NovoNorm also contains the following excipients: Microcrystalline cellulose (E460), calcium hydrogen phosphate, anhydrous; maize starch, polacrilin potassium, povidone K25, glycerol 85%, magnesium stearate, meglumine and poloxamer 188. The 1-mg tablet also contains iron oxide yellow (E172) and the 2-mg tablet contains iron oxide red (E172).
Pharmacotherapeutic Group: Oral antidiabetic agent.
Pharmacology: Pharmacodynamics: Novonorm is an oral antidiabetic agent containing repaglinide which helps the pancreas produce more insulin and thereby lower the blood sugar (glucose). NovoNorm is a novel short-acting oral secretogogue. NovoNorm lowers the blood glucose levels acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning β-cell in the pancreatic islets.
NovoNorm closes ATP-dependent potassium channels in the β-cell membrane via a target protein different from other secretagogues. This depolarises the β-cell and leads to an opening of the calcium channels with a resulting increase in calcium influx. This induces insulin secretion from the β-cell.
Pharmacokinetics: NovoNorm is rapidly absorbed from the gastrointestinal (GI) tract with a rapid increase in the plasma concentration of the drug. The peak plasma level occurs with 1 hr post-administration. After reaching the peak, the plasma level decreases rapidly and is eliminated within 4-6 hrs. The plasma elimination half-life (t½) is approximately 1 hr. NovoNorm is >98% bound to plasma proteins in humans. NovoNorm is almost completely metabolised and no metabolites with clinically relevant hypoglycaemic effect have been identified.
NovoNorm and its metabolites are excreted primarily via the bile. A small fraction of <8% of the administered dose appears in the urine primarily as metabolites. Less than 1% of the parent drug is recovered in the faeces.
Type 2 diabetes whose hyperglycaemia is not controlled satisfactorily by diet, weight reduction and exercise.
NovoNorm can be used in combination with metformin. Combination therapy with NovoNorm and metformin results in synergistic improvement in glycaemic control compared to NovoNorm or metformin alone.
The dosage should be determined by the physician, according to the patient's requirements as determined by blood glucose titrations. The recommended starting dose is 0.5 mg initially titrated on a weekly or biweekly basis. If patients are transferred from another oral hypoglycaemic agent the recommended starting dose is 1 mg.
The recommended maximum single dose is 4 mg taken with main meals. The total maximum daily dose should not exceed 16 mg.
The dosing and dose titration should be done carefully in debilitated and malnourished patients. If used in combination with metformin, it may be required to lower the dosage of NovoNorm. Although NovoNorm is mainly excreted via the bile, caution is still advised in patients with renal insufficiency.
Administration: NovoNorm should be taken before main meals (ie, preprandially). The insulinotropic response to a meal occurs within 30 min after an oral dose of NovoNorm. Doses are usually taken with 30 min of the meal but time may vary from immediately preceding the meal to as long as 30 min before the meal.
As with all oral hypoglycaemic agents, overdose may result in hypoglycaemic symptoms (see Precautions: Hypoglycaemia). Should these symptoms occur, adequate action should be taken to correct low blood glucose eg, eating glucose tablets or taking a high sugar snack or drink. When hypoglycaemic symptoms have disappeared or when blood sugar has stabilised, continue treatment with NovoNorm. More severe hypoglycaemia with seizure, loss of consciousness or coma should be treated with IV glucose.
Hypersensitivity to repaglinide or any of the excipients in NovoNorm.
Type 1 diabetes (insulin-dependent diabetes mellitus, C-peptide negative diabetes). Diabetic ketoacidosis with or without coma. Severe hepatic function disorders. Concomitant use of gemfibrozil (a lipid-lowering drug) may cause enhancement and prolongation of the effect of NovoNorm.
