Nateglinide

Pronunciation

(na te GLYE nide)

U.S. Brand Names

Starlix®

Generic Available

Canadian Brand Names

Starlix®

Use

Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) as monotherapy when hyperglycemia cannot be managed by diet and exercise alone; in combination with metformin or a thiazolidinedione to lower blood glucose in patients whose hyperglycemia cannot be controlled by exercise, diet, or a single agent alone

Pregnancy Risk Factor

Pregnancy Implications

Safety and efficacy in pregnant women have not been established. Do not use during pregnancy. Abnormal blood glucose levels are associated with a higher incidence of congenital abnormalities. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.

Lactation

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to nateglinide or any component of the formulation; diabetic ketoacidosis, with or without coma (treat with insulin); type 1 diabetes mellitus (insulin dependent, IDDM)

Warnings/Precautions

Use with caution in patients with moderate-to-severe hepatic impairment. Use caution in severe renal dysfunction, elderly, malnourished, or patients with adrenal/pituitary dysfunction; may be more susceptible to glucose-lowering effects. All oral hypoglycemic agents are capable of producing hypoglycemia. Proper patient selection, dosage, and instructions to the patients are important to avoid hypoglycemic episodes. It may be necessary to discontinue nateglinide and administer insulin if the patient is exposed to stress (ie, fever, trauma, infection, surgery). Indicated for adjunctive therapy with metformin; not to be used as a substitute for metformin monotherapy. Combination treatment with sulfonylureas is not recommended (no additional benefit). Patients not adequately controlled on oral agents which stimulate insulin release (eg, glyburide) should not be switched to nateglinide or have nateglinide added to therapy. Safety and efficacy in pediatric patients have not been established.

Adverse Reactions

As reported with nateglinide monotherapy:

1% to 10%:

Central nervous system: Dizziness (4%)

Endocrine & metabolic: Hypoglycemia (2%), increased uric acid

Gastrointestinal: Weight gain

Neuromuscular & skeletal: Arthropathy (3%)

Respiratory: Upper respiratory infection (10%)

Miscellaneous: Flu-like symptoms (4%)

Postmarketing and/or case reports: Rash, pruritus, urticaria

Overdosage/Toxicology

In case of overdose, hypoglycemic symptoms would be expected. Severe hypoglycemic reactions should be treated with intravenous glucose. Dialysis is not effective.

Drug Interactions

Substrate (major) of CYP2C8/9, 3A4; Inhibits CYP2C8/9 (weak)

Beta-blockers, nonselective: May potentiate hypoglycemic effect when given with nateglinide; monitor

Corticosteroids: May see poor glycemic control when given with nateglinide; monitor

CYP2C8/9 inducers: May decrease the levels/effects of nateglinide. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.

CYP2C8/9 inhibitors: May increase the levels/effects of nateglinide. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of nateglinide. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of nateglinide. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Glyburide: No additional glycemic control with concurrent use; should not be used in combination

MAO inhibitors: May potentiate hypoglycemic effect when given with nateglinide; monitor

Metformin: Greater reductions of fasting plasma glucose and Hb A1c with concurrent use

NSAIDs: May potentiate hypoglycemic effect when given with nateglinide; monitor

Salicylates: May potentiate hypoglycemic effect when given with nateglinide; monitor

Sympathomimetics: May see reduced hypoglycemic effect when given with nateglinide; monitor

Thiazide diuretics: May see reduced effectiveness of nateglinide; monitor

Thyroid replacement products: May see poor glycemic control when given with nateglinide; monitor

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (increased risk of hypoglycemia).

Food: Rate of absorption is decreased and time to Tmax is delayed when taken with food. Food does not affect AUC. Multiple peak plasma concentrations may be observed if fasting. Not affected by composition of meal.

