Repaglinide 1 mg Tablet, 100-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Glinide class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Repaglinide 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). Repaglinide helps your body regulate the amount of glucose (sugar) in your blood. It decreases the amount of glucose by stimulating the pancreas to release insulin. Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, q...
Read the full MedlinePlus article ↗- Repaglinide helps your pancreas release insulin when you eat a meal, which brings your blood sugar down. If you have type 2 diabetes, your body either doesn't make enough insulin o...
- What exactly does repaglinide do, and why do I need it?
- Repaglinide works by triggering insulin release, and you want that insulin to be available when food hits your bloodstream. Take it within 30 minutes before each meal. If you forge...
- Why do I have to take it right before eating? What happens if I forget?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Repaglinide — tap one for details:
Repaglinide may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII REK4960K2U
Butylated hydroxyanisole is a synthetic preservative that prevents oils and fats in medicines from spoiling or becoming rancid. It keeps the medicine stable and extends its shelf life.
-
UNII L11K75P92J
A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
-
UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
-
UNII PDC6A3C0OX
Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII 6HG8UB2MUY
Meglumine is a sugar-alcohol compound used as a solubilizer and pH buffer in medicines. It helps dissolve drugs that don't mix well in water and maintains stable acidity levels in the formulation.
-
UNII 0BZ5A00FQU
Polacrilin potassium is a synthetic polymer that absorbs water and swells. It acts as a disintegrant, helping tablets or capsules break apart quickly so the active ingredient can be absorbed in your body.
-
UNII LQA7B6G8JG
A synthetic polymer made by combining water-soluble compounds. It acts as a surfactant and solubilizer to help mix oil and water-based ingredients, improving the medicine's texture and how active ingredients dissolve.
-
UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
-
UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
11 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.094 | $9.37 / 100 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.1849 | $18.49 / 100 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.1282 | $12.82 / 100 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Repaglinide 1 mgthis 33342-0249-11 | Macleods | 100 tablets | $0.094 | AB | Availability likely | — |
| Repaglinide 1 mg 57237-0158-01 | Rising | 100 tablets | $0.094 | AB | Availability likely | — |
| Repaglinide 1 mg 60687-0560-21 | American | 30 tablets | $0.094 | AB | Availability likely | — |
| Repaglinide 1 mg 62135-0947-90 | Chartwell | 90 tablets | $0.094 | AB | Availability likely | — |
| Repaglinide 1 mg 65862-0671-01 | Aurobindo | 100 tablets | $0.094 | — | Availability likely | — |
| Repaglinide 1 mg 72603-0811-01 | NorthStar | 100 tablets | $0.094 | AB | Availability likely | — |
| Repaglinide 1 mg 72162-2558-01 | Bryant | 100 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 33342-0249-11 You're viewing this | 100 TABLET in 1 BOTTLE (33342-249-11) | $0.0937 / ea | $9.37 | 2023-03-22 | Active |
| 33342-0249-44 | 1000 TABLET in 1 BOTTLE (33342-249-44) | — | — | 2023-03-22 | Active |
You're viewing the smallest of 2 pack sizes for this product.
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 33342-0249-11?
What is the difference between NDC 33342-0249-11 and NDC 33342-0249-44?
What NDC number is used to bill for this package of Repaglinide 1 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS & USAGE 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 ▾
2 DOSAGE & 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 )
2.1Recommended 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 )].
2.2Patients 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.
2.3Dose 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 ▾
3 DOSAGE FORMS & 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 ▾
4 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 Cautions ▾
5 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 )
5.1Hypoglycemia 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.
5.2Serious 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.
5.3Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with repaglinide tablets.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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-in…
🔄 Drug Interactions ▾
7 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 De…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactation: repaglinide tablets is not recommended when breastfeeding ( 8.2 )
8.1Pregnancy 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).
8.2Lactation 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.
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.
8.5Geriatric 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.
