Repaglinide
Tablet · Oral
Uses
Repaglinide tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitation of Use: Repaglinide tablets should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Repaglinide tablets are glinide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitation of Use: Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis ( 1 )
Dosage and administration
• The recommended starting dose is 0.5 mg orally before each meal if HbA1c is less than 8%; and 1 or 2 mg orally before each meal if HbA1c is 8% or greater. ( 2.1 )
• The recommended dose range is 0.5 mg to 4 mg before meals, with a maximum daily dose of 16 mg. ( 2.1 )
• The patient’s dose should be doubled up to 4 mg with each meal until satisfactory glycemic control is achieved. At least one week should elapse to assess response after each dose adjustment. ( 2.1 )
• Instruct patients to skip the dose of repaglinide tablets if a meal is skipped. In patients who experience hypoglycemia, the dose of repaglinide tablets should be reduced. ( 2.1 ; 5.1 )
• Instruct patients to take repaglinide tablets within 30 minutes before meals. ( 2.1 )
• In patients with severe renal impairment (CrCl = 20 – 40 mL/min), recommended starting dose is 0.5 mg orally before each meal. ( 2.2 )
• Dose modifications are required when used concominantly with some medications. ( 2.3 , 7 ) 2.1 Recommended Dosage and Administration The recommended starting dose for patients whose HbA 1c is less than 8% is 0.5 mg orally before each meal. For patients whose HbA 1c is 8% or greater the starting dose is 1 or 2 mg orally before each meal. The recommended dose range is 0.5 mg to 4 mg before meals, with a maximum daily dose of 16 mg. The patient’s dose should be doubled up to 4 mg with each meal until satisfactory glycemic control is achieved. At least one week should elapse to assess response after each dose adjustment. Instruct patients to take repaglinide tablets within 30 minutes before meals. Repaglinide tablets may be dosed 2, 3, or 4 times a day in response to changes in the patient’s meal pattern. In patients who skip meals, instruct patients to skip the scheduled dose of repaglinide tablets to reduce the risk of hypoglycemia. In patients who experience hypoglycemia, the dose of repaglinide tablets should be reduced [see Warnings and Precautions ( 5.1 )]. 2.2 Patients with Severe Renal Impairment In patients with severe renal impairment (CrCl = 20 – 40 mL/min) initiate repaglinide tablets 0.5 mg orally before each meal. Gradually titrate the dose, if needed to achieve glycemic control. 2.3 Dose Modifications for Drug Interactions Dosage adjustments are recommended in patients taking concomitant strong CYP3A4 or CYP2C8 inhibitors or strong CYP3A4 or CYP2C8 inducers [see Drug Interactions (7.1), Clinical Pharmacology ( 12.3 )]. Concomitant use with gemfibrozil is contraindicated [see Contraindications ( 4 )]. Avoid concomitant use of repaglinide tablets with clopidogrel. If concomitant use cannot be avoided, initiate repaglinide tablets at 0.5 mg before each meal and do not exceed a total daily dose of 4 mg [see Drug Interactions (7.1), Clinical Pharmacology ( 12.3 )]. Do not exceed a total daily dose of 6 mg of repaglinide tablets in patients receiving cyclosporine [see Drug Interactions (7.1), Clinical Pharmacology ( 12.3 )].
