B-12 Compliance: Package Insert and Label Information

B-12 COMPLIANCE- cyanocobalamin, isopropyl alcohol
RX PHARMA-PACK, INC.

CYANOCOBALAMIN

INJECTION, USP

American Regent, Inc.

RX ONLY

DESCRIPTION

Cyanocobalamin Injection, USP is a sterile solution of cyanocobalamin for intramuscular or subcutaneous injection. Each mL contains 1000 mcg cyanocobalamin.

Each vial also contains Sodium Chloride, 0.9%. Benzyl Alcohol, 1.5%, is present as a preservative. Hydrochloric acid and/or sodium hydroxide may have been added during manufacture to adjust the pH (range 4.5-7.0).

Cyanocobalamin appears as dark red crystals or as an amorphous or crystalline red powder. It is very hygroscopic in the anhydrous form, and sparingly soluble in water (1:80). It is stable to autoclaving for short periods at 121°C. The vitamin B12 coenzymes are very unstable in light.

The chemical name is 5,6-dimethyl-benzimidazolyl cyanocobamide; the molecular formula is C63 H88 CoN14 O14 P. The cobalt content is 4.34%. The molecular weight is 1355.39.

The structural formula is represented below.

Cyanocobalamin Structural Formula
(click image for full-size original)

Cyanocobalamin Structural Formula

CLINICAL PHARMACOLOGY

Vitamin B12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis.

Cyanocobalamin is quantitatively and rapidly absorbed from intramuscular and subcutaneous sites of injection; the plasma level of the compound reaches its peak within 1 hour after intramuscular injection. Absorbed vitamin B12 is transported via specific B12 binding proteins, transcobalamin I and II to the various tissues. The liver is the main organ for vitamin B12 storage.

Within 48 hours after injection of 100 or 1000 mcg of vitamin B12 , 50 to 98% of the injected dose may appear in the urine. The major portion is excreted within the first eight hours. Intravenous administration results in even more rapid excretion with little opportunity for liver storage.

Gastrointestinal absorption of vitamin B12 depends on the presence of sufficient intrinsic factor and calcium ions. Intrinsic factor deficiency causes pernicious anemia, which may be associated with subacute combined degeneration of the spinal cord. Prompt parenteral administration of vitamin B12 prevents progression of neurologic damage.

The average diet supplies about 5 to 15 mcg/day of vitamin B12 in a protein-bound form that is available for absorption after normal digestion. Vitamin B12 is not present in foods of plant origin, but is abundant in foods of animal origin. In people with normal absorption, deficiencies have been reported only in strict vegetarians who consume no products of animal origin (including no milk products or eggs).

Vitamin B12 is bound to intrinsic factor during transit through the stomach; separation occurs in the terminal ileum in the presence of calcium, and vitamin B12 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. Oral absorption is considered too undependable to rely on in patients with pernicious anemia or other conditions resulting in malabsorption of vitamin B12 .

Cyanocobalamin is the most widely used form of vitamin B12 , and has hematopoietic activity apparently identical to that of the antianemia factor in purified liver extract. Hydroxycobalamin is equally as effective as cyanocobalamin, and they share the cobalamin molecular structure.

INDICATIONS AND USAGE

Cyanocobalamin is indicated for vitamin B12 deficiencies due to malabsorption which may be associated with the following conditions:

  • Addisonian (pernicious) anemia
  • Gastrointestinal pathology, dysfunction, or surgery, including gluten enteropathy or sprue, small bowel bacteria overgrowth, total or partial gastrectomy
  • Fish tapeworm infestation
  • Malignancy of pancreas or bowel
  • Folic acid deficiency

It may be possible to treat the underlying disease by surgical correction of anatomic lesions leading to small bowel bacterial overgrowth, expulsion of fish tapeworm, discontinuation of drugs leading to vitamin malabsorption (see DRUG INTERACTION) , use of a gluten-free diet in nontropical sprue, or administration of antibiotics in tropical sprue. Such measures remove the need for long-term administration of cyanocobalamin.