Hypoglycaemia: NovoNorm, like other insulin secretagogues, is capable of producing hypoglycaemia. This can occur when the patient takes a dose of NovoNorm that is higher than what was recommended, during more frequent exercise, or during concomitant administration with other medicines (see Interactions). Symptoms of hypoglycaemia can include: cold sweat; cool, pale skin; headache; rapid heart beat; feeling sick; hunger; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; anxiety; confusion and difficulty in concentrating.
Combination treatment with metformin is associated with an increased risk of hypoglycaemia. If hyperglycaemia persists after combination, adequate control may no longer be possible with oral hypoglycaemic agents and insulin would be required.
Hyperglycaemia: Hyperglycaemia may also occur with exposure to stress eg, fever, trauma, severe illness or infection, major surgery, or if the dose of NovoNorm taken is lower than recommended. Symptoms of hyperglycaemia can include: increased urination; thirst; dry skin and dry mouth.
Renal and Hepatic Impairment. If the patient is about to to have major surgery or have recently suffered a severe illness or infection.
No clinical studies have been conducted in patients with impaired hepatic function, in patients <18 years and in patients >75 years. Thus, use of NovoNorm in these patient groups is not recommended.
Effects on the Ability to Drive or Operate Machinery: As with all oral hypoglycaemic agents, patients should be advised to take precautions to avoid hypoglycaemia whilst driving.
Use in pregnancy & lactation: There are no studies of NovoNorm in pregnant or lactating women. Use in pregnancy and lactation should be avoided.
There are no studies of NovoNorm in pregnant or lactating women. Use in pregnancy and lactation should be avoided.
As with other hypoglycaemic agents, the following adverse events have been seen: Common (May affect up to 1 in 10 patients)
: Hypoglycaemia, stomach pain; diarrhoea. Rare (May affect up to 1 in 1000 patients):
Acute coronary syndrome (ACS).
Very Rare (May affect up to 1 in 10,000 patients):
Allergy (eg, swelling, difficulty in breathing, rapid heart beat, dizziness, sweating, which could be signs of anaphylactic reaction), vomiting; constipation; visual disturbances; severe liver problems, abnormal liver function, increased liver enzymes.
Hypoglycaemic coma or unconsciousness; hypersensitivity reactions (eg, rash, itchy, reddening and swelling of the skin; nausea.
Substances that may Enhance the Hypoglycaemic Effect of NovoNorm: Monoamine oxidase inhibitors (MAOIs), nonselective β-blocking agents, ACE inhibitors, NSAIDs, salicylates, octreotide, alcohol and anabolic steroids. β-blocking agents may mask the symptoms of hypoglycaemia. Alcohol may intensify and prolong the hypoglycaemic effect of NovoNorm.
Substances that may Reduce the Hypoglycaemic Effect of NovoNorm: Oral contraceptives, thiazides, glucocorticoids, danazol, thyroid hormones and sympathomimetics.
NovoNorm does not influence the pharmacokinetic properties of digoxin, theophylline or warfarin.
Cimetidine does not affect the pharmacokinetic properties of NovoNorm.
In vitro studies indicate that NovoNorm is primarily metabolised by CYP3A4. Hence, CYP3A4 inhibitors eg, ketoconazole, itraconazole, erythromycin, clarithromycin, fluconazole and mibefradil may increase the plasma levels of NovoNorm. Compounds that induce CYP3A4 ie, rifampicin or phenytoin may decrease the plasma levels of NovoNorm. Since the magnitude of an inducing or inhibiting effect is not known, these drug combinations are contraindicated.
Store in a dry place at 15°-25°C. Protect from moisture.
A10BX02 - repaglinide ; Belongs to the class of other blood glucose lowering drugs excluding insulins. Used in the treatment of diabetes.
Tab 0.5 mg (white, round, convex, engraved with Novo Nordisk logo [Apis bull]) x 90's. 1 mg (yellow, round, convex, engraved with Novo Nordisk logo [Apis bull]) x 90's. 2 mg (peach, round, convex, engraved with Novo Nordisk logo [Apis bull]) x 90's.