Albiglutide (Tanzeum): Drug Monograph
- As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- Limitations of Use:
- Not recommended as first-line therapy for patients inadequately controlled on diet and exercise.
- Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
- Not for patients with pre-existing severe gastrointestinal disease.
- Has not been studied in combination with prandial insulin.
- General Notes:
- Administer once weekly at any time of day. The lyophilized powder contained within the Pen must be reconstituted prior to administration.
- Can be given without regard to meals
- Inject subcutaneously in the abdomen, thigh, or upper arm on the same day each week.
- If a dose is missed, administer within 3 days of missed dose.
- Type 2 Diabetes Mellitus: 30 mg subcutaneously once weekly. The dose can be increased to 50 mg once weekly in patients requiring additional glycemic control (usually done after at least 4 weeks of use).
- No dosage adjustment with mild, moderate or severe renal impairment (eGFR 15 to 89 mL/min/1.73 m2).
- Use caution when initiating or escalating doses of albiglutide in patients with renal impairment.
- Thyroid C-cell tumors have occurred in animal studies. However, it is unknown whether albiglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans.
- Patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with albiglutide.
- Patients should be counseled regarding the risk and symptoms of thyroid tumors.
- Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
- History of serious hypersensitivity to albiglutide or any product components
- Pancreatitis: Discontinue promptly if suspected and do not restart if confirmed.
- Hypoglycemia: Can occur when used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Consider lowering sulfonylurea or insulin dosage when starting albiglutide.
- Hypersensitivity Reactions
- Renal Impairment:
Monitor renal function in patients with renal impairment reporting severe
adverse gastrointestinal reactions.
- Macrovascular Outcomes: There have been no clinical trials establishing conclusive evidence of macrovascular risk reduction with albiglutide or any other antidiabetic drug.
- Risk of thyroid C-cell tumors
- No data are available with regard to overdosage in humans.
- Anticipated symptoms may be severe nausea and vomiting.
- Appropriate supportive treatment should be initiated as dictated by the patient's clinical signs and symptoms.
- A prolonged period of observation and treatment for these symptoms may be necessary, taking into account the half-life of albiglutide (5 days).
- Delays gastric emptying. May impact absorption of concomitantly administered oral medications.
- Pregnancy: Pregnancy Category C
- Labor and Delivery: None
- Nursing Mothers: It is not known if albiglutide is excreted into human milk during lactation. Discontinue nursing or discontinue albiglutide.
- Renal Impairment: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions.
- Hepatic Impairment: None
- Pediatric Patients: Safety and effectiveness have not been established in pediatric patients (younger than 18 years).
- Geriatric Patients: No overall differences in safety or effectiveness were observed between elderly patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
- It is not known if albiglutide is excreted into human milk during lactation. Discontinue nursing or discontinue albiglutide.
- Albiglutide is an agonist of the Glucagon-Like Peptide-1 (GLP-1) receptor and augments glucose-dependent insulin secretion while also slowing gastric emptying.
- Albiglutide lowers fasting glucose and reduces postprandial glucose excursions in patients with type 2 diabetes mellitus.
- In a Phase II trial in Japanese patients with type 2 diabetes mellitus who received albiglutide 30 mg, a reduction (22%) in postprandial glucose AUC (0-3 h) was observed at steady state (Week 16) compared with placebo following a mixed meal.
- A single dose of albiglutide 50 mg subcutaneous (SC) did not impair glucagon response to low glucose concentrations.
- Gastric Motility: Albiglutide slowed gastric emptying compared with placebo for both solids and liquids but mainly when albiglutide 100 mg (2 times the maximum approved dosage) was administered as a single dose in healthy subjects.
- Cardiac Electrophysiology: At doses up to the maximum recommended dose (50 mg), albiglutide does not prolong the QTc to any clinically relevant extent.
- Absorption: Maximum concentrations of albiglutide were reached at 3 to 5 days post-dosing. Steady-state exposures are achieved following 4 to 5 weeks of once-weekly administration.
- Similar exposure is achieved with SC administration of albiglutide in the abdomen, thigh, or upper arm.
- The absolute bioavailability is not known.
- Volume of Distribution: The mean estimate is 11 L.
- Protein Binding: Since albiglutide is an albumin fusion molecule, plasma protein binding has not been assessed.
