Trulicity
Generic
Name: dulaglutide
Dosage Form: injection, solution
Medically reviewed on July 1, 2018
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 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 (5.1),
and Nonclinical Toxicology (13.1)].
· 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 (4) and Warnings and Precautions (5.1)].
Indications
and Usage for Trulicity
Trulicity® is indicated as an
adjunct to diet and exercise to improve glycemic control in adults with type 2
diabetes mellitus.
Limitations
of Use
·
Trulicity is not recommended
as a first-line therapy for patients who have inadequate glycemic control on
diet and exercise because of the uncertain relevance of rodent C-cell tumor
findings to humans. Prescribe Trulicity only to patients for whom the potential
benefits outweigh the potential risk [see Warnings
and Precautions (5.1)].
·
Trulicity has not been
studied in patients with a history of pancreatitis [see
Warnings and Precautions (5.2)]. Consider other
antidiabetic therapies in patients with a history of pancreatitis.
·
Trulicity should not be used
in patients with type 1 diabetes mellitus or for the treatment of diabetic
ketoacidosis. Trulicity is not a substitute for insulin.
·
Trulicity has not been
studied in patients with severe gastrointestinal disease, including severe
gastroparesis. The use of Trulicity is not recommended in patients with
pre-existing severe gastrointestinal disease [see
Warnings and Precautions (5.6)].
Trulicity
Dosage and AdministrationDosage
The recommended initiating
dose of Trulicity is 0.75 mg once weekly. The dose may be increased to 1.5 mg
once weekly for additional glycemic control. The maximum recommended dose is
1.5 mg once weekly.
Administer Trulicity once
weekly, any time of day, with or without food. Trulicity should be injected
subcutaneously in the abdomen, thigh, or upper arm.
If a dose is missed,
instruct patients to administer 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.
Concomitant
Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
When initiating Trulicity,
consider reducing the dosage of concomitantly administered insulin
secretagogues (e.g., sulfonylureas) or insulin to reduce the risk of
hypoglycemia [see Warnings and Precautions (5.3)].
Important
Administration Instructions
Prior to initiation of
Trulicity, patients should be trained by their healthcare professional on
proper injection technique. Training reduces the risk of administration errors
such as improper injection site, needle sticks, and incomplete dosing. Refer to
the accompanying Instructions for Use for complete administration instructions
with illustrations. The instructions can also be found at www.Trulicity.com.
When using Trulicity with
insulin, instruct patients to administer as separate injections and to never
mix the products. It is acceptable to inject Trulicity and insulin in the same
body region but the injections should not be adjacent to each other.
When injecting in the same
body region, advise patients to use a different injection site each week.
Trulicity must not be administered intravenously or intramuscularly.
Trulicity solution should be
visually inspected for particulate matter and discoloration prior to
administration.
Dosage
Forms and Strengths
·
Injection: 0.75 mg/0.5 mL
solution in a single-dose pen
·
Injection: 1.5 mg/0.5 mL
solution in a single-dose pen
Contraindications
•
Medullary Thyroid Carcinoma
Trulicity 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) [see Warnings and Precautions (5.1)].
•
Hypersensitivity
Trulicity is contraindicated
in patients with a prior 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 (5.4)].
Warnings
and PrecautionsRisk 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 [see Nonclinical Toxicology (13.1)].
Glucagon-like peptide (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. This patient had pretreatment calcitonin
levels approximately 8 times the upper limit of normal (ULN). 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 value 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.
Pancreatitis
In Phase 2 and Phase 3 clinical
studies, 12 (3.4 cases per 1000 patient years) pancreatitis-related adverse
reactions were reported in patients exposed to Trulicity versus 3 in
non-incretin comparators (2.7 cases per 1000 patient years). An analysis of
adjudicated events revealed 5 cases of confirmed pancreatitis in patients
exposed to Trulicity (1.4 cases per 1000 patient years) versus 1 case in
non-incretin comparators (0.88 cases per 1000 patient years).
After initiation of
Trulicity, observe patients carefully for signs and symptoms of pancreatitis,
including persistent severe abdominal pain. If pancreatitis is suspected,
promptly discontinue Trulicity. If pancreatitis is confirmed, Trulicity should
not be restarted. Trulicity has not been evaluated in patients with a prior
history of 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 Trulicity is used in combination with insulin secretagogues
(e.g., sulfonylureas) or insulin. Patients may require a lower dose of
sulfonylurea or insulin to reduce the risk of hypoglycemia in this
setting [see Dosage and Administration (2.2),
Adverse Reactions (6.1)].
Hypersensitivity
Reactions
There have been postmarketing reports of serious
hypersensitivity reactions including anaphylactic reactions and angioedema in
patients treated with Trulicity [see Adverse
Reactions (6.2)]. If a hypersensitivity
reaction occurs, discontinue Trulicity; treat promptly per standard of care,
and monitor until signs and symptoms resolve. Do not use in patients with a
previous hypersensitivity reaction to Trulicity [see
Contraindications (4)].
Anaphylaxis and angioedema
have been 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
because it is unknown whether such patients will be predisposed to anaphylaxis
with Trulicity.
Acute
Kidney Injury
In patients treated with
GLP-1 receptor agonists, including Trulicity, 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.
Because these reactions may worsen renal function, use caution when initiating
or escalating doses of Trulicity in patients with renal impairment. Monitor
renal function in patients with renal impairment reporting severe adverse
gastrointestinal reactions [see Use in Specific
Populations (8.7)].
Severe
Gastrointestinal Disease
Use of Trulicity may be
associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions (6.1)].
Trulicity has not been studied in patients with severe gastrointestinal
disease, including severe gastroparesis, and is therefore not recommended in
these patients.
Macrovascular
Outcomes
There have been no clinical
studies establishing conclusive evidence of macrovascular risk reduction with
Trulicity.
Adverse
Reactions
The following serious
reactions are described below or elsewhere in the prescribing information:
·
Risk of Thyroid C-cell
Tumors [see Warnings and Precautions (5.1)]
·
Pancreatitis [see Warnings and Precautions (5.2)]
·
Hypoglycemia with
Concomitant Use of Insulin Secretagogues or Insulin [see
Warnings and Precautions (5.3)]
·
Hypersensitivity
reactions [see Warnings and Precautions (5.4)]
·
Acute Kidney Injury [see Warnings and Precautions (5.5)]
·
Severe Gastrointestinal
Disease [see Warnings and Precautions (5.6)]
Clinical
Studies Experience
Because clinical studies are
conducted under widely varying conditions, adverse reaction rates observed in
the clinical studies of a drug cannot be directly compared to rates in the
clinical studies 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 the placebo-controlled trials [see Clinical Studies (14)].
These data reflect exposure
of 1670 patients to Trulicity and a mean duration of exposure to Trulicity of
23.8 weeks. Across the treatment arms, the mean age of patients was 56 years,
1% were 75 years or older and 53% were male. The population in these studies
was 69% White, 7% Black or African American, 13% Asian; 30% were of Hispanic or
Latino ethnicity. At baseline, the population had diabetes for an average of
8.0 years and had a mean HbA1c of 8.0%. At baseline, 2.5% of the population
reported retinopathy. Baseline estimated renal function was normal or mildly
impaired (eGFR ≥60mL/min/1.73 m2) in 96.0% of the pooled study populations.
Table 1 shows common adverse
reactions, excluding hypoglycemia, associated with the use of Trulicity in the
pool of placebo-controlled trials. These adverse reactions were not present at
baseline, occurred more commonly on Trulicity than on placebo, and occurred in
at least 5% of patients treated with Trulicity.
Table 1: Adverse Reactions in
Placebo-Controlled Trials Reported in ≥5% of Trulicity-Treated Patients
|
|
a Includes diarrhea, fecal volume
increased, frequent bowel movements.
|
|
b Includes retching, vomiting,
vomiting projectile.
|
|
c Includes abdominal discomfort,
abdominal pain, abdominal pain lower, abdominal pain upper, abdominal
tenderness, gastrointestinal pain.
|
|
d Includes fatigue, asthenia, malaise.
|
|
Note: Percentages reflect the
number of patients that reported at least 1 treatment-emergent occurrence of
the adverse reaction.
|
|
Adverse Reaction
|
Placebo
(N=568)
%
|
Trulicity 0.75 mg
(N=836)
%
|
Trulicity 1.5 mg
(N=834)
%
|
|
Nausea
|
5.3
|
12.4
|
21.1
|
|
Diarrheaa
|
6.7
|
8.9
|
12.6
|
|
Vomitingb
|
2.3
|
6.0
|
12.7
|
|
Abdominal Painc
|
4.9
|
6.5
|
9.4
|
|
Decreased
Appetite
|
1.6
|
4.9
|
8.6
|
|
Dyspepsia
|
2.3
|
4.1
|
5.8
|
|
Fatigued
|
2.6
|
4.2
|
5.6
|
Gastrointestinal Adverse Reactions
In the pool of
placebo-controlled trials, gastrointestinal adverse reactions occurred more
frequently among patients receiving Trulicity than placebo (placebo 21.3%,
0.75 mg 31.6%, 1.5 mg 41.0%). More patients receiving Trulicity 0.75
mg (1.3%) and Trulicity 1.5 mg (3.5%) discontinued treatment due to
gastrointestinal adverse reactions than patients receiving placebo (0.2%).
Investigators graded the severity of gastrointestinal adverse reactions
occurring on 0.75 mg and 1.5 mg of Trulicity as “mild” in 58% and 48% of cases,
respectively, “moderate” in 35% and 42% of cases, respectively, or “severe” in
7% and 11% of cases, respectively.
In addition to the reactions
in Table 1, the following adverse reactions
were reported more frequently in Trulicity-treated patients than placebo
(frequencies listed, respectively, as: placebo; 0.75 mg; 1.5 mg):
constipation (0.7%, 3.9%, 3.7%), flatulence (1.4%, 1.4%, 3.4%), abdominal
distension (0.7%, 2.9%, 2.3%), gastroesophageal reflux disease (0.5%, 1.7%,
2.0%), and eructation (0.2%, 0.6%, 1.6%).
