Dosage & administration
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Trulicity prescribing information
- 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 TRULICITY 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[see Warnings and Precautions (), and Nonclinical Toxicology (
5.1 Risk of Thyroid C-cell TumorsIn 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
[see Nonclinical Toxicology ]. Glucagon-like peptide-1 (GLP-1) receptor agonists have induced thyroid C-cell adenomas and carcinomas in mice and rats at clinically relevant exposures. It is unknown whether TRULICITY will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined.One case of MTC was reported in a patient treated with TRULICITY in a clinical trial. This patient had pretreatment calcitonin levels approximately 8 times the upper limit of normal (ULN). An additional case of C-cell hyperplasia with elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND). 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.
TRULICITY 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 TRULICITY and inform them of symptoms of thyroid tumors (e.g. a 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 treated with TRULICITY. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values 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.
)]13.1 Carcinogenesis, Mutagenesis, and Impairment of FertilityA 2-year carcinogenicity study was conducted with dulaglutide in male and female rats at doses of 0.05, 0.5, 1.5, and 5 mg/kg (0.2-, 3-, 8-, and 24-fold the MRHD of 4.5 mg once weekly based on AUC) administered by subcutaneous injection twice weekly. In rats, dulaglutide caused a dose-related and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and/or carcinomas) compared to controls, at ≥3-fold the MRHD based on AUC. A statistically significant increase in C-cell adenomas was observed in rats receiving dulaglutide at ≥0.5 mg/kg. Numerical increases in thyroid C-cell carcinomas occurred at 5 mg/kg (24 times the MRHD based on AUC) and were considered to be treatment-related despite the absence of statistical significance.
A 6-month carcinogenicity study was conducted with dulaglutide in rasH2 transgenic mice at doses of 0.3, 1, and 3 mg/kg administered by subcutaneous injection twice weekly. Dulaglutide did not produce increased incidences of thyroid C-cell hyperplasia or neoplasia at any dose.
Dulaglutide is a recombinant protein; no genotoxicity studies have been conducted.
Human relevance of thyroid C-cell tumors in rats is unknown and could not be determined by clinical studies or nonclinical studies
[see Boxed Warningand Warnings and Precautions ].In fertility and early embryonic development studies in male and female rats, no adverse effects of dulaglutide on sperm morphology, mating, fertility, conception, and embryonic survival were observed at up to 16.3 mg/kg (55-fold the MRHD based on AUC). In female rats, an increase in the number of females with prolonged diestrus and a dose-related decrease in the mean number of corpora lutea, implantation sites, and viable embryos were observed at ≥4.9 mg/kg (≥13-fold the MRHD based on AUC), which occurred in the presence of decreased maternal food consumption and body weight gain.
. - TRULICITY 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 TRULICITY 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 treated with TRULICITY[see Contraindications () and Warnings and Precautions (
4 CONTRAINDICATIONSTRULICITY is 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)[see Warnings and Precautions ].
- Serious hypersensitivity reaction to dulaglutide or to any of the product components. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with TRULICITY[see Warnings and Precautions ].
- Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 .
- Patients with a serious hypersensitivity reaction to dulaglutide or any of the product components .
)]5.1 Risk of Thyroid C-cell TumorsIn 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
[see Nonclinical Toxicology ]. Glucagon-like peptide-1 (GLP-1) receptor agonists have induced thyroid C-cell adenomas and carcinomas in mice and rats at clinically relevant exposures. It is unknown whether TRULICITY will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined.One case of MTC was reported in a patient treated with TRULICITY in a clinical trial. This patient had pretreatment calcitonin levels approximately 8 times the upper limit of normal (ULN). An additional case of C-cell hyperplasia with elevated calcitonin levels following treatment was reported in the cardiovascular outcomes trial (REWIND). 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.
TRULICITY 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 TRULICITY and inform them of symptoms of thyroid tumors (e.g. a 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 treated with TRULICITY. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin values 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.
. - Personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
| Warnings and Precautions | ||
Severe Gastrointestinal Adverse Reactions (Use of TRULICITY has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions ] . In the pool of placebo-controlled trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving TRULICITY (0.75 mg 2.2%, 1.5 mg 4.3%) than placebo (1.4%).TRULICITY is not recommended in patients with severe gastroparesis. | 11/2024 | |
| Warnings and Precautions | ||
Pulmonary Aspiration During General Anesthesia or Deep Sedation (TRULICITY delays gastric emptying [see Clinical Pharmacology ] . There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking TRULICITY, including whether modifying preoperative fasting recommendations or temporarily discontinuing TRULICITY could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking TRULICITY. | 11/2024 | |
TRULICITY® is indicated:
- As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.
- To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.
- The recommended starting dosage of TRULICITY is 0.75 mg injected subcutaneously once weekly. Follow the dosage escalation below to reduce the risk of gastrointestinal adverse reactions[see Warnings and Precautions and Adverse Reactions ].
- After 4 weeks, the dosage may be increased to 1.5 mg once weekly for additional glycemic control.
- If additional glycemic control is needed, increase the dosage in 1.5 mg increments after at least 4 weeks on the current dosage.
- The maximum recommended dosage is 4.5 mg injected subcutaneously once weekly.
