Sitagliptin/ Metformin

Registered South African indications:

• Diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Breastfeeding 
• Renal disease or renal dysfunction (e.g., serum creatinine levels ≥133µmol/L in males, ≥124 µmol/L in females, or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicaemia
• Hepatic impairment
• Acute or chronic metabolic acidosis, including lactic acidosis or diabetic ketoacidosis (with or without coma)
• Diabetic pre-coma
• Acute conditions with the potential to alter renal function, such as:
  • Dehydration
  • Severe infection
  • Shock
• Acute or chronic disease which may cause tissue hypoxia, such as:
  • Cardiac or respiratory failure
  • Recent myocardial infarction
  • Shock
• Acute alcohol intoxication or alcoholism

Cautions

• Moderate renal impairment
• Elderly
• Dehydration 
• History of pancreatitis 
• Diabetes mellitus type I
• Surgery

Forms avail. in SA covered in this monograph: tab

Diabetes mellitus

Sitagliptin/ Metformin
50/500 (mg)
50/850 (mg)
50/1000 (mg)

• Oral (tab): 1 tab, 12hrly; Max: Sitagliptin 100mg/24hrs

No established for use in children under 18 years

Pregnancy 

• Caution
• There are no adequate data from the use of sitagliptin in pregnant women. Studies in animals have shown reproductive toxicity at high doses of sitagliptin
• A limited amount of data suggests the use of metformin in pregnant women is not associated with an increased risk of congenital malformations. Animal studies with metformin do not indicate harmful effects with respect to pregnancy, embryonic or foetal development, parturition or postnatal development
• Sitagliptin/metformin should not be used during pregnancy. If a patient wishes to become pregnant or if a pregnancy occurs, treatment should be discontinued and the patient switched to insulin treatment as soon as possible

Breastfeeding

• Contraindicated 
• No studies in lactating animals have been conducted with the combined active substances of this medicinal product. In studies performed with the individual active substances, both sitagliptin and metformin are excreted in the milk of lactating rats. Metformin is excreted in human milk in small amounts. It is not known whether sitagliptin is excreted in human milk. Sitagliptin/metformin must therefore not be used in women who are breastfeeding

Renal Impairment

• Renal disease or renal dysfunction (e.g. serum creatinine levels ≥133µmol/L in males, ≥124 µmol/L in females, or abnormal creatinine clearance): Contraindicated
• Severe: Contraindicated

Hepatic Impairment

• Contraindicated

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Somnolence

Respiratory Disorders

• Interstitial lung disease

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Flatulence
• Constipation
• Upper abdominal pain
• Acute pancreatitis
• Fatal and non-fatal haemorrhagic and necrotizing pancreatitis

Genitourinary Disorders

• Impaired renal function
• Acute renal failure

Musculoskeletal Disorders

• Arthralgia
• Myalgia
• Pain in extremity
• Back pain
• Arthropathy

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Angioedema
• Rash
• Urticaria
• Cutaneous vasculitis
• Exfoliative skin conditions
• Bullous pemphigoid

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity

• Alcohol 
• Iodated contrast agents 
• Non-steroidal anti-inflammatory drugs
• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor blockers
• Diuretics
• Cimetidine
• Cyclosporin
• Glucocorticoids
• CYP3A4 inhibitors
• Organic anion transport 3 substrates
• P-glycoprotein substrates
• Digoxin

Renal function

Sitagliptin
Sitagliptin acts by inhibiting dipeptidyl peptidase 4 activity which results in increased fasting and postprandial endogenous levels of the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide. Increased levels of these incretin hormones sensitise beta cells to glucose thus resulting in improved glucose-dependent insulin secretion from the pancreas. Increased levels of incretin hormones also suppress glucagon secretion from pancreatic alpha cells when blood glucose is normal or elevated.

Metformin
Metformin is a biguanide which decreases basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia. Metformin reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis and it increases insulin sensitivity, improving peripheral glucose uptake and utilisation and it delays intestinal glucose absorption. Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase and increases the transport capacity of all types of membrane glucose transporters known to date. 

COMBINATION PREPARATIONS

Metformin/ Sitagliptin

Tablet 500mg/50mg

• Janumet (MSD) originator

Tablet 850mg/50mg

• Janumet (MSD) originator

Tablet 1000mg/50mg

• Janumet (MSD) originator