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 6 placebo- and active-controlled trials evaluating the use of
Trulicity as monotherapy and add-on therapy to oral medications or insulin.[see Clinical Studies (14)].
In this pool, a total of 3342 patients with type 2 diabetes were treated with
Trulicity for a mean duration of 52 weeks. The mean age of patients was 56
years, 2% were 75 years or older and 51% were male. The population in these
studies was 71% White, 7% Black or African American, 11% Asian; 32% were of
Hispanic or Latino ethnicity. At baseline, the population had diabetes for an
average of 8.2 years and had a mean HbA1c of 7.6-8.5%. At baseline, 5.2% of the
population reported retinopathy. Baseline estimated renal function was normal
or mildly impaired (eGFR ≥60 ml/min/1.73 m2) in 95.7% of the Trulicity
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
Table
2 summarizes the incidence of documented symptomatic
(≤70 mg/dL glucose threshold) and severe hypoglycemia in the
placebo-controlled clinical studies.
Table 2: Incidence (%) of Documented
Symptomatic and Severe Hypoglycemia Adverse Reactions in Placebo-Controlled
Trials
|
|
|
Placebo
|
Trulicity 0.75 mg
|
Trulicity 1.5 mg
|
|
Add-on to Metformin
|
|
(26 weeks)
|
N=177
|
N=302
|
N=304
|
|
Documented symptomatic
|
1.1%
|
2.6%
|
5.6%
|
|
Severe
|
0
|
0
|
0
|
|
Add-on to Metformin + Pioglitazone
|
|
(26 weeks)
|
N=141
|
N=280
|
N=279
|
|
Documented symptomatic
|
1.4%
|
4.6%
|
5.0%
|
|
Severe
|
0
|
0
|
0
|
|
Add-on to Glimepiride
|
|
(24 weeks)
|
N=60
|
-
|
N=239
|
|
Documented symptomatic
|
1.7%
|
-
|
11.3%
|
|
Severe
|
0
|
-
|
0
|
|
In Combination with Insulin Glargine ± Metformin
|
|
(28 weeks)
|
N=150
|
-
|
N=150
|
|
Documented symptomatic
|
30.0%
|
-
|
35.3%
|
|
Severe
|
0
|
-
|
0.7%
|
Hypoglycemia was more
frequent when Trulicity was used in combination with a sulfonylurea or
insulin [see Warnings and Precautions (5.3)]. In
a 78-week clinical trial, documented symptomatic hypoglycemia occurred in 39%
and 40% of patients when Trulicity 0.75 mg and 1.5 mg, respectively, was
co-administered with a sulfonylurea. Severe hypoglycemia occurred in 0% and
0.7% of patients when Trulicity 0.75 mg and 1.5 mg, respectively, was
co-administered with a sulfonylurea. Documented symptomatic hypoglycemia
occurred in 85% and 80% of patients when Trulicity 0.75 mg and 1.5 mg,
respectively, was co-administered with prandial insulin. Severe hypoglycemia
occurred in 2.4% and 3.4% of patients when Trulicity 0.75 mg and 1.5 mg,
respectively, was co-administered with prandial insulin.
Heart Rate Increase and Tachycardia Related Adverse Reactions
Trulicity 0.75 mg and 1.5 mg
resulted in a mean increase in heart rate (HR) of 2-4 beats per minute (bpm).
The long-term clinical effects of the increase in HR have not been
established [see Warnings and Precautions (5.7)].
Adverse reactions of sinus
tachycardia were reported more frequently in patients exposed to Trulicity.
Sinus tachycardia was reported in 3.0%, 2.8%, and 5.6% of patients treated with
placebo, Trulicity 0.75 mg and Trulicity 1.5 mg, respectively. Persistence of
sinus tachycardia (reported at more than 2 visits) was reported in 0.2%, 0.4%
and 1.6% of patients treated with placebo, Trulicity 0.75 mg and Trulicity 1.5
mg, respectively. Episodes of sinus tachycardia, associated with a concomitant
increase from baseline in heart rate of ≥15 beats per minute, were reported in
0.7%, 1.3% and 2.2% of patients treated with placebo, Trulicity 0.75 mg and
Trulicity 1.5 mg, respectively.
Immunogenicity
Across four Phase 2 and five
Phase 3 clinical studies, 64 (1.6%) Trulicity-treated patients developed
anti-drug antibodies (ADAs) to the active ingredient in Trulicity (i.e.,
dulaglutide).
Of the 64
dulaglutide-treated patients that developed dulaglutide ADAs, 34 patients (0.9%
of the overall population) had dulaglutide-neutralizing antibodies, and 36
patients (0.9% of the overall population) developed antibodies against native
GLP-1.
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 dulaglutide cannot be directly compared with the incidence of
antibodies of other products.
Hypersensitivity
Systemic hypersensitivity
adverse reactions sometimes severe (e.g., severe urticaria, systemic rash,
facial edema, lip swelling) occurred in 0.5% of patients on Trulicity in the
four Phase 2 and five Phase 3 studies.
Injection-site Reactions
In the placebo-controlled
studies, injection-site reactions (e.g., injection-site rash, erythema) were
reported in 0.5% of Trulicity-treated patients and in 0.0% of placebo-treated
patients.
PR Interval Prolongation and Adverse Reactions of First Degree
Atrioventricular (AV) Block
A mean increase from
baseline in PR interval of 2-3 milliseconds was observed in Trulicity-treated
patients in contrast to a mean decrease of 0.9 milliseconds in placebo-treated
patients. The adverse reaction of first degree AV block occurred more
frequently in patients treated with Trulicity than placebo (0.9%, 1.7% and 2.3%
for placebo, Trulicity 0.75 mg and Trulicity 1.5 mg, respectively). On
electrocardiograms, a PR interval increase to at least 220 milliseconds was
observed in 0.7%, 2.5% and 3.2% of patients treated with placebo, Trulicity
0.75 mg and Trulicity 1.5 mg, respectively.
Amylase and Lipase Increase
Patients exposed to Trulicity
had mean increases from baseline in lipase and/or pancreatic amylase of 14% to
20%, while placebo-treated patients had mean increases of up to 3%.
Postmarketing
Experience
The following additional
adverse reactions have been reported during post-approval use of Trulicity.
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.
·
Anaphylactic reactions, angioedema [see Contraindications (4),
Warnings and Precautions (5.6), Patient Counseling Information (17)].
·
Increased serum creatinine,
acute renal failure or worsening of chronic renal failure, sometimes requiring
hemodialysis [see Warnings and Precautions (5.5)
and Patient Counseling Information (17)].
Drug
InteractionsOral
Medications
Trulicity slows gastric
emptying and thus has the potential to reduce the rate of absorption of concomitantly
administered oral medications. Caution should be exercised when oral
medications are concomitantly administered with Trulicity. Drug levels of oral
medications with a narrow therapeutic index should be adequately monitored when
concomitantly administered with Trulicity. In clinical pharmacology studies,
Trulicity did not affect the absorption of the tested, orally administered
medications to a clinically relevant degree [see
Clinical Pharmacology (12.3)].
USE IN
SPECIFIC POPULATIONSPregnancy
Risk
Summary
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 [see
Clinical Considerations]. Based on animal reproduction studies,
there may be risks to the fetus from exposure to dulaglutide during pregnancy.
Trulicity should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
In pregnant rats
administered dulaglutide during organogenesis, early embryonic deaths, fetal
growth reductions, and fetal abnormalities occurred at systemic exposures at
least 14-times human exposure at the maximum recommended human dose (MRHD) of
1.5 mg/week. In pregnant rabbits administered dulaglutide during organogenesis,
major fetal abnormalities occurred at 13-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 [see Data].
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
a HbA1c >10. The estimated background risk of miscarriage for the indicated
population is unknown. In theU.S.general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2–4% and 15–20%,
respectively.
Clinical
Considerations
Disease-associated maternal and/or embryo/fetal risk
Poorly controlled diabetes
in pregnancy increases the maternal risk for diabetic ketoacidosis,
pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery
complications. Poorly controlled diabetes increases the fetal risk for major
birth defects, stillbirth, and macrosomia related morbidity.
Data
Animal Data
Pregnant rats given
subcutaneous doses of 0.49, 1.63, or 4.89 mg/kg dulaglutide every 3 days
during organogenesis had systemic exposures 4-, 14-, and 44-times human
exposure at the maximum recommended human dose (MRHD) of 1.5 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 1-, 4-, and
13-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 F0 maternal 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 2-, 4-, and 16-times human exposure at the
MRHD, based on plasma AUC comparison. F1 pups from F0maternal rats given 1.63 mg/kg dulaglutide had
statistically significantly lower mean body weight from birth through
post-natal day 63 for males and postnatal day 84 for females. F1 offspring 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. F1 female offspring of
the F0 maternal
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 theBielwater 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 F1 female rats is not known.
Lactation
Risk
Summary
There are no data on the
presence of dulaglutide in human milk, the effects on the breastfed infant, or
the effects on milk production. The presence of dulaglutide in milk of treated
lactating animals was not determined. The developmental and health benefits of
breastfeeding should be considered along with the mother's clinical need for
Trulicity and any potential adverse effects on the breastfed infant from
Trulicity or from the underlying maternal condition.
Pediatric
Use
Safety and effectiveness of
Trulicity have not been established in pediatric patients. Trulicity is not
recommended for use in pediatric patients younger than 18 years.
Geriatric
Use
In the pool of placebo- and
active-controlled trials [see Adverse Reactions (6.1)],
620 (18.6%) Trulicity-treated patients were 65 years of age and over and 65
Trulicity-treated patients (1.9%) patients were 75 years of age and over. No
overall differences in safety or efficacy were detected between these patients
and younger patients, but greater sensitivity of some older individuals cannot
be ruled out.
Hepatic
Impairment
There is limited clinical
experience in patients with mild, moderate, or severe hepatic impairment.
Therefore, Trulicity should be used with caution in these patient populations.
In a clinical pharmacology
study in subjects with varying degrees of hepatic impairment, no clinically
relevant change in dulaglutide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12.3)].
