CYANOCOBALAMIN- cyanocobalamin injection, s olution

Vitruvias Therapeutics
----------
Cyanocobalamin Injection USP 1000 mcg/mL
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 and
Water for Injection q.s. 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
C63H88CoN14O14P. The cobalt content is 4.34%. The molecular weight is 1355.39.
The structural formula is represented below.

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 Interactions), 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.
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 Tes ts
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 Tes t Interactions

Persons taking most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B12
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.

Carcinogenes is , Mutagenes is , 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.

Nurs ing 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 Us e
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
To report SUSPECTED ADVERSE REACTIONS, contact Vitruvias Therapeutics at 1-844-451-
5944 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 Intes tinal Abs orption

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 Tes t
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 69680-
1 mL Vial Boxes of 10
112-10
NDC 69680-
1 mL Vial Boxes of 25
112-25
NDC 69680- 10 mL Multiple
Boxes of 10
113-99 Dose Vial
NDC 69680- 30 mL Multiple
Boxes of 5
121-05 Dose Vial

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
PROTECT FROM LIGHT
Use only if solution is clear and seal intact.
Product of France
Manufactured By:
UBI Pharma, Inc.
Hsin Chu Hsien 30351, Taiwan
Manufactured for:
Vitruvias Therapeutics
Auburn, Alabama 36830
Code No.: I112-01 1219R3
Revised: 12/2019
To request additional information or if you have questions concerning this drug please phone Vitruvias
Therapeutics at 1-844-451-5944.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-
FDA 1088.
L487-01

PRINCIPAL DISPLAY PANEL - 1 mL Vial Box Label

Cyanocobalamin
Injection, USP
1000 mcg/mL
NDC 69680–112–10
10 x 1 mL VIALS
For Intramuscular or Subcutaneous Use Only
Each mL contains: Cyanocobalamin 1000 mcg, Sodium Chloride 0.9%,
Benzyl Alcohol 1.5%, Water for Injection q.s. pH (range 4.5 - 7.0)
adjusted with Hydrochloric Acid and/or Sodium Hydroxide.
WARNING: PROTECT FROM LIGHT. Store at 20° to 25°C (68° to
77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP
Controlled Room Temperature). Directions for Use: See Package Insert.
Rx Only
Product of France
Mfd. by:
UBI Pharma, Inc.
Taiwan
Mfd. for:
Vitruvias Therapeutics
Auburn, AL 36830
Rev. 04/19
PRINCIPAL DISPLAY PANEL - 10 mL Vial Box
Cyanocobalamin
Injection, USP
10,000 mcg/10 mL (1,000 mcg/mL)
NDC 69680–113–99
10 x 10 mL
MULTIPLE DOSE VIALS
For Intramuscular or Subcutaneous Use Only
Each mL contains: Cyanocobalamin 1000 mcg, Benzyl Alcohol 1.5%,
Sodium Chloride 0.9%, Water for Injection q.s. pH (range 4.5 - 7.0)
adjusted with Hydrochloric Acid and/or Sodium Hydroxide.
WARNING: PROTECT FROM LIGHT. Store at 20° to 25°C (68° to 77°F);
excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled
Room Temperature).
Directions for Use: See Package Insert.
Product of France
Rx Only
Rev. 06/18
Mfd. by:
UBI Pharma, Inc.
Taiwan
Mfd. for:
Vitruvias Therapeutics
Auburn, AL 36830
PRINCIPAL DISPLAY PANEL - 30 mL Vial Box
Cyanocobalamin
Injection, USP
30,000 mcg/30 mL (1,000 mcg/mL)
NDC 69680–121–05
5 x 30 mL
MULTIPLE DOSE VIALS
For Intramuscular or Subcutaneous Use Only
Each mL contains: Cyanocobalamin 1000 mcg, Benzyl Alcohol 1.5%,
Sodium Chloride 0.9%, Water for Injection q.s. pH (range 4.5 - 7.0)
adjusted with Hydrochloric Acid and/or Sodium Hydroxide.
WARNING: PROTECT FROM LIGHT. Store at 20° to 25°C (68° to 77°F);
excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled
Room Temperature).
Directions for Use: See Package Insert.
Product of France
Rx Only
Rev. 06/18
Mfd. by:
UBI Pharma, Inc.
Taiwan
Mfd. for:
Vitruvias Therapeutics
Auburn, AL 36830
CYANOCOBALAMIN
cyanocobalamin injection, solution

Product Information
Prod uct T yp e HUMAN PRESCRIPTIO N DRUG Ite m Cod e (S ource ) NDC:6 9 6 8 0 -112

Route of Ad minis tration INTRAMUSCULAR

Active Ing redient/Active Moiety

Ing redient Name Basis o f Streng th Streng th
Cya no c o ba la min (UNII: P6 YC3EG20 4) (Cya no c o ba la min - UNII:P6 YC3EG20 4) Cya no c o ba la min 10 0 0 ug in 1 mL

