Nateglinide

Dosage Forms & Strengths

tablet

• 60mg
• 120mg

Type 2 DM Monotherapy, or With Metformin

120 mg PO q8hr; 60 mg PO q8hr if patient near goal HbA1C

Take dose 1-30 minutes before meal

Safety & efficacy not established

Nateglinide is an oral drug used to lower blood sugar (glucose) levels in type 2 diabetes. It is in a class of drugs called meglitinides which also includes repaglinide (Prandin). Approximately 90% of patients with diabetes have type 2 diabetes. Type 2 diabetes usually occurs in adults and is associated with obesity and a strong family history of diabetes. Insulin is an important hormone that controls the blood level of glucose. Type 2 diabetics have an inability to control blood glucose levels. This is caused by reduced secretion of insulin from the pancreas after meals and resistance of the body's cells to the effect of insulin which is to stimulate the cells to remove glucose from the blood. This leads to high levels of blood glucose. Nateglinide stimulates cells in the pancreas to produce insulin in a manner similar to the class of drugs called sulfonylureas, for example, glyburide (Diabeta, Glynase and Micronase), which also are used in type 2 diabetes. However, nateglinide appears to have a faster onset and a shorter duration of action than sulfonylureas. The benefit of this faster, shorter effect may be to prevent the rapid, transient rise in blood glucose that occurs in diabetics immediately following a meal. Nateglinide was approved by the FDA in December 2000.

Nateglinide comes as a tablet and is typically taken by mouth three times a day.

Your dosage will be based on your medical condition, the number of meals you consume in a day, and your response to treatment.

Take the medicine before meals. If you skip a meal, skip the dose of nateglinide. If you add a meal, take an extra dose.

Your doctor may start you on a lower dose of nateglinide and gradually increase it.

If you consume liquid meals, you may need a higher dose of nateglinide. Talk to your doctor about this.

Follow the instructions on your prescription label carefully. Don't take more or less of the drug than is prescribed.

Nateglinide Overdose

If you suspect an overdose, you should contact a poison-control center or emergency room immediately.

You reach a poison-control center at (800) 222-1222.

Missed Dose of Nateglinide

If you miss a dose of nateglinide, take it as soon as you remember, but only if you're getting ready to eat a meal.

Skip the missed dose if it's almost time for your next scheduled dose.

Don't take extra medicine to make up for a missed dose.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if nateglinide crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using nateglinide.

Take the missed dose as soon as you remember, but only if you are getting ready to eat a meal. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. You may have signs of low blood sugar, such as extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

Avoid drinking alcohol. It lowers blood sugar and may interfere with your diabetes treatment.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Starlix

Available Dosage Forms:

• Tablet

Therapeutic Class: Hypoglycemic

Chemical Class: Meglitinide

Follow carefully the special meal plan that your doctor gave you. This is the most important part of controlling your condition and is necessary if the medicine is to work properly. Also, exercise regularly and test for sugar in your blood or urine as directed.

nateglinide is usually taken between 1 and 30 minutes before a meal. If you skip the meal, also skip the scheduled dose of nateglinide.

Use nateglinide as directed even if you feel well and do not notice any signs of high blood sugar. Remember that nateglinide will not cure your diabetes, but it does help to control it. You must to continue to take it as directed if you expect to lower your blood sugar and keep it low. You may have to take an antidiabetic medicine for the rest of your life. If high blood sugar is not treated, it can cause serious problems, such as blood vessel disease, eye disease, heart failure, or kidney disease.

Dosing

The dose of nateglinide will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of nateglinide. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For type 2 diabetes:
    • Adults—60 to 120 mg three times a day taken between one and thirty minutes before meals.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of nateglinide, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Take it before your next main meal.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Use nateglinide as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take 1 to 30 minutes before meals.
• If a meal is skipped, skip the dose. If a meal is added, add a dose for that meal.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

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:

• Signs of a common cold.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Table 2 includes a list of drugs with clinically important drug interactions when concomitantly administered or withdrawn with Nateglinide and instructions for managing or preventing them.