Renal
Impairment
In the four Phase 2 and five
Phase 3 randomized clinical studies, at baseline, 50 (1.2%) Trulicity-treated
patients had mild renal impairment (eGFR ≥60 but <90 mL/min/1.73 m2), 171 (4.3%)
Trulicity-treated patients had moderate renal impairment (eGFR ≥30 but
<60 mL/min/1.73 m2), and no Trulicity-treated patients had severe renal impairment
(eGFR <30 mL/min/1.73 m2). In a 52-week clinical trial, 270 (71%) Trulicity-treated
patients had moderate renal impairment (eGFR ≥ 30 but
<60 mL/min/1.73 m2) and 112 (29%) Trulicity-treated patients had severe renal
impairment (eGFR ≥ 15 but < 30 mL/min/1.73 m2) [see
Clinical Studies (14.3)]. No overall differences in
safety or effectiveness were observed in this study.
In a clinical pharmacology
study in subjects with renal impairment, including end-stage renal disease
(ESRD), no clinically relevant change in dulaglutide PK was observed. In the
52-week Phase 3 study in patients with type 2 diabetes and moderate to severe
renal impairment, the PK behavior of Trulicity 0.75 mg and 1.5 mg
once weekly was similar to that demonstrated in previous clinical studies [see Clinical Pharmacology (12.3)].
No dose adjustment is
recommended in patients with renal impairment including end-stage renal disease
(ESRD). Monitor renal function in patients with renal impairment reporting
severe adverse gastrointestinal reactions. There is limited clinical experience
in patients with ESRD. Trulicity should be used with caution in patients with
ESRD [see Warning and Precautions (5.5),
Clinical Pharmacology (12.3)].
Gastroparesis
Dulaglutide slows gastric
emptying. Trulicity has not been studied in patients with preexisting
gastroparesis.
Overdosage
Overdoses have been reported
in clinical studies. Effects associated with these overdoses were primarily
mild or moderate gastrointestinal events (e.g., nausea, vomiting) and
non-severe hypoglycemia. In the event of overdose, appropriate supportive care
(including frequent plasma glucose monitoring) should be initiated according to
the patient's clinical signs and symptoms.
Trulicity
Description
Trulicity contains
dulaglutide, a human GLP-1 receptor agonist. The molecule is a fusion protein
that consists of 2 identical, disulfide-linked chains, each containing an
N-terminal GLP-1 analog sequence covalently linked to the Fc portion of a
modified human immunoglobulin G4 (IgG4) heavy chain by a small peptide linker
and is produced using mammalian cell culture. The GLP-1 analog portion of
dulaglutide is 90% homologous to native human GLP-1 (7-37). Structural
modifications were introduced in the GLP-1 part of the molecule responsible for
interaction with the enzyme dipeptidyl-peptidase-IV (DPP-4). Additional
modifications were made in an area with a potential T-cell epitope and in the
areas of the IgG4 Fc part of the molecule responsible for binding the
high-affinity Fc receptors and half-antibody formation. The overall molecular
weight of dulaglutide is approximately 63 kilodaltons.
Trulicity is a clear,
colorless, sterile solution. Each 0.5 mL of Trulicity solution contains 0.75
mg or 1.5 mg of dulaglutide. Each single-dose pen contains 0.5 mL of
solution and the following excipients: citric acid anhydrous (0.07 mg),
mannitol (23.2 mg), polysorbate 80 (0.10 mg), trisodium citrate dihydrate (1.37
mg), in water for injection.
Trulicity -
Clinical PharmacologyMechanism
of Action
Trulicity contains
dulaglutide, which is a human GLP-1 receptor agonist with 90% amino acid
sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the
GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl
cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic
AMP (cAMP) in beta cells leading to glucose-dependent insulin release.
Dulaglutide also decreases glucagon secretion and slows gastric emptying.
Pharmacodynamics
Trulicity lowers fasting
glucose and reduces postprandial glucose (PPG) concentrations in patients with
type 2 diabetes mellitus. The reduction in fasting and postprandial glucose can
be observed after a single dose.
Fasting
and Postprandial Glucose
In a clinical pharmacology
study in adults with type 2 diabetes mellitus, treatment with once weekly
Trulicity resulted in a reduction of fasting and 2-hour PPG concentrations, and
postprandial serum glucose incremental AUC, when compared to placebo
(-25.6 mg/dL,-59.5 mg/dL, and -197 mg h/dL, respectively);
these effects were sustained after 6 weeks of dosing with the 1.5 mg dose.
First-
and Second-Phase Insulin Secretion
Both first-and second-phase
insulin secretion were increased in patients with type 2 diabetes treated with
Trulicity compared with placebo.
Insulin
and Glucagon Secretion
Trulicity stimulates
glucose-dependent insulin secretion and reduces glucagon secretion. Treatment
with Trulicity 0.75 mg and 1.5 mg once weekly increased fasting insulin from
baseline at Week 26 by 35.38 and 17.50 pmol/L, respectively, and C-peptide
concentration by 0.09 and 0.07 nmol/L, respectively, in a Phase 3 monotherapy
study. In the same study, fasting glucagon concentration was reduced by 1.71 and
2.05 pmol/L from baseline with Trulicity 0.75 mg and 1.5 mg, respectively.
Gastric
Motility
Dulaglutide causes a delay
of gastric emptying. The delay is largest after the first dose and diminishes
with subsequent doses.
Cardiac
Electrophysiology (QTc)
The effect of dulaglutide on
cardiac repolarization was tested in a thorough QTc study. Dulaglutide did not
produce QTc prolongation at supratherapeutic doses of 4 and 7 mg.
Pharmacokinetics
The pharmacokinetics of
dulaglutide is similar between healthy subjects and patients with type 2
diabetes mellitus. Following subcutaneous administration, the time to maximum
plasma concentration of dulaglutide at steady-state ranges from 24 to 72 hours,
with a median of 48 hours. After multiple-dose administration of 1.5 mg to
steady state, the mean peak plasma concentration (Cmax) and total systemic
exposure (AUC) of dulaglutide were 114 ng/mL (range 56 to 231 ng/mL)
and 14,000 ng*h/mL (range 6940 to 26,000 ng*h/mL), respectively;
accumulation ratio was approximately 1.56. Steady-state plasma dulaglutide
concentrations were achieved between 2 and 4 weeks following once weekly
administration. Site of subcutaneous administration (abdomen, upper arm, and
thigh) had no statistically significant effect on the exposure to dulaglutide.
Absorption – The mean absolute bioavailability of dulaglutide
following subcutaneous administration of single 0.75 mg and 1.5 mg doses
was 65% and 47%, respectively.
Distribution – The mean volumes of distribution after subcutaneous
administration of Trulicity 0.75 mg and 1.5 mg to steady state were
approximately 19.2 L (range 14.3 to 26.4 L) and 17.4 L (range 9.3 to 33
L), respectively.
Metabolism – Dulaglutide is presumed to be degraded into its
component amino acids by general protein catabolism pathways.
Elimination – The mean apparent clearance at steady state of
dulaglutide is approximately 0.111 L/h for the 0.75 mg dose, and 0.107 L/h for
the 1.5 mg dose. The elimination half-life of dulaglutide for both doses is
approximately 5 days.
Specific
Populations
No dose adjustment of
dulaglutide is needed based on age, gender, race, ethnicity, body weight, or
renal or hepatic impairment. The effects of intrinsic factors on the PK of
dulaglutide are shown in Figure 1.
Figure 1: Impact of intrinsic factors on dulaglutide
pharmacokinetics.
Renal – Dulaglutide systemic
exposure was increased by 20, 28, 14 and 12% for mild, moderate, severe, and
ESRD renal impairment sub-groups, respectively, compared to subjects with
normal renal function. The corresponding values for increase in Cmax were 13, 23, 20 and
11%, respectively (Figure 1). Additionally, in a 52 week
Phase 3 study in patients with type 2 diabetes and moderate to severe renal
impairment, the PK behavior of Trulicity 0.75 mg and 1.5 mg once weekly was
similar to that demonstrated in previous clinical studies [see Warning and Precautions (5.5),
Use in Specific Population (8.7)].
Hepatic - Dulaglutide
systemic exposure decreased by 23, 33 and 21% for mild, moderate and severe
hepatic impairment groups, respectively, compared to subjects with normal
hepatic function, and Cmax was decreased by a similar magnitude (Figure
1). [see Use in Specific Population
(8.6)].
Drug
Interactions
The potential effect of
co-administered medications on the PK of dulaglutide and vice-versa was studied
in several single- and multiple-dose studies in healthy subjects, patients with
type 2 diabetes mellitus, and patients with hypertension.
Potential
for Dulaglutide to Influence the Pharmacokinetics of Other Drugs
Dulaglutide slows gastric
emptying and, as a result, may reduce the extent and rate of absorption of
orally co-administered medications. In clinical pharmacology studies,
dulaglutide did not affect the absorption of the tested orally administered medications
to any clinically relevant degree.
Pharmacokinetic (PK)
measures indicating the magnitude of these interactions are presented in Figure
2. No dose adjustment is recommended for any of the evaluated
co-administered medications.
Figure 2: Impact of dulaglutide on the pharmacokinetics of
co-administered medications.
Potential
for Co-administered Drugs to Influence the Pharmacokinetics of Dulaglutide
In a clinical pharmacology
study, the coadministration of a single dose of dulaglutide (1.5 mg) with
steady-state sitagliptin (100 mg) caused an increase in dulaglutide AUC
and Cmax of
approximately 38% and 27%, which is not considered clinically relevant.
Nonclinical
ToxicologyCarcinogenesis,
Mutagenesis, and Impairment of Fertility
A 2-year carcinogenicity
study was conducted with dulaglutide in male and female rats at doses of 0.05,
0.5, 1.5, and 5.0 mg/kg (0.5-, 7-, 20-, and 58-fold the MRHD of
1.5 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 ≥7-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 (58 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,
1.0, and 3.0 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
Warning and Warnings and Precautions (5.1)].
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 (130-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 (≥32-fold the MRHD based
on AUC), which occurred in the presence of decreased maternal food consumption
and body weight gain.
