Repaglinide;Uses, Dosage, Side Effects, Drug Interactions

Repaglinide
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Repaglinide is a nonsulfonylurea insulin secretagogue belonging to the melgitinide class with hypoglycemic activity. Repaglinide is rapidly absorbed and has a rapid onset and short duration of action. This agent is metabolized in the liver by CYP2C8 and CYP3A4 and its metabolites are excreted in the bile. Repaglinide has a half-life of one hour.
Repaglinide is a benzoic acid derivative that stimulates insulin secretion from the pancreas and is used in the therapy of type 2 diabetes. Repaglinide has been linked to rare instances of clinically apparent acute liver injury.

Repaglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release. Repaglinide induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal.

Mechanism of Action of Repaglinide

Repaglinide activity is dependent on the presence of functioning β cells and glucose. In contrast to sulfonylurea insulin secretagogues, 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). Repaglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.

Indications of Repaglinide

  • Type 2 Diabetes Mellitus
  • Repaglinide is an oral medication used in addition to diet and exercise for blood sugar control in type 2 diabetes mellitus
  • As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • Repaglinide is indicated in adults with type 2 diabetes mellitus whose hyperglycemia can no longer be controlled satisfactorily by diet, weight reduction and exercise. Repaglinide is also indicated in combination with metformin in adults with type 2 diabetes mellitus who are not satisfactorily controlled on metformin alone.
  • Treatment should be initiated as an adjunct to diet and exercise to lower the blood glucose in relation to meals.
  • Repaglinide is indicated in adults with type 2 diabetes mellitus whose hyperglycemia can no longer be controlled satisfactorily by diet, weight reduction and exercise. Repaglinide is also indicated in combination with metformin in adults with type 2 diabetes mellitus who are not satisfactorily controlled on metformin alone.
  • Treatment should be initiated as an adjunct to diet and exercise to lower the blood glucose in relation to meals.
  • Repaglinide is indicated in adults with type 2 diabetes mellitus whose hyperglycemia can no longer be controlled satisfactorily by diet, weight reduction and exercise.
  • Repaglinide is also indicated in combination with metformin in adults with type 2 diabetes mellitus who are not satisfactorily controlled on metformin alone.
  • Treatment should be initiated as an adjunct to diet and exercise to lower the blood glucose in relation to meals.
  • Repaglinide is indicated in patients with type 2 diabetes (Non-Insulin-Dependent Diabetes Mellitus (NIDDM)) whose hyperglycemia can no longer be controlled satisfactorily by diet, weight reduction and exercise. Repaglinide is also indicated in combination with metformin in type 2 diabetes patients who are not satisfactorily controlled on metformin alone.
  • Treatment should be initiated as an adjunct to diet and exercise to lower the blood glucose in relation to meals.
  • Repaglinide is a short-acting oral secretagogue. It is indicated for adults with type 2 diabetes mellitus whose hyperglycemia can no longer be controlled satisfactorily by diet, weight reduction and exercise. Repaglinide is also indicated in combination with metformin in adults with type 2 diabetes mellitus who are not satisfactorily controlled on metformin alone. Treatment should be initiated as an adjunct to diet and exercise to lower the blood glucose in relation to meals.

Contra-Indications of Repaglinide

  • Low blood sugar
  • Pituitary hormone deficiency
  • Decreased function of the adrenal gland
  • Inadequate vitamin B12
  • Excess body acid
  • Extreme loss of body water
  • The habit of drinking too much alcohol
  • Alcohol intoxication
  • Heart attack
  • Suddenly serious symptoms of heart failure
  • Liver problems
  • Recent operation
  • Fever
  • Shock
  • Severe vomiting
  • Severe diarrhea
  • Serious lack of oxygen in the blood
  • Weakened patient
  • Injury
  • Sepsis syndrome
  • X-Ray Study with intravenous iodine contrast agent
  • Kidney disease with a likely reduction in kidney function
  • Acute inflammation of the pancreas
  • Chronic inflammation of the pancreas

Dosage of Repaglinide

Strengths: 0.5 mg; 1 mg; 2 mg

Diabetes Type 2

Individualize therapy:

  • Dose preprandially 2, 3, or 4 times a day

For patients not previously treated with antidiabetic agents or whose glycosylated hemoglobin (HbA1c) is less than 8%

  • Initial dose: 0.5 mg orally with each meal

For patients previously treated with antidiabetic agents or whose HbA1c is 8% or higher

  • Initial dose: 1 or 2 mg orally with each meal

Dose Adjustments

  • Based upon blood glucose response, double the preprandial dose up to a maximum mealtime dose of 4 mg until a satisfactory glycemic response is achieved; allow at least 1 week to assess response after each dose adjustment.
  • Recommended Dose Range: 0.5 to 4 mg orally with each meal
  • Maximum Daily Dose: 16 mg per day

Side Effects of Repaglinide

Most common

More common

Less common

  • Abnormal stools
  • bad, unusual, or unpleasant (after) taste
  • change in taste
  • difficulty with moving
  • discoloration of the fingernails or toenails
  • flu-like symptoms
  • joint pain
  • rash
  • a runny nose
  • sneezing
  • stuffy nose
  • swollen joints

Drug Interactions of Repaglinide

Repaglinide may interact with following drugs, supplements & may decrease the efficacy of the drug

Pregnancy & Lactation of Repaglinide

FDA Pregnancy Category C

Pregnancy

This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.

Lactations

It is not known whether repaglinide passes into breast milk.  If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.

References

Repaglinide

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