Overview
11 DESCRIPTION Repaglinide 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 solid with molecular formula C 27 H 36 N 2 O 4 and a...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 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. 12.
Indications
- 1 INDICATIONS AND 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 a 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)
Common Doses
- 0.5 mg
- 2 mg
- 4 mg
- 16 mg
Dosage
2 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.
Contraindications
- 4 CONTRAINDICATIONS Repaglinide tablets are contraindicated in patients with: Concomitant use of gemfibrozil [see Drug Interactions (7) ] Known hypersensitivity to repaglinide or any inactive ingredients Concomitant use with gemfibrozil (4) Known hypersensitivity to repaglinide or any inactive ingredients (4)
Side Effects
- 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 were: hypoglycemia, upper respiratory infection, headache, sinusitis, arthralgia, nausea, diarrhea, and back pain. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Rising Health, LLC at 1-833-395-6928 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS Clinically Important Drug Interactions with Repaglinide Table 3 includes a list of drugs with clinically important drug interactions when administered concomitantly with repaglinide and instructions for preventing or managing them. Table 3: Clinically Important Drug Interactions with Repaglinide Gemfibrozil Clinical Impact: Gemfibrozil significantly increased repaglinide exposures by 8.1 fold [see Clinical Pharmacology (12.3) ] Intervention: Do not administer repaglinide to patients receiving gemfibrozil [see Contraindications (4) ] .