Nateglinide

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Nateglinide uses


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 should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Nateglinide is 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)

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 .

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3 DOSAGE FORMS AND STRENGTHS


Tablets: 60 mg and 120 mg (3)

4 CONTRAINDICATIONS

Nateglinide is contraindicated in patients with a history of hypersensitivity to Nateglinide or its active ingredients.

5 WARNINGS AND PRECAUTIONS


5.1 Hypoglycemia

All glinides, including Nateglinide, can cause hypoglycemia . Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).

Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy (nerve disease), in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) , or in patients who experience recurrent hypoglycemia.

Factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content), changes in level of physical activity, changes to coadministered medication , and concomitant use with other antidiabetic agents. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia .

Patients should take Nateglinide before meals and be instructed to skip the dose of Nateglinide if a meal is skipped . Patients and caregivers must be educated to recognize and manage hypoglycemia. Self- monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.

5.2 MacrovascularOutcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Nateglinide.

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6 ADVERSE REACTIONS

The following serious adverse reaction is also described elsewhere in the labeling:

Hypoglycemia


Placebo


Nateglinide


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. Non-severe hypoglycemia occurred in 2.4 % of Nateglinide treated patients and 0.4 % of placebo treated patients .

Weight Gain

Patients treated with Nateglinide had statistically significant mean increases in weight compared to placebo. In clinical trials, the mean weight increases with Nateglinide 60 mg (3 times daily) and Nateglinide 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 alone, Nateglinide 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.


To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-272-5525 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. 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.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Nateglinide. 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.

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7 DRUG INTERACTIONS

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.


Drugs That May Increase the Blood-Glucose-Lowering Effect of Nateglinide 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), alcohol.


Intervention:


Dose reductions and increased frequency of glucose monitoring may be required when Nateglinide is coadministered with these drugs.


Drugs and Herbals That May Reduce the Blood-Glucose-Lowering Effect of Nateglinide 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 is 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 is coadministered with these drugs.


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8 USE IN SPECIFIC POPULATIONS

8.1 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).

8.3 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 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.

8.4 Pediatric Use

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

8.5 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.

8.6 Renal Impairment

No dosage adjustment is recommended in patients with mild to severe renal impairment .

8.7 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 .

10 OVERDOSAGE

There have been no instances of overdose with Nateglinide 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 is highly protein bound, dialysis is not an efficient means of removing it from the blood.

11 DESCRIPTION

Nateglinide, USP is an oral blood glucose-lowering drug of the glinide class. Nateglinide, (-)-N-[(trans-4-isopropylcyclohexane)carbonyl]-D-phenylalanine, is 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. It is freely soluble in methanol, ethanol, and chloroform, soluble in ether, sparingly soluble in acetonitrile and octanol, and practically insoluble in water. Nateglinide biconvex tablets contain 60 mg, or 120 mg, of Nateglinide, USP for oral administration.

Inactive Ingredients: colloidal silicon dioxide, fumaric acid, hypromellose, iron oxide (black and red), lactose monohydrate, alpha-lactose monohydrate, magnesium stearate, polysorbate 80, sodium starch glycolate, starch (maize), titanium dioxide, and FD&C red No. 40 aluminum lake.

1

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Nateglinide lowers blood glucose levels by stimulating insulin secretion from the pancreas. This action is dependent upon functioning beta-cells in the pancreatic islets. Nateglinide interacts with the ATP-sensitive potassium channel on pancreatic beta-cells. The subsequent depolarization of the beta cell opens the calcium channel, producing calcium influx and insulin secretion. The extent of insulin release is glucose dependent and diminishes at low glucose levels. Nateglinide is highly tissue selective with low affinity for heart and skeletal muscle.

12.2 Pharmacodynamics

Nateglinide stimulates pancreatic insulin secretion within 20 minutes of oral administration. When Nateglinide is dosed before meals, the peak rise in plasma insulin occurs approximately 1 hour after dosing and falls to baseline by 4 hours after dosing.

12.3 Pharmacokinetics

In patients with Type 2 diabetes, multiple dose administration of Nateglinide over the dosage range of 60 mg to 240 mg shows linear pharmacokinetics for both AUC and Cmax. In patients with Type 2 diabetes, there is no apparent accumulation of Nateglinide upon multiple dosing of up to 240 mg three times daily for 7 days.