Requirements of vitamin B12 in excess of normal (due to pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, hepatic and renal disease) can usually be met with oral supplementation.

Cyanocobalamin Injection, USP is also suitable for the vitamin B12 absorption test (SCHILLING TEST).

CONTRAINDICATIONS

Sensitivity to cobalt and/or vitamin B12 is a contraindication.

WARNINGS

Patients with early Leber’s disease (hereditary optic nerve atrophy) who were treated with cyanocobalamin suffered severe and swift optic atrophy.

Hypokalemia and sudden death may occur in severe megaloblastic anemia which is treated intensely.

Anaphylactic shock and death have been reported after parenteral vitamin B12 administration. An intradermal test dose is recommended before Cyanocobalamin Injection, USP is administered to patients suspected of being sensitive to this drug.

This product contains Benzyl Alcohol. Benzyl Alcohol has been reported to be associated with a fatal “Gasping Syndrome” in premature infants.

This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired.

Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General Precautions: Vitamin B12 deficiency that is allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord. Doses of folic acid greater than 0.1 mg per day may result in hematologic remission in patients with vitamin B12 deficiency. Neurologic manifestations will not be prevented with folic acid, and if not treated with vitamin B12 , irreversible damage will result. Doses of cyanocobalamin exceeding 10 mcg daily may produce hematologic response in patients with folate deficiency. Indiscriminate administration may mask the true diagnosis.

Information for Patients: Patients with pernicious anemia should be informed that they will require monthly injections of vitamin B12 for the remainder of their lives. Failure to do so will result in return of the anemia and in development of incapacitating and irreversible damage to the nerves of the spinal cord. Also, patients should be warned about the danger of taking folic acid in place of vitamin B12 , because the former may prevent anemia but allow progression of subacute combined degeneration.

A vegetarian diet which contains no animal products (including milk products or eggs) does not supply any vitamin B12 . Patients following such a diet, should be advised to take oral vitamin B12 regularly. The need for vitamin B12 is increased by pregnancy and lactation. Deficiency has been recognized in infants of vegetarian mothers who were breast fed, even though the mothers had no symptoms of deficiency at the time.

Laboratory Tests: During the initial treatment of patients with pernicious anemia, serum potassium must be observed closely the first 48 hours and potassium replaced if necessary. Hematocrit, reticulocyte count, vitamin B12 , folate and iron levels should be obtained prior to treatment.

Hematocrit and reticulocyte counts should be repeated daily from the fifth to seventh days of therapy and then frequently until the hematocrit is normal. If folate levels are low, folic acid should also be administered. If reticulocytes have not increased after treatment or if reticulocyte counts do not continue at least twice normal as long as the hematocrit is less than 35%, diagnosis or treatment should be reevaluated. Repeat determinations of iron and folic acid may reveal a complicating illness that might inhibit the response of the marrow.

Patients with pernicious anemia have about 3 times the incidence of carcinoma of the stomach as the general population, so appropriate tests for this condition should be carried out when indicated.

Drug/Laboratory Test Interactions: Persons taking most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B12 diagnostic blood assays.

Colchicine para-aminosalicylic acid and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B12 .

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long term studies in animals to evaluate carcinogenic potential have not been done. There is no evidence from long-term use in patients with pernicious anemia that cyanocobalamin is carcinogenic. Pernicious anemia is associated with an increased incidence of carcinoma of the stomach, but this is believed to be related to the underlying pathology and not to treatment with cyanocobalamin.

Pregnancy: Teratogenic Effects. Pregnancy Category C: Adequate and well-controlled studies have not been done in pregnant women. However, vitamin B12 is an essential vitamin and requirements are increased during pregnancy. Amounts of vitamin B12 that are recommended by the Food and Nutrition
Board, National Academy of Science-National Research Council for pregnant women (4 mcg daily) should be consumed during pregnancy.

