Exenatide

Registered South African indications:

• Diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• History of medullary thyroid carcinoma (MTC) or those at high risk thereof (known carriers of multiple endocrine neoplasia type 2 (MEN2), familial MTC mutations, unknown carrier status or if a family history of MEN2 or MTC)  

Cautions

• Hypersensitivity to metacresol  
• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment, including dialysis and ESRD
• Elderly
• Type 1 diabetes mellitus
• Diabetic ketoacidosis
• Severe gastrointestinal disease, including gastroparesis
• History of pancreatitis
• May impair ability to drive and operate machinery

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

Non insulin-dependant diabetes mellitus

• SC: Initial: 5μg, 12hrly for 1 month; Maintenance: 10μg, 12hrly; Admin. 60min period before morning and evening meal; Max: 20μg/24hrs

To be admin. in the thigh, abdomen or upper arm

Not to be admin. by IV or IM routes

Do not admin. after meal

If an injection is missed, the treatment should be continued with the next scheduled dose

See additional prescribing points 

Not established for use in children below 18 years

Pregnancy

• Caution
• There are no adequate data from the use of exenatide in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Exenatide should not be used during pregnancy and the use of insulin is recommended
• If a patient wishes to become pregnant, or pregnancy occurs, treatment with exenatide should be discontinued

Breastfeeding

• Caution; not recommended
• It is unknown whether exenatide is excreted in human milk. Exenatide should not be used if breastfeeding

Fertility

• No fertility studies in humans have been conducted

Renal Impairment

• CrCl 50-80ml/min: No dosage adjustment recommended
• CrCl 30-50ml/min: Caution; no dose adjustment recommended
  Dose escalation from 5-10μg should proceed conservatively
• CrCl <30 ml/min, dialysis or ESRD: Caution; dose adjustment recommended
  Not recommended for use  

Hepatic Impairment

• No dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Dose escalation from 5-10μg should proceed conservatively in patients >70 years

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous system Disorders

• Headache
• Dizziness
• Dysgeusia
• Somnolence
• Asthenia

Gastrointestinal disorders

• Intestinal obstruction
• Nausea and vomiting
• Diarrhoea
• Dyspepsia
• Abdominal pain
• Gastroesophageal reflux disease
• Abdominal distension
• Acute pancreatitis
• Eructation
• Constipation
• Flatulence
• Cholelithiosis (gallstones)

Genitourinary Disorders

• Acute renal failure
• Worsened chronic renal failure
• Renal impairment
• Increased serum creatinine

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Decreased appetite
• Rapid weight loss
• Dehydration

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Alopecia
• Macular and papular rash
• Pruritus
• Urticaria
• Angioneurotic oedema
• Injection site reaction

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reaction
• Drug-induced thrombocytopaenia (DITP)

• Antibiotics
• Warfarin
• HMG CoA reductase inhibitors
• Proton pump inhibitors

None routine. Specific cases may require

• Serum glucose
• HbA1C
• Renal function

Coadministration with other antidiabetic agents

• Immediate-release exenatide is recommended for use in patients with type 2 diabetes mellitus who are already receiving metformin, a sulphonylurea, pioglitazone and/or a basal insulin
• When immediate-release exenatide is added to existing metformin and/or pioglitazone therapy, the current dose of metformin and/or pioglitazone can be continued as no increased risk of hypoglycaemia is anticipated, compared to metformin or pioglitazone alone. When immediate-release exenatide is added to sulphonylurea therapy, a reduction in the dose of sulphonylurea should be considered to reduce the risk of hypoglycaemia. When immediate-release exenatide is used in combination with basal insulin, the dose of basal insulin should be evaluated. In patients at increased risk of hypoglycaemia reducing the dose of basal insulin should be considered
• The dose of immediate-release exenatide does not need to be adjusted on a day-by-day basis depending on self-monitored glycaemia. Blood glucose self-monitoring is necessary to adjust the dose of sulphonylurea or insulin, particularly when exenatide therapy is started and insulin is reduced. A stepwise approach to insulin dose reduction is recommended

Coadministration with orally administered agents

• The effect of immediate-release exenatide to slow gastric emptying may reduce the extent and rate of absorption of orally administered agents. Patients taking agents with either a narrow therapeutic ratio or that require careful clinical monitoring should be followed closely
• These agents should be taken in a standardised way in relation to the exenatide injection. For example, if to be administered with food, patients should be advised to take them with a meal when exenatide is not administered. For agents that are particularly dependent on threshold concentrations for efficacy, such as oral antibiotics, patients should be advised to take these agents at least 1 hour before the exenatide injection

Risk of medullary thyroid carcinoma

• An increase in thyroid C-cell tumours have been observed in animals exposed to exenatide which was not observed in human studies. Exenatide should therefore not be used in patients at high risk of medullary thyroid carcinoma (known carriers of multiple endocrine neoplasia type 2 (MEN2), familial MTC mutations, unknown carrier status or if a family history of MEN2 or MTC)

Exenatide is a glucagon-like peptide-1 receptor agonist that exhibits several antihyperglycaemic actions with its mechanism of action mediated by cyclic adenosine monophosphate and/or other intracellular signalling pathways. Exenatide increases, on a glucose-dependent basis, the secretion of insulin from pancreatic beta cells. Exenatide suppresses glucagon secretion which is known to be inappropriately elevated in type 2 diabetes. Lower glucagon concentrations lead to decreased hepatic glucose output. However, exenatide does not impair the normal glucagon response and other hormone responses to hypoglycaemia. Exenatide slows gastric emptying thereby reducing the rate at which meal-derived glucose appears in the circulation.

Injection (per 20μl) 5μg

• Byetta (AstraZeneca) 

Injection (per 40μl) 10μg

• Byetta (AstraZeneca)