Absorption

Absolute bioavailability of Nateglinide is approximately 73%. Plasma profiles are characterized by multiple plasma concentration peaks when Nateglinide is administered under fasting conditions. This effect is diminished when Nateglinide is taken prior to a meal. Following oral administration immediately prior to a meal, the mean peak plasma Nateglinide concentrations (Cmax) generally occur within 1 hour (Tmax) after dosing. Tmax is independent of dose.

The pharmacokinetics of Nateglinide are not affected by the composition of a meal (high protein, fat, or carbohydrate). However, peak plasma levels are significantly reduced when Nateglinide is administered 10 minutes prior to a liquid meal as compared to solid meal. When given with or after meals, the extent of Nateglinide absorption (AUC) remains unaffected. However, there is a delay in the rate of absorption characterized by a decrease in Cmax and a delay in time to peak plasma concentration (Tmax).

Nateglinide did not have any effect on gastric emptying in healthy subjects as assessed by acetaminophen testing.

Distribution

Following intravenous (IV) administration of Nateglinide, the steady-state volume of distribution of Nateglinide is estimated to be approximately 10 L in healthy subjects. Nateglinide is extensively bound (98%) to serum proteins, primarily serum albumin, and to a lesser extent α1 acid glycoprotein. The extent of serum protein binding is independent of drug concentration over the test range of 0.1 to 10 mcg/mL.

Elimination

In healthy volunteers and patients with type 2 diabetes mellitus, Nateglinide plasma concentrations declined with an average elimination half-life of approximately 1.5 hours.

Metabolism

In vitro drug metabolism studies indicate that Nateglinide is predominantly metabolized by the cytochrome P450 isozyme CYP2C9 (70%) and to a lesser extent CYP3A4 (30%).

The major routes of metabolism are hydroxylation followed by glucuronide conjugation. The major metabolites are less potent antidiabetic agents than Nateglinide. The isoprene minor metabolite possesses potency similar to that of the parent compound Nateglinide.

Excretion

Nateglinide and its metabolites are rapidly and completely eliminated following oral administration. Eighty-three percent of the 14C-nateglinide was excreted in the urine with an additional 10% eliminated in the feces. Approximately 16% of the 14C-nateglinide was excreted in the urine as parent compound.

Specific Populations

Renal Impairment

No pharmacokinetic data are available in subjects with mild renal impairment (CrCl 60 to 89 mL/min). Compared to healthy matched subjects, patients with type 2 diabetes mellitus and moderate and severe renal impairment (CrCl 15 to 50 mL/min) not on dialysis displayed similar apparent clearance, AUC, and Cmax. Patients with type 2 diabetes and renal failure on dialysis exhibited reduced overall drug exposure (Cmax decreased by 49%; not statistically significant). However, hemodialysis patients also experienced reductions in plasma protein binding compared to the matched healthy volunteers.

Hepatic Impairment

In patients with mild hepatic impairment, the mean increase in Cmax and AUC of Nateglinide were 37% and 30 % respectively, as compared to healthy matched control subjects. There is no data on pharmacokinetics of Nateglinide in patients with moderate-to-severe hepatic impairment.

Gender

No clinically significant differences in Nateglinide pharmacokinetics were observed between men and women.

Race

Results of a population pharmacokinetic analysis including subjects of Caucasian, Black, and other ethnic origins suggest that race has little influence on the pharmacokinetics of Nateglinide.

Age

Age does not influence the pharmacokinetic properties of Nateglinide.

Drug Interactions:

In vitro assessment of drug interactions

Nateglinide is a potential inhibitor of the CYP2C9 isoenzyme in vivo as indicated by its ability to inhibit the in vitro metabolism of tolbutamide. Inhibition of CYP3A4 metabolic reactions was not detected in in vitro experiments.

In vitro displacement studies with highly protein-bound drugs such as furosemide, propranolol, captopril, nicardipine, pravastatin, glyburide, warfarin, phenytoin, acetylsalicylic acid, tolbutamide, and metformin showed no influence on the extent of Nateglinide protein binding. Similarly, Nateglinide had no influence on the serum protein binding of propranolol, glyburide, nicardipine, warfarin, phenytoin, acetylsalicylic acid, and tolbutamide in vitro. However, prudent evaluation of individual cases is warranted in the clinical setting.

