QUALITATIVE AND QUANTITATIVE COMPOSITION

Qbal 500mcg Tablets
Each tablet contains:
Mecobalamin JP …. 500mcg
(Product Specs.: JP)
Product contains Lactose

Qbal 500mcg/mL Injection
Each ampoule contains:
Mecobalamin JP …. 500mcg
(Product Specs.: Bosch)

PHARMACEUTICAL FORM
Tablets and Injection

CLINICAL PARTICULARS
Therapeutic indications
Qbal tablets and Injection are indicated for the treatment of peripheral neuropathies including diabetic neuropathy in adult patients.
Qbal Injection is also indicated in the management of megaloblastic anemia caused by vitamin B₁₂ deficiency in adults.

Posology and method of administration
A sensitivity history should be obtained from the patient prior to administration of vitamin B₁₂.
An intradermal test dose is recommended before vitamin B₁₂ is administered to patients who may be sensitive to cobalamins.
For oral use: The usual adult dosage for oral use is 3 tablets (1500μg of mecobalamin) daily divided into three doses. The dosage may be adjusted depending on the patient’s age and symptoms.
For Intravenous or Intramuscular use
Peripheral neuropathies: The usual dosage for adults is 1 ampoule (500μg of mecobalamin) daily, 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 (500μg of mecobalamin) daily, 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.

Contraindications

• Patients with known or suspected hypersensitivity to methylcobalamin.
• Neonates or premature infants.
• Existing hypervitaminosis.

Special Warnings and Precautions for use
The therapeutic response to vitamin B₁₂ may be impaired by concurrent infection, uremia, folic acid or iron deficiency or by drugs with bone marrow suppressing effects such as chloramphenicol.
A sensitivity history should be obtained from the patient prior to administration of vitamin B₁₂. An intradermal test dose is recommended before vitamin B₁₂ is administered to patients who may be sensitive to cobalamins.
Serum potassium is to be carefully monitored during the initial phase of treatment in pernicious anaemia.
Vitamin B₁₂ deficiency that is allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord. Folic acid may potentiate the neurological complications of vitamin B₁₂ deficiency, so should not be administered to patients with pernicious anaemia 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.

Interaction with other medicinal products and other forms of interaction
Colchicine para-aminosalicylic acid and heavy alcohol intake for longer than two weeks may produce malabsorption of vitamin B₁₂. Serum concentrations of cyanocobalamin may be lowered by oral contraceptives.
Vitamin B₁₂ concentrations in the blood may be reduced following administration of large and continuous doses of folic acid. Folic acid administration may impair the therapeutic response to cyanocobalamin.
The therapeutic response to vitamin B₁₂ may be impaired by drugs with bone marrow suppressing effects such as chloramphenicol.

Fertility, Pregnancy and lactation
Fertility: No data available.

Use in pregnancy: Vitamin B₁₂ crosses the placental barrier. There are no studies establishing the safety of this drug during pregnancy. It is not recommended for pregnancy unless the expected benefits outweigh any potential risk to the fetus.
Megaloblastic anemia occurring during pregnancy is usually due to folic acid deficiency rather than vitamin B₁₂ deficiency. Mecobalamin should not be used for the treatment of megaloblastic anemia of pregnancy caused by folic acid deficiency.

Lactation: Vitamin B₁₂ is known to be excreted in human milk. Nursing mothers should not use this preparation unless clearly needed and recommended by physician.

Effects on ability to drive and use machines
There are no data about unfavorable influence on the active attention, reflexes and motor activity.

Undesirable effects

• Anaphylactoid reaction such as decrease in blood pressure or dyspnea may occur.
• Other Adverse Reactions: Hypersensitivity, rash, erythema, pruritus, dizziness, agitation, anxiety, headache, hot sensation, diaphoresis, and pain/induration at the site of I.M. injection. Pulmonary edema, congestive heart failure (CHF), peripheral vascular thrombosis, polycythemia vera (bone marrow disorder), mild transient diarrhea, itching, transitory exanthema, feeling of swelling of entire body have also been reported with parenteral vitamin B-containing substances.

