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Black Box Warning
WARNING: RISK OF THYROID C-CELL TUMORS
See full prescribing information for complete Boxed Warning.
* Carcinogenicity of albiglutide could not be assessed in rodents, but other glucagon-like peptide-1 (GLP-1) receptor agonists have caused thyroid C-cell tumors in rodents at clinically relevant exposures. Human relevance of GLP-1 receptor agonist induced C-cell tumors in rodents has not been determined. It is unknown whether TANZEUM™ causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans.
TANZEUM is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of TANZEUM and inform them of the symptoms of thyroid tumors (e.g., mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with TANZEUM.
Overview
Albiglutide is a {{{drugClass}}} that is FDA approved for the treatment of type 2 diabetes mellitus in adults. There is a Black Box Warning for this drug as shown here. Common adverse reactions include upper respiratory tract infection, diarrhea, nausea, and injection site reaction..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
TANZEUM is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Limitations of Use
TANZEUM is not recommended as first-line therapy for patients inadequately controlled on diet and exercise because of the uncertain relevance of the rodent C-cell tumor findings to humans. Prescribe TANZEUM only to patients for whom the potential benefits are considered to outweigh the potential risk.
TANZEUM has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
TANZEUM is not indicated in the treatment of patients with type 1 diabetes mellitus or for the treatment of patients with diabetic ketoacidosis. TANZEUM is not a substitute for insulin in these patients.
TANZEUM has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis. The use of TANZEUM is not recommended in patients with pre-existing severe gastrointestinal disease.
TANZEUM has not been studied in combination with prandial insulin.
Dosage
The recommended dosage of TANZEUM is 30 mg once weekly given as a subcutaneous injection in the abdomen, thigh, or upper arm region. The dosage may be increased to 50 mg once weekly if the glycemic response is inadequate.
TANZEUM may be administered at any time of day without regard to meals. Instruct patients to administer TANZEUM once a week on the same day each week. The day of weekly administration may be changed if necessary as long as the last dose was administered 4 or more days before.
If a dose is missed, instruct patients to administer as soon as possible within 3 days after the missed dose. Thereafter, patients can resume dosing on their usual day of administration. If it is more than 3 days after the missed dose, instruct patients to wait until their next regularly scheduled weekly dose.
Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
When initiating TANZEUM, consider reducing the dosage of concomitantly administered insulin secretagogues (e.g., sulfonylureas) or insulin to reduce the risk of hypoglycemia.
Dosage in Patients with Renal Impairment
No dose adjustment is needed in patients with mild, moderate, or severe renal impairment (eGFR 15 to 89 mL/min/1.73 m2). Use caution when initiating or escalating doses of TANZEUM in patients with renal impairment. Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions.
Reconstitution of the Lyophilized Powder
The lyophilized powder contained within the Pen must be reconstituted prior to administration. See Patient Instructions for Use for complete administration instructions with illustrations. The instructions may also be found at www.TANZEUM.com. Instruct patients as follows:
Pen Reconstitution
Hold the Pen body with the clear cartridge pointing up to see the [1] in the number window.
To reconstitute the lyophilized powder with the diluent in the Pen, twist the clear cartridge on the Pen in the direction of the arrow until the Pen is felt/heard to “click” into place and the [2] is seen in the number window. This mixes the diluent with the lyophilized powder.
Slowly and gently rock the Pen side-to-side 5 times to mix the reconstituted solution of TANZEUM. Advise the patient to not shake the Pen hard to avoid foaming.
Wait 15 minutes for the 30-mg Pen and 30 minutes for the 50-mg Pen to ensure that the reconstituted solution is mixed.
Preparing Pen for Injection
Slowly and gently rock the Pen side-to-side 5 additional times to mix the reconstituted solution.
Visually inspect the reconstituted solution in the viewing window for particulate matter. The reconstituted solution will be yellow in color. After reconstitution, use TANZEUM within 8 hours.
Holding the Pen upright, attach the needle to the Pen. Gently tap the clear cartridge to bring large bubbles to the top.
Alternate Method of Reconstitution
The Patient Instructions for Use provide directions for the patient to wait 15 minutes for the 30-mg Pen and 30 minutes for the 50-mg Pen after the lyophilized powder and diluent are mixed to ensure reconstitution.
Healthcare professionals may utilize the following alternate method of reconstitution. Because this method relies on appropriate swirling and visual inspection of the solution, it should only be performed by healthcare professionals.
