Methycobal

Methycobal

mecobalamin

Manufacturer:

Eisai

Distributor:

DKSH
Full Prescribing Info
Contents
Mecobalamin.
Description
Tablet: Each tablet contains 500 μg of mecobalamin.
(See Table 1.)

Click on icon to see table/diagram/image

Physicochemistry: Nonproprietary name: Mecobalamin (JAN, INN).
Chemical name: Coα-[α-(5, 6-Dimethyl-1H-benzoimidazol-1-yl)]-Coβ-methylcobamide.
Molecular formula: C63H91CoN13O14P.
Molecular weight: 1344.38.
Mecobalamin occurs as dark red crystals or crystalline powder. It is sparingly soluble in water, slightly soluble in ethanol (99.5), and practically insoluble in acetonitrile. It is degraded by light.
Injection: METHYCOBAL is a clear, red liquid containing the following ingredients, and contained in brown ampoule (one-point-cut type). (See Table 2.)

Click on icon to see table/diagram/image

Excipients/Inactive Ingredients: Tablet: It also contains carnauba wax, microcrystalline cellulose, titanium oxide, stearic acid, calcium stearate, sucrose, talc, precipitated calcium carbonate, corn starch, lactose hydrate, white shellac, hydroxypropylcellulose, pullulan, povidone, macrogol 6000 and hydrated silicon dioxide as inactive ingredients.
Action
Pharmacology: Mecobalamin is a kind of endogenous coenzyme B12: Mecobalamin plays an important role in transmethylation as a coenzyme of methionine synthetase in the synthesis of methionine from homocysteine.
Mecobalamin is well transported to nerve cell organelles, and promotes nucleic acid and protein synthesis: Mecobalamin is better transported to nerve cell organelles than cyanocobalamin in rats. It has been shown in experiments with cells from the brain origin and spinal nerve cells in rats to be involved in the synthesis of thymidine from deoxyuridine, promotion of deposited folic acid utilization and metabolism of nucleic acid. Also, mecobalamin promotes nucleic acid and protein synthesis in rats more than cobamamide does.
Mecobalamin promotes axonal transport and axonal regeneration: Mecobalamin normalizes axonal skeletal protein transport in sciatic nerve cells from rat models with streptozotocin-induced diabetes mellitus. It 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.
Mecobalamin promotes myelination (phospholipid synthesis): Mecobalamin promotes the synthesis of lecithin, the main constituent of medullary sheath lipids, and increases myelination of neurons in rat tissue culture more than cobamamide does.
Mecobalamin restores delayed synaptic transmission and diminished neurotransmitters 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 brain tissue levels of acetylcholine in rats fed a choline-deficient diet.
Injection: Mecobalamin promotes the maturation and division of erythroblasts, thereby alleviating anemia: It is well known that vitamin B12-deficiency may cause specific megaloblastic anemia. Mecobalamin promotes nucleic acid synthesis in bone marrow and promotes the maturation and division of erythroblasts, thereby increasing erythrocyte production. Mecobalamin brings about a rapid recovery of diminished red blood cell, hemoglobin, and hematocrit in vitamin B12-deficient rats.