In vivo assessment of drug interactions

The effect of coadministered drugs on the pharmacokinetics of Nateglinide and the effect of Nateglinide on pharmacokinetics of coadministered drugs are shown in Tables 3 and 4. No clinically relevant change in pharmacokinetic parameters of either agent was reported when Nateglinide was coadministered with glyburide, metformin, digoxin, warfarin, and diclofenac.


Coadministered drug


Dosing regimen of coadministered drug


Dosing regimen of Nateglinide


Change in Cmax


Change in AUC


Glyburide


10 mg once daily for 3 weeks


120 mg three times a day, single dose


8.78% ↓


3.53% ↓


Metformin


500 mg three times a

day for 3 weeks


120 mg three times a day, single dose


AM: 7.14% ↑

PM: 11.4% ↓


AM: 1.51% ↑

PM: 5.97% ↑


Digoxin


1 mg, single dose


120 mg three times a day, single dose


AM: 2.17% ↓

PM: 3.19% ↑


AM: 7.62% ↑

PM: 2.22% ↑


Warfarin


30 mg, single dose


120 mg three times a day for 4 days


2.65% ↑


3.72% ↓


Diclofenac


75 mg, single dose


120 mg twice daily,

single dose


AM: 13.23% ↓

*PM: 3.76% ↑


AM: 2.2% ↓

*PM: 7.5% ↑


AM: after morning dose; PM: after evening dose; * after second dose; ↑: increase in the parameter; ↓: decrease in the parameter


Coadministered drug


Dosing regimen of coadministered drug


Dosing regimen of Nateglinide


Change in Cmax


Change in AUC


Glyburide


10 mg once daily for 3 weeks


120 mg three times a day, single dose


3.18% ↓


7.34% ↓


Metformin


500 mg three times a day for 3 weeks


120 mg three times a day, single dose


AM: 10.7% ↑

PM: 0.40% ↑


AM: 13.3% ↑

PM: 2.27% ↓


Digoxin


1 mg, single dose


120 mg three times a day, single dose


5.41% ↓


6.58% ↑


Warfarin


30 mg, single dose


120 mg three times a day for 4 days


R-warfarin: 1.03% ↓

S-warfarin: 0.85% ↓


R-warfarin: 0.74% ↑

S-warfarin: 7.23% ↑


Diclofenac


75 mg, single dose


120 mg twice daily, single dose


2.19% ↑


7.97% ↑


AM: after morning dose; PM: after evening dose; SD: single dose; ↑: increase in the parameter; ↓: decrease in the parameter


13 NONCLINICAL TOXICOLOGY

13.1 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 to 40 times and in mice 10 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).

14 CLINICAL STUDIES

14.1 Monotherapy

In a 24-week, double-blind, placebo-controlled study, patients with type 2 diabetes were randomized to receive either Nateglinide or placebo. Patients previously treated with antidiabetic medications were required to discontinue that medication for at least 2 months before randomization.

At Week 24, treatment with Nateglinide before meals resulted in statistically significant reductions in mean HbA1C and mean fasting plasma glucose (FPG) compared to placebo. The reductions in HbA1C and FPG were similar for patients naïve to, and those previously exposed to, antidiabetic medications.


HbA 1C (%)


Placebo




N=168


Nateglinide

60 mg

three times daily

before meals

N=167


Nateglinide

120 mg

three times daily

before meals

N=168


Baseline (mean)

Change from baseline (mean)

Difference from placebo (mean)

FPG (mg/dL)


8.0

+0.2

N=172


7.9

-0.3

-0.5 a

N=171


8.1

-0.5

-0.7 a

N=169


Baseline (mean)

Change from baseline (mean)

Difference from placebo (mean)


167.9

+9.1


161.0

+0.4

-8.7 a


166.5

-4.5

-13.6 a


a p-value ≤ 0.004


14.2 MonotherapyCompared to Glyburide

In a 24-week, double-blind, active-controlled trial, patients with type 2 diabetes who had been on a sulfonylurea for 3 or more months and who had a baseline HbA1C greater than or equal to 6.5% were randomized to receive Nateglinide (60 mg or 120 mg three times daily before meals) or glyburide 10 mg once daily. Patients randomized to Nateglinide had significant increases in mean HbA1C and mean FPG at endpoint compared to patients randomized to glyburide.