Follow Step A (Inspect Your Pen and Mix Your Medication) in the Instructions for Use. Make sure you have:
Inspected the Pen for [1] in the number window and expiration date.
Twisted the clear cartridge until [2] appears in the number window and a “click” is heard. This combines the medicine powder and liquid in the clear cartridge.
Hold the Pen with the clear cartridge pointing up and maintain this orientation throughout the reconstitution.
Gently swirl the Pen in small circular motions for at least one minute. Avoid shaking as this can result in foaming, which may affect the dose.
Inspect the solution, and if needed, continue to gently swirl the Pen until all the powder is dissolved and you see a clear yellow solution that is free of particles. A small amount of foam, on top of the solution at the end of reconstitution, is normal.
For 30-mg Pen: Complete dissolution usually occurs within 2 minutes but may take up to 5 minutes, as confirmed by visual inspection for a clear yellow solution free of particles.
For 50-mg Pen: Complete dissolution usually occurs within 7 minutes but may take up to 10 minutes.
After reconstitution, continue to follow the steps in the Instructions for Use, starting at Step B: Attach the Needle.
DOSAGE FORMS AND STRENGTHS
TANZEUM is supplied as follows:
For injection: 30-mg lyophilized powder in a single-dose Pen (pen injector) for reconstitution.
For injection: 50-mg lyophilized powder in a single-dose Pen (pen injector) for reconstitution.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Albiglutide in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Albiglutide in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Albiglutide in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Albiglutide in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Albiglutide in pediatric patients.
Contraindications
Medullary Thyroid Carcinoma
TANZEUM is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Hypersensitivity
TANZEUM is contraindicated in patients with a prior serious hypersensitivity reaction to albiglutide or to any of the product components.
Warnings
WARNING: RISK OF THYROID C-CELL TUMORS
See full prescribing information for complete Boxed Warning.
* Carcinogenicity of albiglutide could not be assessed in rodents, but other glucagon-like peptide-1 (GLP-1) receptor agonists have caused thyroid C-cell tumors in rodents at clinically relevant exposures. Human relevance of GLP-1 receptor agonist induced C-cell tumors in rodents has not been determined. It is unknown whether TANZEUM™ causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans.
TANZEUM is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with the use of TANZEUM and inform them of the symptoms of thyroid tumors (e.g., mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with TANZEUM.
Risk of Thyroid C-cell Tumors
Carcinogenicity of albiglutide could not be assessed in rodents due to the rapid development of drug-clearing, anti-drug antibodies. Other GLP-1 receptor agonists have caused dose-related and treatment-duration-dependent thyroid C-cell tumors (adenomas or carcinomas) in rodents. Human relevance of GLP-1 receptor agonist induced C-cell tumors in rodents has not been determined. It is unknown whether TANZEUM causes thyroid C-cell tumors, including MTC, in humans.
Across 8 Phase III clinical trials, MTC was diagnosed in 1 patient receiving TANZEUM and 1 patient receiving placebo. Both patients had markedly elevated serum calcitonin levels at baseline. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans.
TANZEUM is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of TANZEUM and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, or persistent hoarseness).
Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with TANZEUM. Such monitoring may increase the risk of unnecessary procedures, due to the low specificity of serum calcitonin testing for MTC and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.
Acute Pancreatitis
In clinical trials, acute pancreatitis has been reported in association with TANZEUM.
Across 8 Phase III clinical trials, pancreatitis adjudicated as likely related to therapy occurred more frequently in patients receiving TANZEUM (6 of 2,365 [0.3%]) than in patients receiving placebo (0 of 468 [0%]) or active comparators (2 of 2,065 [0.1%]).
After initiation of TANZEUM, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, promptly discontinue TANZEUM. If pancreatitis is confirmed, TANZEUM should not be restarted.
TANZEUM has not been studied in patients with a history of pancreatitis to determine whether these patients are at increased risk for pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin
The risk of hypoglycemia is increased when TANZEUM is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Therefore, patients may require a lower dose of sulfonylurea or insulin to reduce the risk of hypoglycemia in this setting.
Hypersensitivity Reactions
Across 8 Phase III clinical trials, a serious hypersensitivity reaction with pruritus, rash, and dyspnea occurred in a patient treated with TANZEUM. If hypersensitivity reactions occur, discontinue use of TANZEUM; treat promptly per standard of care and monitor until signs and symptoms resolve.