Dosage forms and strengths
• 0.5 mg tablets (white to off-white, round, biconvex, uncoated tablets debossed with ‘ML24’ on one side and plain on other side)
• 1 mg tablets (yellow, round, biconvex, uncoated tablets debossed with ‘ML25’ on one side and plain on other side)
• 2 mg tablets (peach, round, biconvex, uncoated tablets debossed with ‘ML26’ on one side and plain on other side) Tablets: 0.5 mg, 1 mg, 2 mg ( 3 )
Contraindications
Repaglinide tablets are contraindicated in patients with:
• Concomitant use of gemfibrozil [see Drug Interactions ( 7.1 )]
• Known hypersensitivity to repaglinide or any inactive ingredients
• Concomitant use with gemfibrozil ( 4 )
• Known hypersensitivity to repaglinide or any inactive ingredients ( 4 )
Warnings and precautions
• Hypoglycemia: repaglinide tablets may cause hypoglycemia. Skip the scheduled dose of repaglinide tablets if a meal is skipped to reduce the risk of hypoglycemia. Reduce the dose of repaglinide tablets if hypoglycemia occurs. ( 5.1 )
• Serious Cardiovascular Adverse Reactions with Concomitant NPH-insulin: repaglinide tablets are not indicated for use in combination with NPH-insulin. ( 5.2 )
• Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with repaglinide tablets. ( 5.3 ) 5.1 Hypoglycemia All glinides, including repaglinide tablets, can cause hypoglycemia [see Adverse Reactions ( 6.1 )]. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ( 7 )], or in patients who experience recurrent hypoglycemia. Factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content), changes in level of physical activity, changes to co-administered medication [see Drug Interactions ( 7 )], and concomitant use with other antidiabetic agents. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ( 8.6 , 8.7 )]. Patients should administer repaglinide tablets before meals and be instructed to skip the dose of repaglinide tablets if a meal is skipped. In patients who experience hypoglycemia, the dose of repaglinide tablets should be reduced [see Dosage and Administration ( 2.1 )]. Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. 5.2 Serious Cardiovascular Adverse Reactions with Concomitant Use with NPH-insulin Across seven controlled trials, there were six serious adverse events of myocardial ischemia in patients treated with repaglinide tablets plus NPH-insulin from two studies, and one event in patients using insulin formulations alone from another study [See Adverse Reactions ( 6.1 )]. Repaglinide tablets are not indicated for use in combination with NPH-insulin. 5.3 Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with repaglinide tablets.
Side effects
The following serious adverse reaction is also described elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (5% or greater incidence) among patients treated with repaglinide tablets were: hypoglycemia, upper respiratory infection, headache, sinusitis, arthralgia, nausea, diarrhea, and back pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar Rx LLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice. Repaglinide tablets have been administered to 2931 individuals during clinical trials. Approximately 1500 of these individuals with type 2 diabetes have been treated for at least 3 months, 1000 for at least 6 months, and 800 for at least 1 year. The majority of these individuals (1228) received repaglinide tablets in one of five 1-year, active-controlled trials. Over one year, 13% of repaglinide tablets patients were discontinued due to adverse reactions. The most common adverse reactions leading to withdrawal were hyperglycemia, hypoglycemia, and related symptoms. Table 1 lists the common adverse reactions for repaglinide tablets patients compared to placebo in trials 12 to 24 weeks duration. Table 1: Adverse Reactions (%) occurring ≥ 2% in Repaglinide Tablets Treated Patients from Pool of 12 to 24 Week Placebo Controlled Trials* Repaglinide Tablets N=352 Placebo N=108 Upper Respiratory Infection 16 8 Headache 11 10 Sinusitis 6 2 Arthralgia 6 3 Nausea 5 5 