Nateglinide
FDA Drug Information • Also known as: Nateglinide
- Brand Names
- Nateglinide
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION Nateglinide Tablets, USP are an oral blood glucose-lowering drug of the glinide class. Nateglinide Tablets, (-)-N- [(trans-4-isopropylcyclohexane)carbonyl]-D-phenylalanine, are structurally unrelated to the oral sulfonylurea insulin secretagogues. The structural formula is as shown: Nateglinide, USP is a white powder with a molecular weight of 317.43 g/mol. It is freely soluble in methanol, ethanol, and chloroform, soluble in ether, sparingly soluble in acetonitrile and octanol, and practically insoluble in water. Nateglinide Tablets, USP biconvex tablets contain 60 mg, or 120 mg, of nateglinide for oral administration. Inactive Ingredients: colloidal silicon dioxide, corn starch, hypromellose, mannitol, polyethylene glycol, povidone, sodium starch glycolate, sodium stearyl fumarate, talc, titanium dioxide. In addition, the 60 mg contains iron oxide red and the 120 mg contains iron oxide yellow. nateglinide-structure
What Is Nateglinide Used For?
1 INDICATIONS AND USAGE Nateglinide Tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use : Nateglinide Tablets should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Nateglinide Tablets are a glinide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use : Not for treating type 1 diabetes mellitus or diabetes ketoacidosis ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION The recommended dose of Nateglinide Tablets is 120 mg orally three times daily before meals. The recommended dose of Nateglinide Tablets is 60 mg orally three times daily before meals in patients who are near glycemic goal when treatment is initiated. Instruct patients to take Nateglinide Tablets 1 to 30 minutes before meals. In patients who skip meals, instruct patients to skip the scheduled dose of Nateglinide Tablets to reduce the risk of hypoglycemia [see Warnings and Precautions (5.1) ] . Recommended dose is 120 mg three times daily ( 2 ) In patients who are near glycemic goal when treatment is initiated, 60 mg three times daily may be administered. ( 2 ) Administer 1 to 30 minutes before meals ( 2 ) If a meal is skipped, skip the scheduled dose to reduce the risk of hypoglycemia. ( 2 , 5.1 )
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reaction is also described elsewhere in the labeling: Hypoglycemia [see Warnings and Precautions (5.1) ] Common adverse reactions associated with Nateglinide Tablets (3% or greater incidence) were upper respiratory tract infection, back pain, flu symptoms, dizziness, arthropathy, diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, approximately 2,600 patients with type 2 diabetes mellitus were treated with Nateglinide Tablets. Of these, approximately 1,335 patients were treated for 6 months or longer and approximately 190 patients for one year or longer. Table 1 shows the most common adverse reactions associated with Nateglinide Tablets. Table 1: Adverse Reactions other than Hypoglycemia (%) occurring Greater than or Equal to 2% in Nateglinide Tablets-Treated Patients from Pool of 12 to 64 week Placebo Controlled Trials Placebo Nateglinide Tablets N=458 N=1441 Preferred Term Upper Respiratory Infection 8.1 10.5 Back Pain 3.7 4.0 Flu Symptoms 2.6 3.6 Dizziness 2.2 3.6 Arthropathy 2.2 3.3 Diarrhea 3.1 3.2 Accidental Trauma 1.7 2.9 Bronchitis 2.6 2.7 Coughing 2.2 2.4 Hypoglycemia Episodes of severe hypoglycemia (plasma glucose less than 36 mg/dL) were reported in two patients treated with Nateglinide Tablets. Non-severe hypoglycemia occurred in 2.4 % of Nateglinide Tablets treated patients and 0.4 % of placebo-treated patients [see Warnings and Precautions (5.1) ]. Weight Gain Patients treated with Nateglinide Tablets had statistically significant mean increases in weight compared to placebo. In clinical trials, the mean weight increases with Nateglinide Tablets 60 mg (3 times daily) and Nateglinide Tablets 120 mg (3 times daily) compared to placebo were 1.0 kg and 1.6 kg respectively. Laboratory Test Increases in Uric Acid: There were increases in mean uric acid levels for patients treated with Nateglinide Tablets alone, Nateglinide Tablets in combination with metformin, metformin alone, and glyburide alone. The respective differences from placebo were 0.29 mg/dL, 0.45 mg/dL, 0.28 mg/dL, and 0.19 mg/dL. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Nateglinide Tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity Reactions: Rash, itching, and urticaria Hepatobiliary Disorders: Jaundice, cholestatic hepatitis, and elevated liver enzymes
Drug Interactions
