PACKAGE INSERT TEMPLATE FOR MECOBALAMIN TABLET & CAPSULE

Brand or Product Name

[Product name] Tablet 500µg
[Product name] Capsule 500µg

Name and Strength of Active Substance(s)

Mecobalamin ….mg

Product Description
[Visual description of the appearance of the product (eg colour etc)]
eg White sugar-coated tablet
Orange opaque, size '1' hard vegetable capsules, containing light pink powder.

Pharmacodynamics

(1) Mecobalamin is a kind of endogenous coenzyme B12 :

As a coenzyme of methionine synthetase, mecobalamin plays an important role in
transmethylation in the synthesis of methionine from homocysteine.

(2) Mecobalamin is well transported to nerve cell organelles, and promotes nucleic acid and
protein synthesis :
Experiments in rats show that mecobalamin is better transported to nerve cell organelles than
cyanocobalamin and promotes nucleic acid and protein synthesis more than cobamamide does.
Experiments with cells from the brain origin and spinal nerve cells in rats also show
mecobalamin to be involved in the synthesis of thymidine from deoxyuridine, promotion of
deposited folic acid utilization and metabolism of nucleic acid.

(3) Mecobalamin promotes axonal transport and axonal regeneration :

In rat models with streptozotocin-induced diabetes mellitus, mecobalamin normalizes axonal
skeletal protein transport in sciatic nerve cells. Mecobalamin exhibits neuropathologically and
electrophysiologically inhibitory effects on nerve degeneration in neuropathies induced by drugs,
such as adriamycin, acrylamide, and vincristine (in rats and rabbits), models of axonal
degeneration in mice and neuropathies in rats with spontaneous diabetes mellitus.

(4) Mecobalamin promotes myelination (phospholipid synthesis) :

Mecobalamin promotes the synthesis of lecithin which is the main constituent of medullary
sheath lipid. It also increases myelination of neurons in rat tissue culture more than cobamamide
does.

(5) Mecobalamin restores delayed synaptic transmission and diminished neurotransmitters back
to normal :
Mecobalamin restores end-plate potential induction early by increasing nerve fiber excitability in
the crushed sciatic nerve in rats. In addition, mecobalamin normalizes diminished levels of
acetylcholine in brain tissue of rats fed with a choline-deficient diet.

Updated March 2013

Pharmacokinetics

(1) Absorption
Vitamin B12 substances bind to intrinsic factor, a glycoprotein secreted by the gastric mucosa,
and are then actively absorbed from the gastrointestinal tract. Absorption is impaired in patients
with an absence of intrinsic factor, with a malabsorption syndrome or with disease or
abnormality of the gut, or after gastrectomy. Absorption from the gastrointestinal tract can also
occur by passive diffusion; little of the vitamin present in food is absorbed in this manner
although the process becomes increasingly important with larger amounts such as those used
therapeutically.

(i) Single-dose administration

When mecobalamin was administered orally to healthy adult male volunteers at single doses of
120 µg and 1,500 µg) during fasting, the peak serum total vitamin B12 concentration was
reached after 3 hrs for both doses, and this was dose-dependent.
Note) A single dose of 1,500 µg is unapproved.

(ii) Repeated-dose administration

When mecobalamin was administered orally to healthy adult male volunteers at a dose of 1,500
µg daily for 12 consecutive weeks, the serum concentration increased for the first 4 weeks after
administration, rising to about twice as high as the initial value. Thereafter, there was a gradual
increase which peaked at about 2.8 times the initial value at the 12th week
of dosing. The serum concentration declined after the last administration (12 weeks), but was
still about 1.8 times the initial value 4 weeks after the last administration.

(2) Distribution
Vitamin B12 is extensively bound to specific plasma proteins called transcobalamins;
transcobalamin II appears to be involved in the rapid transport of the cobalamins to tissues.
Vitamin B12 is stored in the liver. Vitamin B12 diffuses across the placenta and also appears in
breast milk.

(3) Excretion
Vitamin B12 is excreted in the bile, and undergoes extensive enterohepatic recycling; part of a
dose is excreted in the urine, most of it in the first 8 hours; urinary excretion, however, accounts
for only a small fraction in the reduction of total body stores acquired by dietary means.

