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cyanocobalamin 500 ug Spray, 4 bottles — NDC 45802-0491-84 package photo

cyanocobalamin 500 ug Spray, 4 bottles

by Padagis Israel Pharmaceuticals Ltd · 4 BOTTLE, UNIT-DOSE in 1 CARTON (45802-491-84) / 1 SPRAY in 1 BOTTLE, UNIT-DOSE
NDC 45802-0491-84
🏷️ FDA NDC (as labeled) 45802-491-84 billing pads the product segment with a zero
Rx only Generic 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 →
⚠️
Other active recalls for Cyanocobalamin (different manufacturers) — 2 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Jul 24, 2026 — Presence of Particulate Matter: Product contaminated with particulate matter identified as hair, glass and/or paraformaldehyde (American Regent, Inc.) · FDA recall D-0793-2026
Class II · Jul 24, 2026 — Presence of Particulate Matter: Product contaminated with particulate matter identified as hair, glass and/or paraformaldehyde (American Regent, Inc.) · FDA recall D-0792-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 45802-491-84
Product NDC 45802-491
11-digit billing NDC 45802049184
NCPDP billing unit EA — each (per item)
RxCUI 861113
UNII P6YC3EG204
Application # ANDA212458
SPL Set ID 971e5f30-55c2-4193-9dd8-b43a1862b92a
Established class (EPC) Vitamin B12
Chemical class Vitamin B 12
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2023-12-28
Route NASAL
Dosage form SPRAY
Substance CYANOCOBALAMIN
GPI-14 82100010002020
GCN Seq No 072532
GCN 36786
HICL code 001053
Ingredient (HICL) Cyanocobalamin (Vitamin B-12)
HIC1 code C
Therapeutic class — broad (HIC1) Electrolyte Balance/Metabolism/Nutrition
HIC2 code C6
Therapeutic class — intermediate (HIC2) Vitamins
HIC3 code C6L
Therapeutic class — specific (HIC3) Vitamin B12 Preparations
AHFS code 88:08.00.00
AHFS class Vitamin B Complex
FDB label name CYANOCOBALAMIN 500 MCG SPRAY
FDB brand name Cyanocobalamin
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 45802-491-84 — 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 → 45802-0491-84. 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 Vitamin B12 class.

Pharmacologic class Vitamin B12
Drug family (ATC) Vitamin B12 (cyanocobalamin and analogues)
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

LabelerPadagis Israel Pharmaceuticals Ltd
Application holderPADAGIS ISRAEL PHARMACEUTICALS LTD
FDA applicationANDA212458 (ANDA)
Labeler code45802
First marketedDec 2023
Product typeHuman Prescription Drug
Portfolio175 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 CYANOCOBALAMIN 500 MCG SPRAY Ingredient Cyanocobalamin (Vitamin B-12)
📖 What it is MedlinePlus · NLM

Cyanocobalamin nasal gel is used to prevent a lack of vitamin B12 that may be caused by any of the following: pernicious anemia (lack of a natural substance needed to absorb vitamin B12 from the intestine); certain diseases, infections or medications that decrease the amount of vitamin B12 absorbed from food; or a vegan diet (strict vegetarian diet that does not allow any animal products including eggs and dairy products). Lack of vitamin B12 can cause anemia (condition in which the red blood cells do not bring enough oxygen to the organs) and permanent damage to the nerves. This anemia must b...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It's a prescription form of vitamin B12, used when your body can't get enough B12 on its own. That can happen because of a condition called pernicious anemia — where your stomach c...
  • What is cyanocobalamin actually used for?
  • The injection goes directly into a muscle or under the skin, bypassing the gut entirely — which makes it the most reliable option, especially for pernicious anemia, where lifelong...
  • What's the difference between the shot and the nasal spray?
📖 Read our full Cyanocobalamin 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 F5UM2KM3W7
    Benzalkonium chloride is a chemical compound that works as a preservative and antimicrobial agent in medications. It prevents bacterial and fungal growth in liquid formulations to keep the product safe during storage and use.
  • UNII 2968PHW8QP
    A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
  • UNII PDC6A3C0OX
    Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
  • UNII 1Q73Q2JULR
    Sodium citrate is a salt derived from citric acid. It works as a buffer to maintain the medicine's pH level and may also help improve taste or act as a preservative in the formulation.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