Animal
Toxicology and/or Pharmacology
Zucker diabetic fatty (ZDF)
rats were given 0.5, 1.5, or 5.0 mg/kg/twice weekly of dulaglutide (3-,
8-, and 30-fold the MRHD based on AUC) for 3 months. Increases of 12% to 33% in
total and pancreatic amylase, but not lipase, were observed at all doses
without microscopic pancreatic inflammatory correlates in individual animals.
Other changes in the dulaglutide-treated animals included increased interlobular
ductal epithelium without active ductal cell proliferation (≥0.5 mg/kg),
increased acinar atrophy with/without inflammation (≥1.5 mg/kg), and
increased neutrophilic inflammation of the acinar pancreas (5 mg/kg).
Treatment of monkeys for 12
months with 8.15 mg/kg/twice weekly of dulaglutide (nearly 500-fold the
MRHD based on AUC) demonstrated no evidence of pancreatic inflammation or
pancreatic intraepithelial neoplasia. In 4 of 19 monkeys on dulaglutide
treatment, there was an increase in goblet cells within the pancreatic ducts,
but no differences from the control group in total amylase or lipase at study
termination. There were no proliferative changes in the thyroid C-cells.
Clinical
Studies
Trulicity has been studied
as monotherapy and in combination with metformin, sulfonylurea, metformin and
sulfonylurea, metformin and thiazolidinedione, basal insulin with or without
metformin, and prandial insulin with or without metformin. Trulicity has also
been studied in patients with type 2 diabetes mellitus and moderate to severe
renal impairment.
The studies evaluated the
use of Trulicity 0.75 mg and 1.5 mg. Uptitration was not performed in any of
the trials; patients were initiated and maintained on either 0.75 mg or 1.5 mg
for the duration of the trials. In patients with type 2 diabetes mellitus,
Trulicity produced reductions from baseline in HbA1c compared to placebo. No
overall differences in glycemic effectiveness were observed across demographic
subgroups (age, gender, race/ethnicity, duration of diabetes).
Monotherapy
In a 52-week double-blind
study (26 week primary endpoint), 807 patients inadequately treated with diet
and exercise, or with diet and exercise and one anti-diabetic agent used at
submaximal dose, were randomized to Trulicity 0.75 mg once weekly, Trulicity
1.5 mg once weekly, or metformin 1500 to 2000 mg/day following a two week
washout. Seventy-five percent (75%) of the randomized population were treated
with one antidiabetic agent at the screening visit. Most patients previously
treated with an antidiabetic agent were receiving metformin (~90%) at a median
dose of 1000 mg daily and approximately 10% were receiving a sulfonylurea.
Patients had a mean age of
56 years and a mean duration of type 2 diabetes of 3 years. Forty-four percent
were male. The White, Black and Asian race accounted for 74%, 7% and 8% of the
population, respectively. Twenty-nine percent of the study population were from
theUS.
Treatment with Trulicity
0.75 mg and 1.5 mg once weekly resulted in reduction in HbA1c from baseline
at the 26 week primary timepoint (Table
3). The difference in observed effect size between Trulicity
0.75 mg and 1.5 mg, respectively, and metformin excluded the
pre-specified non-inferiority margin of 0.4%.
Table 3: Results at Week 26 in a Trial of
Trulicity as Monotherapya
|
|
Abbreviation: HbA1c = hemoglobin A1c.
|
|
a Intent-to-treat population. Last
observation carried forward (LOCF) was used to impute missing data. Data
post-onset of rescue therapy are treated as missing. At Week 26, primary
efficacy was missing for 10%, 12% and 14% of individuals randomized to
Trulicity 0.75 mg, Trulicity 1.5 mg and metformin, respectively.
|
|
b Least-squares mean adjusted for
baseline value and other stratification factors.
|
|
‡ Subjects included in the analysis
are a subset of the ITT population that had at least one post-baseline
assessment. The primary analysis included 265 individuals in each of the
treatment arms.
|
|
|
26-Week Primary Time Point
|
|
Trulicity 0.75 mg
|
Trulicity 1.5 mg
|
Metformin
1500-2000 mg
|
|
Intent-to-Treat (ITT) Population (N)‡
|
270
|
269
|
268
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
7.6
|
7.6
|
7.6
|
|
Change from
baselineb
|
-0.7
|
-0.8
|
-0.6
|
|
Fasting Serum Glucose (mg/dL) (Mean)
|
|
Baseline
|
161
|
164
|
161
|
|
Change from baselineb
|
-26
|
-29
|
-24
|
|
Body Weight (kg) (Mean)
|
|
Baseline
|
91.8
|
92.7
|
92.4
|
|
Change from
baselineb
|
-1.4
|
-2.3
|
-2.2
|
Combination
Therapy
Add-on
to Metformin
In this 104-week
placebo-controlled, double-blind study (52-week primary endpoint), 972 patients
were randomized to placebo, Trulicity 0.75 mg once weekly, Trulicity
1.5 mg once weekly, or sitagliptin 100 mg/day (after 26 weeks,
patients in the placebo treatment group received blinded sitagliptin
100 mg/day for the remainder of the study), all as add-on to metformin.
Randomization occurred after an 11-week lead-in period to allow for a metformin
titration period, followed by a 6-week glycemic stabilization period. Patients
had a mean age of 54 years; mean duration of type 2 diabetes of 7 years; 48%
were male; race: White, Black and Asian were 53%, 4% and 27%, respectively; and
24% of the study population were in the US.
At the 26 week
placebo-controlled time point, the HbA1c change was 0.1%, -1.0%, -1.2%, and
-0.6% for placebo, Trulicity 0.75 mg, Trulicity 1.5 mg, and sitagliptin,
respectively. The percentage of patients who achieved HbA1c <7.0% was 22%,
56%, 62%, 39% for placebo, Trulicity 0.75 mg, Trulicity 1.5 mg, and
sitagliptin, respectively. At 26 weeks, there was a mean weight reduction of
1.4 kg, 2.7 kg, 3.0 kg, and 1.4 kg for placebo, Trulicity 0.75 mg, Trulicity
1.5 mg, and sitagliptin, respectively. There was a mean reduction of fasting
glucose of 9 mg/dL, 35 mg/dL, 41 mg/dL, and 18 mg/dL for placebo, Trulicity
0.75 mg, Trulicity 1.5 mg, and sitagliptin, respectively.
Treatment with Trulicity
0.75 mg and 1.5 mg once weekly resulted in a statistically
significant reduction in HbA1c compared to placebo (at 26 weeks) and compared
to sitagliptin (at 26 and 52), all in combination with metformin (Table
4 and Figure
3).
Table 4: Results at Week 52 of Trulicity
Compared to Sitagliptin used as Add-On to Metformina
|
|
Abbreviations: HbA1c = hemoglobin A1c.
|
|
a All ITT patients randomized after
the dose-finding portion of the study. Last observation carried forward
(LOCF) was used to impute missing data. At Week 52 primary efficacy was
missing for 15%, 19%, and 20% of individuals randomized to Trulicity 0.75 mg,
Trulicity 1.5 mg and sitagliptin, respectively.
|
|
b Least-squares (LS) mean adjusted for
baseline value and other stratification factors.
|
|
‡ Subjects included in the analysis are a
subset of the ITT population that had at least one post-baseline assessment.
The primary analysis included 276, 277, and 270 individuals randomized to
Trulicity 0.75 mg, Trulicity 1.5 mg and sitagliptin, respectively.
|
|
†† Multiplicity adjusted 1-sided
p-value <0.001, for superiority of Trulicity compared to sitagliptin,
assessed only for HbA1c.
|
|
## p<0.001 Trulicity compared to
sitagliptin, assessed only for HbA1c <7.0%.
|
|
|
52-Week Primary Time Point
|
|
Trulicity
0.75 mg
|
Trulicity
1.5 mg
|
Sitagliptin
100 mg
|
|
Intent-to-Treat (ITT) Population (N)‡
|
281
|
279
|
273
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
8.2
|
8.1
|
8.0
|
|
Change from
baselineb
|
-0.9
|
-1.1
|
-0.4
|
|
Difference from
sitagliptinb (95% CI)
|
-0.5 (-0.7, -0.3)††
|
-0.7 (-0.9, -0.5)††
|
-
|
|
Percentage of patients HbA1c <7.0%
|
49##
|
59##
|
33
|
|
Fasting Plasma Glucose (mg/dL) (Mean)
|
|
Baseline
|
174
|
173
|
171
|
|
Change from
baselineb
|
-30
|
-41
|
-14
|
|
Difference from
sitagliptinb (95% CI)
|
-15 (-22, -9)
|
-27 (-33, -20)
|
-
|
|
Body Weight (kg) (Mean)
|
|
Baseline
|
85.5
|
86.5
|
85.8
|
|
Change from
baselineb
|
-2.7
|
-3.1
|
-1.5
|
|
Difference from
sitagliptinb (95% CI)
|
-1.2 (-1.8, -0.6)
|
-1.5 (-2.1, -0.9)
|
-
|
Figure 3: Adjusted Mean HbA1c Change at each Time Point (ITT,
MMRM) and at Week 52 (ITT, LOCF)
Add-on
to Sulfonylurea
In this 24-week
placebo-controlled, double-blind study, 299 patients were randomized to and
received placebo or once weekly Trulicity 1.5 mg, both as add-on to
glimepiride. Patients had a mean age of 58 years; mean duration of type 2 diabetes
of 8 years, 44% were male; race: White, Black, and Asian were 83%, 4%, and 2%,
respectively; and 24% of the study population were in the US.
At 24 weeks, treatment with
once weekly Trulicity 1.5 mg resulted in a statistically significant
reduction in HbA1c compared to placebo (Table
5).