Inactive Ing redients

Ing redient Name Streng th
Wa te r (UNII: 0 59 Q F0 KO 0 R)
Be nz yl Alc o ho l (UNII: LKG8 49 4WBH)
So dium Chlo ride (UNII: 451W47IQ 8 X)

Product Characteristics
Color RED S core
S hap e S iz e
Flavor Imp rint Cod e
Contains
Packag ing
# Item Co de Packag e Descriptio n Marketing Start Date Marketing End Date
1 NDC:6 9 6 8 0 -112-25 25 in 1 BO X 0 1/0 2/20 19
1 NDC:6 9 6 8 0 -112-0 1 1 mL in 1 VIAL; Type 0 : No t a Co mbina tio n Pro duc t
2 NDC:6 9 6 8 0 -112-10 10 in 1 BO X 0 6 /15/20 19
2 NDC:6 9 6 8 0 -112-0 1 1 mL in 1 VIAL; Type 0 : No t a Co mbina tio n Pro duc t

Marketing Information
Marke ting Cate gory Ap p lication Numb e r or Monograp h Citation Marke ting S tart Date Marke ting End Date
ANDA ANDA20 9 255 0 1/0 2/20 19

CYANOCOBALAMIN
cyanocobalamin injection, solution

Product Information
Prod uct T yp e HUMAN PRESCRIPTIO N DRUG Ite m Cod e (S ource ) NDC:6 9 6 8 0 -113

Route of Ad minis tration INTRAMUSCULAR

Active Ing redient/Active Moiety

Ing redient Name Basis o f Streng th Streng th
Cya no c o ba la min (UNII: P6 YC3EG20 4) (Cya no c o ba la min - UNII:P6 YC3EG20 4) Cya no c o ba la min 10 0 0 ug in 1 mL

Inactive Ing redients

Ing redient Name Streng th
Wa te r (UNII: 0 59 Q F0 KO 0 R)
Be nz yl Alc o ho l (UNII: LKG8 49 4WBH)
So dium Chlo ride (UNII: 451W47IQ 8 X)

Product Characteristics
Color RED S core
S hap e S iz e
Flavor Imp rint Cod e
Contains

Packag ing
Marketing Start Marketing End
# Item Co de Packag e Descriptio n
Date Date
NDC:6 9 6 8 0 -113-
1 10 in 1 BO X 0 1/0 2/20 19
99
NDC:6 9 6 8 0 -113- 10 mL in 1 VIAL, MULTI-DO SE; Type 0 : No t a Co mbina tio n
1
10 Pro duc t
 10 Pro duc t

Marketing Information
Marke ting Cate gory Ap p lication Numb e r or Monograp h Citation Marke ting S tart Date Marke ting End Date
ANDA ANDA20 9 255 0 1/0 2/20 19

CYANOCOBALAMIN
cyanocobalamin injection, solution

Product Information
Prod uct T yp e HUMAN PRESCRIPTIO N DRUG Ite m Cod e (S ource ) NDC:6 9 6 8 0 -121

Route of Ad minis tration INTRAMUSCULAR

Active Ing redient/Active Moiety

Ing redient Name Basis o f Streng th Streng th
Cya no c o ba la min (UNII: P6 YC3EG20 4) (Cya no c o ba la min - UNII:P6 YC3EG20 4) Cya no c o ba la min 10 0 0 ug in 1 mL

Inactive Ing redients

Ing redient Name Streng th
Wa te r (UNII: 0 59 Q F0 KO 0 R)
Be nz yl Alc o ho l (UNII: LKG8 49 4WBH)
So dium Chlo ride (UNII: 451W47IQ 8 X)

Product Characteristics
Color RED S core
S hap e S iz e
Flavor Imp rint Cod e
Contains

Packag ing
Marketing Start Marketing End
# Item Co de Packag e Descriptio n
Date Date
NDC:6 9 6 8 0 -121-
1 5 in 1 BO X 0 2/12/20 20
05
NDC:6 9 6 8 0 -121- 30 mL in 1 VIAL, MULTI-DO SE; Type 0 : No t a Co mbina tio n
1
30 Pro duc t

Marketing Information
Marke ting Cate gory Ap p lication Numb e r or Monograp h Citation Marke ting S tart Date Marke ting End Date
ANDA ANDA20 9 255 0 2/12/20 20
Labeler - Vitruvias T herapeutics (079200795)

Establishment
Name Ad d re s s ID/FEI Bus ine s s Op e rations
Unite d Bio me dic a l MANUFACTURE(6 9 6 8 0 -112, 6 9 6 8 0 -113, 6 9 6 8 0 -121) , PACK(6 9 6 8 0 -112, 6 9 6 8 0 -113,
6 58 8 71159
Inc Pha rma 6 9 6 8 0 -121) , ANALYSIS(6 9 6 8 0 -112, 6 9 6 8 0 -113, 6 9 6 8 0 -121)

Revised: 2/2020 Vitruvias Therapeutics