5 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 DailyMedingredient 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 eaPer package
Retail pharmacies payNADAC · weekly $98.834 $395.34 / 4 spray
Medicaid paysCMS SDUD · 12 mo $964.95 $3,859.78 / 4 spray
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
NADAC price history (per ea) — tap or hover for the price & month
Dec 2025 Feb 2026 May 2026 Aug 2026 $124.178 $98.834
▼ Down 12% over the last 9 months.
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
cyanocobalamin 500 ugthis 45802-0491-84 Padagis 4 bottles $98.834 AB Availability likely
Nascobal 500 ug 49884-0270-82 Par 4 sprays $171.739 Availability likely +74%
Cyanocobalamin 500 ug 43386-0237-60 Lupin 4 sprays AB FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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

🏛️
2023
On the market since
Dec 2023
📍
2026
Currently FDA-listed
3 years listed
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

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.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 45802-0491-84, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
7.6K
Units reimbursed last 4 qtrs
3.7K
Gross reimbursed last 4 qtrs
$3.56M
Avg / prescription
$465.54
Avg / unit
$964.97
Latest quarter Q4 2025
1.4KRx
Medicaid pays / ea
$964.97
gross reimbursed
vs
NADAC / ea
$98.8340
acquisition cost
=
Spread
+$866.14
+876% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care
90% FFS
Fee-for-service · 6,841 Rx Managed care · 797 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 1,894 units · 9.7 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: 11 units · 0.3 per 100k residents NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: 5 units · 0.0 per 100k residents OH Pennsylvania: 69 units · 0.5 per 100k residents PA New Jersey: 260 units · 2.8 per 100k residents NJ Massachusetts: no data reported MA California: 49 units · 0.1 per 100k residents CA Utah: no data reported UT Colorado: 20 units · 0.3 per 100k residents CO Nebraska: no data reported NE Missouri: 46 units · 0.7 per 100k residents MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 17 units · 0.2 per 100k residents VA Maryland: no data reported MD Connecticut: 1,083 units · 29.9 per 100k residents CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 41 units · 0.4 per 100k residents NC South Carolina: no data reported SC Delaware: 15 units · 1.5 per 100k residents DE Oklahoma: no data reported OK Louisiana: 176 units · 3.8 per 100k residents LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
0.029.9
gray = no data reported
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Connecticut 29.9 /100k
2 New York 9.7 /100k
3 Louisiana 3.8 /100k
4 New Jersey 2.8 /100k
5 Delaware 1.5 /100k
6 Missouri 0.7 /100k
7 Pennsylvania 0.5 /100k
8 North Carolina 0.4 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

🔬 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 Cyanocobalamin — the ingredient across all brands.

Top reported reactions

Fatigue3,429
Nausea2,832
Headache2,445
Pain2,324
Diarrhoea2,292
Dyspnoea2,190
Vomiting1,857

Age at onset

Neonate10
Infant7
Child18
Adolescent36
Adult3,397
Elderly3,703

Reporter sex

34,374 reports
Male · 35%
Female · 65%
Unknown · 0%

Serious outcomes

Hospitalization13,775
Death3,418
Disabling1,753
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 3,306 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
45802-0491-84 You're viewing this 4 BOTTLE, UNIT-DOSE in 1 CARTON (45802-491-84) / 1 SPRAY in 1 BOTTLE, UNIT-DOSE 2023-12-28 Active

📄 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.
🎯 Indications and Usage ~2 min read