7 DRUG INTERACTIONS Table 2 includes a list of drugs with clinically important drug interactions when concomitantly administered or withdrawn with Nateglinide Tablets and instructions for managing or preventing them. Table 2: Clinically Significant Drug Interactions with Nateglinide Tablets Drugs That May Increase the Blood-Glucose-Lowering Effect of Nateglinide Tablets and Susceptibility to Hypoglycemia Drugs: Nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, monoamine oxidase inhibitors, non-selective beta-adrenergic- blocking agents, anabolic hormones (e.g. methandrostenolone), guanethidine, gymnema sylvestre, glucomannan, thioctic acid, and inhibitors of CYP2C9 (e.g. amiodarone, fluconazole, voriconazole, sulfinpyrazone) or in patients known to be poor metabolizers of CYP2C9 substrates, alcohol. Intervention: Dose reductions and increased frequency of glucose monitoring may be required when Nateglinide Tablets are coadministered with these drugs. Drugs and Herbals That May Reduce the Blood-Glucose-Lowering Effect of Nateglinide Tablets and Increase Susceptibility to Hyperglycemia Drugs: Thiazides, corticosteroids, thyroid products, sympathomimetics, somatropin, somatostatin analogues (e.g., lanreotide, octreotide), and CYP inducers (e.g., rifampin, phenytoin and St John’s Wort). Intervention: Dose increases and increased frequency of glucose monitoring may be required when Nateglinide Tablets are coadministered with these drugs. Drugs That May Blunt Signs and Symptoms of Hypoglycemia Drugs: beta-blockers, clonidine, guanethidine, and reserpine Intervention: Increased frequency of glucose monitoring may be required when Nateglinide Tablets are coadministered with these drugs. Drugs That May Increase the Potential for Hypoglycemia : Nateglinide Tablets dose reductions and increased frequency of glucose monitoring may be required when co-administered ( 7 ) Drugs That May Increase the Potential for Hyperglycemia : Nateglinide Tablets dose increases and increased frequency of glucose monitoring may be required when co-administered ( 7 ) Drugs That May Blunt Signs and Symptoms of Hypoglycemia : Increased frequency of glucose monitoring may be required when co-administered ( 7 )
Contraindications
4 CONTRAINDICATIONS Nateglinide Tablets are contraindicated in patients with a history of hypersensitivity to Nateglinide Tablets or its inactive ingredients. History of hypersensitivity to nateglinide or its inactive ingredients ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary The available data from published literature and the applicant’s pharmacovigilance with use of Nateglinide Tablets in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations ). Nateglinide Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In animal reproduction studies, there was no teratogenicity in rats and rabbits administered oral nateglinide during organogenesis at approximately 27 and 8 times the maximum recommended human dose (MRHD), respectively, based on body surface area (BSA). The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a HbA1c > 7 and has been reported to be as high as 20% to 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% to 4% and 15% to 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 In embryofetal development studies, nateglinide administered orally during the period of organogenesis was not teratogenic in rats at doses up to 1,000 mg/kg (corresponding to 27 times the MRHD of 120 mg three times per day, based on BSA). In rabbits, embryonic development was adversely affected at 500 mg/kg/day and the incidence of...
Overdosage
10 OVERDOSAGE There have been no instances of overdose with Nateglinide Tablets in clinical trials. However, an overdose may result in an exaggerated glucose-lowering effect with the development of hypoglycemic symptoms. Hypoglycemic symptoms without loss of consciousness or neurological findings should be treated with oral glucose and adjustments in dosage and/or meal patterns. Severe hypoglycemic reactions with coma, seizure, or other neurological symptoms should be treated with intravenous glucose. As Nateglinide Tablets are highly protein bound, dialysis is not an efficient means of removing it from the blood.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied 60 mg Pink, round shaped, biconvex, film-coated tablets, debossed with “N7” on one side and plain on other side. Bottles of 90 ......................... NDC 16571-758-09 Bottles of 100 ....................... NDC 16571-758-01 Bottles of 500 ....................... NDC 16571-758-50 120 mg Yellow, oval shaped, biconvex, film-coated tablets, debossed with “N5” on one side and plain on other side. Bottles of 90 ......................... NDC 16571-759-09 Bottles of 100 ....................... NDC 16571-759-01 Bottles of 500 ....................... NDC 16571-759-50 Storage and Handling Store at 25ºC (77ºF); excursions permitted to 15ºC-30ºC (59ºF-86ºF). [See USP Controlled Room Temperature.] Dispense in a tight container, USP.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.