- Metabolism: Since albiglutide is an albumin fusion protein, it likely follows a metabolic pathway similar to native human serum albumin, which is catabolized primarily in the vascular endothelium.
- Elimination: The mean apparent clearance of albiglutide is 67 mL/h
- Half-Life: Approximately 5 days, making albiglutide suitable for once-weekly administration.
- Specific Patient Populations:
- Age, Gender, Race, and Body Weight: No clinically relevant effect on the pharmacokinetics.
- Pediatric: No pharmacokinetic data are available in pediatric patients.
- Renal: In a population pharmacokinetic analysis including a Phase III trial in patients with mild, moderate, and severe renal impairment, exposures were increased by approximately 30% to 40% in severe renal impairment compared with those observed in type 2 diabetic patients with normal renal function.
- Hepatic: No clinical trials were conducted to examine the effects of mild, moderate, or severe hepatic impairment on the pharmacokinetics of albiglutide. Therapeutic proteins such as albiglutide are catabolized by widely distributed proteolytic enzymes, which are not restricted to hepatic tissue; therefore, changes in hepatic function are unlikely to have any effect on the elimination of albiglutide.
- Drug Interactions: In multiple-dose, drug-drug interaction trials no significant change in systemic exposures of the co-administered drugs were observed, except simvastatin. When albiglutide was co-administered with simvastatin, Cmax of simvastatin and its active metabolite simvastatin acid was increased by approximately 18% and 98%, respectively. In the same trial, AUC of simvastatin decreased by 40% and AUC of simvastatin acid increased by 36%. Clinical relevance of these changes has not been established. Additionally, no clinically relevant pharmacodynamic effects on luteinizing hormone follicle-stimulating hormone, or progesterone were observed when albiglutide and a combination oral contraceptive were co-administered. Albiglutide did not significantly alter the pharmacodynamic effects of warfarin as measured by the international normalized ratio (INR).
- Instruct patients that the pen should be used within 8 hours of reconstitution prior to attaching the needle.
- After attaching the supplied needle, remove air bubbles by slowly twisting the Pen until you see the  in the number window. At the same time, the injection button will be automatically released from the bottom of the Pen.
- Use immediately after the needle is attached and primed. The product can clog the needle if allowed to dry in the primed needle.
- After subcutaneously inserting the needle into the skin in the abdomen, thigh, or upper arm region, press the injection button. Hold the injection button until you hear a "click" and then hold the button for 5 additional seconds to deliver the full dose.
- Instruct patients when using albiglutide with insulin, to administer as separate injections and to never mix the products. It is acceptable to inject albiglutide and insulin in the same body region but the injections should not be adjacent to each other.
- Advise patients to use a different injection site each week when injecting in the same body region. Albiglutide must not be administered intravenously or intramuscularly.
- Instruct patients about self-management practices, including the importance of proper storage, injection technique, timing of dosage of albiglutide and concomitant oral drugs, and recognition and management of hypoglycemia.
- Inform patients that thyroid C-cell tumors have been observed in rodents treated with some GLP-1 receptor agonists and the human relevance of this finding is unknown. Counsel patients to report symptoms of thyroid tumors to their physician.
- Advise patients that persistent, severe abdominal pain that may radiate to the back and which may (or may not) be accompanied by vomiting is the hallmark symptom of acute pancreatitis. Instruct patients to discontinue albiglutide promptly and to contact their physician if persistent, severe abdominal pain occurs.
- The risk of hypoglycemia is increased when albiglutide is used in combination with an agent that induces hypoglycemia, such as sulfonylurea or insulin. Instructions for hypoglycemia should be reviewed with patients and reinforced when initiating therapy with albiglutide, particularly when concomitantly administered with a sulfonylurea or insulin.
- Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking albiglutide and seek medical advice promptly if such symptoms occur.
- Inform patients not to take an extra dose of albiglutide to make up for a missed dose. If a dose is missed, instruct patients to take a dose as soon as possible within 3 days after the missed dose. Instruct patients to then take their net dose at their usual weekly time. If it has been longer than 3 days after the missed dose, instruct patient to wait and take albiglutide at the next usual weekly time.
Black Box Warnings
Mechanism of Action
MESH Terms & Keywords