caution should be taken when administering pyridostigmine bromide to individuals with known bromide sensitivity. A skin rash may be observed in bromide-sensitive patients, which usually subsides upon discontinuance of the medication. The risks and benefits of administration must be weighed against the potential for rash or other adverse reactions in these individuals.

5.4Serious Adverse Reactions, Such as Difficulty Breathing, Severe Dizziness, Loss of Consciousness Pyridostigmine bromide can cause serious adverse reactions such as difficulty breathing, severe dizziness, or loss of consciousness. If these adverse rea…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Risk of Improper Use of Pyridostigmine Bromide [see Warnings and Precautions (5.1) ] Individuals at Increased Risk of Anticholinergic Adverse Reactions [see Warnings and Precautions (5.2) ] Use in Bromide-Sensitive Individuals [see Warnings and Precautions (5.3) ] Serious Adverse Reactions, Such as Difficulty Breathing, Severe Dizziness, Loss of Consciousness [see Warnings and Precautions (5.4) ] Most common adverse reactions ( ≥ 3% ) are diarrhea, abdominal pain, dysmenorrhea, and twitch.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reactions to pyridostigmine bromide are typically of two varieties: muscarinic and nicotinic. Muscarinic adverse reactions include abdominal cramps, bloating, flatulence, diarrhea, emesis, increased peristalsis, nausea, hypersalivation, urinary incontinence, increased bronchial secretion, diaphoresis, miosis, and lacrimation.

Nicotinic adverse reactions are comprised chiefly of muscle cramps, fasciculations, and weakness. In a controlled study of 90 healthy volunteers comparing immediate-release pyridostigmine bromide 30 mg every 8 hours, which provides exposures comparable to pyridostigmine bromide 105 mg extended-release tablets once daily, to placebo for 21 days, the adverse reactions that were reported in 2% or more of subjects is included in Table 1. The most common adverse reactions (≥ 3%) are diarrhea, abdominal pain, dysmenorrhea, and twitch.

Table 1: Incidence of Adverse Reactions ≥ 2% Adverse Reaction Pyridostigmine N = 60 % Placebo N = 30 % Diarrhea 7 0 Abdominal pain 7 0 Dysmenorrhea 5 0 Twitch 3 0 Myalgia 2 0 Dry skin 2 0 Urinary frequency 2 0 Epistaxis 2 0 Amblyopia 2 0 Hypesthesia 2 0 Neck pain 2 0 Other less common adverse reactions seen during controlled and uncontrolled clinical trials for pyridostigmine include the following: Pulmonary: Exacerbation of acute bronchitis and asthma Cardiovascular: Elevated blood pressure, decreased heart rate (4-6 beats per minute), chest tightness Eyes: Change in vision, eye pain Neurologic: Headache, hypertonia, difficulty in concentrating, confusion, disturbed sleep, tingling of extremities, numbness of the tongue Skin: Increased sweating, rash, alopecia Digestive: Vomiting, borborygmi, nausea, bloating, flatulence General: Warm sensation, lethargy/drowsiness, depressed mood During safety studies at the recommended dosage of immediate release pyridostigmine bromide 30 mg every 8 hours, which provides exposures comparable to pyridostigmine bromide 105 mg extended-release tablets once daily, there were two reports of loss of consciousness, one of which also included urinary and fecal incontinence, stiffness of the upper torso and arms, post-syncopal skin pallor, post-syncopal confusion, and post-syncopal weakness.

Central Nervous System Adverse Reactions Pyridostigmine bromide is a quaternary ammonium compound and does not readily cross the blood-brain barrier. Compared to the peripheral effects of pyridostigmine bromide, central nervous system manifestations are less frequent and less serious, primarily consisting of headache and vertigo, with minor and clinically insignificant changes in heart rate, blood pressure, and respiratory function.

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Mefloquine: Additive effect on gastrointestinal tract and atrial rate. ( 7.1 ) Anticholinesterase drugs for glaucoma treatment: Additive effect. ( 7.2 ) Narcotics: Exacerbation of bradycardia possible.

( 7.3 ) Depolarizing neuromuscular blocking agents: Increased effect. ( 7.4 ) Non-depolarizing neuromuscular blocking agents: Dose may need to be increased. ( 7.4 ) Aminoglycoside antibiotics, local and some general anesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all.