1 INDICATIONS AND USAGE Cyanocobalamin Nasal Spray is indicated for: • Vitamin B 12 maintenance therapy in adult patients with pernicious anemia who are in remission following intramuscular vitamin B 12 therapy and who have no nervous system involvement • Treatment of adult patients with dietary, drug-induced, or malabsorption-related vitamin B 12 deficiency not due to pernicious anemia • Prevention of vitamin B 12 deficiency in adult patients with vitamin B 12 requirements in excess of normal Limitations of Use • Cyanocobalamin Nasal Spray should not be used for the vitamin B 12 absorption test (Schilling test). • In patients with correctible or temporary causes of vitamin B 12 deficiency, the benefit of continued long-term use of Cyanocobalamin Nasal Spray following adequate correction of vitamin B 12 deficiency and underlying disease has not been established. • The effectiveness of Cyanocobalamin Nasal Spray in patients with active symptoms of nasal congestion, allergic rhinitis or upper respiratory infection has not been determined.

Treatment with Cyanocobalamin Nasal Spray should be deferred until symptoms have subsided. Cyanocobalamin Nasal Spray is a vitamin B 12 indicated for: • Vitamin B 12 maintenance therapy in adult patients with pernicious anemia who are in remission following intramuscular vitamin B 12 therapy and who have no nervous system involvement ( 1 ) • Treatment of adult patients with dietary, drug-induced, or malabsorption-related vitamin B 12 deficiency not due to pernicious anemia ( 1 ) • Prevention of vitamin B 12 deficiency in adult patients with vitamin B 12 requirements in excess of normal ( 1 ) Limitations of Use: • Should not be used for the vitamin B 12 absorption test (Schilling test).

( 1 ) • In patients with correctible or temporary causes of vitamin B 12 deficiency the benefit of continued long-term use following correction of vitamin B 12 deficiency and underlying disease has not been established. ( 1 ) • In patients with active symptoms of nasal congestion, allergic rhinitis or upper respiratory infection effectiveness has not been established. ( 1 )

⏱️ Dosage and Administration ~3 min read

2 DOSAGE AND ADMINISTRATION • Prior to treatment, obtain hematocrit, reticulocyte count, vitamin B 12 , folate, and iron levels. ( 2.1 ) • The recommended initial dose is one spray (500 mcg) in one nostril once weekly. ( 2.2 ) • Administer at least one hour before or one hour after ingestion of hot foods or liquids.

( 2.2 ) • Monitor serum B 12 levels periodically. Obtain a serum B 12 level and peripheral blood count one month after treatment initiation, then subsequently at intervals of 3 to 6 months. ( 2.3 ) • If serum levels of B 12 decline after one month of treatment, consider increasing the dose.

Assess serum B 12 level one month after each dose adjustment. If serum B 12 levels are persistently low, consider alternative therapy (e.g., intramuscular or subcutaneous vitamin B 12 therapy). ( 2.3 ) • See Full Prescribing Information to see what other therapies should be administered with Cyanocobalamin Nasal Spray.

( 2.4 )

2.1Testing and Other Considerations Prior to Dosing Prior to treatment, obtain hematocrit, reticulocyte count, vitamin B 12 , folate, and iron levels [see Dosage and Administration (2.4) ] . Consider the potential for concomitant drugs to interfere with vitamin B 12 and folate diagnostic blood assays [see Drug Interactions (7) ] . In patients with suspected cobalamin hypersensitivity, consider administering an intradermal test dose of parenteral vitamin B 12 prior to use of Cyanocobalamin Nasal Spray [see Warnings and Precautions (5.2) ] .

2.2Recommended Dosage The recommended initial dose of Cyanocobalamin Nasal Spray is one spray (500 mcg) administered in ONE nostril once weekly. Administer Cyanocobalamin Nasal Spray at least one hour before or one hour after ingestion of hot foods or liquids since hot foods may cause nasal secretions and a resulting loss of medication. Defer use of Cyanocobalamin Nasal Spray in patients with nasal congestion, allergic rhinitis, or upper respiratory infections until after symptoms have subsided.

