Dulaglutide

• Trulicity slows down transit of food and drugs through the intestine and, therefore, may reduce the absorption of drugs that are taken by mouth. Caution should be used when combining Trulicity with oral medications.
• Blood levels of drugs that have a narrow therapeutic index should be monitored when they are combined with Trulicity.

Black Box Warnings

Risk of thyroid C-cell tumors

• Causes thyroid C-cell tumors in rodents; human risk could not be determined
• Contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN-2)
• Counsel patients regarding potential risk of MTC with therapy and inform them of symptoms of thyroid tumors (e.g., mass in the neck, dysphagia, dyspnea, persistent hoarseness); routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients receiving therapy

Contraindications

Hypersensitivity

Personal or family history of medullary thyroid carcinoma (MTC)

Multiple endocrine neoplasia type 2 (MEN-2)

Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with dulaglutide

Cautions

Nonclinical studies in rodents showed increased incidence of thyroid C-cell tumors (see Black Box Warnings and Contraindications); routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with dulaglutide; significantly elevated serum calcitonin may indicate MTC; patients with MTC usually have values >50 ng/L; if serum calcitonin is measured and found to be elevated, evaluate patient further; patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated

Acute pancreatitis reported (rare); discontinue if pancreatitis suspected and do not restart if confirmed

Hypoglycemia may occur when used in combination with insulin secretagogues (eg, sulfonylureas) or insulin; consider lowering sulfonylurea or insulin dosage when starting dulaglutide

Systemic hypersensitivity reactions reported; anaphylaxis and angioedema reported with other GLP-1 receptor agonists; use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist; unknown whether such patients will be predisposed to anaphylaxis with drug; discontinue if such reactions occur

Acute renal failure and worsening of chronic renal failure (some requiring hemodialysis) reported with treatment with glucagonlike peptide-1 (GLP-1) receptor agonists

May be associated with GI adverse reactions, sometimes severe; counsel patients to take precautions to avoid fluid depletion; has not been studied in patients with severe GI disease, including severe gastroparesis

Clinical trials have not established conclusive evidence of macrovascular risk reduction with GLP-1 agonists or any other antidiabetic drug

Slows gastric emptying and may affect absorption of concomitantly administered PO drugs

Mechanism of Action

Incretin mimetic; analogue of human glucagonlike peptide-1 (GLP-1); acts as GLP-1 receptor agonist to increase insulin secretion in the presence of elevated blood glucose; delays gastric emptying to decrease postprandial glucose; also decreases glucagon secretion

Absorption

Absolute bioavailability: 65% (0.75 mg/dose); 47% (1.5 mg/dose)

Peak plasma concentration: 114 ng/mL

AUC: 14,000 ng•h/mL

Distribution

Vd: 19.2 L (0.75 mg/dose); 17.4 L (1.5 mg/dose)

Metabolism

Thought to be degraded into its component amino acids by general protein catabolism pathways

Elimination

Half-life: 5 days

Clearance: ~0.1 L/hr

Dulaglutide is an injectable prescription medicine that may improve blood sugar (glucose) control in adults with type 2 diabetes, when used with a diet and exercise program.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if dulaglutide crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using dulaglutide.

WARNING: RISK OF THYROID C-CELL TUMORS
In male and female rats, dulaglutide causes a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether dulaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance could not be determined from clinical or nonclinical studies.

Dulaglutide is contraindicated in patients with a personal or family history of MTC and 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 dulaglutide. Counsel regarding the risk factors and symptoms of thyroid tumors.
 

Dulaglutide is an injectable diabetes medicine that helps control blood sugar levels.

Dulaglutide is used together with diet and exercise to improve blood sugar control in adults with type 2 diabetes mellitus. Dulaglutide is usually given after other diabetes medicines have been tried without success.

This medicine is not for treating type 1 diabetes.

Dulaglutide may also be used for purposes not listed in this medication guide.

Never share an injection pen or prefilled syringe with another person, even if the needle has been changed. Sharing these devices can allow infections or disease to pass from one person to another.

• Importance of patients reading the medication guide prior to initiating therapy and each time the prescription is refilled. 1 11

• Importance of informing patients that dulaglutide causes benign and malignant thyroid C-cell tumors in rats and that relevance of this finding to humans is unknown.1 11 Patients should report symptoms of thyroid tumors (e.g., a lump in the neck, persistent hoarseness, dysphagia, dyspnea) to their clinician.1 11

• Importance of informing patients of the possibility of acute pancreatitis with dulaglutide therapy.1 11 Importance of patients informing clinicians if they have a history of pancreatitis.1 11 Importance of informing patients about signs and symptoms of pancreatitis, including persistent severe abdominal pain sometimes radiating to the back that may or may not be accompanied by vomiting; importance of patients discontinuing dulaglutide and promptly notifying clinician if such signs or symptoms occur.1 11

• Importance of informing patients of risk of hypoglycemia, particularly if concomitant therapy with an insulin secretagogue (e.g., sulfonylurea) or insulin is used.1 11 Importance of reviewing signs, symptoms, and management of hypoglycemia.1 11

• Importance of informing patients of possibility of hypersensitivity reactions.1 11 Patients should be instructed to discontinue dulaglutide and promptly seek medical advice if symptoms of hypersensitivity occur.1 11

• Importance of informing patients of potential risk of adverse GI effects and possibility of dehydration due to such adverse effects; advise patients to take precautions to avoid fluid depletion.1 11 Importance of informing patients of potential risk of worsening renal function, which may require dialysis in some cases.1 11

• Importance of patients reading the manufacturer's instructions for use before starting dulaglutide therapy.1 11 Importance of instructing patients regarding proper use, storage, and disposal of injection pen.1 11 After dispensing, store pens in refrigerator, or at room temperature for up to 14 days; protect injection pens from light and do not freeze.1 12

• Importance of informing patients not to take an extra dose of dulaglutide to make up for a missed dose.1 If a dose is missed, patients should take the dose as soon as possible if there are at least 3 days (72 hours) until the next dose; the next dose can be taken on their usual weekly day.1 11 If there are less than 3 days until the next dose, the missed dose should be skipped and patients should take the next dose on their usual weekly day.1 11

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 11

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., pancreatitis).1 11

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.
• Give dulaglutide into clean, dry, healthy skin on the belly, upper leg, or upper arm.
• Take with or without food.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• Take the same day each week.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Follow how to use as you have been told by the doctor or read the package insert.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• Wash your hands before and after use.
• Move site where you give the shot each time.
• Do not mix this medicine in the same syringe with insulin.
• Give dulaglutide at some other site from where you gave your insulin if you are also getting insulin.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is less than 3 days (72 hours) until your next dose, skip the missed dose. Take your next dose on your normal day.
• Do not take 2 doses at the same time or extra doses.

Dulaglutide is an agonist of human glucagon-like peptide-1 (GLP-1) receptor and augments glucose dependent insulin secretion and slows gastric emptying.

Distribution

Vd: ~17 to 19 L

Metabolism

Degradation to amino acids by protein catabolism pathways.

Time to Peak

Plasma: 24 to 72 hours

Half-Life Elimination

~5 days

No dosage adjustment necessary; use caution when initiating or escalating doses.

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulin: GLP-1 Agonists may enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Sulfonylureas: GLP-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Caution is recommended.

A decision should be made to discontinue breastfeeding or discontinue the drug taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Data not available The effects in the nursing infant are unknown.