Renal Impairment
In patients treated with GLP-1 receptor agonists, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure, which may sometimes require hemodialysis. Some of these events were reported in patients without known underlying renal disease. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In a trial of TANZEUM in patients with renal impairment, the frequency of such gastrointestinal reactions increased as renal function declined. Because these reactions may worsen renal function, use caution when initiating or escalating doses of TANZEUM in patients with renal impairment.
Macrovascular Outcomes
There have been no clinical trials establishing conclusive evidence of macrovascular risk reduction with TANZEUM or any other antidiabetic drug.
Adverse Reactions
Clinical Trials Experience
The following serious reactions are described below or elsewhere in the prescribing information:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Pool of Placebo-Controlled Trials
The data in Table 1 are derived from 4 placebo-controlled trials. TANZEUM was used as monotherapy in 1 trial and as add-on therapy in 3 trials. These data reflect exposure of 923 patients to TANZEUM and a mean duration of exposure to TANZEUM of 93 weeks. The mean age of participants was 55 years, 1% of participants were 75 years or older and 53% of participants were male. The population in these studies was 48% white, 13% African/African American, 7% Asian, and 29% Hispanic/Latino. At baseline, the population had diabetes for an average of 7 years and had a mean HbA1c of 8.1%. At baseline, 17% of the population in these studies reported peripheral neuropathy and 4% reported retinopathy. Baseline estimated renal function was normal or mildly impaired (eGFR >60 mL/min/1.73 m2) in 91% of the study population and moderately impaired (eGFR 30 to 60 mL/min/1.73 m2) in 9%.
Table 1 shows common adverse reactions excluding hypoglycemia associated with the use of TANZEUM in the pool of placebo-controlled trials. These adverse reactions were not present at baseline, occurred more commonly on TANZEUM than on placebo, and occurred in at least 5% of patients treated with TANZEUM.
This image is provided by the National Library of Medicine.
Gastrointestinal Adverse Reactions
In the pool of placebo-controlled trials, gastrointestinal complaints occurred more frequently among patients receiving TANZEUM (39%) than patients receiving placebo (33%). In addition to diarrhea and nausea (see Table 1), the following gastrointestinal adverse reactions also occurred more frequently in patients receiving TANZEUM: vomiting (2.6% versus 4.2% for placebo versus TANZEUM), gastroesophageal reflux disease (1.9% versus 3.5% for placebo versus TANZEUM), and dyspepsia (2.8% versus 3.4% for placebo versus TANZEUM). Constipation also contributed to the frequently reported reactions. In the group treated with TANZEUM, investigators graded the severity of GI reactions as “mild” in 56% of cases, “moderate” in 37% of cases, and “severe” in 7% of cases. Discontinuation due to GI adverse reactions occurred in 2% of individuals on TANZEUM or placebo.
Injection Site Reactions
In the pool of placebo-controlled trials, injection site reactions occurred more frequently on TANZEUM (18%) than on placebo (8%). In addition to the term injection site reaction (see Table 1), the following other types of injection site reactions also occurred more frequently on TANZEUM: injection site hematoma (1.9% versus 2.1% for placebo versus TANZEUM ), injection site erythema (0.4% versus 1.7% for placebo versus TANZEUM), injection site rash (0% versus 1.4% for placebo versus TANZEUM), injection site hypersensitivity (0% versus 0.8% for placebo versus TANZEUM), and injection site hemorrhage (0.6% versus 0.7% for placebo versus TANZEUM). Injection site pruritus also contributed to the frequently reported reactions. The majority of injection site reactions were judged as “mild” by investigators in both groups (73% for TANZEUM versus 94% for placebo). More patients on TANZEUM than on placebo: discontinued due to an injection site reaction (2% versus 0.2%), experienced more than 2 reactions (38% versus 20%), had a reaction judged by investigators to be “moderate” or “severe” (27% versus 6%) and required local or systemic treatment for the reactions (36% versus 11%).
Pool of Placebo- and Active-controlled Trials
The occurrence of adverse reactions was also evaluated in a larger pool of patients with type 2 diabetes participating in 7 placebo- and active-controlled trials. These trials evaluated the use of TANZEUM as monotherapy, and as add-on therapy to oral antidiabetic agents, and as add-on therapy to basal insulin. In this pool, a total of 2,116 patients with type 2 diabetes were treated with TANZEUM for a mean duration of 75 weeks. The mean age of patients treated with TANZEUM was 55 years, 1.5% of the population in these studies was 75 years or older and 51% of participants were male. Forty-eight percent of patients were white, 15% African/African American, 9% Asian, and 26% were Hispanic/Latino. At baseline, the population had diabetes for an average of 8 years and had a mean HbA1c of 8.2%. At baseline, 21% of the population reported peripheral neuropathy and 5% reported retinopathy. Baseline estimated renal function was normal or mildly impaired (eGFR >60 mL/min/1.73 m2) in 92% of the population and moderately impaired (eGFR 30 to 60 mL/min/1.73 m2) in 8% of the population.