2.3Monitoring, Dosage Modifications, and Treatment Duration Monitoring for Response and Safety Monitor serum B 12 levels periodically during therapy to establish adequacy of therapy. Obtain a serum B 12 level and peripheral blood count one month after treatment initiation, then subsequently at intervals of 3 to 6 months [see Warnings and Precautions (5.3)]. Dosage Modifications If serum levels of B 12 decline after one month of treatment with Cyanocobalamin Nasal Spray, consider increasing the dose.

Assess serum B 12 level one month after each dose adjustment. If serum B 12 levels are persistently low, consider alternative therapy (e.g., intramuscular or subcutaneous vitamin B 12 therapy). Treatment Duration In patients whose underlying cause of vitamin B 12 deficiency has been corrected and are deemed no longer at risk for vitamin B 12 deficiency, discontinue Cyanocobalamin Nasal Spray.

The safety and effectiveness of continued long-term use in these individuals has not been established. In patients with pernicious anemia, continue appropriate vitamin B 12 treatment indefinitely.

2.4Administration of Cyanocobalamin Nasal Spray with Other Therapy Cyanocobalamin Nasal Spray should be administered with other therapy(ies) in: - Patients with concurrent folate and vitamin B 12 deficiency: Administer folic acid in addition to Cyanocobalamin Nasal Spray - Patients with concurrent iron and vitamin B 12 deficiency: Administer iron in addition to Cyanocobalamin Nasal Spray - Patients with correctible causes of vitamin B 12 deficiency: Consider measures to treat the underlying condition associated with vitamin B 12 deficiency in addition to treatment with Cyanocobalamin Nasal Spray

💊 Dosage Forms and Strengths 33 words

3 DOSAGE FORMS AND STRENGTHS Nasal spray: 500 mcg/0.1 mL (per actuation), packaged in a single-use device containing 0.125 mL of solution Nasal spray: 500 mcg cyanocobalamin/0.1 mL (per actuation) ( 3 )

Contraindications 58 words

4 CONTRAINDICATIONS Cyanocobalamin Nasal Spray is contraindicated in patients with hypersensitivity to cobalt and/or vitamin B 12 or any of its excipients [see Warnings and Precautions (5.2) ] . Anaphylactic shock and death have been reported after parenteral vitamin B 12 administration in sensitive patients. • Hypersensitivity to cobalt, vitamin B 12 or any excipients ( 4 )

⚠️ Warnings and Cautions ~3 min read

5 WARNINGS AND PRECAUTIONS • Severe Optic Atrophy in Patients with Leber’s Disease: Patients with early Leber’s disease who were treated with vitamin B 12 suffered severe and swift optic atrophy. Cyanocobalamin Nasal Spray is not recommended for use in these patients. ( 5.1 ) • Anaphylactic Reactions: Anaphylactic shock and death have been reported after parenteral vitamin B 12 administration.

If patients are to start Cyanocobalamin Nasal Spray before having tolerated cyanocobalamin parenterally, consider administering an intradermal test dose of parenteral vitamin B 12 to patients suspected of cyanocobalamin hypersensitivity. ( 2.1 , 5.2 ) • Masking of Folate Deficiency with Vitamin B 12 Use: Doses of vitamin B 12 exceeding 10 mcg daily may produce hematologic response in patients with folate deficient megaloblastic anemia and may therefore mask a previously unrecognized folate deficiency. Assess both vitamin B 12 and folate levels prior to initiating therapy with Cyanocobalamin Nasal Spray or with folic acid.

( 5.3 ) • Hypokalemia and Thrombocytosis Due to Intense Treatment of Megaloblastic Anemia: Hypokalemia and sudden death may occur in severe megaloblastic anemia that is treated intensely with vitamin B 12 . Monitor serum potassium levels and platelet count during therapy. ( 5.4 ) • Unmasking of Polycythemia Vera: Vitamin B 12 deficiency may suppress the signs of polycythemia vera.