Nursing Mothers: Vitamin B12 is known to be excreted in human milk. Amounts of vitamin B12 that are recommended by the Food and Nutrition Board, National Academy of Science-National Research Council for lactating women (4 mcg daily) should be consumed during lactation.

Pediatric Use: Intake in children should be in the amount (0.5 to 3 mcg daily) recommended by the Food and Nutrition Board, National Academy of Science-National Research Council.

ADVERSE REACTIONS

Generalized: Anaphylactic shock and death have been reported with administration of parenteral vitamin B12 (see WARNINGS).

Cardiovascular: Pulmonary edema and congestive heart failure early in treatment; peripheral vascular thrombosis.

Hematological: Polycythemia vera

Gastrointestinal: Mild transient diarrhea

Dermatological: Itching; transitory exanthema

Miscellaneous: Feeling of swelling of entire body

OVERDOSAGE

No overdosage has been reported with this drug.

DOSAGE AND ADMINISTRATION

Avoid using the intravenous route. Use of this product intravenously will result in almost all of the vitamin being lost in the urine.

Pernicious Anemia: Parenteral vitamin B12 is the recommended treatment and will be required for the remainder of the patient’s life. The oral form is not dependable. A dose of 100 mcg daily for 6 or 7 days should be administered by intramuscular or deep subcutaneous injection. If there is clinical improvement and if a reticulocyte response is observed, the same amount may be given on alternate days for seven doses, then every 3 to 4 days for another 2 to 3 weeks. By this time hematologic values should have become normal. This regimen should be followed by 100 mcg monthly for life. Folic acid should be administered concomitantly if needed.

Patients with Normal Intestinal Absorption: Where the oral route is not deemed adequate, initial treatment similar to that for patients with pernicious anemia may be indicated depending on the severity of the deficiency. Chronic treatment should be with an oral B12 preparation. If other vitamin deficiencies are present, they should be treated.

Schilling Test: The flushing dose is 1000 mcg.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED

Cyanocobalamin Injection, USP 1000 mcg/mL

NDC 0517-0031-25 1 mL Fill in a 2 mL Vial Boxes of 25

NDC 0517-0032-25 10 mL Multiple Dose Vial Boxes of 25

NDC 0517-0130-01 30 mL Multiple Dose Vial Boxes of 1

Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) (See USP Controlled Room Temperature).

PROTECT THE PRODUCT FROM LIGHT.

IN0031
Rev. 10/18
MG #10565

AMERICAN
REGENT, INC.
SHIRLEY, NY 11967

ALCOHOL PREP PAD

ALCOHOL PREP- isopropyl alcohol swab

Dynarex Corporation

Disclaimer: Most OTC drugs are not reviewed and approved by FDA, however they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.

ACTIVE INGREDIENT

Isopropyl Alcohol, 70 % v/v

PURPOSE

Antiseptic

USE

For preparation of the skin prior to injection.

WARNINGS

  • For external use only
  • Flammable, keep away from flame or fire
  • Not for use with electrocautinary devices or procedures
  • Do not use in eyes
  • Sterile unless package is damaged or open

Stop use and ask a doctor if:

  • Irritation or redness develops
  • Condition persists for more than 72 hours
  • Cleansing of an injection site

Keep out of reach of children.

In case of accidental ingestion, seek professional assistance or consult a poison control center immediately.

DIRECTIONS

Wipe injection site vigorously and discard.