Stability

Store at 25°C (77°F)

Mechanism of Action

A phenylalanine derivative, nonsulfonylurea hypoglycemic agent used in the management of type 2 diabetes mellitus (noninsulin dependent, NIDDM); stimulates insulin release from the pancreatic beta cells to reduce postprandial hyperglycemia; amount of insulin release is dependent upon existing glucose levels

Pharmacodynamics/Kinetics

Onset of action: Insulin secretion: ~20 minutes

Peak effect: 1 hour

Duration: 4 hours

Absorption: Rapid

Distribution: 10 L

Protein binding: 98%, primarily to albumin

Metabolism: Hepatic via hydroxylation followed by glucuronide conjugation via CYP2C9 (70%) and CYP3A4 (30%) to metabolites

Bioavailability: 73%

Half-life elimination: 1.5 hours

Time to peak: 1 hour

Excretion: Urine (83%, 16% as unchanged drug); feces (10%)

Dosage

Children: Safety and efficacy have not been established

Adults: Management of type 2 diabetes mellitus: Oral: Initial and maintenance dose: 120 mg 3 times/day, 1-30 minutes before meals; may be given alone or in combination with metformin or a thiazolidinedione; patients close to Hb A1c goal may be started at 60 mg 3 times/day

Elderly: No changes in safety and efficacy were seen in patients 65 years; however, some elderly patients may show increased sensitivity to dosing

Dosage adjustment in renal impairment: No specific dosage adjustment is recommended for patients with mild-to-severe renal disease; patients on dialysis showed reduced medication exposure and plasma protein binding. Patients with severe renal dysfunction are more susceptible to glucose-lowering effect; use with caution.

Dosage adjustment in hepatic impairment: Increased serum levels seen with mild hepatic insufficiency; no dosage adjustment is needed. Has not been studied in patients with moderate to severe liver disease; use with caution.

Administration

Patients who are anorexic or NPO will need to have their dose held to avoid hypoglycemia.

Monitoring Parameters

Glucose and Hb A1c levels, weight, lipid profile

Reference Range

Target range: Adults:

Fasting blood glucose: <110 mg/dL

Glycosylated hemoglobin: <6%

Dietary Considerations

Nateglinide should be taken 1-30 minutes prior to meals. Scheduled dose should not be taken if meal is missed. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take this medication exactly as directed, 1-30 minutes before a meal. If you skip a meal (or add an extra meal) skip (or add) a dose for that meal. Do not change dosage or discontinue without first consulting prescriber. Follow dietary and lifestyle recommendations of provider. You will be instructed in signs of hypo- or hyperglycemia by healthcare provide or diabetic educator; be alert for adverse hypoglycemia (tachycardia, profuse perspiration, tingling of lips and tongue, seizures, or change in sensorium) and follow prescriber's instructions for intervention. Note that unusual strenuous exercise, excessive alcohol intake, or acute reduction in caloric intake may increase risk of hypoglycemia. Persistent nausea or vomiting, or severely decreased dietary intake may increase risk of hyperglycemia. May cause mild side effects during first weeks of therapy (dizziness, weight gain, mild muscle aches or pain, or flu-like symptoms); if these do not diminish, notify prescriber. Report signs of respiratory infection or other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.

Additional Information

An increase in weight was seen in nateglinide monotherapy, which was not seen when used in combination with metformin.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness

Mental Health: Effects on Psychiatric Treatment

May cause weight gain; psychotropics may produce additive effects. Beta-blockers and MAOIs may potentiate the hypoglycemic effects of nateglinide. May cause flu-like symptoms; take this into consideration if also concerned about SSRI discontinuation syndrome.

Dosage Forms

Tablet: 60 mg, 120 mg

References

"American Diabetes Association: Clinical Practice Recommendations 2000," Diabetes Care , 2000, 23(Suppl 1):1-116.

International Brand Names

Fastic® (JP); Glinate® (IN); Starlix® (BR, CA, CH, CO, CR, DE, DK, DO, EC, ES, FI, GB, GT, HN, HU, ID, IE, NO, PA, PL, SE, SG, SI, SV, TR, YU); Starsis® (JP)

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

Home > Medical Reference > Complementary Medicine