Table 5: Results at Week 24 of Trulicity
Compared to Placebo as Add-On to Glimepiridea
|
|
Abbreviations: HbA1c = hemoglobin A1c.
|
|
a Intent-to-treat population. Data
post-onset of rescue therapy are treated as missing. At Week 24 primary
efficacy was missing for 10% and 12% of individuals randomized to Trulicity
1.5 mg and placebo, respectively.
|
|
b Least-squares mean from ANCOVA
adjusted for baseline value and other stratification factors. Placebo
multiple imputation, with respect to the baseline values, was used to model a
wash-out of the treatment effect for subjects having missing Week 24 data.
|
|
c Patients with missing HbA1c data at
Week 24 were considered as non-responders.
|
|
†† p<0.001 for superiority of
Trulicity 1.5 mg compared to placebo, overall type I error controlled.
|
|
|
24-Week Primary Time Point
|
|
Placebo
|
Trulicity
1.5 mg
|
|
Intent-to-Treat (ITT) Population (N)
|
60
|
239
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
8.4
|
8.4
|
|
Change from
baselineb
|
-0.3
|
-1.3
|
|
Difference from
placebob (95% CI)
|
|
-1.1 (-1.4, -0.7)††
|
|
Percentage of patients HbA1c <7.0%c
|
17
|
50††
|
|
Fasting Serum Glucose (mg/dL) (Mean)
|
|
Baseline
|
175
|
178
|
|
Change from
baselineb
|
2
|
-28
|
|
Difference from
placebob (95% CI)
|
|
-30 (-44, -15)††
|
|
Body Weight (kg) (Mean)
|
|
Baseline
|
89.5
|
84.5
|
|
Change from
baselineb
|
-0.2
|
-0.5
|
|
Difference from
placebob (95% CI)
|
|
-0.4 (-1.2, 0.5)
|
Add-on
to Metformin and Thiazolidinedione
In this 52-week
placebo-controlled study (26-week primary endpoint), 976 patients were
randomized to and received placebo, Trulicity 0.75 mg once weekly,
Trulicity 1.5 mg once weekly, or exenatide 10 mcg BID, all as add-on
to maximally tolerated doses of metformin (≥1500 mg per day) and pioglitazone
(up to 45 mg per day). Exenatide treatment group assignment was open-label
while the treatment assignments to placebo, Trulicity 0.75 mg, and
Trulicity 1.5 mg were blinded. After 26 weeks, patients in the placebo
treatment group were randomized to either Trulicity 0.75 mg once weekly or
Trulicity 1.5 mg once weekly to maintain study blind. Randomization
occurred after a 12-week lead-in period; during the initial 4 weeks of the
lead-in period, patients were titrated to maximally tolerated doses of
metformin and pioglitazone; this was followed by an 8-week glycemic
stabilization period prior to randomization. Patients randomized to exenatide
started at a dose of 5 mcg BID for 4 weeks and then were escalated to
10 mcg BID. Patients had a mean age of 56 years; mean duration of type 2
diabetes of 9 years; 58% were male; race: White, Black and Asian were 74%, 8%
and 3%, respectively; and 81% of the study population were in the US.
Treatment with Trulicity
0.75 mg and 1.5 mg once weekly resulted in a statistically
significant reduction in HbA1c compared to placebo (at 26 weeks) and compared
to exenatide at 26 weeks (Table 6 and Figure
4). Over the 52-week study period, the percentage of patients
who required glycemic rescue was 8.9% in the Trulicity 0.75 mg once weekly +
metformin and pioglitazone treatment group, 3.2% in the Trulicity 1.5 mg once
weekly + metformin and pioglitazone treatment group, and 8.7% in the exenatide
BID + metformin and pioglitazone treatment group.
Table 6: Results at Week 26 of Trulicity
Compared to Placebo and Exenatide, All as Add-On to Metformin and
Thiazolidinedionea
|
|
Abbreviations: BID = twice daily; HbA1c =
hemoglobin A1c.
|
|
a Intent-to-treat population. Last
observation carried forward (LOCF) was used to impute missing data. Data
post-onset of rescue therapy are treated as missing. At Week 26, primary
efficacy was missing for 23%, 10%, 7% and 12% of individuals randomized to
placebo, Trulicity 0.75 mg, Trulicity 1.5 mg, and exenatide,
respectively.
|
|
b Least-squares (LS) mean adjusted for
baseline value and other stratification factors.
|
|
‡ Subjects included in the analysis
are a subset of the ITT population that had at least one post-baseline
assessment. The primary analysis included 119, 269, 271 and 266 individuals
randomized to placebo, Trulicity 0.75 mg, Trulicity 1.5 mg, and
exenatide, respectively.
|
|
‡‡ Multiplicity adjusted 1-sided
p-value <0.001, for superiority of Trulicity compared to placebo, assessed
only for HbA1c.
|
|
†† Multiplicity adjusted 1-sided
p-value <0.001, for superiority of Trulicity compared to exenatide,
assessed only for HbA1c.
|
|
** p<0.001 Trulicity compared to
placebo, assessed only for HbA1c <7.0%.
|
|
## p<0.001 Trulicity compared to
exenatide, assessed only for HbA1c <7.0%.
|
|
|
26-Week Primary Time Point
|
|
Placebo
|
Trulicity
0.75 mg
|
Trulicity
1.5 mg
|
Exenatide
10 mcg BID
|
|
Intent-to-Treat (ITT) Population (N)‡
|
141
|
280
|
279
|
276
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
8.1
|
8.1
|
8.1
|
8.1
|
|
Change from
baselineb
|
-0.5
|
-1.3
|
-1.5
|
-1.0
|
|
Difference from
placebob (95% CI)
|
-
|
-0.8 (-1.0, -0.7)‡‡
|
-1.1 (-1.2, -0.9)‡‡
|
-
|
|
Difference from
exenatideb (95% CI)
|
-
|
-0.3 (-0.4, -0.2)††
|
-0.5 (-0.7, -0.4)††
|
-
|
|
Percentage of patients HbA1c <7.0%
|
43
|
66**, ##
|
78**, ##
|
52
|
|
Fasting Serum Glucose (mg/dL) (Mean)
|
|
Baseline
|
166
|
159
|
162
|
164
|
|
Change from
baselineb
|
-5
|
-34
|
-42
|
-24
|
|
Difference from
placebob (95% CI)
|
-
|
-30 (-36, -23)
|
-38 (-45, -31)
|
-
|
|
Difference from
exenatideb (95% CI)
|
-
|
-10 (-15, -5)
|
-18 (-24, -13)
|
-
|
|
Body Weight (kg) (Mean)
|
|
Baseline
|
94.1
|
95.5
|
96.2
|
97.4
|
|
Change from
baselineb
|
1.2
|
0.2
|
-1.3
|
-1.1
|
|
Difference from
placebob (95% CI)
|
-
|
-1.0 (-1.8, -0.3)
|
-2.5 (-3.3, -1.8)
|
-
|
|
Difference from
exenatideb (95% CI)
|
-
|
1.3 (0.6, 1.9)
|
-0.2 (-0.9, 0.4)
|
-
|
Figure 4: Adjusted Mean HbA1c Change at Each Time Point (ITT,
MMRM) and at Week 26 (ITT, LOCF)
Add-on
to Metformin and Sulfonylurea
In this 78-week (52-week
primary endpoint) open-label comparator study (double-blind with respect to
Trulicity dose assignment), 807 patients were randomized to and received
Trulicity 0.75 mg once weekly, Trulicity 1.5 mg once weekly, or
insulin glargine once daily, all as add-on to maximally tolerated doses of
metformin and glimepiride. Randomization occurred after a 10-week lead-in
period; during the initial 2 weeks of the lead-in period, patients were
titrated to maximally tolerated doses of metformin and glimepiride. This was
followed by a 6- to 8-week glycemic stabilization period prior to
randomization.
Patients randomized to
insulin glargine were started on a dose of 10 units once daily. Insulin
glargine dose adjustments occurred twice weekly for the first 4 weeks of
treatment based on self-measured fasting plasma glucose (FPG), followed by once
weekly titration through Week 8 of study treatment, utilizing an algorithm that
targeted a fasting plasma glucose of <100 mg/dL. Only 24% of patients were
titrated to goal at the 52 week primary endpoint. The dose of glimepiride could
be reduced or discontinued after randomization (at the discretion of the
investigator) in the event of persistent hypoglycemia. The dose of glimepiride
was reduced or discontinued in 28%, 32%, and 29% of patients randomized to
Trulicity 0.75 mg, Trulicity 1.5 mg, and glargine.
Patients had a mean age of
57 years; mean duration of type 2 diabetes of 9 years; 51% were male; race:
White, Black and Asian were 71%, 1% and 17%, respectively; and 0% of the study
population were in the US.
Treatment with Trulicity
once weekly resulted in a reduction in HbA1c from baseline at 52 weeks when
used in combination with metformin and sulfonylurea (Table
7). The difference in observed effect size between Trulicity
0.75 mg and 1.5 mg, respectively, and glargine in this trial excluded
the pre-specified non-inferiority margin of 0.4%.
Table 7: Results at Week 52 of Trulicity
Compared to Insulin Glargine, Both as Add-on to Metformin and Sulfonylureaa
|
|
Abbreviations: HbA1c = hemoglobin A1c.
|
|
a Intent-to-treat population. Last
observation carried forward (LOCF) was used to impute missing data. Data
post-onset of rescue therapy are treated as missing. At Week 52, primary
efficacy was missing for 17%, 13% and 12% of individuals randomized to
Trulicity 0.75 mg, Trulicity 1.5 mg and glargine, respectively.
|
|
b Least-squares (LS) mean adjusted for
baseline value and other stratification factors.
|
|
‡ Subjects included in the analysis
are a subset of the ITT population that had at least one post-baseline
assessment. The primary analysis included 267, 263 and 259 individuals
randomized to Trulicity 0.75 mg, Trulicity 1.5 mg, and glargine,
respectively.
|
|
|
52-Week Primary Time Point
|
|
Trulicity
0.75 mg
|
Trulicity
1.5 mg
|
Insulin Glargine
|
|
Intent-to-Treat (ITT) Population (N)‡
|
272
|
273
|
262
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
8.1
|
8.2
|
8.1
|
|
Change from
baselineb
|
-0.8
|
-1.1
|
-0.6
|
|
Fasting Serum Glucose (mg/dL) (Mean)
|
|
Baseline
|
161
|
165
|
163
|
|
Change from
baselineb
|
-16
|
-27
|
-32
|
|
Difference from
insulin glargineb (95% CI)
|
16 (9, 23)
|
5 (-2, 12)
|
-
|
|
Body Weight (kg) (Mean)
|
|
Baseline
|
86.4
|
85.2
|
87.6
|
|
Change from
baselineb
|
-1.3
|
-1.9
|
1.4
|
|
Difference from
insulinb (95% CI)
|
-2.8 (-3.4, -2.2)
|
-3.3 (-3.9, -2.7)
|
-
|
Combination
Therapy with Basal Insulin, with or without Metformin
In this 28-week
placebo-controlled, double-blind study, 300 patients were randomized to placebo
or once weekly Trulicity 1.5 mg, as add-on to titrated basal insulin
glargine (with or without metformin). Patients had a mean age of 60 years; mean
duration of type 2 diabetes of 13 years, 58% were male; race: White, Black, and
Asian were 94%, 4%, and 0.3%, respectively; and 20% of the study population was
in the US.
