Bydureon

Bydureon is the brand name of exenatide, which is an injectable medication used to treat people with type 2 diabetes.

Type 2 diabetes occurs when the body doesn't produce or use the hormone insulin properly.

Bydureon is used along with diet and exercise to help control blood sugar levels and aid in weight loss. It's a long-acting form of the medication contained in another brand name drug known as Byetta.

The medicine is in a class of drugs known as incretin mimetics, which work by prompting the pancreas to release insulin when blood sugar levels are high and slowing the emptying of the stomach.

The Food and Drug Administration (FDA) approved Bydureon in 2012. It's manufactured by AstraZeneca.

Bydureon Warnings

Bydureon shouldn't be used to treat people with type 1 diabetes, a disease that occurs when the body doesn't produce any insulin.

The drug also shouldn't be used by someone who is in a state of diabetic ketoacidosis (a condition that causes dangerously high blood sugar levels).

Don't use Bydureon in place of insulin. It's not known whether this medicine is safe to use along with insulin.

Bydureon caused thyroid tumors in animal studies. However, it's not known whether the drug has the same effect in humans.

Don't take this medicine if you have any of the following:

• Thyroid cancer
• A family history of thyroid cancer
• Multiple endocrine neoplasia type 2 (a type of cancer that can affect the thyroid, adrenal glands, and parathyroid)

Stop taking Bydureon immediately if you experience any signs of pancreatitis (inflammation of the pancreas), which may include severe pain in your upper stomach that spreads to your back along with nausea, vomiting, and a fast heart rate.

Bydureon and the drug Byetta both contain the active ingredient exenatide and shouldn't be used together.

Before taking Bydureon, tell your doctor if you have or have ever had any of the following conditions:

• Kidney disease
• A kidney transplant
• A stomach disorder that causes slow digestion
• Pancreatitis or gallstones
• Dehydration
• High triglyceride levels
• High blood pressure

You should also tell your health care provider if you've ever consumed large amounts of alcohol or suffered from alcoholism before taking Bydureon.

This medicine may cause changes in your blood sugar. You should know the symptoms of a high and low blood sugar episode and what to do if you experience them.

Illnesses, injuries, or unusual stress can impact your blood sugar levels. They may also affect how much Bydureon you need.

Talk to your physician if you experience any of these conditions while taking this medicine.

Your doctor will likely want to check your blood sugar levels often while you are taking Bydureon. Keep all appointments with your health care provider and laboratory.

Bydureon will help control type 2 diabetes, but it won't cure the condition. Continue to take this medicine even if you feel well.

Don't stop taking this drug without first talking to your physician.

Pregnancy and Bydureon

It's not known whether Bydureon will harm an unborn baby.

Tell your doctor if you're pregnant or plan to become pregnant before using this medicine.

It's also not known whether Bydureon passes into breast milk or could harm a breastfeeding baby. Tell your doctor if you're breastfeeding before taking this drug.

BYDUREON is an extended-release formulation of exenatide, administered as an injection once every 7 days (weekly).

Type 2 Diabetes Mellitus

BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [see Clinical Studies].

Important Limitations Of Use

BYDUREON is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans. Prescribe BYDUREON only to patients for whom the potential benefits are considered to outweigh the potential risk BYDUREON is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans. Prescribe BYDUREON only to patients for whom the potential benefits are considered to outweigh the potential risk [see WARNINGS AND PRECAUTIONS].

BYDUREON is not a substitute for insulin. BYDUREON should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

The concurrent use of BYDUREON with insulin has not been studied and cannot be recommended.

BYDUREON and BYETTA® (exenatide) injection both contain the same active ingredient, exenatide, and therefore should not be used together.

Based on postmarketing data, exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. BYDUREON has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYDUREON. Other antidiabetic therapies should be considered in patients with a history of pancreatitis [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Included as part of the PRECAUTIONS section.

Use Bydureon exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Bydureon dose your doctor recommends will be based on the following:

• other medications you are taking
• how you respond to this medication

The recommended dose of Bydureon is 2 mg injected once every seven days (weekly). The dose can be administered at any time of day, with or without meals.

If you use too much Bydureon, call your doctor or local Poison Control Center right away.

• Too much Bydureon can cause your blood sugar to drop quickly and you may have symptoms of low blood sugar. You may need medical treatment right away.
• Too much Bydureon can also cause severe nausea and vomiting.

In the U.S.