40-80% of the cumulative amount of total B12 excreted in the urine by 24 hrs after single-dose
administration was excreted within the first 8 hrs.

(4) Elimination Half-life

12.5 hrs (single-dose oral administration; calculated from the average of 24-48 hour values)

Indication
Peripheral neuropathies

Updated March 2013

Recommended Dosage

Adult Dosage
The usual adult dosage for oral use is 3 tablets (1,500 µg of mecobalamin) daily divided into
three doses. The dosage may be adjusted depending on the patient’s age and symptoms.

Mode of administration
Oral

Contraindications
Hypersensitivity to mecobalamin or other components of the formulation.

Warnings and Precautions

This product should not be used aimlessly for more than one month unless it is effective.

Vitamin B12 should, if possible, not be given to patients with suspected vitamin B12 deficiency
without first confirming the diagnosis. Where it is desirable to start therapy immediately,
combined treatment for both deficiencies may be started once suitable samples have been taken
to permit diagnosis of the deficiency, and the patient converted to the appropriate treatment once
the cause of the anaemia is known. Regular monitoring of the blood is advisable.

Although the haematological symptoms of B12 deficiency and folate deficiency are similar, it is
important to distinguish between them since the use of folate alone in B12-deficient
megaloblastic anaemia can improve haematological symptoms without preventing aggravation of
accompanying neurological symptoms, and may lead to severe nervous system sequelae such as
subacute combined degeneration of the spinal cord. Use of doses greater than 10 micrograms
daily may produce a haematological response in patients with folate deficiency and
indiscriminate use may mask the precise diagnosis. Conversely, folate may mask vitamin B12
deficiency.

Precautions concerning use

(1) Administration : Mecobalamin is susceptible to photolysis . Light decreases the content of
mecobalamin and tablets may change colour (eg. turn reddish) with exposure to moisture.
Therefore, this product should be used promptly after the package is opened, and caution should
be taken so as not to expose the tablets/capsules to light/moisture.

(2) Caution in handing over drug : For drugs that are dispensed in a press-through package(PTP),
instruct the patient to remove the drug from the package prior to use. [It has been reported that, if
the PTP sheet is swallowed, the sharp corners of the sheet may puncture the esophageal mucosa,
causing perforation and resulting in serious complications such as mediastinitis.]

Other Precautions
The prolonged use of larger doses of mecobalamin is not recommended for patients whose
occupation requires the handling of mercury or mercury compounds.

Updated March 2013

Interactions with Other Medicaments

Absorption of vitamin B12 from the gastrointestinal tract may be reduced by neomycin,
aminosalicylic acid, histamine H2-antagonists, omeprazole, and colchicine.

Serum concentrations may be decreased by use of oral contraceptives.

Many of these interactions are unlikely to be of clinical significance but should be taken into
account when performing assays for blood concentrations.

Statement on Usage During Pregnancy and Lactation

Pregnancy
There are no data available for mecobalamin to be used in pregnant women.

Lactation
There are no data available for mecobalamin to be used in lactating women. However, since
vitamin B12 is distributed into breast milk, The American Academy of Pediatrics considers its
use to be usually compatible with breast feeding.

Adverse Effects / Undesirable Effects

Dermatologic Effects: Rash ; In the event of such symptoms, treatment should be discontinued.

Gastrointestinal Effects: Anorexia, nausea/vomiting and diarrhea

Neurologic Effects (Central nervous system): Headache

Others:
 Anaphylactoid reaction : decrease in blood pressure or dyspnea, may occur. Patients should
be carefully observed. In the event of such symptoms, treatment should be discontinued
immediately and appropriate measures taken.

 Hot sensation

 Diaphoresis

 Pain/induration at the site of intramuscular injection

Updated March 2013

Overdose and Treatment
There have been no reports, in the literature, of overdosage with mecobalamin.

Storage Conditions
[eg. Store below…. C ; Sugar-coated tablets should be protected from light and moisture after
opening package.]

Dosage Forms and Packaging Available

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Name and Address of Manufacturer

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Name and Address of Marketing Authorization Holder

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Date of Revision of Package Insert

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Updated March 2013