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of Nateglinide in pregnant women. It is unknown whether Nateglinide can cause fetal harm when administered to a pregnant woman. Nateglinide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In the rabbit, embryonic development was adversely affected and the incidence of gall bladder agenesis or small gallbladder was increased at a dose of 500 mg/kg (approximately 27 times the human therapeutic exposure of 120 mg three times daily, based on body surface area). Nateglinide was not teratogenic in rats at doses up to 1,000 mg/kg (approximately 27 times the human therapeutic exposure based on body surface area).

Nursing Mothers

It is not known whether Nateglinide is excreted in human milk. Nateglinide is excreted in rat milk. Offspring of rats exposed to 1,000 mg/kg Nateglinide (approximately 27 times the human therapeutic exposure of 120 mg three times daily, based on body surface area) had lower body weight. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made as to whether Nateglinide should be discontinued in nursing mothers, or if mothers should discontinue nursing.

Pediatric Use

The safety and effectiveness of Nateglinide have not been established in pediatric patients.

Geriatric Use

436 patients 65 years and older, and 80 patients 75 years and older were exposed to Nateglinide in clinical studies. No differences were observed in safety or efficacy of Nateglinide between patients age 65 and over, and those under age 65. However, greater sensitivity of some older individuals to Nateglinide therapy cannot be ruled out.

Renal Impairment

No dosage adjustment is recommended in patients with mild to severe renal impairment [see Clinical Pharmacology (12.3)].

Hepatic Impairment

No dose adjustment is recommended for patients with mild hepatic impairment. Use of Nateglinide in patients with moderate-to-severe hepatic impairment has not been studied and therefore, should be used with caution in these patients [see Clinical Pharmacology (12.3)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity:

Nateglinide did not increase tumors in two year carcinogenicity studies conducted in mice and rats. Oral doses of Nateglinide up to 900 mg/kg in rats and 400 mg/kg in mice were tested, which produced exposures in rats approximately 30 times to 40 times and in mice 10 times to 30 times the human therapeutic exposure of Nateglinide at a dose of 120 mg three times daily, based on AUC.

Mutagenesis:

Nateglinide was not genotoxic in the in vitro Ames test, mouse lymphoma assay, chromosome aberration assay or in the in vivo mouse micronucleus test.

Impairment of Fertility:  

Fertility was unaffected by administration of Nateglinide to rats at doses up to 600 mg/kg (approximately 16 times the human therapeutic exposure with a recommended Nateglinide dose of 120 mg three times daily before meals).

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

Limitations of use: Should not be used in patients with type 1 diabetes mellitus or diabetic ketoacidosis.

Mild impairment (Child-Pugh class A): No dosage adjustment necessary although pharmacokinetics are altered (peak and total exposure increases).

Moderate to severe impairment (Child-Pugh class B or C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, use with caution due to potential for hypoglycemia.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience common cold symptoms. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Mild hepatic impairment: No adjustment recommended
Moderate to severe hepatic impairment: Use caution

Administration advice:
-Take orally 1 to 30 minutes before a meal.
-Patients who skip a meal should be instructed to skip the dose for that meal.

General:
-This drug is not indicated to treat patients with type 1 diabetes or diabetic ketoacidosis as these conditions should be treated with insulin.
-Secondary failure may occur; prior to classifying a patient as a secondary failure it is important to assess dose and dietary adherence.

Monitoring:
-Periodic measures of fasting blood glucose and glycosylated hemoglobin should be performed to assess efficacy.

Patient advice:
-Patients should understand the importance of adhering to dietary instructions and regular physical activity; patients should understand strenuous exercise and alcohol intake may increase the risk of hypoglycemia.
-Patients should be aware of the symptoms of hypoglycemia and its management; they should be cautioned about driving and the use of machinery, especially when optimum stabilization has not been achieved, e.g., during a transition from other medications or during irregular use.
-During periods of stress such as fever, trauma, infection, or surgery, management of diabetes may change and patients should be advised to seek medical advice.
-Drug interactions may occur and patients should speak with their healthcare provider regarding all their medications, prescription and over the counter drugs.
-Advise patient to speak to physician or health care professional if pregnant, intend to become pregnant, or are breastfeeding.