Indications

Comet 850 (Metformin Hydrochloride tablet) is indicated as an adjunct to diet and exercise to improve glycemic control in children and adults with type 2 diabetes mellitus.

Comet TM XR (Metformin Hydrochloride extended-release tablet) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
mellitus.

Pharmacology

Metformin is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia.

Dosage & Administration

Dosage of Comet 850 or Comet TM XR must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose.

The maximum recommended daily dose of Comet TM is 2550 mg in adults and 2000 mg in pediatric patients (10-16 years of age); the maximum recommended daily dose of

Comet TM XR in adults is 2000 mg. Comet TM should be given in divided doses with meals while Comet TM XR should generally be given once daily with the evening meal.CometTM XR tablet must be swallowed whole and never be crushed or chewed. CometTM or CometTM XR should be started at a low dose, with gradual dose escalation, both
to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

Recommended Dosing Schedule
a) Adults: The usual starting dose of CometTM is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly
or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks.
Doses above 2000 mg may be better tolerated given three times a day with meals. The usual starting dose of CometTM XR is 500 mg once daily with the evening meal. Dosage
increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on CometTM XR
2000 mg once daily, a trial of Comet TM XR 1000 mg twice daily should be considered. Patients receiving Comet TM treatment may be safely switched to Comet TM XR once
daily at the same total daily dose, up to 2000 mg once daily.

b) Pediatrics: The usual starting dose of CometTM is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum
of 2000 mg per day, given in divided doses. The safety and effectiveness of CometTM in pediatric patients below 10 years have not been established.

Interaction

No information is available about the interaction of Metformin and furosemide when co-administered chronically. Nifedipine appears to enhance the absorption of Metformin.
Metformin had minimal effects on nifedipine. Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with Metformin by competing for common renal tubular transport systems. Metformin had no effect on cimetidine pharmacokinetics. Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium
channel blocking drugs, and isoniazid.

Contraindications

Comet 850 is contraindicated in patients with:
1. Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels > 1.5 mg/dL [males], > 1.4 mg/dL [females] or abnormal creatinine clearance).
2. Known hypersensitivity to metformin hydrochloride. 3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

Side Effects

Blood and lymphatic system disorders: Not known: Hemolytic anemia

Metabolism and nutrition disorders: Very rare: Lactic acidosis. Decrease of vitamin B12 absorption with a decrease of serum levels during long-term use of metformin. Consideration of such etiology is recommended if a patient presents with megaloblastic anemia. Cases of peripheral neuropathy in patients with vitamin B12 deficiency have been reported in post-marketing experience (frequency not known)

Nervous system disorders: Common: Taste disturbance. Not known: Encephalopathy

Gastrointestinal disorders: Very common: Gastrointestinal disorders, such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. These undesirable effects occur most frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.

Hepatobiliary disorders: Very rare: Isolated reports of liver function test abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders: Very rare: Skin reactions, such as erythema, pruritus, urticaria.

Pregnancy & Lactation

Pregnancy Category B. Most experts recommend that insulin should be used during pregnancy to maintain blood glucose levels as close to normal as possible. Both Metformin
immediate and extended-release tablets should not be used during pregnancy unless clearly needed.

Precautions & Warnings

Metformin is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive Metformin. In patients with advanced age, metformin should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function.

Therapeutic Class

Biguanides

Storage Conditions

Store at cool and dry place and keep away from light. Keep out of reach of children.

Pharmaceutical Name