Nateglinide

Pronunciation

Pronunciation: na-te-GLYE-nide
Class: Meglitinide

Trade Names

Starlix
- Tablets 60 mg
- Tablets 120 mg

Pharmacology

Lowers blood glucose levels by stimulating insulin secretion from the pancreas.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Rapidly absorbed immediately prior to a meal. Oral T max is 1 h (prior to a meal); bioavailability is approximately 73%. Food delays T max and C max .

Distribution

Nateglinide protein binding is 98% (primarily albumin, and to a lesser extent to alpha-1 acid glycoprotein). Vd is 10 L (IV).

Metabolism

Hydroxylation followed by glucuronide conjugation via CYP2C9 (70%) and CYP3A4 (30%).

Elimination

Nateglinide is eliminated in urine (83% as metabolites, 16% as parent compound) and feces (10%). The half-life is 1.5 h.

Special Populations

Renal Function Impairment

Compared with healthy subjects, patients with type 2 diabetes and moderate to severe renal impairment (CrCl 15 to 50 mL/min) not on dialysis, displayed similar clearance, AUC, and C max . Patients with renal failure on dialysis exhibited reduced overall drug exposure. Hemodialysis patients experienced a reduction in plasma protein binding.

Hepatic Function Impairment

The peak and total exposure of nateglinide were increased 30% (mild hepatic insufficiency). Use with caution (chronic hepatic insufficiency).

Elderly

Pharmacokinetics not affected by age. No dosage adjustment is needed in elderly patients.

Gender

No clinically important differences in pharmacokinetics between men and women. No dosage adjustment is needed based on gender.

Race

Race has little influence of the pharmacokinetics.

Indications and Usage

As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Contraindications

Type 1 diabetes; diabetic ketoacidosis; hypersensitivity to nateglinide or its ingredients.

Dosage and Administration

Adults

PO 120 mg 3 times daily, 1 to 30 min before meals, alone or in combination with metformin or a thiazolidinedione. The 60 mg dose of nateglinide may be used, alone or in combination with metformin or a thiazolidinedione, in patients whose glycosylated hemoglobin (HbA 1c ) is near goal levels when treatment is initiated.

General Advice

  • May be used alone or in combination with metformin or a thiazolidinedione. Not to be used in combination with sulfonylureas or other secretogogues or for the treatment of type 1 diabetes.
  • If a meal is skipped, the dose should be skipped to reduce the risk of hypoglycemia.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F). Keep tightly closed.

Drug Interactions

Corticosteroids, rifamycins, sympathomimetics, thiazide diuretics, thyroid products

May reduce the hypoglycemic effects of nateglinide.

Fluconazole, MAOIs, nonselective beta-adrenergic blocking agents, NSAIDs, salicylates

May potentiate the hypoglycemic effects of nateglinide.

Laboratory Test Interactions

Uric acid levels may be increased.

Adverse Reactions

CNS

Dizziness (4%).

GI

Diarrhea (3%).

Hepatic

Cholestatic hepatitis, elevated LFTs, jaundice (postmarketing).

Hypersensitivity

Rash, itching, urticaria (postmarketing).

Metabolic-Nutritional

Hypoglycemia (2%).

Respiratory

Upper respiratory tract infection (11%); bronchitis (3%); coughing (2%).

Miscellaneous

Back pain, flu-like symptoms (4%); arthropathy, accidental trauma (3%).

Precautions

Monitor

Assess response to therapy with periodic glucose values and glycosolated hemoglobin levels.


Pregnancy

Category C . Insulin is recommended to maintain blood glucose levels during pregnancy.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Use with caution in patients with moderate to severe impairment or chronic liver disease.

Special Risk Patients

Patients with type 2 diabetes and renal failure on dialysis may exhibit reduced overall drug exposure.

Hypoglycemia

May occur and the risk may be increased by strenuous exercise, alcohol ingestion, insufficient caloric intake on an acute or chronic basis, or use in combination with other oral antidiabetic agents.

Secondary failure

Transient loss of glycemic control may occur in patients with fever, infection, trauma, or surgery. At such times, it may be necessary to discontinue nateglinide and administer insulin.

Overdosage

Symptoms

Coma, exaggerated glucose lowering with hypoglycemic symptoms, neurological symptoms, seizure.

Patient Information

  • Advise patient or caregiver to read patient information leaflet before using the first time and with each refill.
  • Instruct patient to take prescribed dose immediately before or up to 30 min before each meal.
  • Instruct patient that if meal is missed to skip the dose for that meal to reduce risk of hypoglycemia.
  • Educate patient or caregiver regarding diabetes and its management, including target ranges for blood sugar control. Instruct patient or caregiver that this medication is not a substitute for diet and exercise, and to continue to follow prescribed regimens.
  • Educate patient or caregiver regarding potential long-term complications of diabetes and need for regular general physical and eye examinations.
  • Ensure patient or caregiver understands how to use home glucose monitor and has a plan for monitoring and recording blood sugar measurements (eg, log). Advise patient to take log to each visit with health care provider.
  • Educate patient regarding value of periodic A 1c testing to confirm level of glucose control.
  • Review symptoms of hypoglycemia (eg, low blood sugar) and hyperglycemia (eg, high blood sugar), and action plans to undertake in the event either occurs.
  • Advise patient to discuss with health care provider a plan for managing each of the following situations: medication dosing during accidental ingestion of too little or too much medication; change in physical activity; inadequate food intake or a skipped meal; intercurrent conditions (eg, infection, sick days, stress, trauma, vomiting); missed dose of medication; travel across time zones.
  • Instruct patient to notify health care provider if experiencing severe, continuous, or frequent hypoglycemic episodes; hypoglycemic episodes with few or no warning symptoms; or continuous or severe hyperglycemia.
  • Advise patient to carry medical identification of diabetes (eg, bracelet, card).

Copyright © 2009 Wolters Kluwer Health.

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