COBAL is indicated in the treatment of peripheral neuropathies

Route of administration: Oral

1-1-1       Usual adult dose

The usual daily dose for adults is 3 tablets, equivalent to a total of 1500 µg of Mecobalamin.

Administrated orally in 3 divided doses.

The dose should be adjusted according to the age of patient and severity of symptoms.

q  COBAL should not be administrated for extensive periods (months) to patients who show no clinical response.

Prolonged use of larger doses of COBAL is not recommended for patients whose occupation requires handling mercury or its compounds

COBAL has the potential to interact with certain medications such as:

q  Chloramphenicol

q  Proton pump inhibitors

q  H2 receptor antagonitists

Metformin

1-1-1       Use during pregnancy

COBAL may be taken during pregnancy if the benefit to the mother is greater than the risk to the baby. You are best to talk to your doctor and make a decision together.

1-1-2       Use during lactation

Methylcobalamin is distributed into breast milk in amounts similar to those in maternal plasma, and distribution in breast milk allows for adequate intakes of methylcobalamin by beast- feeding infants.

It is unlikely that COBAL would cause an impairment of driving performance or compromise the ability to use machinery.

The most common adverse reactions include:

q  Gastrointestinal symptoms such as anorexia.

q  Gastrointestinal disorder

q  Nausea – vomiting

q  Diarrhea

q  Skin rash

Saudi Arabia: To report any side effect(s): National Pharmacovigilance and Drug Safety Center (NPC): call NPC at +966-11-2038222 , Exts: 2317- 2356- 2340, Fax: +966-11-205-7662,

E-mail: npc.drug@sfda.gov.sa Reporting hotline: 19999

 Website: www.sfda.gov.sa/npc

Vitamin B12 preparations in general are usually nontoxic, even in large doses.

 Pharmacotherapeutic group: Vitamin B ₁₂ supplement

ATC Code: B03BA05                                                       

1. Promotion of the metabolism of nucleic acids, proteins and lipids
Experiments with a brain-derived cell line from albino rats have shown that mecobalamin, by acting as a coenzyme in the formation of methionine from homocysteine, is involved in the synthesis of thymidylate from deoxyundylate, and promotes the synthesis of DNA and RNA. It has also been demonstrated. In experiments using neuroglia, that mecobalamin enhances the formation of lecithin, a major component of the myelin sheath.

2. Extensive uptake by nerve tissues and improvement of metabolic disturbances
Mecobalamin, a methylated form of vitamin B₁₂ (CH₃-B₁₂) that occurs in high concentrations in the blood and the cerebrospinal fluid, has been observed in rats to be taken up into nerve cell organelles more actively and extensively than CN-B₁₂. Experimentation using sciatic nerve cells from rats with experimental diabetes has also demonstrated that Mecobalamin helps maintain axonal function by promoting the synthesis of structural proteins and by normalizing the transport velocity of these proteins.

3. Repair of nerve injury
Mecobalamin has been demonstrated, by neuropathological and electrophysiological studies, to inhibit nerve fiber degeneration in rats and rabbits with neuropathy induced by drugs such as Adriamycin and Vincristine or with Streptozotocin - induced diabetes. The effects of mecobalamin were also studied in guinea pig models with compression-induced facial palsy. The recovery process was evaluated using examinations of the blink reflex, evoked electromyograms, and histological observations. Mecobalamin was found to be as effective as steroids in accelerating the repair of injured nerve tissue.

1. Single dose administration
After oral administration of single doses of 120 µg or 1,500 µg of mecobalamin to healthy adult subjects, dose-dependent peak plasma concentrations were reached in 3 hours in both cases. The half-life, increase of plasma concentration of total B₁₂, and ^AUC¹² were as shown below.

Of the cumulative amount of total B₁₂ recovered in the urine by 24 hours after oral administration, 40 to 80 percent was excreted within the first 8 hours.

*1 Calculated by the trapezoidal formula from the increment in observed 12-hour values, as compared to pre-drug values.

*2 Calculated from the average of 24-48 hour values.

Mean ± Standard error.

2. Repeated dose administration

Plasma concentrations of total B₁₂ were measured in healthy subjects given an oral daily dose of 1,500 µg of COBAL for 12 consecutive weeks. Plasma B₁₂ concentrations were also monitored in the same patients for the 4 weeks immediately following the last administration. The plasma concentration increased for the first 4 weeks after administration, reaching a value twice as high as the initial concentration. Thereafter, there was a gradual increase which reached a peak at approximately 280% of the initial value at the 12th week of dosing. The plasma concentration declined after the last administration (12 weeks), but was still approximately 180% of the initial level 4 weeks after the last administration.

Clinical Studies
1. Clinical effects

In clinical studies, including double-blind trials, COBAL Tablets produced good or excellent relief of symptoms in 44.5% (5,503/12,373) of patients with peripheral neuropathies. In double-blind controlled comparative trials of COBAL Tablets with cobalamin (DBCC) or mecobalamin administered in lower doses (120 µg), the efficacy and usefulness of COBAL Tablets were confirmed.

2. Adverse reactions

Out of 15,180 patients treated with COBAL Tablets, adverse reactions were reported in 146 patients (0.96%). The most common adverse reactions include gastrointestinal symptoms such as anorexia in 52 patients (0.34%), gastrointestinal disorders in 38 patients (0.25%), nausea-vomiting in 18 patients (0.18%), diarrhea in 17 patients (0.11%). and skin rash in 14 patients (0.09%).

3. Effects on laboratory values
No changes in laboratory values have been attributed to Methycobal treatment

Animal Studies
1. Distribution

In rats given a 25 µg oral dose of ⁵⁷Co-labelled mecobalamin, radioactivity was found to be higher in the kidneys, adrenal glands, pancreas, liver, and stomach (listed in order of magnitude), whereas the muscles, testes, brain, and nerves did not show significant radioactivity 72 hours after administration.

2. Acute toxicity LD₅₀ (mg/kg)

3. Subacute toxicity
The oral administration of mecobalamin, at doses of 0.2, 2.0 and 20mg/kg/day to rats of both sexes for 1 consecutive month, resulted in no remarkable changes in the general condition of the animals, the body weights, blood and urine analytical results, organ weights, or histopathology.

4. Chronic toxicity
In rats of both sexes, given an oral dose of 0.2, 2.0 and 20mg/kg/day of mecobalamin for 6 consecutive months, no remarkable changes were noted in the general condition of the animals, the body weights, blood and urine analytical results, organ weights, or histopathology.

5. Reproduction tests
In mature nulliparous mice and rats, administered an oral dose of 0.2, 2.0, and 20mg/kg/day of mecobalamin during organogenesis, no abnormalities or signs of teratogenicity were noted in fetuses or neonates

1-1   List of excipients        

Not applicable

Do not store above 30ºC, protected from light and humidity.

q Boxes of 30 stripped Tablets of COBAL 500 µg Tablets.

Boxes of 105 stripped Tablets of COBAL 500 µg Tablets

No special requirements.

                   Any unused product or waste material should be disposed of in

                   accordance with local requirements.