In the pool of placebo- and active-controlled trials, the types and frequency of common adverse reactions excluding hypoglycemia were similar to those listed in Table 1.
Other Adverse Reactions
Hypoglycemia
The proportion of patients experiencing at least one documented symptomatic hypoglycemic episode on TANZEUM and the proportion of patients experiencing at least one severe hypoglycemic episode on TANZEUM in clinical trials is shown in Table 2. Hypoglycemia was more frequent when TANZEUM was added to sulfonylurea or insulin.
This image is provided by the National Library of Medicine.
Pneumonia
In the pool of 7 placebo- and active-controlled trials, the adverse reaction of pneumonia was reported more frequently in patients receiving TANZEUM (1.8%) than in patients in the all-comparators group (0.8%). More cases of pneumonia in the group receiving TANZEUM were serious (0.4% for TANZEUM versus 0.1% for all comparators).
Atrial Fibrillation/Flutter
In the pool of 7 placebo- and active-controlled trials, adverse reactions of atrial fibrillation (1.0%) and atrial flutter (0.2%) were reported more frequently for TANZEUM than for all comparators (0.5% and 0%, respectively). In both groups, patients with events were generally male, older, and had underlying renal impairment or cardiac disease (e.g., history of arrhythmia, palpitations, congestive heart failure, cardiomyopathy, etc.).
Appendicitis
In the pool of placebo- and active-controlled trials, serious events of appendicitis occurred in 0.3% of patients treated with TANZEUM compared with 0% among all comparators.
Immunogenicity
In the pool of 7 placebo- and active-controlled trials, 116 (5.5%) of 2,098 patients exposed to TANZEUM tested positive for anti-albiglutide antibodies at any time during the trials. None of these antibodies were shown to neutralize the activity of albiglutide in an in vitro bioassay. Presence of antibody did not correlate with reduced efficacy as measured by HbA1c and fasting plasma glucose or specific adverse reactions.
Consistent with the high homology of albiglutide with human GLP-1, the majority of patients (approximately 79%) with anti-albiglutide antibodies also tested positive for anti-GLP-1 antibodies; none were neutralizing. A minority of patients (approximately 17%) who tested positive for anti-albiglutide antibodies also transiently tested positive for antibodies to human albumin.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to albiglutide cannot be directly compared with the incidence of antibodies of other products.
Liver Enzyme Abnormalities
In the pool of placebo- and active-controlled trials, a similar proportion of patients experienced at least one event of alanine aminotransferase (ALT) increase of 3-fold or greater above the upper limit of normal (0.9% and 0.9% for all comparators versus TANZEUM). Three subjects on TANZEUM and one subject in the all-comparator group experienced at least one event of ALT increase of 10-fold or greater above the upper limit of normal. In one of the 3 cases an alternate etiology was identified to explain the rise in liver enzyme (acute viral hepatitis). In one case, insufficient information was obtained to establish or refute a drug-related causality. In the third case, elevation in ALT (10 times the upper limit of normal) was accompanied by an increase in total bilirubin (4 times the upper limit of normal) and occurred 8 days after the first dose of TANZEUM. The etiology of hepatocellular injury was possibly related to TANZEUM but direct attribution to TANZEUM was confounded by the presence of gallstone disease diagnosed on ultrasound 3 weeks after the event.
Gamma Glutamyltransferase (GGT) Increase
In the pool of placebo-controlled trials, the adverse event of increased GGT occurred more frequently in the group treated with TANZEUM (0.9% and 1.5% for placebo versus TANZEUM).
Heart Rate Increase
In the pool of placebo-controlled trials, mean heart rate in patients treated with TANZEUM was higher by an average of 1 to 2 bpm compared with mean heart rate in patients treated with placebo across study visits. The long-term clinical effects of the increase in heart rate have not been established.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Albiglutide in the drug label.
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Drug Interactions
TANZEUM did not affect the absorption of orally administered medications tested in clinical pharmacology studies to any clinically relevant degree. However, TANZEUM causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with TANZEUM.