INACTIVE INGREDIENT

  • Water

OTHER INFORMATION

  • Store at room temperature: 15 deg C to 30 deg C 59 deg F to 86 deg F
  • Avoid excessive heat

Reorder No. 1113

Made in China

Manufactured for:

Dynarex Corporation

Orangeburg, NY 10962

www.dynarex.com

Revised: 11/2019

PRINCIPAL DISPLAY PANEL: B-12 Compliance Injection Kit

NDC 49836-527-01

RX-Only

B-12 Compliance
Injection Kit

Kit Contains:
1 Cyanocobalamin Injection, USP 1,000 mcg/mL (1 mL)
1 Sterile Isopropyl Alcohol 70% Prep Pad
1 Pair Nitrile Powder Free sterile Gloves (Size 7.5)
1 Sterile Towel Drape
1 Sterile Adhesive Bandage

1 Dose

Needles and Syringes Not Included

B-12 Compliance
Injection Kit

DISTRIBUTED BY:
SCHMIGS
HAUPPAUGE, NY 11788
NDC 49836-527-01

MANUFACTURED BY:
Rx P harma Pack
HAUPPAUGE, NY 11788

Questions/Comments 1-844-632-7898

Kit Contents:

Cyanocobalamin Injection, USP 1,000 mcg/mL*
(Manufactured by American Regent)
Each mL contains: benzyl alcohol 1.5%; sodium chloride 9mg;
Water for Injection q.s. pH adjusted with hydrochloric acid or sodium hydroxide if necessary.

Sterile Alcohol Prep Pad (Dynarex)*
Gamma-Sterilized* Isopropyl Alcohol, 70% by Volume

Nitrile Powder Free Sterile Gloves (Dynarex) — Size 7.5*
Sterile Towel Drape (Dynarex)*

Sterile Adhesive Bandage (Dynarex)*

*Internal package components remain sterile when stated as long as items are unopened and undamaged.

WARNING: KEEP THIS AND ALL MEDICATION
OUT OF THE REACH OF CHILDREN. IN CASE OF
ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL
ASSISTANCE OR CONTACT A POISON CONTROL
CENTER IMMEDIATELY.

PROTECT FROM LIGHT

STORE AT CONTROLLED ROOM TEMPERATURE
20º-25ºC (68º-77º F) [SEE USP CONTROLLEDROOM TEMPERATURE]

For Single use Only.

SUSTAINABLE Certified SourcingFORESTRY www.sfiprogram.orgINITIATIVE SFI-01376

REV 09/2015

This product is not eligible for Medicare or Medicaid reimbursement

B-12 Compliance Injection Kit
(click image for full-size original)

B-12 Compliance Injection Kit

B-12 COMPLIANCE cyanocobalamin, isopropyl alcohol kit
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:49836-527
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:49836-527-01 1 KIT in 1 CARTON None
Quantity of Parts
Part # Package Quantity Total Product Quantity
Part 1 1 VIAL, SINGLE-USE 1 mL
Part 2 1 POUCH 0.55 mL
Part 1 of 2
CYANOCOBALAMIN cyanocobalamin injection, solution
Product Information
Route of Administration INTRAMUSCULAR DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CYANOCOBALAMIN (CYANOCOBALAMIN) CYANOCOBALAMIN 1000 ug in 1 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE
BENZYL ALCOHOL
WATER
Packaging
# Item Code Package Description Multilevel Packaging
1 1 mL in 1 VIAL, SINGLE-USE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA080737 09/30/1990
Part 2 of 2
STERILE ALCOHOL PREP PADS isopropyl alcohol swab
Product Information
Route of Administration TOPICAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ISOPROPYL ALCOHOL (ISOPROPYL ALCOHOL) ISOPROPYL ALCOHOL 0.7 mL in 1 mL
Inactive Ingredients
Ingredient Name Strength
WATER
Packaging
# Item Code Package Description Multilevel Packaging
1 0.55 mL in 1 POUCH None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
OTC MONOGRAPH NOT FINAL part333A 07/01/2010
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA080737 10/23/2015 07/31/2021
Labeler — RX PHARMA-PACK, INC. (962149634)
Establishment
Name Address ID/FEI Operations
RX PHARMA-PACK, INC. 962149634 PACK (49836-527)

Revised: 10/2020 RX PHARMA-PACK, INC.

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