Pharmacodynamics: Clinical Studies: Tablet: Mecobalamin was administered orally to patients with peripheral neuropathies at doses of 1,500 μg and 120 μg (low-dose group) daily divided into three doses for 4 consecutive weeks in a double-blind clinical trial. In the chronic stage and fixed stage in peripheral neuropathies, the improvement rate for moderately to remarkably improved was 17.6% (6/34) in 1,500 μg group and 9.7% (3/31) in 120 μg group. The improvement rate for fairly to remarkably improved was 64.7% (22/34) in the 1,500 μg group and 41.9% (13/31) in the 120 μg group. The dose of 1,500 μg/day was thus demonstrated to be useful. In a placebo-controlled double-blind clinical trial, mecobalamin and cobamamide were administered orally to patients with peripheral neuropathies at doses of 1,500 μg daily for 4 consecutive weeks. The rates for moderately to remarkably improved for peripheral neuropathies were 38.6% (17/44) for mecobalamin, 22.2% (10/45) for cobamamide and 26.7% (12/45) for placebo. Mecobalamin was thus demonstrated to be useful.
Injection: Clinical efficacy: Mecobalamin was administered intramuscularly to patients with peripheral neuropathies in single doses of 500 μg and 100 μg (low-dose group) daily 3 times a week for 4 consecutive weeks in a double-blind clinical trial. In the chronic stage and fixed stage of peripheral neuropathies in the 500 μg group aggravation of symptoms was significantly suppressed compared to the low-dose group and this dose was thus demonstrated to be useful. In a placebo-controlled double-blind clinical trial, mecobalamin was administered intravenously or intramuscularly to patients with peripheral neuropathies at a single dose of 500 μg daily 3 times a week for 4 consecutive weeks. The improvement rate for intravenous administration was 38.7% (24/62) for moderately to remarkably improved and 74.2% (46/62) for fairly to remarkably improved. The improvement rate for intramuscular administration was 46.3% (25/54) for moderately to remarkably improved and 81.5% (44/54) for fairly to remarkably improved. The equivalence of mecobalamin efficacy for both administration routes was thus demonstrated. The diseases of subjects in the trial were diabetic neuropathy, polyneuritis, cervical spondylosis, sciatica, alcoholic neuropathy, facial paralysis and mononeuritis, etc.
When mecobalamin was administered to patients with megaloblastic anemia due to vitamin B12 deficiency, their hemograms and symptoms improved in 3 weeks to 2 months after starting administration.
Pharmacokinetics: Tablet: Single dose administration: When Methycobal was administered orally to healthy adult male volunteers at single doses of 120 μg and 1,500 μg note) during fasting, the peak serum total vitamin B12 (abbreviated to B12) concentration was reached after 3 hrs for both doses, and this was dose-dependent. The half-life, increment in the serum total B12 concentration and ΔAUC012 by 12 hrs after administration are shown in the following figure and table. 40 to 90% of the cumulative amount of total B12 excreted in the urine by 24 hrs after administration was excreted within the first 8 hrs.
Note) A single dose of 1,500 μg is unapproved. (See Figure 1 and Table 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Repeated dose administration: Methycobal was administered orally to healthy adult male volunteers at a dose of 1,500 μg daily for 12 consecutive weeks and changes in the serum total B12 concentration were determined until 4 weeks after the last administration. 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. (See Figure 2.)