8.6Renal 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 p…
🤰 Pregnancy ▾
8.1Pregnancy 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 ▾
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric 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 ▾
10 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics A four-week, double-blind, placebo-controlled dose-response trial was conducted in 138 patients with type 2 diabetes using doses ranging from 0.25 (not an approved dose) to 4 mg taken with each of three meals. Repaglinide tablets therapy resulted in dose-proportional glucose lowering over the full dose range. Plasma insulin levels increased after meals and reverted toward baseline before the next meal.
Most of the fasting blood glucose-lowering effect was demonstrated within 1-2 weeks. In a double-blind, placebo-controlled, 3-month dose titration study, repaglinide or placebo doses for each patient were increased weekly from 0.25 mg (not an approved dose) through 0.5, 1, and 2 mg, to a maximum of 4 mg, until a fasting plasma glucose (FPG) level <160 mg/dL was achieved or the maximum dose reached. The dose that achieved the targeted control or the maximum dose was continued to end of study.
FPG and 2-hour post-prandial glucose (PPG) increased in patients receiving placebo and decreased in patients treated with repaglinide. Differences between the repaglinide-and placebo-treated groups were -61 mg/dL (FPG) and -104 mg/dL (PPG) (Table 4). Table 4: Repaglinide Tablets vs Placebo Mean Change from Baseline after 3 Months of Treatment Repaglinide Placebo N 66 33 Fasting Plasma Glucose (mg/dL) Baseline 220.2 215.3 Change from baseline (at last visit) -31.0*
30.3Post Prandial Glucose (mg/dL) Baseline 261.7 245.2 Change from baseline (at last visit) -47.6* 56.5 * : p< 0.05 for between group difference The dosing of repaglinide relative to meal-related insulin release was studied in three trials including 58 patients. Glycemic control was maintained during a period in which the meal and dosing pattern was varied (2, 3 or 4 meals per day; before meals x 2, 3, or 4) compared with a period of 3 regular meals and 3 doses per day (before meals x 3). Blood glucose-lowering effect did not differ when repaglinide was administered at the start of a meal, 15 minutes before, or 30 minutes before the meal.
12.3Pharmacokinetics The pharmacokinetic parameters of repaglinide obtained from a single-dose, crossover study in healthy subjects and from a multiple-dose, parallel, dose-proportionality (0.5, 1, 2 and 4 mg) study in patients with type 2 diabetes are summarized in Tables 5 and 6. These data indicate that repaglinide did not accumulate in serum. Clearance of oral repaglinide did not change over the 0.5 -4 mg dose range, indicating a linear relationship between dose and plasma drug levels.
Table 5: Pharmacokinetic Parameters for Repaglinide in Healthy Subjects Parameter CL (based on i.v.) 38 ± 16 L/hr Vss (based on i.v.) 31 ± 12 L AbsBio 56 ± 9% CL = total body clearance Vss = volume of distribution at steady state AbsBio = absolute bioavailability Table 6: Pharmacokinetic Parameters for Repaglinide in Patients with Type 2 Diabetes* Pharmacokinetic Parameter Dose (mg) AUC 0-24 hr (ng/mL*hr) Mean (SD) C max0-5 hr (ng/mL) Mean (SD) 0.5 68.9 (154.4) 9.8 (10.2) 1 125.8 (129.8) 18.3 (9.1) 2 152.4 (89.60) 26.0 (13.0) 4 447.4 (211.3) 65.8 (30.1) T max0-5 hr Means (SD) T ½ Means (Ind Range) 0.5 - 4 1.0 – 1.4 (0.3 – 0.5) hr 1.0 – 1.4 (0.4 – 8.0) hr *dosed preprandially with three meals Absorption After oral administration, repaglinide is completely a…
🧬 Mechanism of Action ▾
12.1Mechanism 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 / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 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 33342-248-11 Bottles of 1000 NDC 33342-248-44 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 33342-249-11 Bottles of 1000 NDC 33342-249-44 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 33342-250-11 Bottles of 1000 NDC 33342-250-44 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.
📋 Description ▾
11 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
💬 Information for Patients ▾
17 PATIENT COUNSELING 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: Macleods Pharma USA, INC,. Princeton, NJ 08540 Manufactured by: Macleods Pharmaceutical Ltd. At Oxalis Labs Baddi, Himachal Pradesh, INDIA Revised: 04/2023