( 7.4 ) Drugs converted to pantothenic acid (e.g., dexpanthenol): Additive effect. ( 7.5 )

7.1Mefloquine Concomitant use of mefloquine and pyridostigmine bromide may have additive effects on the gastrointestinal tract, the most common of which is loose bowels. Additive effects on the atrial rate may also occur with concomitant use of mefloquine and pyridostigmine bromide.

7.2Other Anticholinesterase Drugs Concomitant use of anticholinesterase drugs used in the treatment of glaucoma and pyridostigmine bromide may have an additive effect that may cause or exacerbate problems with night vision.

7.3Narcotics The bradycardia associated with the use of narcotics may exacerbate pyridostigmine-induced bradycardia.

7.4Drugs that Interfere with Neuromuscular Transmission Particular caution should be observed in the administration of depolarizing neuromuscular blocking agents (e.g., succinylcholine) during surgery since the degree of neuromuscular blockade that ensues may be enhanced by previously administered pyridostigmine bromide. Doses of non-depolarizing neuromuscular blocking agents (e.g., pancuronium bromide) may need to be increased in patients previously administered pyridostigmine bromide. Atropine antagonizes the muscarinic effects of pyridostigmine bromide, and this interaction is utilized to counteract the muscarinic symptoms of pyridostigmine bromide toxicity.

Anticholinesterase agents are sometimes effective in reversing neuromuscular block induced by aminoglycoside antibiotics. However, aminoglycoside antibiotics, local and some general anesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all, during treatment with pyridostigmine bromide.

7.5Drugs Converted to Pantothenic Acid Concomitant use of drugs that are converted to pantothenic acid in vivo (e.g., dexpanthenol) and pyridostigmine bromide may have additive effects by increasing production of acetylcholine.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Renal impairment: Increased risk of side effects; careful dose selection. In persons with renal impairment, renal function monitoring may be useful. ( 8.6 )

8.1Pregnancy Risk Summary Available data from case reports and case series over decades of use with pyridostigmine bromide have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Treatment with pyridostigmine bromide for soman nerve agent poisoning during pregnancy should not be delayed because exposure to soman during pregnancy may increase the risk of maternal and fetal morbidity and mortality. In animal studies, oral administration of pyridostigmine during organogenesis resulted in adverse developmental effects (increased embryofetal mortality and fetal structural abnormalities), at clinically relevant doses (see Data) .

The 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 clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data Oral administration of pyridostigmine to pregnant rats during organogenesis resulted in increases in embryofetal deaths and incidences of fetal skeletal variations at the highest dose tested (30 mg/kg/day), which was also maternally toxic. A slight increase in the incidence of hydronephrosis was observed at all dose levels (lowest dose tested was 3 mg/kg/day). A no-effect dose for adverse effects on embryofetal development in the rat was not identified.

The lowest dose tested (3 mg/kg/day) is less than the recommended human dose (105 mg) on a body surface area (mg/m 2 ) basis. Oral administration of pyridostigmine to pregnant rabbits during organogenesis resulted in an increase in the incidence of visceral variations at the highest dose tested (45 mg/kg/day), which was also maternally toxic. An increased incidence of blood vessel variations was observed at all doses (lowest dose tested was 5 mg/kg/day).

A no-effect dose for adverse effects on embryofetal development in the rabbit was not identified. The lowest dose tested (5 mg/kg/day) is less than the recommended human dose on a body surface area (mg/m2) basis.

8.2Lactation Risk Summary Pyridostigmine bromide is present in human milk. Based on limited data, pyridostigmine bromide was not detected in the plasma of infants who were breastfed by mothers taking pyridostigmine bromide. There are no data on the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pyridostigmine bromide and any potential adverse effects on the breastfed infant from pyridostigmine bromide or from the underlying maternal condition.

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5Geriatric Use Clinical studies of pyridostigmine bromide did not contain sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

Because elderly patients are more likely to have decreased renal function [see Clinical Pharmacology (12.3) ], care should be taken in dose selection, and it may be useful to monitor renal function.

8.6Renal Impairment This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Caution…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Available data from case reports and case series over decades of use with pyridostigmine bromide have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Treatment with pyridostigmine bromide for soman nerve agent poisoning during pregnancy should not be delayed because exposure to soman during pregnancy may increase the risk of maternal and fetal morbidity and mortality. In animal studies, oral administration of pyridostigmine during organogenesis resulted in adverse developmental effects (increased embryofetal mortality and fetal structural abnormalities), at clinically relevant doses (see Data) .