Click on icon to see table/diagram/image

Injection: Single-dose administration: Mecobalamin was administered intramuscularly or intravenously to 12 healthy adult male volunteers at a single dose of 500 μg. The time to reach peak serum total vitamin B12 (abbreviated to B12) concentration (tmax) was 0.9 hr after intramuscular administration and immediately to 3 minutes after intravenous administration, and the increment (except endogenous serum total B12) in peak serum total vitamin B12 concentration (ΔCmax) was 22.4 ng/mL after intramuscular administration and 85.0 ng/mL after intravenous administration. The area under the serum total B12 concentration-time curve (ΔAUC) calculated by increment of the actual values at 144 hr after administration was 204.1ng·hr/mL after intramuscular administration and 358.6ng·hr/mL after intravenous administration. On the other hand, the rate of binding saturation showed a similar increase in both groups of subjects for 144 hr after administration. (See Figure 3 and Table 4.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Repeated-dose administration: Mecobalamin was administered intravenously to 6 healthy adult male volunteers at a single dose of 500 μg daily for 10 consecutive days. Serum total vitamin B12 concentration determined before each administration increased from day to day. After 2 days of administration, the serum total vitamin B12 concentration was 5.3±1.8ng/mL, about 1.4 times the 24 hr value (3.9±1.2ng/mL) after administration. At 3 days of administration it had increased to 6.8±1.5ng/mL, about 1.7 times the 24 hr value, and this concentration was maintained until the last dosing.
Indications/Uses
Peripheral neuropathies.
Injection: Megaloblastic anemia caused by vitamin B12 deficiency.
Dosage/Direction for Use
Tablet: The usual daily dose for adults is 3 tablets, equivalent to a total of 1,500 μg of mecobalamin, administered orally in 3 divided doses. The dose may be adjusted according to the age of patient and severity of symptoms.
Injection: Peripheral neuropathies: The usual dosage for adults is 1 ampoule (500 μg of mecobalamin) per day, administered intramuscularly or intravenously 3 times a week. The dosage may be adjusted depending on the patient's age and symptoms.
Megaloblastic anemia: The usual dosage for adults is 1 ampoule (500 μg of mecobalamin) per day, administered intramuscularly or intravenously 3 times a week. After about 2 months of medication, the dose should be reduced to a single administration of 1 ampoule at 1 to 3 months intervals for maintenance therapy.
Overdosage
Injection: Experience to date with deliberate or accidental overdose is limited. No specific antidote is known. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilised.
Contraindications
Injection: Hypersensitivity to any form of vitamin B12 or D-mannitol.
Special Precautions
Tablet: General: Methycobal should not be administered for extensive periods (months) to patients who show no clinical response.
Precautions concerning Use: 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: Prolonged use of larger doses of Methycobal is not recommended for patients whose occupation requires handling mercury or its compounds.
Injection: METHYCOBAL should not be used aimlessly for more than one month unless it is effective.
Precautions concerning Use: Administration: METHYCOBAL is susceptible to photolysis. It should be used promptly after the package is opened, and caution should be taken so as not to expose the ampoules to direct light.
Intramuscular administration: In intramuscular administration, caution should be exercised, by following the instructions mentioned as follows to avoid adverse effects on tissues or nerves: Avoid repeated injection at the same site. Particular caution should be exercised when administering METHYCOBAL to prematures, neonates, nursing infants and children.
Do not inject in densely innervated site.
If insertion of the injection needle causes intense pain or if blood flows back into the syringe, withdraw the needle immediately and inject at a different site.
Opening the ampoule: METHYCOBAL is supplied in one-point-cut ampoules. The cut point of the ampoules should be wiped with an alcohol swab before opening.
Use In Pregnancy & Lactation
Injection: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy. Clinical studies have been done on pregnant women and no harmful effects have been reported. Methycobal with the approved dosage can be used during pregnancy.
It has been shown that mecobalamin is excreted in the milk of lactating rats.
Adverse Reactions
Tablet: Adverse reactions were reported in 146 of 15,180 patients (0.96%). (At the end of the investigation for incidence of adverse reactions). (See Table 5.)

Click on icon to see table/diagram/image

Injection: Adverse reactions were reported in 13 of 2,872 patients (0.45%). (At the end of the reexamination period).
Clinically significant adverse reactions (incidence unknown): Anaphylactoid reactions: Anaphylactoid reactions, such as 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.
Other adverse reactions: See Table 6.

Click on icon to see table/diagram/image
Drug Interactions
Injection: Not applicable.
Caution For Usage
Injection: Cautions: METHYCOBAL is packaged in LPE packs (Light Protect Easy open pack) to ensure quality during storage. The LPE pack should be opened immediately before using.
Incompatibility: Not applicable.
Storage
Tablet: Methycobal Tablets should be stored below 30°C.
Methycobal Tablets should be protected from moisture and light. (Light decomposes the active ingredient and the tablets may turn reddish with humidity).
Injection: METHYCOBAL should be stored below 30°C and protected from light.
ATC Classification
B03BA05 - mecobalamin ; Belongs to the class of vitamin B12 (cyanocobalamin and analogues). Used in the treatment of anemia.
Tab: NP; Inj: C
Presentation/Packing
Tab 500 mcg (white, sugar-coated) x 100's, 500's. Inj 500 mcg/mL (clear, red liquid in amp) x 10's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in