• Bydureon
• Byetta

Available Dosage Forms:

• Powder for Suspension, Extended Release
• Solution

Therapeutic Class: Antidiabetic

Pharmacologic Class: Glucagon-Like Peptide-1 Receptor Agonist

Exenatide injection is used together with diet and exercise to treat type 2 diabetes.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of exenatide injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of exenatide injection in the elderly. However, elderly patients are more likely to have kidney problems, which may require caution and an adjustment in the dose for patients receiving exenatide injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Balofloxacin
• Besifloxacin
• Ciprofloxacin
• Enoxacin
• Fleroxacin
• Flumequine
• Gatifloxacin
• Gemifloxacin
• Lanreotide
• Levofloxacin
• Lomefloxacin
• Moxifloxacin
• Nadifloxacin
• Norfloxacin
• Octreotide
• Ofloxacin
• Pasireotide
• Pazufloxacin
• Pefloxacin
• Prulifloxacin
• Rufloxacin
• Sparfloxacin
• Thioctic Acid
• Tosufloxacin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Atenolol
• Betaxolol
• Bisoprolol
• Carteolol
• Carvedilol
• Celiprolol
• Digoxin
• Esmolol
• Insulin
• Insulin Aspart, Recombinant
• Insulin Bovine
• Insulin Degludec
• Insulin Detemir
• Insulin Glargine, Recombinant
• Insulin Glulisine
• Insulin Lispro, Recombinant
• Labetalol
• Levobunolol
• Metipranolol
• Metoprolol
• Nadolol
• Nebivolol
• Oxprenolol
• Penbutolol
• Pindolol
• Practolol
• Propranolol
• Sotalol
• Timolol
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetic ketoacidosis (ketones in the blood) or
• Type 1 diabetes—Should not be used in patients with these conditions. Insulin is needed to control these conditions.

• Gallstones or
• Kidney disease (including kidney transplant) or
• Pancreatitis (inflammation of the pancreas), history of or
• Thyroid tumor—Use with caution. May make these conditions worse.

• Gastroparesis (stomach does not empty food normally) or
• Kidney disease, severe or
• Multiple endocrine neoplasia syndrome type 2 (MEN 2) or
• Stomach or bowel disease, severe or
• Thyroid cancer, history of—Should not be used in patients with these conditions.

The following serious adverse reactions are described below or elsewhere in the prescribing information:

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Bydureon was assessed in six comparator-controlled trials in patients who entered the studies not achieving adequate glycemic control on their current therapy. In a double-blind 26-week trial, patients on diet and exercise were treated with Bydureon 2 mg once every 7 days (weekly), sitagliptin 100 mg daily, pioglitazone 45 mg daily, or metformin 2000 mg daily. In a double-blind 26-week trial, patients on metformin were treated with Bydureon 2 mg once every 7 days (weekly), sitagliptin 100 mg daily, or pioglitazone 45 mg daily. In an open-label 26-week trial, patients on metformin or metformin plus sulfonylurea were treated with Bydureon 2 mg once every 7 days (weekly) or optimized insulin glargine. In two open-label 24- to 30-week studies, patients on diet and exercise or metformin, a sulfonylurea, a thiazolidinedione, or combination of oral agents were treated with Bydureon 2 mg once every 7 days (weekly) or BYETTA 10 mcg twice daily. In an open-label 26-week trial, patients on metformin, a sulfonylurea, metformin plus a sulfonylurea, or metformin plus pioglitazone were treated with Bydureon 2 mg every 7 days (weekly) or liraglutide 1.8 mg once daily.

The incidence of withdrawal due to adverse events was 4.1% (N=57) for Bydureon-treated patients, 4.9% (N=13) for BYETTA-treated patients, and 2.9% (N=46) for other comparator-treated patients in the six comparator-controlled 24- to 30-week trials. The most common classes of adverse reactions (0.5%) leading to withdrawal for Bydureon-treated patients were, Gastrointestinal Disorders 1.6% (N=22) versus 4.1% (N=11) for BYETTA and 1.9% (N=30) for other comparators, and Administration Site Conditions 0.8% (N=11) versus 0.0% for BYETTA and 0.2% (N=3) for other comparators. The most frequent events within each of these respective classes were, nausea 0.4% (N=6) for Bydureon versus 1.5% (N=4) for BYETTA and 0.8% (N=12) for other comparators, and injection-site nodule, 0.4% (N=6) for Bydureon versus 0.0% for BYETTA and 0.0% for other comparators.

Table 1 summarizes the incidence and rate of minor hypoglycemia in the six comparator-controlled 24- to 30-week trials of Bydureon used as monotherapy or as add-on to metformin, a sulfonylurea, a thiazolidinedione, or combination of these oral antidiabetic agents. In these trials, an event was classified as minor hypoglycemia if there were symptoms of hypoglycemia with a concomitant glucose <54 mg/dL and the patient was able to self-treat.