Diarrhea 5 2 Back Pain 5 4 Rhinitis 3 3 Constipation 3 2 Vomiting 3 3 Paresthesia 3 3 Chest pain 3 1 Bronchitis 2 1 Dyspepsia 2 2 Urinary tract infection 2 1 Tooth disorder 2 0 Allergy 2 0 *See trial descriptions in Clinical Trials ( 14 ) Hypoglycemia In clinical trials with repaglinide tablets, hypoglycemia is the most commonly observed adverse reaction. Mild or moderate hypoglycemia occurred in 31% of repaglinide tablets treated patients and 7% of placebo treated patients [see Warnings and Precautions ( 5.1 ]). Hypoglycemia was reported in 16% of 1228 repaglinide tablets patients, 20% of 417 glyburide patients, and 19% of 81 glipizide patients in 1-year controlled trials. Of repaglinide tablets-treated patients with symptomatic hypoglycemia, none developed coma or required hospitalization. In a 24-week placebo controlled trial, patients who were naïve to oral hypoglycemic agent therapy and patients with a HbA 1c below 8% at baseline had a higher frequency of hypoglycemia. Weight Gain There was no average gain in body weight when patients previously treated with oral hypoglycemic agents were switched to repaglinide tablets. The average weight gain in patients treated with repaglinide tablets and not previously treated with sulfonylurea drugs was 3.3%. Cardiovascular Events The incidence of total serious cardiovascular adverse events, including ischemia, was higher for repaglinide tablets (51/1228 or 4%) than for sulfonylurea drugs (13/498 or 3%) in controlled comparator clinical trials. Table 2: Summary of Serious Cardiovascular Events in Trials Comparing Repaglinide Tablets to Sulfonylureas (% of total patients with events) Repaglinide Tablets SU* Total Exposed 1228 498 Serious CV Events 4% 3% Cardiac Ischemic Events 2% 2% Deaths due to CV Events 0.5% 0.4% * : glyburide and glipizide Seven controlled clinical trials included repaglinide tablets combination therapy with NPH-insulin (n=431), insulin formulations alone (n=388) or other combinations (sulfonylurea plus NPH-insulin or repaglinide tablets plus metformin) (n=120). There were six serious adverse events of myocardial ischemia in patients treated with repaglinide tablets plus NPH-insulin from two studies, and one event in patients using insulin formulations alone from another study [see Warnings and Precautions ( 5.3 )]. Combination Therapy with Thiazolidinediones Hypoglycemia During 24-week treatment clinical trials of repaglinide tablets-rosiglitazone or repaglinide tablets-pioglitazone combination therapy (a total of 250 patients in combination therapy), hypoglycemia (blood glucose < 50 mg/dL) occurred in 7% of patients in combination therapy compared to 7% for repaglinide tablets monotherapy, and 2% for thiazolidinedione monotherapy. Peripheral Edema and Heart Failure Peripheral edema was reported in 12 out of 250 (4.8%) repaglinide tablets-thiazolidinedione combination therapy patients and 3 out of 124 (2.4%) thiazolidinedione monotherapy patients, with no cases reported in these trials for repaglinide tablets monotherapy. There were reports in 2 of 250 patients (0.8%) treated with repaglinide tablets-thiazolidinedione therapy of episodes of edema with congestive heart failure. Both patients had a prior history of coronary artery disease and recovered after treatment with diuretic agents. No comparable cases in the monotherapy treatment groups were reported. Weight Gain Mean weight increases associated with combination, repaglinide tablets and pioglitazone therapy were 5.5 kg, 0.3 kg, and 2.0 kg respectively. Mean weight increases associated with combination, repaglinide tablets and rosiglitazone therapy were 4.5 kg, 1.3 kg, and 3.3 kg respectively. Infrequent Adverse Events (<1% of Patients) Less common adverse clinical or laboratory events observed in clinical trials included elevated liver enzymes, thrombocytopenia, leukopenia, and anaphylactoid reactions. 6.2 Postmarketing Experience The following additional adverse reactions have been identified during post approval use of repaglinide tablets.