Overdose
Treatment should be symptomatic and general supportive measures should be utilized. No specific antidote is known.

PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
Pharmacotherapeutic Class: Vitamin B₁₂ (cyanocobalamin and analogues).
ATC code: B03BA05.

Mechanism of action: Mecobalamin is a kind of endogenous coenzyme B₁₂ and 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 than cyanocobalamin and promotes nucleic acid and protein synthesis more than cobamamide does.

Mecobalamin normalizes axonal skeletal protein transport in sciatic nerve cells which exhibits neuropathologically and electrophysiologically inhibitory effects on nerve degeneration in neuropathies induced by drugs, such as adriamycin, acrylamide, and vincristine.

Mecobalamin promotes the synthesis of lecithin which is the main constituent of medullary sheath lipid. Restores end-plate potential induction early by increasing nerve fiber excitability in the crushed sciatic nerve. In addition, mecobalamin normalizes diminished levels of acetylcholine in brain tissue of choline-deficient diet.

Mecobalamin promotes nucleic acid synthesis in bone marrow and the maturation and division of erythroblasts, thereby increasing erythrocyte production.

Pharmacokinetic properties
Absorption: Absorbed vitamin B₁₂ is transported via specific B₁₂ binding proteins, transcobalamin I and II to the various tissues. The liver is the main organ for vitamin B₁₂ storage. Prompt parenteral administration of vitamin B₁₂ prevents progression of neurologic damage.
Vitamin B₁₂ is bound to intrinsic factor during transit through the stomach; separation occurs in the terminal ileum in the presence of calcium, and vitamin B₁₂ enters the mucosal cell for absorption. It is then transported by the transcobalamin binding proteins.

A small amount (approximately 1% of the total amount ingested) is absorbed by simple diffusion, but this mechanism is adequate only with very large doses. Oral absorption is considered too undependable to rely on in patients with pernicious anemia or other conditions resulting in malabsorption of vitamin B₁₂.

Excretion: Within 48 hours after injection of 100 or 1000 micrograms of mecobalamin, 50 to 98% of the injected dose may appear in the urine. The major portion is excreted within the first eight hours. Intravenous administration results in even more rapid excretion with little opportunity for liver storage.

PHARMACEUTICAL PROPERTIES
Incompatibilities:
Not applicable.

Shelf life
Qbal 500mcg Tablets: 03 years
Qbal 500mcg/mL Injection: 02 years

Special precautions for storage
Protect from heat, light & moisture, store below 30°C.
The expiration date refers to the product correctly stored at the required condition.
Keep out of the reach of children.
To be sold on the prescription of a registered medical practitioner only.

Nature and contents of container/presentation
Qbal 500mcg Tablets: Pack of 30 Tablets
Qbal 500mcg/mL Injection: Pack of 10 & 50 Ampoules

REGISTRATION HOLDER / MARKETING AUTHORIZATION HOLDER
Head Office:
Bosch Pharmaceuticals (Pvt.) Ltd.,
8, Modern Society, Tipu Sultan Road, Karachi-Pakistan.

Manufacturer:
Bosch Pharmaceuticals (Pvt.) Ltd.,
221-223, Sector 23, Korangi Industrial area, Karachi-Pakistan.

REGISTRATION / MARKETING AUTHORIZATION NUMBER
Qbal 500mcg Tablets: 030222
Qbal 500mcg/mL Injection: 030223

DATE FROM WHICH MARKETING IS AUTHORIZED/RENEWAL OF THE AUTHORIZATION
Qbal 500mcg Tablets: 31-05-2003/30-05-2023
Qbal 500mcg/mL Injection: 31-05-2003/30-05-2023

DATE OF REVISION OF THE TEXT.
18-05-2024