G-5.2 GLP-1 Analogues- formulation(Exenatide)

Name of Medicine

Exenatide

Presentation

Byetta 5 micrograms solution for injection. Byetta 5 microgram pre-filled pen contains 60 doses of sterile, preserved isotonic solution (approximately 1.2 mL). Each dose contains 5 microgram exenatide in 20 microlitres (0.25 mg synthetic exenatide per mL).
Byetta 10 micrograms solution for injection. Byetta 10 microgram pre-filled pen contains 60 doses of sterile, preserved isotonic solution (approximately2.4 mL). Each dose contains 10 microgram exenatide in 40 microlitres (0.25 mg synthetic exenatide per mL).
Bydureon powder for injection in pre-filled pen (Bydureon pen). Each pre-filled pen contains 2 mg of exenatide. After suspension, each pen delivers a dose of 2 mg in 0.65 mL.
Bydureon powder for injection in vial with diluent syringe (Bydureon kit). Each vial contains 2 mg of exenatide. After suspension, a dose of 2 mg in 0.65 mL is delivered. Bydureon is an extended-release microspheres formulation of exenatide. When the product is prepared as instructed, the resulting suspension contains 2 mg exenatide. The suspension is intended for subcutaneous use only, once per week.

Key Practice Points

Therapeutic Indications:

Exenatide is indicated as adjunctive therapy to improve glycaemic management in individuals with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea but are not achieving adequate glycaemic targets.

Exenatide is thought to have a positive effect on glucose levels in five ways.

Increases insulin secretion in response to food.
Suppress pancreatic release of glucagon in response to food.
Slows gastric emptying, which in turn delays how quickly the glucose is absorbed into the blood stream.
Reduces appetite (due to the satiety effect of delayed gastric emptying)
Has a positive effect on fatty liver disease.

For the latest PBS indications for exenatide please see
https://www.pbs.gov.au/pbs/search?term=EXENATIDE&analyse=false&search-type=medicines

Dose:

Byetta:

Exenatide therapy (Byetta) should be initiated at 5 microgram exenatide per dose (start with the 5mcg pen device). Inject twice a day for at least one month. If there are little or no side effects, dose can then be increased to 10 micrograms twice a day if needed for glucose improvement (person centred care). This requires the 10-mcg pen device. Doses higher than 10 micrograms twice a day are not recommended. It is recommended exenatide be injected before the two carbohydrates containing main meals of the day (at least 6 hours or more apart). Exenatide should not be administered after a meal. If an injection is missed, the treatment should be continued with the next scheduled dose.
Each dose of Byetta should be administered as a subcutaneous injection in the thigh, abdomen, or upper arm. Exenatide is not recommended to be administered by intravenous or intramuscular injection. If insulin is administered, exenatide can be injected at the same time, but each should be given as two separate injections. (Diabetes Medscheck counselling on how to use Byetta pen)

Bydureon:

The recommended Bydureon dose is 2 mg exenatide once weekly at any time of the day without regard to meals. There is no need to titrate the dose. After suspension, Bydureon should be administered immediately in the abdomen as a subcutaneous injection. Do not administer intravenously or intramuscularly.
Changing weekly dosing schedule: The day of weekly administration can be changed if the last dose was administered 3 or more days before.
Note: Diabetes MedsCheck is useful with counselling on what to do with missed doses.
Missed dose:
If a dose is missed, it should be administered as soon as noticed, provided the next regularly scheduled dose is due at least 3 days later. Thereafter, the weekly schedule can resume.
Note: Diabetes MedsCheck is useful with counselling on what to do with missed doses.
If a dose is missed and the next regularly scheduled dose is due 1 or 2 days later, the dose should be missed. Resume Bydureon with the next regularly scheduled dose. Note: Diabetes MedsCheck is useful with counselling on what to do with missed doses.

Renal Impairment – In Individuals with moderate renal impairment (creatinine clearance: 30 to 50 mL/min), dose increases from 5 microgram to 10 micrograms should proceed with caution.
Exenatide should not be used with end-stage renal disease or severe renal impairment (creatinine clearance < 30 mL/min)
Bydureon is not recommended for use with end stage renal disease or severe renal impairment (creatinine clearance < 30 mL/min)
Liver dysfunction: Exenatide is cleared predominately by the kidney. Hepatic dysfunction is not expected to affect blood concentrations of exenatide.

Elderly:

No dose adjustment is required in the elderly.

Precautions:

Exenatide has not been studied in individuals with any form of severe gastrointestinal disease, including gastroparesis.
Exenatide should not be sed to treat type 1 diabetes.
Exenatide should be used with caution in those individuals > 70 years. Doses above 5 micrograms should be considered on an individual basis.
There have been reported cases of increased INR with concomitant use of warfarin and exenatide, sometimes associated with bleeding.
Note: Diabetes MedsCheck with referral back to GP for screening due to possible interaction.
Rapid weight loss at a rate of > 1.5 kg per week has been reported in some individuals treated with exenatide. Weight loss of this rate may have harmful consequences.
Note: Diabetes MedsCheck. Enrolment in weight loss program to help maintain weight. Referral to appropriate allied health. Referral back to GP due to side effect profile.
Increased risk of pancreatitis- Recognised risk factors for pancreatitis include a history of pancreatitis, gallstones, alcoholism, and severe hypertriglyceridemia. Clinical judgement should be exercised.
Note: Diabetes MedsCheck to explain signs and symptoms and what to do if such an event should occur.
Should not be used in children under the age of 18 years.
Bydureon – There have been post market reports of serious injection site reactions, including abscesses, cellulitis, ulcers, and necrosis.

Adverse Effects:

Gastrointestinal:

Nausea, abdominal distension and pain, belching, constipation, flatulence, this is usually dose dependent.
Note: Diabetes MedsCheck for side effect profile.

Hypoglycaemia:

Exenatide does not cause hypoglycaemia on its own. However, when used in conjunction with sulfonylureas or insulin hypoglycaemia can occur.
Note: Diabetes Medscheck forside effect for link to hypoglycaemia

Metabolism and nutritional disorders:

dehydration, usually associated with nausea, vomiting, and/or diarrhoea and feeling full so often individuals will forget to drink.
Note: Diabetes MedsCheck for side effect profile, prevention of complications and referral to appropriate allied health care team.

Injection site reactions:

Injection site reactions were higher in exenatide once weekly treated individuals (16%) (Bydureon) compared to exenatide twice daily treated individuals (2-7%).

Contraindications:

Hypersensitivity to exenatide or any active ingredient
end-stage renal disease or severe renal impairment (creatinine clearance < 30 mL/min)

Pharmacokinetic Properties - Summary

Absorption:

Metformin is absorbed through the entire gastrointestinal mucosa. Studies have shown there is a lack of dose proportionally with increasing doses thought to be due to a reduction of absorption. It is therefore thought that metformin absorption is saturable and incomplete.

Distribution:

Plasma protein binding of metformin is negligible.

Excretion:

Renal clearance of metformin is > 400 mL/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Dosage adjustment should therefore occur in those with renal dysfunction and ceased in renal failure. For more detailed information on this product please consult the product information.

More Information

For more detailed information on this product please consult the product information.
https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=PI&q=exenatide&r=/