The mean starting dose of
insulin glargine was 37 units/day for patients receiving placebo and
41 units/day for patients receiving Trulicity 1.5 mg. At
randomization, the initial insulin glargine dose in patients with HbA1c
<8.0% was reduced by 20%.
At 28 weeks, treatment with
once weekly Trulicity 1.5 mg resulted in a statistically significant
reduction in HbA1c compared to placebo (Table
8).
Table 8: Results at Week 28 of Trulicity
Compared to Placebo as Add-On to Basal Insulina
|
|
Abbreviations: HbA1c = hemoglobin A1c.
|
|
a Intent-to-treat population. At Week
28, primary efficacy was missing for 12% and 8% of individuals randomized to
placebo and Trulicity 1.5 mg, respectively.
|
|
b Least-squares mean from ANCOVA
adjusted for baseline value and other stratification factors. Placebo
multiple imputation, with respect to baseline values, was used to model a
wash-out of the treatment effect for subjects having missing Week 28 data.
|
|
c Patients with missing HbA1c data at
Week 28 were considered as non-responders.
|
|
†† p<0.001 for superiority of
Trulicity 1.5 mg compared to placebo, overall type I error controlled.
|
|
† p≤0.005 for superiority of Trulicity
1.5 mg compared to placebo, overall type I error controlled.
|
|
|
28-Week Primary Time Point
|
|
Placebo
|
Trulicity
1.5 mg
|
|
Intent-to-Treat (ITT) Population (N)
|
150
|
150
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
8.3
|
8.4
|
|
Change from
baselineb
|
-0.7
|
-1.4
|
|
Difference from
placebob (95% CI)
|
|
-0.7 (-0.9, -0.5)††
|
|
Percentage of patients HbA1c <7.0%c
|
33
|
67††
|
|
Fasting Serum Glucose (mg/dL) (Mean)
|
|
Baseline
|
156
|
157
|
|
Change from
baselineb
|
-30
|
-44
|
|
Difference from
placebob (95% CI)
|
|
-14 (-23, -4)†
|
|
Body Weight (kg) (Mean)
|
|
Baseline
|
92.6
|
93.3
|
|
Change from
baselineb
|
0.8
|
-1.3
|
|
Difference from
placebob (95% CI)
|
|
-2.1 (-2.9, -1.4)††
|
Combination
Therapy with Prandial Insulin, with or without Metformin
In this 52-week (26-week
primary endpoint) open-label comparator study (double-blind with respect to
Trulicity dose assignment), 884 patients on 1 or 2 insulin injections per day
were enrolled. Randomization occurred after a 9-week lead-in period; during the
initial 2 weeks of the lead-in period, patients continued their pre-study
insulin regimen but could be initiated and/or up-titrated on metformin, based
on investigator discretion; this was followed by a 7-week glycemic
stabilization period prior to randomization.
At randomization, patients
discontinued their pre-study insulin regimen and were randomized to Trulicity
0.75 mg once weekly, Trulicity 1.5 mg once weekly, or insulin
glargine once daily, all in combination with prandial insulin lispro 3 times
daily, with or without metformin. Insulin lispro was titrated in each arm based
on preprandial and bedtime glucose, and insulin glargine was titrated to a
fasting plasma glucose goal of <100 mg/dL. Only 36% of patients randomized
to glargine were titrated to the fasting glucose goal at the 26 week primary
timepoint.
Patients had a mean age of
59 years; mean duration of type 2 diabetes of 13 years; 54% were male; race:
White, Black and Asian were 79%, 10% and 4%, respectively; and 33% of the study
population were in the US.
Treatment with Trulicity
0.75 mg and 1.5 mg once weekly resulted in a reduction in HbA1c from
baseline. The difference in observed effect size between Trulicity 0.75 mg and
1.5 mg, respectively, and glargine in this trial excluded the pre-specified
non-inferiority margin of 0.4%.
Table 9: Results at Week 26 of Trulicity
Compared to Insulin Glargine, Both in Combination with Insulin Lisproa
|
|
Abbreviation: HbA1c = hemoglobin A1c
|
|
a Intent-to-treat population. Last
observation carried forward (LOCF) was used to impute missing data. Data
post-onset of rescue therapy are treated as missing. At Week 26, primary
efficacy was missing for 14%, 15%, and 14% of individuals randomized to
Trulicity 0.75 mg, Trulicity 1.5 mg and glargine, respectively.
|
|
b Least-squares (LS) mean adjusted for
baseline value and other stratification factors.
|
|
‡ Subjects included in the analysis are a
subset of the ITT population that had at least one post-baseline assessment.
The primary analysis included 275, 273 and 276 individuals randomized to
Trulicity 0.75 mg, Trulicity 1.5 mg, and glargine, respectively.
|
|
|
26-Week Primary Time Point
|
|
Trulicity
0.75 mg
|
Trulicity
1.5 mg
|
Insulin Glargine
|
|
Intent-to-Treat (ITT) Population (N)‡
|
293
|
295
|
296
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
8.4
|
8.5
|
8.5
|
|
Change from
baselineb
|
-1.6
|
-1.6
|
-1.4
|
|
Fasting Serum Glucose (mg/dL) (Mean)
|
|
|
|
|
Baseline
|
150
|
157
|
154
|
|
Change from
baselineb
|
4
|
-5
|
-28
|
|
Difference from
insulin glargineb (95% CI)
|
32 (24, 41)
|
24 (15, 32)
|
-
|
|
Body Weight (kg) (Mean)
|
|
|
|
|
Baseline
|
91.7
|
91.0
|
90.8
|
|
Change from
baselineb
|
0.2
|
-0.9
|
2.3
|
|
Difference from
insulin glargineb (95% CI)
|
-2.2 (-2.8, -1.5)
|
-3.2 (-3.8, -2.6)
|
-
|
Moderate to
Severe Chronic Kidney Disease
In this 52-week (26-week
primary endpoint) open-label comparator study (double-blind with respect to
Trulicity dose assignment), a total of 576 patients with type 2 diabetes were randomized
and treated to compare Trulicity 0.75 mg and 1.5 mg with insulin
glargine (NCT01621178).
Patients on insulin and
other antidiabetic therapy (e.g., oral antidiabetic drugs, pramlintide) had
non-insulin therapies discontinued and had their insulin dose adjusted for 12
weeks prior to randomization. Patients on insulin therapy alone maintained a
stable insulin dose for 3 weeks prior to randomization. At randomization,
patients discontinued their pre-study insulin regimen and patients were
randomized to Trulicity 0.75 mg once weekly, Trulicity 1.5 mg once
weekly, or insulin glargine once daily, all in combination with prandial
insulin lispro. For patients randomized to insulin glargine, the initial
insulin glargine dose was based on the basal insulin dose prior to
randomization. Insulin glargine was allowed to be titrated with a fasting
plasma glucose goal of ≤150 mg/dL. Insulin lispro was allowed to be
titrated with a preprandial and bedtime glucose goal of ≤180 mg/dL.
Patients had a mean age of
65 years; a mean duration of type 2 diabetes of 18 years; 52% were male; race:
White, Black, and Asian were 69%, 16%, and 3%, respectively; and 32% of the
study population were in the US. At baseline, overall mean eGFR was
38 mL/min/1.73 m2, 30% of patients had eGFR <30 mL/min/1.73 m2, and 45% of patients had
macroalbuminuria. Patients on over 70 units/day of basal insulin were
excluded from the study.
Treatment with Trulicity
0.75 mg and 1.5 mg once weekly resulted in a reduction in HbA1c at
26-weeks from baseline. The difference in observed effect size between
Trulicity 0.75 mg and 1.5 mg, respectively, and glargine in this
trial excluded the pre-specified non-inferiority margin of 0.4%. Mean fasting
plasma glucose increased in the Trulicity arms (Table 10).
Mean baseline body weight
was 90.9 kg, 88.1 kg, and 88.2 kg in the Trulicity 0.75 mg,
Trulicity 1.5 mg, and insulin glargine arms, respectively. The mean
changes from baseline at week 26 were -1.1, -2, and 1.9 kg in the Trulicity
0.75 mg, Trulicity 1.5 mg, and insulin glargine arms, respectively.
Table 10: Results at Week 26 of Trulicity
Compared to Insulin Glargine, Both in Combination with Insulin Lispro, in
Patients with Moderate to Severe Chronic Kidney Diseasea
|
|
Abbreviation: HbA1c = hemoglobin A1c
|
|
a Intent-to-treat population (all
randomized and treated subjects) was used in the analysis regardless of
discontinuation of study drug or initiation of rescue therapy. At Week 26,
primary efficacy was missing for 12%, 15%, and 9% of individuals randomized
to and treated with Trulicity 0.75 mg, Trulicity 1.5 mg, and
insulin glargine, respectively. Missing data were imputed using multiple
imputation within treatment group.
|
|
b Least-squares (LS) mean from ANCOVA
pattern mixture model adjusted for baseline value and other stratification
factors.
|
|
|
26-Week Primary Time Point
|
|
Trulicity
0.75 mg
|
Trulicity
1.5 mg
|
Insulin Glargine
|
|
Intent-to-Treat Population (N)
|
190
|
192
|
194
|
|
HbA1c (%) (Mean)
|
|
Baseline
|
8.6
|
8.6
|
8.6
|
|
Change from
baselineb
|
-0.9
|
-1.0
|
-1.0
|
|
Difference from
insulin glargineb (95% CI)
|
0.0 (-0.2, 0.3)
|
-0.1 (-0.3, 0.2)
|
|
|
Percentage of patients HbA1c <8.0%
|
73
|
75
|
74
|
|
Fasting Serum Glucose (mg/dL) (Mean)
|
|
Baseline
|
167
|
161
|
170
|
|
Change from
baselineb
|
6
|
14
|
-23
|
|
Difference from
insulin glargineb (95% CI)
|
30 (16, 43)
|
37 (24, 50)
|
|
How
Supplied/Storage and HandlingHow
Supplied
Each Trulicity single-dose
pen is packaged in a cardboard outer carton.
