Glukenil

Glukenil Uses, Dosage, Side Effects, Food Interaction and all others data.

Glukenil stimulates release of insulin from pancreatic β-cells by inhibiting K efflux via closure of ATP regulated K channels. This results in depolarization of the cell and opening of voltage-dependent Ca channels, which increases influx of Ca into the beta cells and causes release of insulin.

Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Glukenil increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.

Trade Name Glukenil
Availability Prescription only
Generic Repaglinide
Repaglinide Other Names Repaglinida, Repaglinide, Repaglinidum
Related Drugs Farxiga, metformin, Trulicity, Lantus, Victoza, Tresiba, Levemir
Type
Formula C27H36N2O4
Weight Average: 452.5857
Monoisotopic: 452.26750765
Protein binding

>98% (e.g. to to albumin and α1-acid glycoprotein)

Groups Approved, Investigational
Therapeutic Class Meglitinide Analogues
Manufacturer
Available Country Argentina
Last Updated: September 19, 2023 at 7:00 am
Glukenil
Glukenil

Uses

Glukenil is used for an adjunct to diet and exercise to lower the blood glucose level in patients with type 2 diabetes mellitus (NIDDM) whose hyperglycaemia cannot be controlled satisfactorily by diet and exercise alone. It is also used for use in combination with Metformin to lower blood glucose in patients whose hyperglycaemia cannot be controlled by exercise, diet, and either Glukenil or Metformin alone. Glukenil binds to specific receptors in the cell membrane leading to the closure of ATP dependent K+ channels and the depolarisation of cell membrane. This in turn, leads to Ca++ influx, increased intracellular Ca++ and the stimulation of insulin secretion.

Glukenil is also used to associated treatment for these conditions: Type 2 Diabetes Mellitus

How Glukenil works

Glukenil activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, repaglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, repaglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of repaglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Glukenil appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.

Dosage

Glukenil dosage

Glukenil has to be taken just before or up to 30 minutes before the meal. Glukenil can be taken two, three or four times a day, depending on how many meals are taken. If a meal is missed, Glukenil should also be avoided. If an extra meal is taken, an extra dose of Glukenil should be taken with that meal. If a dose of Glukenil is missed, it should not be taken between meals.

Rather the usual dose should be taken before the next meal. The dose ranges from 0.5 to 4 mg before each meal. The starting dose of Glukenil in patients with HbA1c <8% is 0.5 mg before each meal. In patients with HbA1c >8% the starting dose is 1 or 2 mg before each meal. The dose may be increased gradually up to 4 mg before each meal.

Side Effects

Hypoglycaemia is possible with all blood glucose lowering drugs. If there are symptoms of low blood glucose (for example, headache, dizziness, tiredness, nervousness or shakiness, rapid heartbeat, or nausea), blood glucose should be tested right away. If it is low (less than 70 mg/dl on a home glucose meter), a simple carbohydrate food (for example, orange juice, quick dissolving sugar, candies, or glucose tablets) should be taken. If the symptoms do not go away, doctor should be informed. Some of the other common symptoms reported by patients taking Glukenil include cold and flu-like symptoms, diarrhoea, joint ache, and back pain. There is some evidence that oral anti-diabetic drugs may increase the risk of heart problems. But experts are not sure what the real risk is, if any, from taking oral anti-diabetic drugs.

Toxicity

LD50 >1 g/kg (rat) (W. Grell)

Precaution

Glukenil should also be used with caution in renal and hepatic insufficiency.

Interaction

The dose of Glukenil may need to be adjusted, if taken with other medications. The possible interactions of Glukenil with other drugs are:

  • Inhibitors of the cytochrome P450 enzyme system (azole antifungals and macrolides) may lead to lower Glukenil clearance and longer half life.
  • Inducers of the cytochrome P450 enzyme system (Rifampin, Phenobarbital, Carbamazepine, Troglitazone, etc.) may accelerate Glukenil metabolism and shorten its effect.
  • Cimetidine has no significant effect on Glukenil absorption or clearance.
  • Glukenil has no significant effect on Digoxin, Theophyllin, or Warfarin.
  • Highly protein bound drugs (e.g., NSAIDs) may increase the plasma level of unbound Glukenil and potentiate its glucose lowering effect. Thus, co-administration of these drugs with Glukenil may increase the risk of hypoglycaemia.
  • The risk of hypoglycaemia may also be increased when hypoglycaemic agents are co-administered with certain drugs such as salicylates, sulphonamides, Chloramphenicol, coumarins, Probenecid, monoamine oxidase (MAO) inhibitors, and adrenergic blockers.

Food Interaction

  • Take before a meal. Glukenil should be taken before each meal of the day.

[Moderate] MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability).

In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.

Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4.

Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

Orange juice is not expected to interact with these drugs.

