Saxagliptin

Registered South African indications:

• Type 2 diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• History of serious hypersensitivity to dipeptidyl peptidase-4 inhibitors
• Severe hepatic impairment
• Previous history of pancreatitis
• Should not be used with type 1 diabetes or for the treatment of diabetic ketoacidosis

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment (eGFR <45 ml/min)
• Type 1 diabetes mellitus
• Treatment of diabetic ketoacidosis
• History of pancreatitis
• Risk factors for hospitalisation for cardiac failure
• History of heart failure
• Immunocompromised patients e.g organ transplantation or human immunodeficiency syndrome patients
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption

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

Non insulin-dependent diabetes mellitus
- As monotherapy when metformin is inappropriate due to intolerance or contraindications
- In combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control

• Oral (tab): 5mg, dly

In combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin may be considered to reduce the risk of hypoglycaemia

Safety and efficacy as triple therapy in combination with metformin and a thiazolidinedione has not been established

Used as an adjunct to diet and exercise to improve glycaemic control

Saxagliptin is not a substitute for insulin in insulin-requiring patients

Can be taken with or without food

Do not split or cut tablets

Not established for use in children below 18 years

Pregnancy

• Caution
• The use of saxagliptin has not been studied in pregnant women
• Studies in animals have shown reproductive toxicity at high doses. The potential risk for humans is unknown
• Saxagliptin should not be used during pregnancy unless clearly necessary

Breastfeeding

• Caution; not recommended 
• It is unknown whether saxagliptin is excreted in human breast milk
• Animal studies have shown excretion of saxagliptin and/or metabolite in milk
• A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy to the woman

Fertility

• The effect of saxagliptin on fertility in humans has not been studied
• Effects on fertility were observed in male and female rats at high doses producing overt signs of toxicity

Renal Impairment

• eGFR ≥45ml/min/1.73m²: No dose adjustment recommended
• eGFR <45ml/min/1.73m²: Caution; dose adjustment recommended
  Reduce dose to 2.5mg, dly. Saxagliptin is not recommended for use in end-stage renal disease requiring haemodialysis

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Contraindicated

Elderly

• No dose adjustment recommended 

Porphyria Information

• Probably not porphyrinogenic (PNP)
  Urinary and upper respiratory tract infections are common side effects and potentially porphyrinogenic

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Fatigue

Cardiovascular Disorders

• Peripheral oedema

Respiratory Disorders

• Upper respiratory tract infection
• Sinusitis
• Nasopharyngitis

Gastrointestinal Disorders

• Gastroenteritis
• Abdominal pain
• Diarrhoea
• Dyspepsia
• Flatulence
• Gastritis
• Nausea and vomiting
• Pancreatitis
• Constipation

Genitourinary Disorders

• Urinary tract infection
• Erectile dysfunction

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Dyslipidaemia
• Hypertriglyceridaemia
• Acute pancreatitis

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash
• Dermatitis
• Pruritus
• Urticaria
• Angioedema
• Bullous pemphigoid

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Anaphylactic reactions including anaphylactic shock
• Decreased lymphocyte count

• CYP3A4 /5 inducers
• Rifampicin
• Carbamazepine
• Dexamethasone
• Phenobarbital
• Phenytoin
• Sulphonylureas
• Insulin
  (see additional prescribing points)

• Blood glucose
• HbA1C
• Renal function

Specific cases may require:

• Lymphocyte count

Use with medicinal products known to cause hypoglycaemia

• Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, a lower dose of sulphonylurea or insulin may be required to reduce the risk of hypoglycaemia when used in combination with saxagliptin

Saxagliptin is a highly potent (Ki: 1.3 nM), selective, reversible, competitive, DPP4 inhibitor. In patients with type 2 diabetes, administration of saxagliptin led to inhibition of DPP4 enzyme activity for a 24-hour period. After an oral glucose load, this DPP4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), decreased glucagon concentrations and increased glucose-dependent beta-cell responsiveness, which resulted in higher insulin and C-peptide concentrations. The rise in insulin from pancreatic beta-cells and the decrease in glucagon from pancreatic alpha-cells were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal. Saxagliptin improves glycaemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes.

Tablet 2.5mg 

• Onglyza (AstraZeneca) originator

Tablet 5mg 

• Onglyza (AstraZeneca) originator