Carton
of 4 Single-Dose Pens
·
0.75 mg/0.5 mL
solution in a single-dose pen (NDC 0002-1433-80)
·
1.5 mg/0.5 mL
solution in a single-dose pen (NDC 0002-1434-80)
Storage and
Handling
·
Store Trulicity in the
refrigerator at 36°F to 46°F (2°C to 8°C). Do not use Trulicity beyond the
expiration date.
·
If needed, each single-dose
pen can be kept at room temperature, not to exceed 86°F (30°C) for a total of
14 days.
·
Do not freeze Trulicity. Do
not use Trulicity if it has been frozen.
·
Trulicity must be protected
from light. Storage of Trulicity in the original carton is recommended until
time of administration.
·
Discard the Trulicity
single-dose pen after use in a puncture-resistant container.
Patient
Counseling Information
See FDA-approved Medication Guide
·
Inform patients that
Trulicity causes benign and malignant thyroid C-cell tumors in rats and that
the human relevance of this finding has not been determined. Counsel patients
to report symptoms of thyroid tumors (e.g., a lump in the neck, persistent
hoarseness, dysphagia, or dyspnea) to their physician [see Boxed
Warning and Warnings and Precautions (5.1)].
·
Inform patients that
persistent severe abdominal pain, that may radiate to the back and which may
(or may not) be accompanied by vomiting, is the hallmark symptom of acute
pancreatitis. Instruct patients to discontinue Trulicity promptly, and to
contact their physician, if persistent severe abdominal pain occurs [see Warnings and Precautions (5.2)].
·
The risk of hypoglycemia may
be increased when Trulicity is used in combination with a medicine that can
cause hypoglycemia, such as a sulfonylurea or insulin. Review and reinforce
instructions for hypoglycemia management when initiating Trulicity therapy,
particularly when concomitantly administered with a sulfonylurea or
insulin [see Warnings and Precautions (5.3)].
·
Patients treated with
Trulicity should be advised of the potential risk of dehydration due to
gastrointestinal adverse reactions and take precautions to avoid fluid
depletion. Inform patients treated with Trulicity of the potential risk for
worsening renal function and explain the associated signs and symptoms of renal
impairment, as well as the possibility of dialysis as a medical intervention if
renal failure occurs [see Warnings and Precautions
(5.5)].
·
Inform patients that serious
hypersensitivity reactions have been reported with use of Trulicity. Advise
patients on the symptoms of hypersensitivity reactions and instruct them to
stop taking Trulicity and seek medical advice promptly if such symptoms
occur [see Warnings and Precautions (5.4)].
·
Advise women to inform their
healthcare provider if they are pregnant or intend to become pregnant [see Use in Specific Populations (8.1)].
·
Prior to initiation of
Trulicity, train patients on proper injection technique to ensure a full dose
is delivered. Refer to the accompanying Instructions for Use for complete
administration instructions with illustrations [see
Dosage and Administration (2.3)].
·
Inform patients of the
potential risks and benefits of Trulicity and of alternative modes of therapy.
Inform patients about the importance of adherence to dietary instructions,
regular physical activity, periodic blood glucose monitoring and HbA1c testing,
recognition and management of hypoglycemia and hyperglycemia, and assessment
for diabetes complications. During periods of stress such as fever, trauma,
infection, or surgery, medication requirements may change and advise patients
to seek medical advice promptly.
·
Each weekly dose of
Trulicity can be administered at any time of day, with or without food. The day
of once weekly administration can be changed if necessary, as long as the last
dose was administered 3 or more days before. If a dose is missed and there are
at least 3 days (72 hours) until the next scheduled dose, it should be
administered as soon as possible. Thereafter, patients can resume their usual
once weekly dosing schedule. If a dose is missed and the next regularly
scheduled dose is due in 1 or 2 days, the patient should not administer the
missed dose and instead resume Trulicity with the next regularly scheduled
dose [see Dosage and Administration (2)].
·
Advise patients treated with
Trulicity of the potential risk of gastrointestinal side effects [see Adverse Reactions (6.1)].
·
Instruct patients to read
the Medication Guide and the Instructions for Use before starting Trulicity
therapy and review them each time the prescription is refilled. Instruct
patients to inform their doctor or pharmacist if they develop any unusual
symptom, or if any known symptom persists or worsens.
·
Inform patients that
response to all diabetic therapies should be monitored by periodic measurements
of blood glucose and HbA1c levels, with a goal of decreasing these levels
towards the normal range. HbA1c is especially useful for evaluating long-term
glycemic control.
Eli
Lilly and Company, Indianapolis, IN 46285, USA
US License Number 1891
Copyright © 2014, 2018, Eli Lilly and Company. All rights
reserved.
TRU-0009-USPI-20180712
|
This Medication Guide has been approved by the U.S.
Food and Drug Administration.
TRU-0004-MG-20170801
|
Revised: August 2017
|
|
Medication Guide
Trulicity® (TRU-li-si-tee) (dulaglutide)
injection, for subcutaneous use
|
|
Read this
Medication Guide before you start using Trulicity and each time you get a
refill. There may be new information. This information does not take the
place of talking to your healthcare provider about your medical condition or
your treatment.
|
|
What
is the most important information I should know about Trulicity?
Trulicity may
cause serious side effects, including:
· Possible thyroid tumors, including cancer. Tell your healthcare provider if you
get a lump or swelling in your neck, hoarseness, trouble swallowing, or
shortness of breath. These may be symptoms of thyroid cancer. In studies with
rats or mice, Trulicity and medicines that work like Trulicity caused thyroid
tumors, including thyroid cancer. It is not known if Trulicity will cause
thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma
(MTC) in people.
· Do
not use Trulicity if you or any of your family have ever had a type of
thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an
endocrine system condition called Multiple Endocrine Neoplasia syndrome type
2 (MEN 2).
|
|
What is Trulicity?
Trulicity is an injectable prescription medicine that may improve blood sugar
(glucose) in adults with type 2 diabetes mellitus, and should be used along
with diet and exercise.
· Trulicity
is not recommended as the first choice of medicine for treating diabetes.
· It is
not known if Trulicity can be used in people who have had pancreatitis.
· Trulicity
is not a substitute for insulin and is not for use in people with type 1
diabetes or people with diabetic ketoacidosis.
· Trulicity
is not recommended for use in people with severe stomach or intestinal
problems.
· It is
not known if Trulicity is safe and effective for use in children. Trulicity
should not be used in children under 18 years of age.
|
|
Do not use Trulicity if:
· You
or any of your family have ever had a type of thyroid cancer called medullary
thyroid carcinoma (MTC) or if you have an endocrine system condition called
Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
· You
are allergic to dulaglutide or any of the ingredients in Trulicity. See "What are the possible side effects of Trulicity?" See
the end of this Medication Guide for a complete list of ingredients in
Trulicity.
|
|
Before using Trulicity, tell your healthcare provider if you have any
medical conditions including:
· Have
or have had problems with your pancreas, kidneys or liver.
· Have
severe problems with your stomach, such as slowed emptying of your stomach
(gastroparesis) or problems with digesting food.
· Are
pregnant or plan to become pregnant. It is not known if Trulicity will harm
your unborn baby. Tell your healthcare provider if you become pregnant while
using Trulicity.
· Are
breastfeeding or plan to breastfeed. It is not known if Trulicity passes into
your breast milk. You and your healthcare provider should decide if you
should breastfeed while taking Trulicity.
Tell your healthcare provider about all the medicines you take, including prescription and
over-the-counter medicines, vitamins, and herbal supplements. Trulicity may
affect the way some medicines work and some medicines may affect the way
Trulicity works.
Before using Trulicity, talk to your healthcare provider
about low blood sugar and how to manage it. Tell your
healthcare provider if you are taking other medicines to treat diabetes
including insulin or sulfonylureas.
Know the medicines you take. Keep a list of them to show your healthcare provider
and pharmacist when you get a new medicine.
|
|
How should I use Trulicity?
· Read
the Instructions for Use that comes with
Trulicity.
· Use
Trulicity exactly as your healthcare provider tells you to.
· Your
healthcare provider should show you how to use Trulicity before you use it
for the first time.
· Trulicity
is injected under the skin (subcutaneously) of your stomach (abdomen), thigh,
or upper arm. Do not inject Trulicity into
a muscle (intramuscularly) or vein (intravenously).
· Use Trulicity 1 time each week on the same day each
week at any time of the day.
· You
may change the day of the week as long as your last dose was given 3 or more days before.
· If
you miss a dose of Trulicity, take the missed dose as soon as possible if
there are at least 3 days (72 hours) until
your next scheduled dose. If there are less than 3 days
remaining, skip the missed dose and take your next dose on the regularly
scheduled day. Do not take 2 doses of Trulicity within 3 days
of each other.
· Trulicity
may be taken with or without food.
· Do not mix insulin and Trulicity together in the same
injection.
· You
may give an injection of Trulicity and insulin in the same body area (such
as, your stomach area), but not right next to each other.
· Change
(rotate) your injection site with each weekly injection. Do not use the same
site for each injection.
· If
you take too much Trulicity, call your healthcare provider or go to the
nearest emergency room right away.
· Do not share your Trulicity pen, syringe, or needles
with another person. You
may give another person an infection or get an infection from them.
