Mecovon®-1000 Injection

Methylcobalamin Injection 1000 mcg/mL

Each 1 ml contains:

Methylcobalamin IP 1000 micrograms

Benzyl Alcohol IP 2% w/v

(as preservative)

Water for injection IP q.s.

Appropriate overages added to compensate the loss on storage

For IM/IV use

1000 mcg/ml

4.1 Therapeutic Indications

Prophylaxis and treatment of macrocytic (megaloblastic) anaemias associated with vitamin B12 deficiency.

Addisonian pernicious anaemia.

For peripheral neuropathies caused by vitamin B12 deficiency.

Schilling test.

4.2 Posology and method of administration

Route of administration: intramuscular/intravenous injection

Adults and Children

Addisonian pernicious anaemia and other macrocytic anaemias without neurological involvement:

Initially: 250 to 1000 mcg on alternate days for one to two weeks, then 250 mcg weekly until the blood count is normal.

Maintenance: 1000 mcg monthly.

Addisonian pernicious anaemia and other macrocytic anaemias with neurological complications:

Initially: 1000 mcg on alternate days as long as improvement is occurring.

Maintenance: 1000 mcg monthly.

Prophylaxis of macrocytic anaemia associated with vitamin B12 deficiency resulting from gastrectomy, some malabsorption syndromes and strict vegetarianism:

250mcg - 1000mcg monthly.

Schilling Test:

An intramuscular injection of 1000 mcg Methylcobalamin is an essential part of this test.

4.3 Contraindications

Hypersensitivity to Methylcobalamin or any other constituents MECOVON-1000 Injection should not be used for the treatment of megaloblastic anaemia of pregnancy unless vitamin B-12 deficiency has been demonstrated. Not to be used in newly born or premature infants.

4.4 Special warnings and precautions for use

Precautions:

The dosage schemes given above are usually satisfactory, but regular examination of the blood is advisable. If megaloblastic anaemia fails to respond to MECOVON-1000 Injection, folate metabolism should be investigated. Doses in excess of 10 mcg daily may produce an incomplete haematological response in patients with folate deficiency. Indiscriminate administration may mask the true diagnosis. The haematological and neurological state should be monitored regularly to ensure adequacy of therapy. Cardiac arrhythmias secondary to hypokalaemia during initial therapy have been reported. Plasma potassium should therefore be monitored during this period. Platelet count should be monitored during the first weeks of use in megaloblastic anaemia due to the possible occurrence of reactive thrombocytosis.

4.5 Interaction with other medicinal products and other forms of interaction

Chloramphenicol-treated patients may respond poorly to MECOVON-1000 Injection. Serum concentrations of Methylcobalamin may be lowered by oral contraceptives but this interaction is unlikely to have clinical significance.

Antimetabolites and most antibiotics invalidate vitamin B12 assays by microbiological techniques.

4.6 Pregnancy and lactation

MECOVON-1000 Injection should not be used for the treatment of megaloblastic anaemia of pregnancy unless vitamin B12 deficiency has been demonstrated. MECOVON-1000 Injection is secreted into breast milk but this is unlikely to harm the infant, and may be beneficial if the mother and infant are vitamin B12 deficient.

4.7 Effects on ability to drive and use machines

None.

4.8 Undesirable effects

Hypersensitivity reactions have been reported including skin reactions (e.g. rash, itching) and exceptionally anaphylaxis. Other symptoms reported include fever, chills, hot flushing, dizziness, malaise, nausea, acneiform and bullous eruptions, tremor and injection site reactions including injection site pain, injection site induration and injection site necrosis. Reactive thrombocytosis can occur during the first weeks of use in megaloblastic anaemia.

Reporting of suspected adverse reactions

• Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com
• Website: http://www.zuventus.co.in/safety.aspx

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

No overdosage has been reported with this drug. Treatment is unlikely to be needed in cases of overdosage.

5.1 Pharmacodynamic properties

Methylcobalamin is a form of vitamin B12.

Vitamin B12 is present in the body mainly as methylcobalamin and as adenosylcobalamin and hydroxocobalamin. These act as co-enzymes in the trans methylation of homocysteine to methionine; in the isomerisation of methylmalonyl co-enzyme to succinyl co-enzyme and with folate in several metabolic pathways respectively.

Vitamin B12 is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis.

Deficiency of Vitamin B12 interferes with haemopoiesis and produces megaloblastic anaemia.

5.2 Pharmacokinetic properties

Cobalamins are absorbed from the gastro-intestinal tract, but may be irregularly absorbed when given in large therapeutic doses. Absorption is impaired in patients with an absence of intrinsic factor, with a malabsorption syndrome or with a disease or abnormality of the gut, or after gastrectomy.

After injection of Methylcobalamin a large proportion is excreted in the urine within 24 hours; the body retains only 55% of a100-microgram dose and 15% of a 1000-microgram dose. 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, excreted in the bile, and undergoes extensive enterohepatic recycling; part of an administered 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. Vitamin B12 diffuses across the placenta and also appears in breast milk.

None stated.

Mecobalamin is a synthetic and active form of vitamin B12 that can cross the blood brain barrier without biotransformation, that may be used to treat or prevent vitamin B12 deficiency and its complications. Upon administration, mecobalamin is able to replace endogenous vitamin B12, increase vitamin B12 levels and improve vitamin B12 deficiency. Vitamin B12 is necessary for hematopoiesis, neural metabolism, DNA and RNA production, and carbohydrate, fat, and protein metabolism. It improves iron functions in the metabolic cycle and assists folic acid in choline synthesis. Its metabolism is interconnected with that of folic acid.

Molecular Formula: C₆₃H₉₁CoN₁₃O₁₄P

Chemical Structure:

8.1 List of excipients

Benzyl alcohol IP (2% w/v) Water for injections IP

8.2 Incompatibilities

None.

8.3 Shelf life

Refer on pack.

8.4 Special precautions for storage

Protect from light and moisture. Do not store above 30°C. Do not freeze. Keep out of the reach of children. Do not use if solution is not clear or has suspended matter.

8.5 Packaging information

5 blister packs of 1 ampule each.

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.