There were no reported events of major hypoglycemia in these six comparator-controlled 24- to 30-week trials. Major hypoglycemia was defined as loss of consciousness, seizure, or coma (or other mental status change consistent with neuroglycopenia in the judgment of the investigator or physician) which resolved after administration of glucagon or glucose or required third-party assistance to resolve because of severe impairment in consciousness or behavior. Patients were to have a concomitant glucose <54 mg/dL.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. 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, comparison of the incidence of antibodies to Bydureon in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Anti-exenatide antibodies were measured at prespecified intervals (4-14 weeks) in all Bydureon-treated patients (N=918) in the five comparator-controlled studies of Bydureon. In these five trials, 452 Bydureon-treated patients (49%) had low titer antibodies (≤125) to exenatide at any time during the trials and 405 Bydureon-treated patients (45%) had low titer antibodies to exenatide at study endpoint (24-30 weeks). The level of glycemic control in these patients was generally comparable to that observed in the 379 Bydureon-treated patients (43%) without antibody titers. An additional 107 Bydureon-treated patients (12%) had higher titer antibodies at endpoint. Of these patients, 50 (6% overall) had an attenuated glycemic response to Bydureon (<0.7% reduction in HbA1c); the remaining 57 (6% overall) had a glycemic response comparable to that of patients without antibodies [see Warnings and Precautions (5.6)]. In the 30-week trial in which anti-exenatide antibody assessments were performed at baseline and at 4-week intervals from week 6 to week 30, the mean anti-exenatide antibody titer in the Bydureon-treated patients peaked at week 6 then declined by 56% from this peak by week 30.

A total of 246 patients with antibodies to exenatide in the BYETTA and Bydureon clinical trials were tested for the presence of cross-reactive antibodies to GLP-1 and/or glucagon. No treatment-emergent cross-reactive antibodies were observed across the range of titers.

Other Adverse Reactions

Tables 2 and 3 summarize adverse reactions with an incidence ≥5% reported in the six comparator-controlled 24- to 30-week trials of Bydureon used as monotherapy or as add-on to metformin, a sulfonylurea, a thiazolidinedione, or combination of these oral antidiabetic agents (the findings in the Bydureon are from a sixth comparator-controlled open label trial of Bydureon are included in Table 3).

N = number of intent-to-treat patients.
Note: Percentages are based on the number of intent-to-treat patients in each treatment group.
† Patients in the sitagliptin, pioglitazone, and metformin treatment groups received weekly placebo injections.

Nausea was the most common adverse reaction associated with initiation of treatment with Bydureon, and usually decreased over time.

In the five comparator-controlled 24- to 30-week trials, injection-site reactions were observed more frequently in patients treated with Bydureon (17.1%) than in patients treated with BYETTA (12.7%), titrated insulin glargine (1.8%), or those patients who received placebo injections (sitagliptin (10.6%), pioglitazone (6.4%), and metformin (13.0%) treatment groups). These reactions for patients treated with Bydureon were more commonly observed in antibody-positive patients (14.2%) compared with antibody-negative patients (3.1%), with a greater incidence in those with higher titer antibodies [see Warnings and Precautions (5.6)]. Incidence of injection-site reactions for patients treated with BYETTA was similar for antibody-positive patients (5.8%) and antibody-negative patients (7.0%). One percent of patients treated with Bydureon withdrew due to injection-site adverse reactions (injection-site mass, injection-site nodule, injection-site pruritus, and injection-site reaction).

Subcutaneous injection-site nodules may occur with the use of Bydureon. In a separate 15-week study in which information on nodules were collected and analyzed, 24 out of 31 subjects (77%) experienced at least 1 injection-site nodule during treatment; 2 subjects (6.5%) reported accompanying localized symptoms. The mean duration of events was 27 days. The formation of nodules is consistent with the known properties of the microspheres used in Bydureon.

Increases in heart rate from baseline ranging from 1.5 to 4.5 beats per minute have been observed in comparator-controlled clinical trials. The long-term effects of the increase in heart rate have not been established.

In three 30-week controlled trials of BYETTA (N=963) add-on to metformin and/or sulfonylurea, adverse reactions (excluding hypoglycemia) with an incidence of ≥1% and reported more frequently than with placebo included nausea (44% BYETTA, 18% placebo), vomiting (13% BYETTA, 4% placebo), diarrhea (13% BYETTA, 6% placebo), feeling jittery (9% BYETTA, 4% placebo), dizziness (9% BYETTA, 6% placebo), headache (9% BYETTA, 6% placebo), dyspepsia (6% BYETTA, 3% placebo), asthenia (4% BYETTA, 2% placebo), gastroesophageal reflux (3% BYETTA, 1% placebo), hyperhidrosis (3% BYETTA, 1% placebo), and decreased appetite (1% BYETTA, <1% placebo). Similar types of adverse reactions were observed in 24-week and 16-week controlled trials of BYETTA used as monotherapy or as add-on to a thiazolidinedione, with or without metformin, respectively.

