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- What is repaglinide, and how does it work (mechanism of action)?
- What brand names are available for repaglinide?
- Is repaglinide available as a generic drug?
- Do I need a prescription for repaglinide?
- What are the side effects of repaglinide?
- What is the dosage for repaglinide?
- Which drugs or supplements interact with repaglinide?
- Is repaglinide safe to take if I'm pregnant or breastfeeding?
- What else should I know about repaglinide?
What is repaglinide, and how does it work (mechanism of action)?
Repaglinide is an oral medication for lowering blood sugar (glucose) in individuals with type 2 diabetes. It is in a class of drugs for treating diabetes type 2 called meglitinides that are chemically unlike other anti-diabetic medications. Nateglinide (Starlix), is another currently available meglitinide. Approximately 90% of patients with diabetes have type 2 or non-insulin dependent diabetes mellitus. Type 2 diabetes usually occurs in adulthood, and is associated with obesity, and a strong family history of diabetes. Glucose intolerance that causes diabetes type 2 is caused by reduced insulin secretion from the pancreas after meals and resistance of the body's cells to insulin's effect which is to stimulate the cells to remove glucose from the blood. This leads to high levels of glucose in the blood.
Like sulfonylureas, for example, glyburide (Diabeta, Glynase), glipizide (Glucotrol, Glucotrol XL), glimepiride (Amaryl), tolbutamide and tolazamide, repaglinide stimulates cells in the pancreas to produce insulin. Glyburide may be more potent than repaglinide at increasing insulin release in persons with low or high blood glucose levels, whereas repaglinide may be more potent in persons with more moderate abnormalities of blood glucose levels. Repaglinide is different because it has a rapid onset of action and a short duration of action. When taken just prior to meals, it promotes the release of insulin that normally occurs with meals and is responsible for preventing blood glucose levels from becoming high. It has been shown to lower hemoglobin A1c (HbA1c) levels by 1.6% to 1.9%. (Hemoglobin A1c is a blood test which measures the effectiveness of a drug in controlling high blood glucose levels over prolonged periods of time; the lower the hemoglobin A1c, the better the control.) Repaglinide was approved by the FDA in 1997.
What are the side effects of repaglinide?
Hypoglycemia (low blood glucose) is the most frequent side effect and it occurs somewhat less frequently with repaglinide than with sulfonylureas such as glyburide and glipizide. Some symptoms of hypoglycemia include:
- heart palpitations,
- numbness around the mouth,
- tingling in the fingers,
- muscle weakness,
- blurred vision,
- cold temperature,
- excessive yawning,
- confusion, or
- loss of consciousness.
Other common side effects include:
- stomach pain,
- back pain,
- upper respiratory infections, and
- chest pain.
Side effects that have been reported post-marketing inlcude:
What is the dosage for repaglinide?
Repaglinide is taken 15 to 30 minutes before a meal. It should be taken with meals and may be administered 2, 3, or 4 times a day.
- For patients with HbA1c < 8% who are receiving treatment for the first time the starting dose is 0.5 mg with each meal.
- Patients who have been treated with other diabetes drugs and whose HbA1c is ≥ 8% should start with 1 or 2 mg with each meal.
- The initial dose may be doubled at weekly intervals until the desired response is achieved or the maximum dose of 4 mg with each meal (16 mg daily) is achieved.
Which drugs or supplements interact with repaglinide?
- Repaglinide is metabolized (eliminated) in the liver by an enzyme called CYP3A4. Drugs that affect this enzyme may affect the blood levels of repaglinide and thus alter its glucose lowering effect. The metabolism of repaglinide may be prevented by ketoconazole (Nizoral), itraconazole (Sporanox), fluconazole (Diflucan), erythromycin (Ery-Tab), and clarithromycin (Biaxin). As a result, blood levels of repaglinide rise and there is an enhanced glucose-lowering effect. Dangerous hypoglycemic (very low blood glucose) reactions could occur. On the other hand, the elimination of repaglinide may be increased with drugs that increase levels of CYP3A4 in the liver, such as barbiturates, carbamazepine (Tegretol), and rifampin (Rifadin). This can result in lower blood levels of repaglinide and hyperglycemia (high blood glucose).
- Some drugs increase blood sugar and therefore reverse the effects of repaglinide. Such drugs include thiazide diuretics (for example, hydrochlorothiazide [Microzide]), loop diuretics (for example, furosemide [Lasix)], amphetamines, glucocorticoids such as prednisone and methylprednisolone (Medrol), estrogens, isoniazid, phenothiazines such as chlorpromazine (Thorazine), phenytoin (Dilantin), somatropin (Genotropin), decongestants and thyroid drugs.
- Anabolic steroids or androgens can increase the risk of developing hypoglycemia in diabetic patients taking glucose-lowering medications.
- MAO inhibitors (for example, isocarboxazid [Marplan] and phenelzine [Nardil], salicylates, and selective serotonin reuptake inhibitors (for example paroxetine (Paxil), fluoxetine (Prozac) and sertraline (Zoloft) also can increase the effects of repaglinide and worsen the chance of developing hypoglycemia.
- Beta blockers, for example, propranolol (Inderal), atenolol (Tenormin), can cause hypoglycemia or hyperglycemia. Also, beta-blockers can blunt some of the body's responses to hypoglycemia such as rapid heart ratea, thus making it difficult for patients to recognize (and treat) hypoglycemic reactions. Nevertheless, beta-blockers have been used successfully in diabetic patients. Treatment with beta-blockers is associated with improved survival in diabetics who are treated with the beta-blocker for high blood pressure.
- Gemfibrozil (Lopid) should not be combined with repaglinide because gemfibrozil may increase blood levels of repaglinide and lead to hypoglycemia.
- Atazanavir (Reyataz) and Trimethoprim (Primsol) can increase the blood levels of repaglinide as well leading to increased risks of hypoglycemia.
Is repaglinide safe to take if I'm pregnant or breastfeeding?
No adequate human studies on the effects of repaglinide on the fetus have been done. Adverse effects have been reported in some animal studies. Animals given repaglinide during both lactation (nursing) and gestation (pregnancy) have developed skeletal defects. Therefore, physicians must weigh the potential benefits and risks of this medication when considering its use in pregnant women.
It is not known whether repaglinide accumulates in breast milk. However, animals given repaglinide during pregnancy and lactation have developed skeletal defects. Because of the possibility of hypoglycemia in nursing infants and the skeletal effects in nursing animals, it is recommended that repaglinide not be used in women who are breastfeeding.
Repaglinide (Prandin) is a drug prescribed to lower blood sugar levels (glucose) in persons with diabetes. Side effects, drug interactions, warnings and precautions, and patient information should be reviewed prior to taking any medication.
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