Treatment with Cyanocobalamin Nasal Spray may unmask this condition. Patients exhibiting clinical or hematologic response consistent with polycythemia vera should be referred for further evaluation. ( 5.5 )

5.1Severe Optic Atrophy in Patients with Leber’s Disease Patients with early Leber’s disease (hereditary optic nerve atrophy) who were treated with vitamin B 12 suffered severe and swift optic atrophy. Cyanocobalamin products, including Cyanocobalamin Nasal Spray, is not recommended for use in patients with Leber’s optic atrophy. For patients with Leber’s disease requiring vitamin B 12 , consider alternative therapy (e.g., hydroxocobalamin) for B 12 supplementation.

5.2Anaphylactic Reactions Anaphylactic shock and death have been reported after parenteral vitamin B 12 administration. If patients are to start Cyanocobalamin Nasal Spray before having tolerated cyanocobalamin parenterally, consider administering an intradermal test dose of parenteral vitamin B 12 to patients suspected of cyanocobalamin hypersensitivity [see Dosage and Administration (2.1) ] .

5.3Masking of Folate Deficiency with Vitamin B 12 Use Doses of vitamin B 12 exceeding 10 mcg daily may produce hematologic response in patients with folate deficient megaloblastic anemia and may therefore mask a previously unrecognized folate deficiency. Vitamin B 12 is not a substitute for folic acid [see Dosage and Administration (2.4) ] . Assess both vitamin B 12 and folate levels prior to initiating therapy with vitamin B 12 , including Cyanocobalamin Nasal Spray, or with folic acid [see Dosage and Administration (2.1) ] .

5.4Hypokalemia and Thrombocytosis Due to Intense Treatment of Megaloblastic Anemia Hypokalemia and sudden death may occur in severe megaloblastic anemia that is treated intensely with vitamin B 12 . Hypokalemia and thrombocytosis can occur upon conversion of severe megaloblastic anemia to normal erythropoiesis with vitamin B 12 therapy. Therefore, serum potassium levels and platelet count should be monitored carefully during therapy [see Dosage and Administration (2.3) ] .

5.5Unmasking of Polycythemia Vera Vitamin B 12 deficiency may suppress the signs of polycythemia vera. Treatment with vitamin B 12 may unmask this condition. Patients exhibiting clinical or hematologic response consistent with polycythemia vera should be referred for further evaluation.

🤒 Adverse Reactions ~1 min read

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Severe Optic Atrophy in Patients with Leber’s Disease [see Warnings and Precautions (5.1) ] . • Anaphylactic Reactions [see Warnings and Precautions (5.2) ] . • Hypokalemia and Thrombocytosis Due to Intense Treatment of Megaloblastic Anemia [see Warnings and Precautions (5.4) ] . The most common adverse reactions (≥ 4%) were infection, headache, glossitis, paresthesia, asthenia, nausea and rhinitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 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 described in Table 1 below are based on data from an eight week cross over trial in which vitamin B 12 deficient patients in hematologic remission received one vitamin B 12 intramuscular injection (N=25) and then received once weekly intranasal administration of another nasal cyanocobalamin formulation (N=24) for 4 weeks.

Table 1. Adverse Reactions Following Intranasal or Intramuscular Administration of Cyanocobalamin In Vitamin B 12 Deficient Patients in Hematologic Remission Adverse Reaction Number of Patients (%) Another Cyanocobalamin Nasal Formulation, 500 mcg (n=24) Intramuscular Cyanocobalamin*, 100 mcg (n=25) Infection a 3 (13) 3 (12) Headache 1 (4) 5 (20) Asthenia 1 (4) 4 (16) Nausea 1 (4) 1 (4) Glossitis 1 (4) 0 (0) Paresthesia 1 (4) 1 (4) Rhinitis 1 (4) 2 (8) a Sore throat, common cold * The data are not an adequate basis for comparison of rates between the study drug and the active control

🔄 Drug Interactions 43 words

7 DRUG INTERACTIONS Chloramphenicol may decrease the efficacy of Cyanocobalamin Nasal Spray when used for treatment of anemia. If Cyanocobalamin Nasal Spray is used for the treatment of anemia concomitantly with chloramphenicol, monitor for reduced efficacy and if needed, consider an alternative therapy.