Postmarketing Experience

Allergy/Hypersensitivity: injection-site reactions [see Warnings and Precautions (5.8)].

The following additional adverse reactions have been reported during postapproval use of BYETTA. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergy/Hypersensitivity: injection-site reactions, generalized pruritus and/or urticaria, macular or papular rash, angioedema; anaphylactic reaction [see Warnings and Precautions (5.7)].

Drug Interactions: increased international normalized ratio (INR), sometimes associated with bleeding, with concomitant warfarin use [see Drug Interactions (7.2)].

Gastrointestinal: nausea, vomiting, and/or diarrhea resulting in dehydration; abdominal distension, abdominal pain, eructation, constipation, flatulence, acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death [see Indications and Usage (1.2) and Warnings and Precautions (5.2)].

Neurologic: dysgeusia; somnolence

Renal and Urinary Disorders: altered renal function, including increased serum creatinine, renal impairment, worsened chronic renal failure or acute renal failure (sometimes requiring hemodialysis), kidney transplant and kidney transplant dysfunction [see Warnings and Precautions (5.4)].

Skin and Subcutaneous Tissue Disorders: alopecia

There were no reports of overdose in the five comparator-controlled 24- to 30-week trials of Bydureon. Effects of overdoses with BYETTA in clinical studies included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations, including severe hypoglycemia requiring parenteral glucose administration. In the event of overdose, appropriate supportive treatment should be initiated according to the patient's clinical signs and symptoms.

Do not use exenatide to treat type 1 diabetes, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin). You should not use exenatide if you have severe kidney disease (or if you are on dialysis), of if you have a severe stomach disorder that causes slow digestion.

You should not use Bydureon if you have a personal or family history of thyroid cancer, or if you have multiple endocrine neoplasia type 2 (cancer that can affect the thyroid, parathryoid, and adrenal glands).

To make sure you can safely use this medication, tell your doctor if you have any of these other conditions:

• kidney disease or a history of kidney transplant;
• problems with digestion;
• a history of pancreatitis or gall stones;
• a history of alcoholism; or
• a history of high triglycerides (a type of fat in blood).

In animal studies, Bydureon caused thyroid tumors. However, very high doses are used in animal studies. It is not known whether these effects would occur in people using doses recommended for human use. Ask your doctor about your personal risk.

FDA pregnancy category C. It is not known whether exenatide will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using Bydureon.

It is not known whether exenatide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using Bydureon.

Use the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 3 days away. Do not use extra medicine to make up the missed dose.

Your pharmacist can provide more information about exenatide (Bydureon).

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Usual Adult Dose for Diabetes Type 2:

Bydureon extended-release:
-Dose: 2 mg subcutaneously once every seven days; administer at any time of day, with or without meals
-Patients may switch from immediate-release exenatide to extended-release exenatide, although prior treatment with immediate-release exenatide is not necessary.
-For patients who do switch, discontinue immediate-release exenatide on initiation of extended-release; transient elevations in blood glucose may occur and generally improve within the first 2 weeks of initiation.

Comments:
-For patients concomitantly receiving a sulfonylurea, a lower dose of the sulfonylurea may be required to reduce the risk of hypoglycemia.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause severe nausea and vomiting, or signs of low blood sugar (headache, hunger, irritability, dizziness, feeling shaky).

Common side effects of Bydureon include: diarrhea, nausea, and vomiting. Other side effects include: dizziness, dyspepsia, fidgeting, and headache. See below for a comprehensive list of adverse effects.

Pregnancy

Limited data with exenatide in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage

Based on animal reproduction studies, there may be risks to the fetus from exposure to exenatide injection during pregnancy

Exenatide extended-release injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

Animal reproduction studies identified increased adverse fetal and neonatal outcomes from exposure to exenatide extended-release during pregnancy or from exposure to exenatide during pregnancy and lactation, in association with maternal effects

Lactation

There is no information on the presence of exenatide, in human milk, the effects of exenatide on the breastfed infant, or the effects of exenatide on milk production

Exenatide was present in the milk of lactating mice; exenatide concentration in milk was up to 2.5% of the concentration in maternal plasma after administering SC injection twice a day

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.