Glyburide

10 mg

Once daily


Nateglinide

60 mg

three times daily

before meals


Nateglinide

120 mg

three times daily

before meals


HbA1C (%)


N=183


N=178


N=179


Baseline (mean)


7.8


8.0


7.9


Change from baseline (mean)


0.3


1.3


1.1


Difference from glyburide


1.0 a


0.9 a


FPG (mmol/L)


N=184


N=182


N=180


Baseline (mean)


9.44


9.67


9.61


Change from baseline (mean)


0.19


3.06


2.84


Difference from glyburide


2.87 a


2.66 a


a p-value <0.001

14.3 Monotherapy and in Combination withMetformin

In a 24-week, double-blind, active- and placebo-controlled study, patients with type 2 diabetes were randomized to receive either Nateglinide alone, metformin alone (500 mg three times daily), a combination of Nateglinide 120 mg (three times daily before meals) and metformin (500 mg three times daily), or placebo. Fifty-seven percent of patients were previously untreated with oral antidiabetic therapy. Patients previously treated with antidiabetic medications were required to discontinue medication for at least 2 months before randomization.

At Week 24, statistically significant reductions in mean HbA1c and FPG were observed with metformin monotherapy compared to Nateglinide monotherapy, and the combination of Nateglinide and metformin compared to either Nateglinide or metformin monotherapy.

Compared to placebo, Nateglinide monotherapy was associated with a statistically significant increase in mean body weight, while no significant change in body weight was observed with metformin monotherapy or combination of Nateglinide and metformin therapy. Among the subset of patients previously treated with other antidiabetic agents, primarily glyburide, HbA1C in the Nateglinide monotherapy group increased slightly from baseline, whereas HbA1C was reduced in the metformin monotherapy group.


HbA1C (%)

All


Placebo

N=160


Nateglinide

120 mg

three times daily

before meals

N=171


Metformin

500 mg

three times daily

N=172


Nateglinide

120 mg

before meals plus Metformin*

N=162


Baseline (mean)


8.3


8.3


8.4


8.4


Change from baseline (mean)


+0.4


-0.4 bc


-0.8 c


-1.5


Difference from placebo


-0.8 a


-1.2 a


-1.9 a


Naïve


N=98


N=99


N=98


N=81


Baseline (mean)


8.2


8.1


8.3


8.2


Change from baseline (mean)


+0.3


-0.7 c


-0.8 c


-1.6


Difference from placebo


-1.0 a


-1.1 a


-1.9 a


Non-Naïve


N=62


N=72


N=74


N=81


Baseline (mean)


8.3


8.5


8.7


8.7


Change from baseline (mean)


+0.6


+0.004 bc


-0.8 c


-1.4


Difference from placebo


-0.6 a


-1.4 a


-2.0 a


FPG (mg/dL)


All


N=166


N=173


N=174


N=167


Baseline (mean)


194.0


196.5


196.0


197.7


Change from baseline (mean)


+8.0


-13.1 bc


-30.0 c


-44.9


Difference from placebo


-21.1 a


-38.0 a


-52.9 a


a p-value ≤ 0.05 vs. placebo

b p-value ≤ 0.03 vs. metformin

c p-value ≤ 0.05 vs. combination

* Metformin was administered three times daily

In another 24-week, double-blind, placebo-controlled trial, patients with type 2 diabetes with HbA1C greater than or equal to 6.8% after treatment with metformin (greater than or equal to 1500 mg daily for at least 1 month) were first entered into a four week run-in period of metformin monotherapy (2000 mg daily) and then randomized to receive either Nateglinide (60 mg or 120 mg three times daily before meals) or placebo as add-on to metformin. At the end of treatment, Nateglinide 60 mg and 120 mg three times daily resulted in a statistically significantly greater reductions in HbA1C compared to placebo when added to metformin (-0.4% and -0.6% for Nateglinide 60 mg and Nateglinide 120 mg plus metformin, respectively).


Placebo

+

metformin


Nateglinide 60 mg

+

metformin


Nateglinide 120 mg

+

metformin


HbA1C (%)


N=150


N=152


N=154


Baseline (mean)


8.2


8.0


8.2


Change from baseline (mean)


0.01


-0.4


-0.6


Difference from metformin


-0.4 a


-0.6 b


a p-value 0.003 vs. metformin

b p-value < 0.001 vs. metformin

All nateglinide/placebo taken three times daily before meals; all metformin 1000 mg twice daily.