The 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 clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data Oral administration of pyridostigmine to pregnant rats during organogenesis resulted in increases in embryofetal deaths and incidences of fetal skeletal variations at the highest dose tested (30 mg/kg/day), which was also maternally toxic. A slight increase in the incidence of hydronephrosis was observed at all dose levels (lowest dose tested was 3 mg/kg/day). A no-effect dose for adverse effects on embryofetal development in the rat was not identified.

The lowest dose tested (3 mg/kg/day) is less than the recommended human dose (105 mg) on a body surface area (mg/m 2 ) basis. Oral administration of pyridostigmine to pregnant rabbits during organogenesis resulted in an increase in the incidence of visceral variations at the highest dose tested (45 mg/kg/day), which was also maternally toxic. An increased incidence of blood vessel variations was observed at all doses (lowest dose tested was 5 mg/kg/day).

A no-effect dose for adverse effects on embryofetal development in the rabbit was not identified. The lowest dose tested (5 mg/kg/day) is less than the recommended human dose on a body surface area (mg/m2) basis.

🧒 Pediatric Use 13 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 119 words ▾

8.5Geriatric Use Clinical studies of pyridostigmine bromide did not contain sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.

Because elderly patients are more likely to have decreased renal function [see Clinical Pharmacology (12.3) ], care should be taken in dose selection, and it may be useful to monitor renal function.

🆘 Overdosage ~1 min read ▾

10 OVERDOSAGE Overdosage of pyridostigmine bromide may result in cholinergic crisis, a state characterized by increasing muscle weakness that, through involvement of the muscles of respiration, may lead to death. Overdosage with pyridostigmine bromide must be differentiated from the acute manifestations of nerve agent poisoning, which may also be characterized by a cholinergic crisis. Extremely high doses of pyridostigmine bromide may also produce central nervous system (CNS) symptoms of agitation, restlessness, confusion, visual hallucinations, and paranoid delusions.

Electrolyte abnormalities, possibly resulting from high serum bromide concentrations, also have been reported. Death may result from cardiac arrest or respiratory paralysis and pulmonary edema. In the treatment of pyridostigmine bromide overdosage, maintaining adequate respiration is of primary importance.

Tracheostomy, bronchial aspiration, and postural drainage may be required to maintain an adequate airway; respiration can be assisted mechanically if required. Supplemental oxygen may be necessary. Pyridostigmine bromide should be discontinued immediately and 1 mg to 4 mg of atropine sulfate administered intravenously.

Additional doses of atropine may be given every 5 to 30 minutes as needed to control muscarinic symptoms. Atropine overdosage should be avoided, as tenacious secretions and bronchial plugs may result. It should be kept in mind that unlike muscarinic effects, the skeletal muscle effects and consequent respiratory paralysis (nicotinic effects), which can occur following pyridostigmine overdosage, are not alleviated by atropine.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Pyridostigmine is a reversible cholinesterase inhibitor.

12.2Pharmacodynamics The mechanism of soman-induced death is reasonably well understood. Death is believed to result primarily from respiratory failure due to irreversible inhibition of the enzyme acetylcholinesterase and the consequent increase in the level of the neurotransmitter acetylcholine 1) at nicotinic receptors at the neuromuscular junction, resulting in pathological stimulation and ultimate failure of the muscles of respiration, 2) at muscarinic receptors in secretory glands and smooth muscle, resulting in excessive respiratory secretions and bronchoconstriction, and 3) at cholinergic receptors in the brain, resulting in central respiratory depression.

The effect of pyridostigmine is presumed to result from its reversible inhibition of a critical number of acetylcholinesterase active sites in the peripheral nervous system, protecting them from irreversible inhibition by soman. (Pyridostigmine bromide is not thought to enter the brain in significant amounts.) When the pyridostigmine bromide-induced inhibition of the enzyme is subsequently reversed, there is a small residual amount of enzyme activity that is adequate to sustain life (provided atropine and 2-PAM are subsequently administered).

An implication of this presumed mechanism is that it is not helpful to give pyridostigmine bromide either just before or during exposure to soman [see Dosage and Administration (2.1 , 2.2) ].

