Nateglinide

Registered South African indications:

• Type 2 diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe hepatic impairment
• Type 1 diabetes (C-peptide negative)
• Diabetic ketoacidosis, with or without coma

Cautions

• Severe renal impairment
• Moderate hepatic impairment
• Elderly
• Monotherapy
• Strenuous exercise
• Malnourished patients
• Adrenal insufficiency
• Pituitary insufficiency
• Alcohol ingestion
• Beta-blocker treatment
• Stress
  - Fever
  - Trauma
  - Infection
  - Surgery
• Patients known to be poor metabolizers for CYP2C9
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Non insulin-dependant diabetes mellitus
- Monotherapy where hyperglycaemia cannot be adequately controlled by diet and physical exercise who have not been chronically treated with other antidiabetic agents
- Combination therapy with metformin in type 2 diabetic patients inadequately controlled despite a maximally tolerated dose of metformin alone

• Oral (tab): 60-120mg, 8hrly admin. within 30min of breakfast, lunch and supper; Max: 180mg/dose

Patients whose hyperglycemia is not adequately controlled with sulphonylurea or other insulin secretagogues should not be switched to nateglinide, nor should nateglinide be added to their treatment regimen

Do not take scheduled dosage if skipping a meal

Dosage should be determined by the physician according to the patient's requirements. Dose adjustments should be based on periodic HbA1c measurements

Symptoms of hypoglycaemia (unconfirmed by blood glucose levels) were observed in patients whose baseline HbA1c was closed to the the therapeutic target (HbA1c <7.5%)

In debilitated or malnourished patients, initial and maintenance dosage should be conservative and careful titration is required to avoid hypoglycaemic reactions

Combination with metformin is associated with an increased risk of hypoglycaemia compared to monotherapy

Not established for use in children below 18 years

Pregnancy

• Contraindicated
• Studies in animals have shown developmental toxicity
• There is no experience in pregnant women, therefore the safety of nateglinide in pregnant women cannot be assessed. Nateglinide, like other oral antidiabetic agents, must not be used during pregnancy

Breastfeeding

• Contraindicated
• Nateglinide is excreted in the milk following a peroral dose to lactating rats
• Although it is not known whether nateglinide is excreted in human milk, the potential for hypoglycaemia in breastfed infants may exist and therefore nateglinide should not be used in breastfeeding women

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe and dialysis patients: Caution; no dose adjustment recommended
  Although there is a 49% decrease in Cmax of nateglinide in dialysis patients, the systemic availability and half-life in diabetic patients with CrCl 15-50ml/min was comparable between renal subjects requiring haemodialysis and healthy subjects. Although safety was not compromised in this population, dose adjustment may be required in view of low Cmax

Hepatic Impairment

• Mild: No dose adjustment recommended
• Moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated

Elderly

• Caution: No dose adjustment recommended
  The clinical experience in patients >75 years is limited

Porphyria Information

• Probably not porphyrinogenic (PNP)
  Common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are nausea, dyspepsia, abdominal pain and diarrhoea. A less common side effect is vomiting

Drugs in Sport

• Permitted - No warnings

Gastrointestinal Disorders

• Abdominal pain
• Diarrhoea
• Dyspepsia
• Nausea and vomiting

Hepatobiliary Disorders

• Elevation in liver enzymes

Endocrine and Metabolic Disorders

• Hypoglycaemia
  - Sweating
  - Trembling
  - Dizziness
  - Increased appetite
  - Palpitations
  - Nausea
  - Fatigue
  - Weakness

Skin and Subcutaneous Tissue Disorders

• Erythema multiforme

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
  - Rash
  - Itching
  - Urticaria

• Beta-blockers
• Angiotensin-converting enzyme inhibitors
• Non-steroidal anti-inflammatory drugs
• Salicylates
• Monoamine oxidase inhibitors
• Non-selective beta-adrenergic-blocking agents
• Anabolic hormones
• Methandrostenolone
• Diuretics
• Corticosteroids
• Beta2 agonists
• Somatropin
• Somatostatin analogues
• Lanreotide
• Octreotide
• Rifampicin
• Phenytoin
• Potent CYP29A inhibitors
• Fluconazole
• Gemfibrozil
• Sulfinpyrazone

Other interactions

• Alcohol
• St John's wort

• Lipid profile
• Fasting blood glucose
• HbA1c
• Weight

Nateglinide is an amino acid (phenylalanine) derivative, which is chemically and pharmacologically distinct from other antidiabetic agents. Nateglinide is a rapid, short-acting oral insulin secretagogue. Its effect is dependent on functioning beta cells in the pancreas islets. Early insulin secretion is a mechanism for the maintenance of normal glycaemic control. Nateglinide closes ATP-dependent potassium channels in the beta-cell membrane with characteristics that distinguish it from other sulphonylurea receptor ligands. This depolarises the beta cell and leads to an opening of the calcium channels. The resulting calcium influx enhances insulin secretion. Nateglinide-induced insulin secretion by pancreatic beta cells is glucose-sensitive, such that less insulin is secreted as glucose levels fall. Conversely, the coadministration of food or a glucose infusion results in an enhancement of insulin secretion.

Tablet 120mg

• Starlix (Novartis) originator