Drug interactions
Clinically Important Drug Interactions with Repaglinide Tablets Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with repaglinide tablets and instructions for preventing or managing them. Table 3: Clinically Important Drug Interactions with Repaglinide Tablets Gemfibrozil Clinical Impact: Gemfibrozil significantly increased repaglinide exposures by 8.1 fold [see Clinical Pharmacology ( 12.3 )] Intervention: Do not administer repaglinide tablets to patients receiving gemfibrozil [see Contraindications ( 4 )] . Clopidogrel Clinical Impact: Clopidogrel increased repaglinide exposures by 3.9-5.1 fold [see Clinical Pharmacology ( 12.3 )] Intervention : Avoid concomitant use of repaglinide tablets with clopidogrel. If concomitant use cannot be avoided, initiate repaglinide tablets at 0.5 mg before each meal and do not exceed a total daily dose of 4 mg [see DOSAGE AND ADMINISTRATION ( 2.3 )] . Increased frequency of glucose monitoring may be required during concomitant use. Cyclosporine Clinical Impact: Cyclosporine increased low dose repaglinide exposures by 2.5 fold [see Clinical Pharmacology ( 12.3 )] Intervention: Daily maximum repaglinide tablets dose should be limited to 6 mg, and increased frequency of glucose monitoring may be required when repaglinide tablets is co-administered with cyclosporine. CYP2C8 and CYP3A4 Inhibitors Intervention: Repaglinide tablets dose reductions and increased frequency of glucose monitoring may be required when co-administered. Examples: Drugs that are known to inhibit CYP3A4 include antifungal agents (ketoconazole, itraconazole) and antibacterial agents (clarithromycin, erythromycin). Drugs that are known to inhibit CYP2C8 include trimethoprim, gemfibrozil, montelukast, deferasirox, and clopidiogrel. CYP2C8 and CYP3A4 Inducers Intervention: Repaglinide tablets dose increases and increased frequency of glucose monitoring may be required when co-administered. Examples: Drugs that induce the CYP3A4 and/or 2C8 enzyme systems include rifampin, barbiturates, and carbamezapine Drugs That May Increase the Risk of Hypoglycemia Intervention: Repaglinide tablets dose reductions and increased frequency of glucose monitoring may be required when co-administered. Examples: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory agents (NSAIDs), pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics Drugs That May Decrease the Blood Glucose Lowering Effect of Repaglinide Tablets Intervention: Repaglinide tablets dose increases and increased frequency of glucose monitoring may be required when co-administered. Examples: Atypical antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Drugs That May Blunt Signs and Symptoms of Hypoglycemia Intervention: Increased frequency of glucose monitoring may be required when repaglinide tablets is co-administered with these drugs. Examples: beta-blockers, clonidine, guanethidine, and reserpine
• Clopidogrel: Avoid concomitant use; if used concomitantly initiate at 0.5 mg before each meal and limit total daily dose to 4 mg ( 7 )
• Cyclosporine: Limit daily dose of repaglinide tablets to 6 mg and increase frequency of glucose monitoring when co-administered ( 7 )
• CYP2C8 and CYP3A4 Inhibitors and Drugs That May Increase the Risk of Hypoglycemia: Co-administration may require repaglinide tablets dose reductions and increased frequency of glucose monitoring ( 7 )
• CYP2C8 and CYP3A4 Inducers and Drugs That May Decrease the Blood Glucose Lowering Effect of repaglinide tablets: Co-administration may require repaglinide tablets dose increases and increased frequency of glucose monitoring ( 7 )
• Drugs That May Blunt Signs and Symptoms of Hypoglycemia: Increased frequency of glucose monitoring may be required when co-administered ( 7 )
Use in specific populations
• Lactation: repaglinide tablets is not recommended when breastfeeding ( 8.2 ) 8.1 Pregnancy Risk Summary Limited available data from case reports and case series with repaglinide tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations ). Teratogenicity was not observed in rats and rabbits administered repaglinide during organogenesis at approximately 60 and 1 times the maximum daily clinical dose, based on body surface area. No adverse developmental effects were observed in offspring of rats administered repaglinide during late gestation and lactation at approximately 4 times the maximum daily clinical dose ( see Data ). The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c>7 and has been reported to be as high as 20-25% in women with a HbA1c>10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions,preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth and macrosomia related morbidity. Data Animal Data Repaglinide was not teratogenic in rats or rabbits at doses 60 times (rats) and approximately 1 times (rabbit) clinical exposure (on a mg/m 2 basis) when administered during the period of organogenesis. Offspring of rat dams exposed to repaglinide at ≥22 times clinical exposure on a mg/m 2 basis during days 17 to 22 of gestation and during lactation were less viable and developed skeletal deformations consisting of shortening, thickening, and bending of the humerus during the postnatal period. This effect was not seen at doses up to 4 times clinical exposure (on a mg/m 2 basis). 