12.3Pharmacokinetics Absorption Pyridostigmine bromide is poorly absorbed from the gastrointestinal tract with an absolute bioavailability of 10% to 20%. Following a single oral dose of 105 mg pyridostigmine bromide extended-release tablet in the fed state, the median T max was 10.00 (5.00 – 18.00) hours with medium fat, medium calorie meal and 16.00 (5.00 – 20.00) hours with high fat, high calorie meal. Effect of Food The pharmacokinetic parameters of pyridostigmine bromide 105 mg extended-release tablets showed a significant food effect in regard to fasted vs. fed and to the types of meals consumed.

Single oral doses were administered to healthy volunteers (N=32) under four different conditions as described below: Fasted state Low Fat, Low Calorie (LFLC): ~450-500 Kcal; fat ~25% Medium Fat, Medium Calorie (MFMC): ~600-650 Kcal; fat ~40% High Fat, High Calorie (HFHC): ~800-1000 Kcal; fat ~50% Following administration of 105 mg pyridostigmine bromide extended-release tablets, the oral bioavailability is greater when taken with food than when taken in the fasted state. Under fed conditions, the exposure was greatest with HFHC meal compared to LFLC meal.

Peak of exposure and overall exposure were similar with MFMC and HFHC meals. The exposure is greatest following a HFHC meal, with a 55% higher C max and 231% higher AUC compared to the fasted state; a 32% higher C max and 89% higher AUC compared to LFLC meal. Compared to HFHC and MFMC meal, the pyridostigmine exposure is lower during the second half of the proposed 24-hour dosing interval under fasted or LFLC meal condition.

Table 2 and Figure 1 below show pyridostigmine concentration-time profile and summary of pharmacokinetic (PK) parameters, respectively, after single dose administration of 105 mg pyridostigmine bromide extended-release tablet under fasted condition, or with food of different fat and calorie contents [see Dosage and Administration (2.1 , 2.2) ] . Figure 1: Effect of Food on Concentration-Time Profile of Pyridostigmine Bromide 105 mg Extended-Release Tablets LFLC=low fat, low calorie; MFMC=medium fat, medium calorie; HFHC=high fat, high calorie Table 2: Summary of Food Effect on PK Parameters of Pyridostigmine Bromide 105 mg Extended-Release Tablets PK Parameters Fasted Low Fat/ Low Calorie Medium Fat/ Medium Calorie High Fat/ High Calorie Mean [SD] Mean [SD] Mean [SD] Mean [SD] C max (ng/mL) 9.30 [4.16] 10.91 [3.55] 13.76 [3.72] 14.43 [3.18] T max * (hours) 4.00 [1.0…

🧬 Mechanism of Action 10 words ▾

12.1Mechanism of Action Pyridostigmine is a reversible cholinesterase inhibitor.

📦 How Supplied / Storage and Handling 181 words ▾

16 HOW SUPPLIED

16.1How Supplied Pyridostigmine bromide extended-release tablets, 105 mg, are supplied as oval, peach, coated, unscored, biconvex tablets imprinted with “A2 463” on one side and plain on the other side. A hole may be visible on one side of the tablet. They are available as follows: Mylar bag containing 10 blister cartons. Each blister carton contains seven (7) tablets. NDC 60846-559-10.

16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature], or store refrigerated between 2°C and 8°C (36°F to 46°F). Protect from heat and moisture. Discard contents of blister pack 3 months after the mylar bag is opened.

16.1How Supplied Pyridostigmine bromide extended-release tablets, 105 mg, are supplied as oval, peach, coated, unscored, biconvex tablets imprinted with “A2 463” on one side and plain on the other side. A hole may be visible on one side of the tablet. They are available as follows: Mylar bag containing 10 blister cartons. Each blister carton contains seven (7) tablets. NDC 60846-559-10.

📋 Description 143 words ▾

11 DESCRIPTION Pyridostigmine bromide is an orally active, reversible cholinesterase inhibitor. Pyridostigmine bromide is a white or almost white, crystalline, deliquescent powder, very soluble in water and alcohol, and practically insoluble in ether. CAS registration number is 101-26-8.