- Recommended starting dosage is 0.75 mg injected subcutaneously once weekly.
- After 4 weeks, the dosage may be increased to 1.5 mg once weekly for additional glycemic control.
- If additional glycemic control is needed, increase dosage in 1.5 mg increments after at least 4 weeks on the current dosage.
- Maximum recommended dosage is 4.5 mg injected subcutaneously once weekly.
- The recommended starting dosage of TRULICITY is 0.75 mg injected subcutaneously once weekly.
- If additional glycemic control is needed, increase the dosage to the maximum recommended dosage of 1.5 mg once weekly after at least 4 weeks on the 0.75 mg dosage to reduce the risk of gastrointestinal adverse reactions[see Warnings and Precautions and Adverse Reactions ].
- Recommended starting dosage is 0.75 mg injected subcutaneously once weekly.
- If additional glycemic control is needed, increase dosage to the maximum recommended dosage of 1.5 mg once weekly after at least 4 weeks on the 0.75 mg dosage.
- If a dose is missed, instruct patients to administer the dose as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
- The day of weekly administration can be changed, if necessary, as long as the last dose was administered 3 or more days before the new day of administration.
- If a dose is missed, administer the missed dose as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose.
- Prior to initiation, train patients and caregivers on proper injection technique[see Instructions for Use].
- Administer TRULICITY once weekly, any time of day, with or without food.
- Inject TRULICITY subcutaneously in the abdomen, thigh, or upper arm.
- Rotate injection sites with each dose.
- Inspect TRULICITY visually before use. It should appear clear and colorless. Do not use TRULICITY if particulate matter or coloration is seen.
- When using TRULICITY with insulin, administer as separate injections and never mix. It is acceptable to inject TRULICITY and insulin in the same body region, but the injections should not be adjacent to each other.
- Administer once weekly at any time of day with or without food.
- Inject subcutaneously in the abdomen, thigh, or upper arm.
Injection: TRULICITY is a clear and colorless solution available as:
- 0.75 mg/0.5 mL solution in a single-dose pen
- 1.5 mg/0.5 mL solution in a single-dose pen
- 3 mg/0.5 mL solution in a single-dose pen
- 4.5 mg/0.5 mL solution in a single-dose pen
Limited data with TRULICITY in pregnant women are not sufficient to determine a drug-associated risk for major birth defects and miscarriage. There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy
In pregnant rats administered dulaglutide during organogenesis, early embryonic deaths, fetal growth reductions, and fetal abnormalities occurred at systemic exposures at least 6-times human exposure at the maximum recommended human dose (MRHD) of 4.5 mg/week. In pregnant rabbits administered dulaglutide during organogenesis, major fetal abnormalities occurred at 5-times human exposure at the MRHD. Adverse embryo/fetal effects in animals occurred in association with decreased maternal weight and food consumption attributed to the pharmacology of dulaglutide
The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with an HbA1c >7% and has been reported to be as high as 20–25% in women with an HbA1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
Pregnant rats given subcutaneous doses of 0.49, 1.63, or 4.89 mg/kg dulaglutide every 3 days during organogenesis had systemic exposures 2-, 6-, and 18-times human exposure at the maximum recommended human dose (MRHD) of 4.5 mg/week, respectively, based on plasma area under the time-concentration curve (AUC) comparison. Reduced fetal weights associated with decreased maternal food intake and decreased weight gain attributed to the pharmacology of dulaglutide were observed at ≥1.63 mg/kg. Irregular skeletal ossifications and increases in post-implantation loss also were observed at 4.89 mg/kg.
In pregnant rabbits given subcutaneous doses of 0.04, 0.12, or 0.41 mg/kg dulaglutide every 3 days during organogenesis, systemic exposures in pregnant rabbits were 0.5-, 2-, and 5-times human exposure at the MRHD, based on plasma AUC comparison. Fetal visceral malformation of lung lobular agenesis and skeletal malformations of the vertebrae and/or ribs were observed in conjunction with decreased maternal food intake and decreased weight gain attributed to the pharmacology of dulaglutide at 0.41 mg/kg.
In a prenatal-postnatal study in F0maternal rats given subcutaneous doses of 0.2, 0.49, or 1.63 mg/kg every third day from implantation through lactation, systemic exposures in pregnant rats were 1-, 2-, and 7-times human exposure at the MRHD, based on plasma AUC comparison. F1pups from F0maternal rats given 1.63 mg/kg dulaglutide had statistically significantly lower mean body weight from birth through postnatal day 63 for males and postnatal day 84 for females. F1offspring from F0maternal rats receiving 1.63 mg/kg dulaglutide had decreased forelimb and hindlimb grip strength and males had delayed balano-preputial separation. Females had decreased startle response. These physical findings may relate to the decreased size of the offspring relative to controls as they appeared at early postnatal assessments but were not observed at a later assessment. F1female offspring of the F0maternal rats given 1.63 mg/kg of dulaglutide had a longer mean escape time and a higher mean number of errors relative to concurrent control during 1 of 2 trials in the memory evaluation portion of the Biel water maze. These findings occurred in conjunction with decreased F0maternal food intake and decreased weight gain attributed to the pharmacologic activity at 1.63 mg/kg. The human relevance of these memory deficits in the F1female rats is not known.