8.2 Lactation Risk Summary There are no data on the presence of repaglinide in human milk, the effects on the breastfeeding infant, or the effects on milk production. The drug is present in animal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk (see Data). Because of the potential for hypoglycemia in breastfed infants, repaglinide tablets is not recommended for use when breastfeeding. Data In rat reproduction studies, measurable levels of repaglinide were detected in the breast milk of the dams and lowered blood glucose levels were observed in the pups. Cross fostering studies indicated that skeletal changes [ see Use in Specific Populations ( 8.1 ) ] could be induced in control pups nursed by treated dams, although this occurred to a lesser degree than those pups treated in utero. 8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients. 8.5 Geriatric Use In clinical studies of 24 weeks or greater duration, 415 patients were over 65 years of age and no patients were greater than 75 years of age. In one-year, active-controlled trials, no differences were seen in effectiveness or adverse events between these subjects and those less than 65. There was no increase in frequency or severity of hypoglycemia in older subjects, but greater sensitivity of some older individuals to repaglinide tablets therapy cannot be ruled out. 8.6 Renal Impairment Pharmacokinetic studies of repaglinide were conducted in patients with mild to moderate renal function impairment (CrCl = 40 – 80 mL/min), and severe renal function impairment (CrCl = 20 – 40 mL/min). Initial dose adjustment is not required in patients with mild to moderate renal dysfunction. However, patients with severe renal function impairment should initiate repaglinide tablets therapy with the 0.5 mg dose and be carefully titrated [see Dosage and Administration ( 2.2 )]. Studies were not conducted in patients with creatinine clearances below 20 mL/min or patients with renal failure requiring hemodialysis. 8.7 Hepatic Impairment A single-dose study was conducted 12 patients with chronic liver disease. Patients with moderate to severe impairment of liver function had higher and more prolonged serum concentrations. Therefore, repaglinide tablets should be used cautiously in patients with impaired liver function. Longer intervals between dose adjustments may be needed to allow full assessment of response.
Pregnancy
8.1 Pregnancy Risk Summary Limited available data from case reports and case series with repaglinide tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations ). Teratogenicity was not observed in rats and rabbits administered repaglinide during organogenesis at approximately 60 and 1 times the maximum daily clinical dose, based on body surface area. No adverse developmental effects were observed in offspring of rats administered repaglinide during late gestation and lactation at approximately 4 times the maximum daily clinical dose ( see Data ). The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c>7 and has been reported to be as high as 20-25% in women with a HbA1c>10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions,preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth and macrosomia related morbidity. Data Animal Data Repaglinide was not teratogenic in rats or rabbits at doses 60 times (rats) and approximately 1 times (rabbit) clinical exposure (on a mg/m 2 basis) when administered during the period of organogenesis. Offspring of rat dams exposed to repaglinide at ≥22 times clinical exposure on a mg/m 2 basis during days 17 to 22 of gestation and during lactation were less viable and developed skeletal deformations consisting of shortening, thickening, and bending of the humerus during the postnatal period. This effect was not seen at doses up to 4 times clinical exposure (on a mg/m 2 basis).
Pediatric use
8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use In clinical studies of 24 weeks or greater duration, 415 patients were over 65 years of age and no patients were greater than 75 years of age. In one-year, active-controlled trials, no differences were seen in effectiveness or adverse events between these subjects and those less than 65. There was no increase in frequency or severity of hypoglycemia in older subjects, but greater sensitivity of some older individuals to repaglinide tablets therapy cannot be ruled out.
Overdosage
Severe hypoglycemic reactions with coma, seizure, or other neurological impairment may occur and constitute medical emergencies requiring immediate hospitalization. Hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring may continue until the physician is assured that the patient is out of danger. Patients should be closely monitored for a minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery. There is no evidence that repaglinide tablets are dialyzable using hemodialysis.