There are no adequate and well-controlled studies of TANZEUM in pregnant women. Nonclinical studies have shown reproductive toxicity, but not teratogenicity, in mice treated with albiglutide at up to 39 times human exposure resulting from the maximum recommended dose of 50 mg/week, based on AUC . TANZEUM should not be used during pregnancy unless the expected benefit outweighs the potential risks.
Due to the long washout period for TANZEUM, consider stopping TANZEUM at least 1 month before a planned pregnancy.
There are no data on the effects of TANZEUM on human fertility. Studies in mice showed no effects on fertility. The potential risk to human fertility is unknown.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Albiglutide in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Albiglutide during labor and delivery.
Nursing Mothers
There are no adequate data to support the use of TANZEUM during lactation in humans.
It is not known if TANZEUM is excreted into human milk during lactation. Given that TANZEUM is an albumin-based protein therapeutic, it is likely to be present in human milk. Decreased body weight in offspring was observed in mice treated with TANZEUM during gestation and lactation. A decision should be made whether to discontinue nursing or to discontinue TANZEUM, taking into account the importance of the drug to the mother and the potential risks to the infant.
Pediatric Use
Safety and effectiveness of TANZEUM have not been established in pediatric patients (younger than 18 years).
Geriatic Use
Of the total number of patients (N = 2,365) in 8 Phase III clinical trials who received TANZEUM, 19% (N = 444) were 65 years and older, and <3% (N = 52) were 75 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Gender
There is no FDA guidance on the use of Albiglutide with respect to specific gender populations.
Race
There is no FDA guidance on the use of Albiglutide with respect to specific racial populations.
Renal Impairment
Of the total number of patients (N = 2,365) in 8 Phase III clinical trials who received TANZEUM, 54% (N = 1,267) had mild renal impairment (eGFR 60 to 89 mL/min/1.73 m2), 12% (N = 275) had moderate renal impairment (eGFR 30 to 59 mL/min/1.73 m2) and 1% (N = 19) had severe renal impairment (eGFR 15 to <30 mL/min/1.73 m2).
No dosage adjustment is required in patients with mild (eGFR 60 to 89 mL/min/1.73 m2), moderate (eGFR 30 to 59 mL/min/1.73 m2), or severe (eGFR 15 to <30 mL/min/1.73 m2) renal impairment.
Efficacy of TANZEUM in patients with type 2 diabetes and renal impairment is described elsewhere. There is limited clinical experience in patients with severe renal impairment (19 subjects). The frequency of GI events increased as renal function declined. For patients with mild, moderate, or severe impairment, the respective event rates were: diarrhea (6%, 13%, 21%), nausea (3%, 5%, 16%), and vomiting (1%, 2%, 5%). Therefore, caution is recommended when initiating or escalating doses of TANZEUM in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Albiglutide in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Albiglutide in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Albiglutide in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Intravenous
Monitoring
There is limited information regarding Monitoring of Albiglutide in the drug label.
Description
IV Compatibility
There is limited information regarding IV Compatibility of Albiglutide in the drug label.
Overdosage
No data are available with regard to overdosage in humans. Anticipated symptoms of an overdose may be severe nausea and vomiting.
In the event of an overdose, 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 TANZEUM (5 days).
Pharmacology
There is limited information regarding Albiglutide Pharmacology in the drug label.
Mechanism of Action
TANZEUM is an agonist of the GLP-1 receptor and augments glucose-dependent insulin secretion. TANZEUM also slows gastric emptying.
TANZEUM lowers fasting glucose and reduces postprandial glucose excursions in patients with type 2 diabetes mellitus. The majority of the observed reduction in fasting plasma glucose occurs after a single dose, consistent with the pharmacokinetic profile of albiglutide. In a Phase II trial in Japanese patients with type 2 diabetes mellitus who received TANZEUM 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 TANZEUM 50 mg subcutaneous (SC) did not impair glucagon response to low glucose concentrations.
Gastric Motility
TANZEUM slowed gastric emptying compared with placebo for both solids and liquids 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), TANZEUM does not prolong QTc to any clinically relevant extent.
Pharmacokinetics
Absorption
Following SC administration of a single 30-mg dose to subjects with type 2 diabetes mellitus, maximum concentrations of albiglutide were reached at 3 to 5 days post-dosing. The mean peak concentration (Cmax) and mean area under the time-concentration curve (AUC) of albiglutide were 1.74 mcg/mL and 465 mcg.h/mL, respectively, following a single dose of 30 mg albiglutide in type 2 diabetes mellitus subjects. Steady-state exposures are achieved following 4 to 5 weeks of once-weekly administration. Exposures at the 30-mg and 50-mg dose levels were consistent with a dose-proportional increase. Similar exposure is achieved with SC administration of albiglutide in the abdomen, thigh, or upper arm. The absolute bioavailability of albiglutide following SC administration has not been evaluated.
