Peripheral neuropathies.

Adults

Peripheral neuropathies

The recommended dose for adults is 3 tablets (1,500 mcg of Methylcobalamin) daily, divided into three doses taken orally. 

The dose may be adjusted depending on the patient’s age and symptoms.

Restain is not recommended for use in children and adolescents.

Method of administration

Oral

Methylcobalamin is susceptible to photolysis. It should be used promptly after the package is opened, and caution

should be taken not to expose it to direct light.

It is not known whether Methylcobalamin Injection can cause clinically significant interactions with other drugs.

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. Methylcobalamin with the approved dosage can be used during pregnancy. It has been shown that mecobalamin is excreted in the milk of lactating rats.

Based on the pharmacodynamic properties and adverse event profile, it is unlikely that Methylcobalamin would cause an impairment of driving performance or compromise the ability to use machinery.

Adverse reactions were reported in 13 of 2,872 patients (0.45%). (At the end of the reexamination period)

(1)  Clinically significant adverse reactions (incidence unknown)

Anaphylaxis

Anaphylaxis, 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.

(2)   Other adverse reactions

Note: In the event of such symptoms, Methylcobalamin should be discontinued.

Reporting of suspected adverse reactions

To report any side effect(s):

Not applicable

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 organelle 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 lipid and increases myelination of neurons in rat tissue culture more than cobalamide does.

Mecobalamin restores delayed synaptic transmission and diminished neurotransmitters to normal. Mecobalamin restores end-plate potential induction early by increasing never 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.

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, haemoglobin, and haematocrit in vitamin B12-deficient rats.

Clinical efficacy and safety

Mecobalamin was administered intramuscularly to patients with peripheral neuropathies at a single dose 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 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 haematological parameters and symptoms improved in 3 weeks to 2 months after starting administration.

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 organelle 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 electro physiologically 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 lipid and increases myelination of neurons in rat tissue culture more than cobalamide does.

Mecobalamin restores delayed synaptic transmission and diminished neurotransmitters to normal. Mecobalamin restores end-plate potential induction early by increasing never 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.

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, haemoglobin, and hematocrit in vitamin B12-deficient rats.

Clinical efficacy and safety

Mecobalamin was administered intramuscularly to patients with peripheral neuropathies at a single dose 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 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 haematological parameters and symptoms improved in 3 weeks to 2 months after starting administration.

Preclinical safety data, including safety pharmacology, single and repeated dose toxicity, genotoxicity, reproductive and developmental toxicity, and antigenicity studies revealed no special findings relevant to humans

o   Tablet Core: Microcrystalline Cellulose (Avicel PH 112), Calcium Carbonate Precipitated, Hydroxypropyl Cellulose Low Substituted (LH-ll), Calcium Stearate, Stearic Acid

o   Film-Coating: Opadry White 03F180012, Isopropyl Alcohol, Purified Water

Not applicable

Store below 30°c

White to pinkish white, round, biconvex, film-coated tablet and plain surface on both sides.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.