👥 Use in Specific Populations 197 words

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary The limited available data on Cyanocobalamin Nasal Spray in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, vitamin B 12 is an essential vitamin and requirements are increased during pregnancy. Animal reproduction studies have not been conducted with vitamin B 12 .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

8.2Lactation Risk Summary Vitamin B 12 is present in the milk of lactating women in concentrations which approximate the mother’s vitamin B 12 blood level. Vitamin B 12 does not appear to pose more than a minimal risk to breastfeeding children.

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

8.5Geriatric Use Clinical studies of cyanocobalamin nasal spray did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

🤰 Pregnancy 92 words

8.1Pregnancy Risk Summary The limited available data on Cyanocobalamin Nasal Spray in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, vitamin B 12 is an essential vitamin and requirements are increased during pregnancy. Animal reproduction studies have not been conducted with vitamin B 12 .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

🧒 Pediatric Use 13 words

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

🧓 Geriatric Use 45 words

8.5Geriatric Use Clinical studies of cyanocobalamin nasal spray did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

🧬 Clinical Pharmacology ~2 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Vitamin B 12 can be converted to coenzyme B 12 in tissues, and as such is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine, a reaction which also requires folate. In the absence of coenzyme B 12 , tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyltetrahydrofolate, and a functional folate deficiency occurs. Vitamin B 12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme systems.

Through these reactions, vitamin B 12 is associated with fat and carbohydrate metabolism and protein synthesis.

12.2Pharmacodynamics Parenteral (intramuscular) administration of vitamin B 12 completely reverses the megaloblastic anemia and GI symptoms of vitamin B 12 deficiency; the degree of improvement in neurologic symptoms depends on the duration and severity of the lesions, although progression of the lesions is immediately arrested. In pernicious anemia patients, once weekly intranasal dosing with 500 mcg B 12 gel resulted in a consistent increase in pre-dose serum B 12 levels during one month of treatment (p < 0.003) above that seen one month after 100 mcg intramuscular dose (Figure 2).

Figure 2. Vitamin B 12 Serum Trough Levels After Intramuscular Solution (IM) of 100 mcg and Nasal Gel (IN) Administration of 500 mcg Cyanocobalamin After Weekly Doses. figure-2

12.3Pharmacokinetics Absorption Vitamin B 12 is bound to intrinsic factor during transit through the stomach; separation occurs in the terminal ileum in the presence of calcium, and vitamin B 12 enters the mucosal cell for absorption. It is then transported by the transcobalamin binding proteins. A small amount (approximately 1% of the total amount ingested) is absorbed by simple diffusion, but this mechanism is adequate only with very large doses.

A three way crossover study in 25 fasting healthy subjects was conducted to compare the bioavailability of the B 12 nasal spray to the B 12 nasal gel and to evaluate the relative bioavailability of the nasal formulations as compared to the intramuscular injection. The peak concentrations after administration of intranasal spray were reached in 1.25 +/- 1.9 hours. The mean peak plasma concentration (C max ) of B 12 , obtained after baseline correction, following administration of intranasal spray were 748 +/-549 pg/mL.

The bioavailability of the B 12 nasal spray was found to be 10% less than the B 12 nasal gel. Distribution In the blood, B 12 is bound to transcobalamin II, a specific B-globulin carrier protein, and is distributed and stored primarily in the liver and bone marrow. Elimination About 3-8 mcg of B 12 is secreted into the GI tract daily via the bile and undergoes some enterohepatic recycling; in normal subjects with sufficient intrinsic factor, all but about 1 mcg is reabsorbed.

