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Dulaglutide


General


Pronunciation

(doo la GLOO tide)


Brand Names: U.S.

  • Trulicity

Indications


Use: Labeled Indications

Type 2 diabetes mellitus: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM)


Contraindications


Serious hypersensitivity to dulaglutide or any component of the formulation; personal or family history of medullary thyroid carcinoma (MTC); patients with multiple endocrine neoplasia syndrome type 2 (MEN2)

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breast-feeding


ALERT: U.S. Boxed 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 of dulaglutide-induced rodent thyroid C-cell tumors has not been determined.

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). Counsel patients regarding the potential risk of MTC with use of dulaglutide and inform them of symptoms of thyroid tumors (eg, 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 dulaglutide.


Dosing and Administration


Dosing: Adult

Type 2 diabetes mellitus: SubQ: 0.75 mg once weekly; may increase to 1.5 mg once weekly if inadequate glycemic response; maximum: 1.5 mg once weekly

Missed doses: If a dose is missed, administer as soon as possible within 3 days after the missed dose; dosing can then be resumed on the usual day of administration. If there are less than 3 days until next scheduled dose, omit the missed dose and resume administration at the next regularly scheduled weekly dose.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

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


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling; use with caution


Administration

Do not inject intravenously or intramuscularly. Inject subcutaneously into the upper arm, thigh, or abdomen; when administering within the same body region, use a different injection site each week. Administer once weekly on the same day each week, without regard to meals or time of day. The day of weekly administration may be changed, as long as the last dose was administered ≥3 days before. If using concomitantly with insulin, administer as separate injections (do not mix); may inject in the same body region as insulin, but not adjacent to one another.


Dietary Considerations

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


Storage

Store at 36 ‚ °F to 46 ‚ °F (2 ‚ °C to 8 ‚ °C). Do not freeze. Protect from light. If needed, each single-dose pen or prefilled syringe can be kept at room temperature, not to exceed 86 ‚ °F (30 ‚ °C) for a total of 14 days.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Pen-injector, Subcutaneous:

Trulicity: 0.75 mg/0.5 mL (0.5 mL); 1.5 mg/0.5 mL (0.5 mL) [contains polysorbate 80]


Drug Interactions

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

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

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


Monitoring Parameters

Plasma glucose, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2016a]), renal function, signs/symptoms of pancreatitis


Adverse Reactions


>10%: Gastrointestinal: Nausea (12% to 21%), diarrhea (9% to 13%), vomiting (6% to 13%), abdominal pain (7% to 10%)

1% to 10%:

Cardiovascular: Sinus tachycardia (3% to 6%), prolongation P-R interval on ECG (3%), first degree atrioventricular block (2%)

Central nervous system: Fatigue (4% to 6%)

Endocrine & metabolic: Hypoglycemia (3% to 6%)

Gastrointestinal: Abdominal pain (7% to 9%), decreased appetite (5% to 9%), dyspepsia (4% to 6%), constipation (4%), flatulence (3%), abdominal distension (2% to 3%), gastroesophageal reflux disease (2%), eructation (1% to 2%)

Immunologic: Antibody development (2%)

<1% (Limited to important or life-threatening): Acute renal failure, chronic renal failure, hypersensitivity reaction, increased serum amylase, increased serum lipase, injection site reaction, pancreatitis


Warnings/Precautions


Special Populations: Renal Function Impairment

Renal impairment: Dulaglutide systemic exposure increased by 20%, 28%, 14%, and 12% for mild, moderate, and severe renal impairment, and ESRD, respectively.


Special Populations: Hepatic Function Impairment

Dulaglutide systemic exposure decreased by 23%, 33%, and 21% for mild, moderate, and severe hepatic impairment, respectively.


Warnings/Precautions

Concerns related to adverse effects:

- Cardiovascular effects: Tachycardia, PR interval prolongation, and first-degree AV block have been observed; use caution in patients with, or at risk (eg, preexisting conduction system abnormalities, underlying structural heart disease, ischemic heart disease, cardiomyopathies) for developing conduction abnormalities.

- Hypersensitivity reactions: Hypersensitivity reactions have been reported; discontinue therapy in the event of a hypersensitivity reaction.

- Pancreatitis: Cases of pancreatitis have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain). If pancreatitis is suspected, discontinue use. Do not resume therapy if pancreatitis is confirmed. Consider antidiabetic therapies other than dulaglutide in patients with a history of pancreatitis.

- Thyroid tumors:[US Boxed Warning] Thyroid C-cell tumors have developed in animal studies with glucagon-like peptide-1 (GLP-1) receptor agonists; it is not known if dulaglutide causes thyroid C-cell tumor, including medullary thyroid carcinoma (MTC) in humans. Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with dulaglutide. Patients should be counseled on the potential risk of MTC with the use of dulaglutide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use is contraindicated in patients with a personal or a family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2). Cases of MTC in humans have been reported in patients treated with the GLP-1 receptor agonist liraglutide. Consultation with an endocrinologist is recommended in patients with thyroid nodules on physical examination or neck imaging and in patients who develop elevated calcitonin concentrations.

Disease-related concerns:

- Gastrointestinal disease: Use is not recommended in patients with preexisting severe gastrointestinal disease, including severe gastroparesis.

- Hepatic impairment: Use with caution in patients with hepatic impairment.

- Renal impairment: Use with caution in patients with renal impairment, particularly during initiation of therapy and dose escalation. Acute renal failure and chronic renal failure exacerbation (sometimes requiring hemodialysis) have been reported; some cases have been reported in patients with no known pre-existing renal disease. A majority of reported cases occurred in patients with nausea/vomiting/diarrhea or dehydration.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

- Appropriate use: Diabetes mellitus: Not recommended for first-line therapy in patients inadequately controlled on diet and exercise alone. Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; not a substitute for insulin.

- Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.


Pregnancy Risk Factor

C


Pregnancy Considerations

The Canadian labeling contraindicates use during pregnancy and recommends that women discontinue therapy at least 1 month before attempting to conceive.

Adverse events have been observed in some animal reproduction studies.

In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2015; Kitzmiller 2008; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ACOG 2013; ADA 2015; Blumer 2013; Kitzmiller 2008). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (Kitzmiller 2008). Other agents are currently recommended to treat diabetes in pregnant women (ACOG 2013; Blumer 2013).


Actions


Pharmacology

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


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience lack of appetite or loss of strength and energy. Have patient report immediately to prescriber signs of thyroid cancer (new lump or swelling in the neck, pain in the front of the neck, cough that does not go away, change in voice that does not go away like hoarseness, or trouble swallowing or breathing), signs of a pancreas problem (pancreatitis; severe abdominal pain, severe back pain, severe nausea, vomiting), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), urinary retention, change in amount of urine passed, severe diarrhea, severe nausea, vomiting, or severe abdominal pain (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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