Description
Repaglinide, USP is an oral blood glucose-lowering drug of the glinide class. Repaglinide, S(+)2-ethoxy-4(2((3-methyl-1-(2-(1-piperidinyl) phenyl)-butyl) amino)-2-oxoethyl) benzoic acid, is chemically unrelated to the oral sulfonylurea insulin secretagogues. Structural Formula of Repaglinide Repaglinide, USP is a white to off-white powder with molecular formula C 27 H 36 N 2 O 4 and a molecular weight of 452.6. Repaglinide tablets, USP contain 0.5 mg, 1 mg, or 2 mg of repaglinide. In addition each tablet contains the following inactive ingredients: dibasic calcium phosphate (anhydrous), microcrystalline cellulose, corn starch, polacrilin potassium, butylated hydroxyanisole, povidone, glycerin (99.8%), magnesium stearate, meglumine, and poloxamer. The 1 mg and 2 mg tablets contain iron oxides (yellow and red, respectively) as coloring agents. str
Mechanism of action
12.1 Mechanism of Action Repaglinide lowers blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta (ß) cells in the pancreatic islets. Insulin release is glucose-dependent and diminishes at low glucose concentrations. Repaglinide closes ATP-dependent potassium channels in the ß-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the ß-cell, which leads to an opening of calcium channels. The resulting increased calcium influx induces insulin secretion. The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle.
How supplied
Repaglinide tablets, USP 0.5 mg are white to off-white, round, biconvex, uncoated tablets debossed with 'ML 24' on one side and plain on other side. Bottles of 100 NDC 72603-810-01 Repaglinide tablets, USP 1 mg are yellow, round, biconvex, uncoated tablets debossed with 'ML 25' on one side and plain on other side. Bottles of 100 NDC 72603-811-01 Repaglinide tablets, USP 2 mg are peach, round, biconvex, uncoated tablets debossed with 'ML 26' on one side and plain on other side. Bottles of 100 NDC 72603-812-01 Store at 20º to 25º C (68º to 77º F); excursions permitted to 15º to 30ºC (59º to 86º F) [See USP Controlled Room Temperature]. Protect from moisture. Keep bottles tightly close. Dispense in tight containers with safety closures.
Patient information
Hypoglycemia Inform patients that repaglinide tablets can cause hypoglycemia and instruct patients and their caregivers on self-management procedures including glucose monitoring and management of hypoglycemia. Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended [see Warnings and Precautions ( 5.1 )]. Administration Instruct patients to take repaglinide tablets within 30 minutes before meals. Instruct patients to skip their dose of repaglinide tablets when a meal is skipped. [see Dosage and Administration ( 2 )]. Drug Interactions Discuss potential drug interactions with patients and inform them of potential drug-drug interactions with repaglinide tablets. [see Drug Interactions ( 7 )]. Manufactured for: Northstar Rx LLC Memphis, TN 38141 Manufactured by: Macleods Pharmaceutical Ltd. At Oxalis Labs Baddi, Himachal Pradesh, 174101 INDIA Revised: 04/2025
Label text from the FDA structured product label by NorthStar RxLLC (revised Sep 15, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Repaglinide in 20 products
Repaglinide NDC products (20)
Frequently asked questions
What is Repaglinide used for?
Repaglinide tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitation of Use: Repaglinide tablets should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Repaglinide tablets are glinide indicated as an adjunct to diet and exercise to improve glycemic control in adults…
What are the side effects of Repaglinide?
The following serious adverse reaction is also described elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (5% or greater incidence) among patients treated with repaglinide tablets were: hypoglycemia, upper respiratory infection, headache, sinusitis, arthralgia, nausea, diarrhea, and back pain. ( 6.1 ) To report SUSPECTED ADVERSE… See the full label for the complete list.
Who makes Repaglinide?
Repaglinide is listed by 7 labelers in the FDA NDC directory, including American Health Packaging, Aurobindo Pharma Limited, Bryant Ranch Prepack, Chartwell RX, LLC.