When B 12 is administered in doses which saturate the binding capacity of plasma proteins and the liver, the unbound B 12 is rapidly eliminated in the urine. Retention of B 12 in the body is dose-dependent. About 80-90% of an intramuscular dose up to 50 mcg is retained in the body; this percentage drops to 55% for a 100 mcg dose, and decreases to 15% when a 1000 mcg dose is given.

🧬 Mechanism of Action 101 words

12.1Mechanism of Action Vitamin B 12 can be converted to coenzyme B 12 in tissues, and as such is essential for conversion of methylmalonate to succinate and synthesis of methionine from homocysteine, a reaction which also requires folate. In the absence of coenzyme B 12 , tetrahydrofolate cannot be regenerated from its inactive storage form, 5-methyltetrahydrofolate, and a functional folate deficiency occurs. Vitamin B 12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form required by many SH-activated enzyme systems.

Through these reactions, vitamin B 12 is associated with fat and carbohydrate metabolism and protein synthesis.

📦 How Supplied / Storage and Handling 67 words

16 HOW SUPPLIED/STORAGE AND HANDLING Cyanocobalamin Nasal Spray is a nasal spray available in a dosage strength of 500 mcg cyanocobalamin/0.1 mL (per actuation). It is supplied in boxes of 4 single-use nasal spray devices and a package insert (NDC 45802-491-84). Protect from light. Keep covered in carton until ready to use. Store upright at controlled room temperature 15°C to 30°C (59°F to 86°F). Protect from freezing.

📋 Description 203 words

11 DESCRIPTION Cyanocobalamin is a synthetic form of vitamin B 12 . The chemical name is 5,6-dimethyl-benzimidazolyl cyanocobamide. The cobalt content is 4.35%.

The molecular formula is C 63 H 88 CoN 14 O 14 P, which corresponds to a molecular weight of 1355.38 and the following structural formula: Figure 1. Cyanocobalamin Nasal Spray Chemical Structure Cyanocobalamin occurs as dark red crystals or orthorhombic needles or crystalline red powder. It is very hygroscopic in the anhydrous form, and sparingly to moderately soluble in water (1:80).

Its pharmacologic activity is destroyed by heavy metals (iron) and strong oxidizing or reducing agents (vitamin C), but not by autoclaving for short periods of time (15-20 minutes) at 121°C. The vitamin B 12 coenzymes are very unstable in light. Cyanocobalamin Nasal Spray is a solution of cyanocobalamin, USP (vitamin B 12 ) for administration as a spray to the nasal mucosa.

Each unit dose device of Cyanocobalamin Nasal Spray contains 0.125 mL of a 500 mcg/0.1 mL solution of cyanocobalamin with benzalkonium chloride in purified water, citric acid, glycerin and sodium citrate. The spray solution has a pH between 4.5 and 5.5. Each spray delivers an average of 500 mcg of cyanocobalamin per actuation. chemical structure image

💬 Information for Patients 196 words

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Instructions for Use). Importance of Adherence to Therapy and Follow-up Advise patients of the importance of adhering to therapy to prevent the development, recurrence, or progression of anemia and the development or progression of neurological manifestations. Patients experiencing symptomatic nasal congestion, allergic rhinitis or an upper respiratory infection should be advised to defer treatment with Cyanocobalamin Nasal Spray until symptoms have subsided.

Counsel patients on the importance of returning for follow-up blood tests every 3 to 6 months to confirm adequacy of therapy [see Dosage and Administration (2.3) ] . Specific Instructions for Administration Advise patients to administer Cyanocobalamin Nasal Spray at least one hour before or one hour after ingestion of hot foods or liquids since hot foods may cause nasal secretions and a resulting loss of medication. Use of Nasal Spray Device Provide patients with instructions on nasal administration of Cyanocobalamin Nasal Spray.

In addition to alerting patients to the instructions contained in the Instructions For Use and instructions supplied on each carton, demonstrate procedures for use to each patient. Manufactured by Padagis® Yeruham, Israel www.padagis.com Rev 02-23 0H800 RC PH1

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.