Sitagliptin

Registered South African indications:

• Type 2 diabetes mellitus

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients

Cautions 

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment (GFR<45ml/min)
• Severe hepatic impairment
• History of pancreatitis
• May impair ability to drive and operate machinery

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

Type 2 diabetes mellitus
- As monotherapy in patients inadequately controlled by diet and exercise alone and for whom metformin in inappropriate due to contraindications or intolerance
- As dual oral therapy in combination with metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control
- As dual oral therapy in combination with a sulphonylurea when diet and exercise plus maximally tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contraindications or intolerance
- As dual oral therapy in combination with a peroxisome proliferator-activated receptor-gamma agonist (i.e. thiazolidinedione) when use of a peroxisome proliferator-activator receptor-gamma agonist is appropriate and when diet and exercise plus the peroxisome proliferator-activated receptor-gamma agonist alone do not provide adequate glycaemic control
- As triple oral therapy in combination with a sulphonylurea and metformin when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control
- As triple oral therapy in combination with a peroxisome proliferator-activated receptor-gamma agonist and metformin when use of a peroxisome proliferator-activated receptor-gamma agonist is appropriate and when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control
- As an add-on to insulin (with or without metformin) when diet and exercise plus stable dose of insulin do not provide adequate glycaemic control

• Oral (tab): 100mg, 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

In combination with metformin and/or a peroxisome proliferator-activated receptor-gamma agonist, the dose of metformin and/or peroxisome proliferator-activated receptor-gamma agonist should be maintained, and sitagliptin administered concomitantly

If a dose is missed, it should be taken as soon as the patient remembers; A double dose should not be taken on the same day

Do not use sitagliptin for treatment of type 1 diabetes or diabetic ketoacidosis

Not established for use in children

Pregnancy

• Caution; positive evidence of risk in animal studies
• There are no adequate data from the use of sitagliptin in pregnant women. Studies in animals have shown reproductive toxicity at high doses. The potential risk for humans is unknown. Due to lack of human data, sitagliptin should not be used during pregnancy

Breastfeeding:

• Caution; not recommended
• It is unknown whether sitagliptin is excreted in human breast milk. Animal studies have shown excretion of sitagliptin in breast milk. Sitagliptin should not be used during breastfeeding

Fertility

• Animal data does not suggest an effect of treatment with sitagliptin on male and female fertility. Human data is lacking

Renal Impairment

• GFR≥45ml/min: No dose adjustment recommended
• GFR<45ml/min: Caution; dose adjustment recommended 

Hepatic Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no information available
  Sitagliptin has not been studied in patients with severe hepatic impairment and care should be exercised. However, because sitagliptin is primarily renally eliminated, severe hepatic impairment is not expected to affected the pharmacokinetics of sitagliptin

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Somnolence

Respiratory Disorders

• Interstitial lung disease
• Upper respiratory tract infection
• Nasopharyngitis

Gastrointestinal Disorders

• Constipation
• Nausea and vomiting (common with metformin)
• Acute pancreatitis
• Haemorrhagic and necrotizing pancreatitis (fatal and non-fatal)
• Flatulence (common with metformin or pioglitazone)
• Diarrhoea  
• Dry mouth

Genitourinary Disorders

• Impaired renal function
• Acute renal failure

Endocrine and Metabolic Disorders

• Hypoglycaemia

Musculoskeletal Disorders

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

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Angioedema
• Rash
• Urticaria
• Cutaneous vasculitis
• Exfoliative skin conditions
• Stevens-Johnson syndrome
• Bullous pemphigoid

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Hypersensitivity reactions
  - Angioedema
  - Exfoliative skin conditions including Stevens-Johnson syndrome
• Anaphylaxis
• Influenza (common with insulin with or without metformin)
• Peripheral oedema (common with pioglitazone or combination of pioglitazone and metformin)

• Digoxin
• CYP3A4 inhibitors (in severe renal impairment or end-stage renal disease)
• Ketoconazole (in severe renal impairment or end-stage renal disease)
• Itraconazole (in severe renal impairment or end-stage renal disease)
• Ritonavir (in severe renal impairment or end-stage renal disease)
• Clarithromycin (in severe renal impairment or end-stage renal disease)
• Ciclosporin

• HbA1c
• Blood glucose
• Renal function

Sitagliptin is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors. The improvement in glycaemic control observed with this medicinal product may be mediated by enhancing the levels of active incretin hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. The activity of GLP-1 and GIP is limited by the DPP-4 enzyme, which rapidly hydrolyzes the incretin hormones to produce inactive products. Sitagliptin prevents the hydrolysis of incretin hormones by DPP-4, thereby increasing plasma concentrations of the active forms of GLP-1 and GIP. By enhancing active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in a glucose-dependent manner.

Tablet 25mg

• Januvia (MSD) originator

Tablet 50mg 

• Januvia (MSD) originator

Tablet 100mg 

• Januvia (MSD) originator

COMBINATION PREPARATIONS

Sitagliptin/ Metformin

Tablet 50mg/500mg

• Janumet (MSD) originator

Sitagliptin/ Metformin

Tablet 50mg/850mg

• Janumet (MSD) originator

Sitagliptin/ Metformin

Tablet 50mg/1000mg

• Janumet (MSD) originator