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DRUGS & SUPPLEMENTS
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Starlix
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Starlix uses
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Starlix tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Limitations of Use:
Starlix should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Starlix 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 Starlix 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 .
- Recommended dose is 120 mg three times daily.
- In patients who are near glycemic goal when treatment is initiated, 60 mg three times daily may be administered. (2)
- Administer 1 to 30 minutes before meals. (2)
- If a meal is skipped, skip the scheduled dose to reduce the risk of hypoglycemia. (2, 5.1)
3 DOSAGE FORMS AND STRENGTHS
- 60 mg tablets: pink, circular, biconvex tablet with “WPI” debossed on one side and “3354” on the other.
- 120 mg tablets: pink, capsule-shaped, biconvex tablet with “WPI” debossed on one side and “3355” on the other.
Tablets: 60 mg and 120 mg (3)
4 CONTRAINDICATIONS
Starlix is contraindicated in patients with a history of hypersensitivity to Starlix or its active ingredients.
- History of hypersensitivity to Starlix inactive ingredients (4)
5 WARNINGS AND PRECAUTIONS
- Hypoglycemia: Starlix may cause hypoglycemia. Administer before meals to reduce the risk of hypoglycemia. Skip the scheduled dose of Starlix if a meal is skipped to reduce the risk of hypoglycemia.
- Macrovascular outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Starlix. (5.2)
5.1 Hypoglycemia
All glinides, including Starlix, 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 Starlix before meals and be instructed to skip the dose of Starlix 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 Starlix.
6 ADVERSE REACTIONS
The following serious adverse reaction is also described elsewhere in the labeling:
Hypoglycemia
| Placebo | Starlix | |
| 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 Starlix. Non-severe hypoglycemia occurred in 2.4 % of Starlix treated patients and 0.4 % of placebo treated patients .
Weight Gain
Patients treated with Starlix had statistically significant mean increases in weight compared to placebo. In clinical trials, the mean weight increases with Starlix 60 mg (3 times daily) and Starlix 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 Starlix alone, Starlix 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.
- Common adverse reactions associated with Starlix (3% or greater incidence) were upper respiratory tract infection, back pain, flu symptoms, dizziness, arthropathy, diarrhea. (6.1)
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 Starlix. 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 Starlix.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Starlix. 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.
- Hypersensitivity reactions: Rash, itching, and urticaria
- Hepatobiliary Disorders: Jaundice, cholestatic hepatitis, and elevated liver enzymes
7 DRUG INTERACTIONS
Table 2 includes a list of drugs with clinically important drug interactions when concomitantly administered or withdrawn with Starlix and instructions for managing or preventing them.
| Drugs That May Increase the Blood-Glucose-Lowering Effect of Starlix 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 Starlix is coadministered with these drugs. |
| Drugs and Herbals That May Reduce the Blood-Glucose-Lowering Effect of Starlix 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 Starlix 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 Starlix is coadministered with these drugs. |
- Drugs That May Increase the Potential for Hypoglycemia: Starlix dose reductions and increased frequency of glucose monitoring may be required when coadministered (7)
- Drugs That May Increase the Potential for Hyperglycemia: Starlix dose increases and increased frequency of glucose monitoring may be required when coadministered (7)
- Drugs That May Blunt Signs and Symptoms of Hypoglycemia: Increased frequency of glucose monitoring may be required when coadministered (7)
8 USE IN SPECIFIC POPULATIONS
- Nursing mothers: Discontinue Starlix or nursing
8.1 Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies of Starlix in pregnant women. It is unknown whether Starlix can cause fetal harm when administered to a pregnant woman. Starlix 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). Starlix 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 Starlix is excreted in human milk. Starlix is excreted in rat milk. Offspring of rats exposed to 1,000 mg/kg Starlix had lower body weight. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made as to whether Starlix should be discontinued in nursing mothers, or if mothers should discontinue nursing.
8.4 Pediatric Use
The safety and effectiveness of Starlix 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 Starlix in clinical studies. No differences were observed in safety or efficacy of Starlix between patients age 65 and over, and those under age 65. However, greater sensitivity of some older individuals to Starlix 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 Starlix 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 Starlix 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 Starlix is highly protein bound, dialysis is not an efficient means of removing it from the blood.
11 DESCRIPTION
Starlix, USP is an oral blood glucose-lowering drug of the glinide class. Starlix, (-)-N-[(trans-4-isopropylcyclohexane)carbonyl]-D-phenylalanine, is structurally unrelated to the oral sulfonylurea insulin secretagogues.
The structural formula is as shown:
Starlix, 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. Starlix biconvex tablets contain 60 mg, or 120 mg, of Starlix, 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.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Starlix lowers blood glucose levels by stimulating insulin secretion from the pancreas. This action is dependent upon functioning beta-cells in the pancreatic islets. Starlix 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. Starlix is highly tissue selective with low affinity for heart and skeletal muscle.
12.2 Pharmacodynamics
Starlix stimulates pancreatic insulin secretion within 20 minutes of oral administration. When Starlix 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 Starlix 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 Starlix upon multiple dosing of up to 240 mg three times daily for 7 days.