Glukenil Alcohol interaction

[Moderate] GENERALLY AVOID:

Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

[Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

Volume of Distribution

31 L following IV administration in healthy individuals

Elimination Route

Rapidly and completely absorbed following oral administration. Peak plasma concentrations are observed within 1 hour (range 0.5-1.4 hours). The absolute bioavailability is approximately 56%. Maximal biological effect is observed within 3-3.5 hours and plasma insulin levels remain elevated for 4-6 hours. When a single 2 mg dose of repaglinide is given to healthy subjects, the area under the curve (AUC) is 18.0 - 18.7 (ng/mL/h)^3.

Half Life

1 hour

Clearance

33-38 L/hour following IV administration

Elimination Route

90% eliminated in feces (<2% as unchanged drug), 8% in urine (0.1% as unchanged drug)

Pregnancy & Breastfeeding use

In pregnancy, safety of Glukenil has not been established. Hence, Glukenil should be used during pregnancy only if it is clearly needed. It is not known whether Glukenil is excreted in human milk. Because many drugs are excreted in human milk and because of potential for serious adverse reactions in nursing infants from Glukenil, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Contraindication

Glukenil is contraindicated in patients with diabetic ketoacidosis, with or without coma, in patients with type I diabetes and in patients with known hypersensitivity to any of the components of the product.

Acute Overdose

Patients receiving up to 80 mg of Glukenil developed few adverse effects other than lowering of blood glucose. Hypoglycemia did not occur when meals were given with these high doses. Severe hypoglycemic reactions with coma, seizure or other neurological impairment occur infrequently.

Storage Condition

Store below 25° C. Protect from moisture.

Innovators Monograph

You find simplified version here Glukenil

Glukenil contains Repaglinide see full prescribing information from innovator Glukenil Monograph, Glukenil MSDS, Glukenil FDA label

FAQ

What is Glukenil used for?

Glukenil is used to treat type 2 diabetes condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood.

How safe is Glukenil?

Glukenil has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.

How does Glukenil work?

Glukenil work by decreasing the amount of glucose by stimulating the pancreas to release insulin.

What are the common side effects of Glukenil?

Common side effects of Glukenil are include:

  • low blood sugar;
  • nausea, diarrhea;
  • headache, back pain;
  • joint pain; or.
  • cold symptoms such as stuffy nose, sneezing, sore throat.

When is the best time to take Glukenil?

Glukenil is usually taken 2 to 4 times daily, within 30 minutes before eating a meal. Follow your doctor's instructions. If you skip a meal, do not take your dose of Glukenil. 

Is Glukenil safe during pregnancy?

There is no evidence about its use during human pregnancy.Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Is Glukenil safe during breastfeeding?

No information is available on the use of Glukenil during breastfeeding. Glukenil is a weak acid that is over 98% protein bound, so it is unlikely to pass into breastmilk in clinically important amounts.It is unlikely to pass into breastmilk in clinically important amounts.

Can I drink alcohol with Glukenil?

Alcohol can increase the risk for severe or prolonged low blood sugar. If you do choose to drink alcohol, avoid drinking on an empty stomach.

Can I drive after taking Glukenil?

You may experience blurred vision, dizziness or drowsiness due to extremely low or high blood sugar while on this medication. So it is advised not to drive or operate any machines.

When should I take Glukenil?

The tablets are taken before meals, any time from 30 minutes before a meal to just before the meal. If you skip a meal, you need to skip the dose of Glukenil.

Can I take Glukenil after eating?

You may take it 15 minutes before a meal to 15 minutes after a meal. Many people take it with the first bite of the meal.

How long does it take for Glukenil to work?

Glukenil starts to work in 30 minutes to an hour. Its effect lasts for a few hours.

How long does Glukenil stay in my system?

Glukenil is rapidly eliminated from the blood stream with a half-life of approximately 1 hour.

How do I take Glukenil?

Glukenil comes as a tablet to take by mouth. The tablets are taken before meals.

Who should not take Glukenil?

You should not use Glukenil if you have type 1 diabetes, severe liver disease, or diabetic ketoacidosis.Also you should not use Glukenil together with gemfibrozil or NPH insulin such as isophane insulin.

Does Glukenil cause weight gain?

Glukenil causes a significant decrease in FBS, HbA1C and triglyceride levels, it is associated with weight gain, which would limit its utility.

What is the best time of day to take Glukenil?

You'll usually take Glukenil once a day. You can take it at any time, for example in the morning or in the evening. Try to take it at the same time every day.

Is Glukenil bad for kidneys?

The pharmacokinetic properties of Glukenil are ideally suited for patients with renal insufficiency.

How long is it safe to take Glukenil?

Glukenil may increase your risk for bladder cancer if you take it for more than 12 months.

What happens if I miss a dose?

Take your dose as soon as you can, but only if you are getting ready to eat a meal. If you skip a meal, skip the missed dose and wait until your next meal.

What happens if I overdose?

Seek emergency medical attention. A repaglinide overdose can cause life-threatening hypoglycemia.
Symptoms of severe hypoglycemia include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

*** Taking medicines without doctor's advice can cause long-term problems.
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