14.4 Add-On Combination Therapy withRosiglitazone

A 24-week, double blind, multicenter, placebo-controlled trial was performed in patients with type 2 diabetes not adequately controlled on rosiglitazone 8 mg daily. The addition of Nateglinide (120 mg three times per day with meals) was associated with statistically significantly greater reductions in HbA1C compared to placebo as add-on to rosiglitazone. The mean change in weight from baseline was +3 kg for patients treated with Nateglinide compared to +1 kg for patients treated with placebo when added to rosiglitazone.


Placebo +

rosiglitazone

8 mg

once daily


Nateglinide

120 mg

before meals +

rosiglitazone

8 mg

once daily


HbA1C (%)


N=191


N=194


Baseline (mean)


8.4


8.3


Change from baseline (mean)


0.03


-0.7


Difference from rosiglitazone (mean)


-0.7 a


a p-value ≤ 0.0001


14.5 Add-On Combination Therapy with Glyburide

In a 12-week study of patients with type 2 diabetes inadequately controlled on glyburide 10 mg once daily, the addition of Nateglinide (60 mg or 120 mg three times daily before meals) did not produce any additional benefit.


Placebo +

glyburide

10 mg

once daily


Nateglinide

60 mg

before meals + glyburide

10 mg

once daily


Nateglinide

120 mg

before meals + glyburide

10 mg

once daily


HbA1C (%)


N=58


N=55


N=54


Baseline (mean)


8.7


8.7


8.7


Change from baseline (mean)


0.3


0.2


-0.02


Difference from glyburide (mean)


-0.1 a


-0.3 b


Placebo or Nateglinide given 10 minutes prior to breakfast, lunch, and dinner; glyburide given with the breakfast dose of Nateglinide or placebo.

a p-value 0.6959

b p-value 0.1246


16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Nateglinide tablets, USP

60 mg

Pink, circular, biconvex tablet with “WPI” debossed on one side and “3354” on the other.

Bottles of 100 NDC 0591-3354-01

120 mg

Pink, capsule-shaped, biconvex tablet with “WPI” debossed on one side and “3355” on the other.

Bottles of 100 NDC 0591-3355-01

Storage and Handling

Store at 20° to 25°C (68° to 77°F).

Dispense in a tight container, USP.

17 PATIENT COUNSELING INFORMATION

Administration

Instruct patients to take Nateglinide 1 to 30 minutes before meals. Instruct patients that skip meals to skip their dose of Nateglinide .

Hypoglycemia

Inform patients that Nateglinide can cause hypoglycemia and instruct patients and their caregivers on self-management procedures including glucose monitoring and management of hypoglycemia. Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended .

Drug Interactions

Discuss potential drug interactions with patients and inform them of potential drug-drug interactions with Nateglinide.

Manufactured by:

Cipla Ltd.

Verna Goa, INDIA

Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA

Revised: March 2017

NDC 0591-3354-01

Nateglinide Tablets, USP

60 mg

100 Tablets

Actavis

Rx Only

1

NDC 0591-3355-01

Nateglinide Tablets, USP

120 mg

100 Tablets

Actavis

Rx Only

1

Nateglinide pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Nateglinide available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.

Price
Nateglinide 120 mg tablet1.73 USD
Nateglinide 60 mg tablet1.66 USD
Starlix 120 mg tablet2.12 USD
Starlix 60 mg tablet2.01 USD
Tablets; Oral; Nateglinide 120 mg
Tablets; Oral; Nateglinide 60 mg

Nateglinide destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Nateglinide Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Nateglinide pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."NATEGLINIDE TABLET [ACTAVIS PHARMA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."NATEGLINIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "nateglinide". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Nateglinide?

Depending on the reaction of the Nateglinide after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Nateglinide not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Nateglinide addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Nateglinide, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Nateglinide consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

One visitor reported frequency of use

How often in a day do you take the medicine?
Are you taking the Nateglinide drug as prescribed by the doctor?

Few medications can be taken Once in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sdrugs.com website users about the frequency of taking the drug Nateglinide is mentioned below.
Visitors%
Once in a day1
100.0%

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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