Distribution
The mean estimate of apparent volume of distribution of albiglutide following SC administration is 11 L. As albiglutide is an albumin fusion molecule, plasma protein binding has not been assessed.
Metabolism
Albiglutide is a protein for which the expected metabolic pathway is degradation to small peptides and individual amino acids by ubiquitous proteolytic enzymes. Classical biotransformation studies have not been performed. Because 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 with an elimination half-life of approximately 5 days, making albiglutide suitable for once-weekly administration.
Specific Patient Populations
Age, Gender, Race, and Body Weight: Based on the population pharmacokinetic analysis with data collected from 1,113 subjects, age, gender, race, and body weight had no clinically relevant effect on the pharmacokinetics of albiglutide.
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 (see Table 3). 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 (see Table 3).
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).
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Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
As albiglutide is a recombinant protein, no genotoxicity studies have been conducted.
Carcinogenicity of albiglutide could not be assessed in rodents due to the rapid development of drug-clearing, anti-drug antibodies. Other GLP-1 receptor agonists have caused thyroid C-cell tumors in rodent carcinogenicity studies. Human relevance of GLP-1 receptor agonist induced rodent thyroid C-cell tumors has not been determined.
In a mouse fertility study, males were treated with SC doses of 5, 15, or 50 mg/kg/day for 7 days prior to cohabitation with females, and continuing through mating. In a separate fertility study, females were treated with SC doses of 1, 5, or 50 mg/kg/day for 7 days prior to cohabitation with males, and continuing through mating. Reductions in estrous cycles were observed at 50 mg/kg/day, a dose associated with maternal toxicity (body weight loss and reduced food consumption). There were no effects on mating or fertility in either sex at doses up to 50 mg/kg/day (up to 39 times clinical exposure based on AUC).
Reproductive and Developmental Toxicity
In order to minimize the impact of the drug-clearing, anti-drug antibody response, reproductive and developmental toxicity assessments in the mouse were partitioned to limit the dosing period to no more than approximately 15 days in each study.
In pregnant mice given SC doses of 1, 5, or 50 mg/kg/day from gestation Day 1 to 6, there were no adverse effects on early embryonic development through implantation at 50 mg/kg/day (39 times clinical exposure based on AUC).
In pregnant mice given SC doses of 1, 5, or 50 mg/kg/day from gestation Day 6 through 15 (organogenesis), embryo-fetal lethality (post-implantation loss) and bent (wavy) ribs were observed at 50 mg/kg/day (39 times clinical exposure based on AUC), a dose associated with maternal toxicity (body weight loss and reduced food consumption).
Pregnant mice were given SC doses of 1, 5, or 50 mg/kg/day from gestation Day 6 to 17. Offspring of pregnant mice given 50 mg/kg/day (39 times clinical exposure based on AUC), a dose associated with maternal toxicity, had reduced body weight pre-weaning, dehydration and coldness, and a delay in balanopreputial separation.
Pregnant mice were given SC doses of 1, 5, or 50 mg/kg/day from gestation Day 15 to lactation Day 10. Increased mortality and morbidity were seen at all doses (≥1 mg/kg/day) in lactating females in mouse pre- and postnatal development studies. Mortalities have not been observed in previous toxicology studies in non-lactating or non-pregnant mice, nor in pregnant mice. These findings are consistent with lactational ileus syndrome which has been previously reported in mice. Since the relative stress of lactation energy demands is lower in humans than mice and humans have large energy reserves, the mortalities observed in lactating mice are of questionable relevance to humans. The offspring had decreased pre-weaning body weight which reversed post-weaning in males but not females at ≥5 mg/kg/day (2.2 times clinical exposure based on AUC) with no other effects on development. Low levels of albiglutide were detected in plasma of offspring.
Lactating mice were given SC doses of 1, 5, or 50 mg/kg/day from lactation Day 7 to 21 (weaning) under conditions that limit the impact of lactational ileus (increased caloric intake and culling of litters). Doses ≥1 mg/kg/day (exposures below clinical AUC) caused reduced weight gain in the pups during the treatment period.
Clinical Studies
There is limited information regarding Clinical Studies of Albiglutide in the drug label.
How Supplied
Storage
There is limited information regarding Albiglutide Storage in the drug label.
Images
Drug Images
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