Absorption
Absolute bioavailability of Starlix is approximately 73%. Plasma profiles are characterized by multiple plasma concentration peaks when Starlix is administered under fasting conditions. This effect is diminished when Starlix is taken prior to a meal. Following oral administration immediately prior to a meal, the mean peak plasma Starlix concentrations (Cmax) generally occur within 1 hour (Tmax) after dosing. Tmax is independent of dose.
The pharmacokinetics of Starlix are not affected by the composition of a meal (high protein, fat, or carbohydrate). However, peak plasma levels are significantly reduced when Starlix is administered 10 minutes prior to a liquid meal as compared to solid meal. When given with or after meals, the extent of Starlix 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).
Starlix did not have any effect on gastric emptying in healthy subjects as assessed by acetaminophen testing.
Distribution
Following intravenous (IV) administration of Starlix, the steady-state volume of distribution of Starlix is estimated to be approximately 10 L in healthy subjects. Starlix 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, Starlix plasma concentrations declined with an average elimination half-life of approximately 1.5 hours.
Metabolism
In vitro drug metabolism studies indicate that Starlix 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 Starlix. The isoprene minor metabolite possesses potency similar to that of the parent compound Starlix.
Excretion
Starlix 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 Starlix were 37% and 30 % respectively, as compared to healthy matched control subjects. There is no data on pharmacokinetics of Starlix in patients with moderate-to-severe hepatic impairment.
Gender
No clinically significant differences in Starlix 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 Starlix.
Age
Age does not influence the pharmacokinetic properties of Starlix.
Drug Interactions:
In vitro assessment of drug interactions
Starlix 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 Starlix protein binding. Similarly, Starlix 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 Starlix and the effect of Starlix 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 Starlix was coadministered with glyburide, metformin, digoxin, warfarin, and diclofenac.
| Coadministered drug | Dosing regimen of coadministered drug | Dosing regimen of Starlix | 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 Starlix | 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: Starlix did not increase tumors in two year carcinogenicity studies conducted in mice and rats. Oral doses of Starlix 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 Starlix at a dose of 120 mg three times daily, based on AUC.
Mutagenesis: Starlix 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 Starlix to rats at doses up to 600 mg/kg (approximately 16 times the human therapeutic exposure with a recommended Starlix 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 Starlix 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 Starlix 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 | Starlix 60 mg three times daily before meals N=167 | Starlix 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 Starlix (60 mg or 120 mg three times daily before meals) or glyburide 10 mg once daily. Patients randomized to Starlix had significant increases in mean HbA1C and mean FPG at endpoint compared to patients randomized to glyburide.
| Glyburide 10 mg Once daily | Starlix 60 mg three times daily before meals | Starlix 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 Starlix alone, metformin alone (500 mg three times daily), a combination of Starlix 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 Starlix monotherapy, and the combination of Starlix and metformin compared to either Starlix or metformin monotherapy.
Compared to placebo, Starlix 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 Starlix and metformin therapy. Among the subset of patients previously treated with other antidiabetic agents, primarily glyburide, HbA1C in the Starlix monotherapy group increased slightly from baseline, whereas HbA1C was reduced in the metformin monotherapy group.
| HbA1C (%) All | Placebo N=160 | Starlix 120 mg three times daily before meals N=171 | Metformin 500 mg three times daily N=172 | Starlix 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 Starlix (60 mg or 120 mg three times daily before meals) or placebo as add-on to metformin. At the end of treatment, Starlix 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 Starlix 60 mg and Starlix 120 mg plus metformin, respectively).
| Placebo + metformin | Starlix 60 mg + metformin | Starlix 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 Starlix (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 Starlix compared to +1 kg for patients treated with placebo when added to rosiglitazone.
| Placebo + rosiglitazone 8 mg once daily | Starlix 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 Starlix (60 mg or 120 mg three times daily before meals) did not produce any additional benefit.
| Placebo + glyburide 10 mg once daily | Starlix 60 mg before meals + glyburide 10 mg once daily | Starlix 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 Starlix given 10 minutes prior to breakfast, lunch, and dinner; glyburide given with the breakfast dose of Starlix or placebo. a p-value 0.6959 b p-value 0.1246 | |||
16 HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
Starlix 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 Starlix 1 to 30 minutes before meals. Instruct patients that skip meals to skip their dose of Starlix .
Hypoglycemia
Inform patients that Starlix 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 Starlix.
Manufactured by:
Cipla Ltd.
Verna Goa, INDIA
Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA
Revised: March 2017
NDC 0591-3354-01
Starlix Tablets, USP
60 mg
100 Tablets
Actavis
Rx Only
1
NDC 0591-3355-01
Starlix Tablets, USP
120 mg
100 Tablets
Actavis
Rx Only
1
Starlix pharmaceutical active ingredients containing related brand and generic drugs:
Starlix available forms, composition, doses:
Starlix destination | category:
Starlix Anatomical Therapeutic Chemical codes:
Starlix pharmaceutical companies:
References
- Dailymed."NATEGLINIDE TABLET [ACTAVIS PHARMA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- 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).
- "nateglinide". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming Starlix?Depending on the reaction of the Starlix after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Starlix 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 Starlix 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.
Review
sdrugs.com conducted a study on Starlix, 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 Starlix 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
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The information was verified by Dr. Rachana Salvi, MD Pharmacology