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Nateglinide

Medically reviewed by Drugs.com. Last updated on Jun 5, 2020.

Pronunciation

(na te GLYE nide)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Starlix: 60 mg, 120 mg

Generic: 60 mg, 120 mg

Brand Names: U.S.

  • Starlix

Pharmacologic Category

  • Antidiabetic Agent, Meglitinide Analog

Pharmacology

Nonsulfonylurea hypoglycemic agent which blocks ATP-dependent potassium channels, depolarizing the membrane and facilitating calcium entry through calcium channels. Increased intracellular calcium stimulates insulin release from the pancreatic beta cells. Nateglinide-induced insulin release is glucose-dependent.

Absorption

Rapid

Distribution

10 L

Metabolism

Hepatic via hydroxylation followed by glucuronide conjugation via CYP2C9 (70%) and CYP3A4 (30%) to metabolites, including M1 (a major metabolite)

Excretion

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

Onset of Action

Insulin secretion: ~20 minutes; Peak effect: 1 hour

Time to Peak

≤1 hour

Duration of Action

4 hours

Half-Life Elimination

1.5 hours

Protein Binding

98%, primarily to albumin

Special Populations: Renal Function Impairment

Accumulation of M1, a major metabolite with modest hypoglycemic activity, was observed following repeated administration in patients with severe renal impairment (CrCl <17 mL/minute/1.73 m2). Hemodialysis sessions did significantly reduce M1 levels in these patients (Inoue 2003).

Special Populations: Hepatic Function Impairment

Cmax increased 37% and AUC increased 30% in patients with mild hepatic insufficiency.

Use: Labeled Indications

Diabetes mellitus, type 2: Treatment of adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control

Contraindications

Hypersensitivity to nateglinide or any component of the formulation

Dosing: Adult

Diabetes mellitus, type 2: Oral: Initial and maintenance dose: 120 mg 3 times daily before meals. Patients close to HbA1c goal at initiation of therapy may be started at 60 mg 3 times daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: Administer 1 to 30 minutes prior to meals. Scheduled dose should not be administered if a meal is missed to avoid hypoglycemia.

Dietary Considerations

Nateglinide should be taken 1 to 30 minutes prior to meals. Scheduled dose should not be taken if meal is missed to avoid hypoglycemia. Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Nateglinide. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Nateglinide. Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Monitor therapy

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Management: Avoid concomitant use of OATP1B1/1B3 substrates in patients receiving the Jynarque brand of tolvaptant. Concentrations and effects of the OATP1B1/1B3 substrate would be expected to increase with combined use. Consider therapy modification

Adverse Reactions

As reported with nateglinide monotherapy:

>10%: Respiratory: Upper respiratory infection (11%)

1% to 10%:

Central nervous system: Dizziness (4%)

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

Neuromuscular & skeletal: Arthropathy (3%)

Respiratory: Flu-like symptoms (4%)

Miscellaneous: Accidental injury (3%)

Postmarketing and/or case reports: Cholestatic hepatitis, hypersensitivity reaction (including pruritus, rash, urticaria), increased liver enzymes, jaundice

Warnings/Precautions

Concerns related to adverse effects:

• Hypoglycemia: May cause hypoglycemia; risk factors include inconsistent nutrition, physical activity changes, concomitant use with other antidiabetic therapy, ethanol use, renal impairment, and hepatic impairment. Appropriate patient selection, dosage, and patient education are important to avoid hypoglycemic episodes.

Disease-related concerns:

• Adrenal/pituitary impairment: Use with caution in patients with adrenal and/or pituitary impairment; may be more susceptible to glucose-lowering effects.

• Bariatric surgery:

– Altered absorption: Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery (Mechanick 2013; Mingrone 2016).

– Hypoglycemia: May increase the risk of hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2013). Insulin secretion and sensitivity may be partially or completely restored after these procedures (gastric bypass is most effective, followed by sleeve, and finally band) (Korner 2009; Peterli 2012). First-phase insulin secretion and hepatic insulin sensitivity have been shown to be significantly improved in the immediate days after gastric bypass and sleeve gastrectomy. The restorative effects of these procedures on peripheral insulin sensitivity may occur later in the 3- to 12-month period after surgery. Where possible, the selection of antidiabetic agents without the potential for hypoglycemia is advised.

• Hepatic impairment: Use with caution in patients with moderate-to-severe hepatic impairment due to risk of hypoglycemia.

• Renal impairment: Use with caution in patients with severe renal impairment; use may result in prolonged hypoglycemia due to accumulation of a metabolite with hypoglycemic activity (Inoue 2003).

• Stress-related states: It may be necessary to discontinue nateglinide and administer insulin if the patient is exposed to stress (eg, fever, trauma, infection, surgery).

Other warnings/precautions:

• Appropriate use: Not for use in patients with diabetic ketoacidosis (DKA) or patients with type 1 diabetes mellitus.

Special populations:

• Malnourished patients: Use with caution in malnourished patients; may be more susceptible to glucose-lowering effects.

Monitoring Parameters

Weight, lipid profile, fasting blood glucose (periodically and during dosage titration), and HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2020]).

Pregnancy Risk Factor

C

Pregnancy Considerations

Information describing the effects of nateglinide on pregnancy outcomes is limited (Twaites 2007).

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Agents other than nateglinide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).

Patient Education

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Common cold symptoms

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.