Pyridostigmine bromide has a molecular formula of C 9 H 13 BrN 2 O 2 , with a molecular weight of 261.12. Its chemical name is 3-hydroxy-1-methylpyridinium bromide dimethylcarbamate, and its structural formula is: Pyridostigmine bromide extended-release tablets contain 105 mg of pyridostigmine bromide (equivalent to 72.87 mg of pyridostigmine base) for oral administration. The inactive ingredients included in the tablet formula are ammonia methacrylate copolymer, ammonium hydroxide, black iron oxide, calcium carbonate, colloidal silicon dioxide, crospovidone, hydroxypropyl cellulose, hypromellose, iron oxide red, iron oxide yellow, magnesium stearate, mannitol, propylene glycol, shellac glaze, sodium bicarbonate, succinic acid, talc, titanium dioxide, and triethyl citrate. structural formula

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Indication and Conditions of Use Advise personnel of the following: Pyridostigmine bromide is approved as a pretreatment against the lethal effects of the chemical nerve agent soman (GD). Pyridostigmine bromide has not been approved for use against other chemical nerve agents including Sarin (GB), Tabun (GA), and VX [see Indications and Usage (1) ] .

The approval is based on safety studies in humans and effectiveness studies conducted in animals. It is not ethical to do effectiveness studies in humans. Human studies would require exposing people to the deadly effects of nerve agents, risking poisoning them or even killing them.

Studies in monkeys and guinea pigs show that pretreatment with pyridostigmine bromide makes the antidotes (atropine and 2-PAM) work better against soman (GD) [see Clinical Studies (14) ] . The main protection against chemical weapons is the chemical protective mask and battle dress overgarments [see Dosage and Administration (2.1 , 2.2) and Warnings and Precautions (5.1) ] . Pyridostigmine bromide is used as a pretreatment against a soman nerve agent attack.

Based on the animal studies, it is thought that any potential benefits from use of pyridostigmine bromide occur only if: It is taken at least several hours before, but not right before, exposure to the nerve agent soman. If it is taken right before (when the nerve gas attack alarm is given) or during nerve agent exposure, it may not work and may make the effects of soman worse. Atropine and 2-PAM are used when symptoms of nerve agent poisoning occur. [see Dosage and Administration (2.1 , 2.2) ] .

Dosage and Administration [see Dosage and Administration (2.1 , 2.2) ] Inform personnel of the following: The chain of command will instruct when it is time to take pyridostigmine bromide, based on the threat of exposure to soman nerve agents. Take one tablet orally once daily, with food, until the chain of command instructs to stop taking pyridostigmine bromide. Do not take on an empty stomach.

Take with a medium fat, medium calorie meal (e.g., meal with 650 calories, 40% fat) or a high fat, high calorie meal (e.g., meal with 1,000 calories, 50% fat). Do not take the tablet with a low fat, low calorie meal (e.g., meal with 400 calories, 25% fat). Take pyridostigmine bromide only as prescribed.

If a dose is missed, take the missed dose as soon as possible. Do not take double or extra doses. There is no known advantage to taking extra pyridostigmine bromide right before soman exposure.

Discontinue pyridostigmine bromide after nerve agent exposure has occurred, and instead: Persons experiencing most or all of the MILD symptoms of nerve agent poisoning (runny nose; watery eyes; small, pinpoint pupils; eye pain; blurred vision; drooling and excessive sweating; cough; chest tightness; rapid breathing; diarrhea; increased urination; confusion; drowsiness; weakness; headache; nausea, vomiting, and/ or abdominal pain; slow or fast heart rate; and/or abnormally low or high blood pressure) should IMMEDIATELY AVOID INHALATION (hold their breath) AND PUT ON THEIR PROTECTIVE MASK.

Then atropine and 2-PAM must be administered. Contact their unit medical officer if adverse reactions from pyridostigmine bromide continue and limit duty performance. Risks in Individuals with Certain Conditions [see Contraindications (4) , Warnings and Precautions (5.2) , and Use in Specific Populations (8.1) ] Instruct personnel to inform their healthcare provider before taking pyridostigmine bromide if they: Are pregnant Have asthma Are allergic to bromide, pyridostigmine, or anticholinesterase drugs Take a beta blocker (a medicine to treat, e.g., high blood pressure) Have high eye pressure (glaucoma) Have any other medical condition, including heart problems, genitourinary or gastrointestinal obstruction, or reflux esophagitis (GERD) Collection of Information The Department…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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