Your dose of Trulicity and other diabetes medicines may need to change
because of:
· Change
in level of physical activity or exercise, weight gain or loss, increased
stress, illness, change in diet, or because of other medicines you take.
|
|
What
are the possible side effects of Trulicity?
Trulicity may cause serious side effects, including:
· See “What is the most important information I should know
about Trulicity?”
· Inflammation of your pancreas (pancreatitis). Stop using Trulicity and call your
healthcare provider right away if you have severe pain in your stomach area
(abdomen) that will not go away, with or without vomiting. You may feel the
pain from your abdomen to your back.
· Low blood sugar (hypoglycemia). Your risk for getting low blood
sugar may be higher if you use Trulicity with another medicine that can cause
low blood sugar, such as a sulfonylurea or insulin.
Signs and symptoms of low blood sugar may include:
|
|
|
· dizziness
or light-headedness
· sweating
· confusion
or drowsiness
· headache
|
· blurred
vision
· slurred
speech
· shakiness
· fast
heartbeat
|
· anxiety,
irritability, or mood changes
· hunger
· weakness
· feeling
jittery
|
|
· Serious allergic reactions. Stop using Trulicity and get medical
help right away if you have any symptoms of a serious allergic reaction
including:
|
|
· swelling
of your face, lips, tongue or throat
· problems
breathing or swallowing
· severe
rash or itching
|
· fainting
or feeling dizzy
· very
rapid heartbeat
|
|
· Kidney problems (kidney failure). In people who have kidney problems,
diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which
may cause kidney problems to get worse.
· Severe stomach problems. Other medicines like Trulicity may
cause severe stomach problems. It is not known if Trulicity causes or worsens
stomach problems.
The most common side effects of Trulicity may include:
|
|
· nausea
· diarrhea
· vomiting
|
· abdominal
pain
· decreased
appetite
|
|
Talk to your
healthcare provider about any side effect that bothers you or does not go
away. These are not all the possible side effects of Trulicity.
Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
|
|
General information about the safe and effective use of Trulicity.
Medicines are sometimes prescribed for purposes other than those listed in a
Medication Guide. Do not use Trulicity for a condition for which it was not
prescribed. Do not give Trulicity to other people, even if they have the same
symptoms you have. It may harm them.
This Medication Guide summarizes the most important information about
Trulicity. If you would like more information, talk with your healthcare
provider. You can ask your pharmacist or healthcare provider for information
about Trulicity that is written for health professionals.
|
|
What are the ingredients in Trulicity?
Active ingredient: dulaglutide
Inactive ingredients: citric acid
anhydrous, mannitol, polysorbate 80, trisodium citrate dihydrate, in water for
injection
Trulicity® is a registered trademark of Eli
Lilly and Company.
Manufactured by: Eli Lilly and Company, Indianapolis, IN 46285, USA, US
License Number 1891
www.Trulicity.com.
Copyright © 2014, 2017 Eli Lilly and Company. All rights reserved.
For more information, go to www.Trulicity.com or call 1-800-545-5979.
|
|
Instructions for Use
|
|
Trulicity® (Trū-li-si-tee)
(dulaglutide)
injection, for subcutaneous use
0.75 mg/0.5 mL Single-Dose Pen
once weekly
|
|
BREAK
SEAL
|
|
BREAK
SEAL
|
|
|
|
|
|
|
|
Information About Trulicity Single-Dose Pen
Please read this Instructions for Use and the Medication
Guide carefully and completely before using your Trulicity Single-Dose Pen.
Talk to your healthcare provider about how to inject Trulicity the right way.
· Trulicity
Single-Dose Pen (Pen) is a disposable, prefilled medicine delivery device.
Each Pen contains 1 dose of Trulicity (0.75 mg/0.5 mL). Each Pen
should only be used 1 time.
· Trulicity is used 1 time each week. You may want to mark your calendar
to remind you when to take your next dose.
|
|
|
|
|
|
|
|
|
Before You Get Started
|
|
|
|
|
|
|
Remove
|
Check
|
Inspect
|
Prepare
|
|
Remove the Pen
from the refrigerator.
|
Check the Pen
label to make sure you have the right medicine and it has not expired.
|
Check the Pen to
make sure that it is not damaged and inspect the medicine to make sure it is
not cloudy, discolored or has particles in it.
|
Wash your hands.
|
|
Choose Your Injection Site
|
|
|
· Your
healthcare provider can help you choose the injection site that is best for
you.
· You
may inject the medicine into your stomach (abdomen) or thigh.
· Another
person may give you the injection in your upper arm.
· Change
(rotate) your injection site each week. You may use the same area of your
body, but be sure to choose a different injection site in that area.
|
|
|
|
|
|
|
|
1 Uncap the Pen
 Make sure the Pen is locked.
· Pull
the Base Cap straight off and throw it away in your household trash.
Do not put the Base Cap back on— this could damage the
needle. Do not touch the needle.
|
|
|
2 Place and Unlock
· Place
the Clear Base flat and firmly against your skin at the injection site.
 Unlock by
turning the Lock Ring.
|
|
|
3 Press and Hold
· Press
and hold the green Injection Button; you will hear a loud click.
 Continue holding the Clear Base firmly
against your skin until you hear a second click. This happens when the needle
starts retracting in about 5-10 seconds.
· Remove
the Pen from your skin.
|
You will know your injection is complete when the gray
plunger is visible.
|
|
|
|
|
|
|
|
Important Information
Disposal of Pen
Storage and Handling
Commonly Asked Questions
Other Information
Where to Learn More
|
|
Disposing of Your Used Pens
· Put
your used Pens in a FDA-cleared sharps disposal container right away after
use. Do not throw away (dispose of) Pens in your
household trash.
· If
you do not have a FDA-cleared sharps disposal container, you may use a
household container that is:
-
made of a heavy-duty plastic,
-
can be closed with a tight-fitting,
puncture-resistant lid, without sharps being able to come out,
-
upright and stable during use,
-
leak-resistant, and
-
properly labeled to warn of hazardous waste inside
the container.
· When
your sharps disposal container is almost full, you will need to follow your
community guidelines for the right way to dispose of your sharps disposal
container. There may be state or local laws about how you should throw away
used needles and syringes. For more information about safe sharps disposal,
and for specific information about sharps disposal in the state that you live
in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
· Do not recycle your used sharps disposal container.
|
|
|
|
|
Storage and Handling
|
|
· Store
your Pen in the refrigerator between 36°F to 46°F (2°C to 8°C).
· You
may store your Pen at room temperature below 86°F (30°C) for up to a total of
14 days.
· Do
not freeze your Pen. If the Pen has been frozen, throw the Pen away and use a
new Pen.
· Storage
of your Pen in the original carton is recommended. Protect your Pen from
direct heat and light.
· The
Pen has glass parts. Handle it carefully. If you drop it on a hard surface,
do not use it. Use a new Pen for your injection.
· Keep
your Trulicity Pen and all medicines out of the reach of children.
|
|
Commonly Asked Questions
|
|
What if I see an air bubble in my Pen?
Air bubbles are normal.
What if I unlock the Pen and press the green Injection
Button before pulling off the Base Cap?
Do not remove the Base Cap. Throw away the Pen and get a new Pen.
What if there is a drop of liquid on the tip of the
needle when I remove the Base Cap?
A drop of liquid on the tip of the needle is normal.
Do I need to hold the Injection Button down until the
injection is complete?
This is not necessary, but it may help you keep the Pen steady and firm
against your skin.
I heard more than 2 clicks during my injection—2 louder
clicks and 1 soft one. Did I get my complete injection?
Some patients may hear a soft click right before the second loud click. That
is the normal operation of the Pen. Do not remove the Pen from your skin
until you hear the second louder click.
What if there is a drop of liquid or blood on my skin
after my injection?
This is normal.
I am not sure if my Pen worked the right way.
Check to see if you have received your dose. Your dose was delivered the
right way if the gray plunger is visible (see
step 3). Also contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or
your healthcare provider for further instructions. Until then, store your Pen
safely to avoid an accidental needle stick.
|
|
|
|
Other Information
|
|
· If
you have vision problems, do not use your Pen without help from a person
trained to use the Trulicity Pen.
|
|
Where to Learn More
|
|
· If
you have any questions or problems with your Trulicity Single-Dose Pen,
contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare
provider.
· For
more information about Trulicity Single-Dose Pen, visit our website at:
www.Trulicity.com.
|
|
|
SCAN THIS CODE TO LAUNCH
www.Trulicity.com
|
|
|
This Instructions for Use has been approved by the U.S. Food and Drug
Administration.
Eli Lilly and Company
Indianapolis, IN 46285, USA
Trulicity is a trademark of Eli Lilly and Company.
Copyright © 2014, 2017 Eli Lilly and Company. All rights reserved.
The Trulicity Pen meets the current dose accuracy and functional requirements
of ISO 11608-1:2012 and 11608-5:2012.
Revised: June 22, 2017
TRULOAI-0002-IFU-20170622
|
|
BREAK
|
Instructions for Use
|
BREAK
|
|
SEAL
|
Trulicity® (Trū-li-si-tee)
(dulaglutide)
injection, for subcutaneous use
0.75 mg/0.5 mL Single-Dose Pen
once weekly
|
SEAL
|
|
|
|
|
|
Information About Trulicity Single-Dose Pen
Please read this Instructions for Use and the Medication
Guide carefully and completely before using your Trulicity Single-Dose Pen.
Talk to your healthcare provider about how to inject Trulicity the right way.
· Trulicity
Single-Dose Pen (Pen) is a disposable, prefilled medicine delivery device.
Each Pen contains 1 dose of Trulicity (0.75 mg/0.5 mL). Each Pen
should only be used 1 time.
· Trulicity is used 1 time each week. You may want to mark your calendar
to remind you when to take your next dose.
|
|
Before You Get Started
|
|
|
|
|
|
|
Remove
|
Check
|
Inspect
|
Prepare
|
|
Remove the Pen
from the refrigerator.
|
Check the Pen
label to make sure you have the right medicine and it has not expired.
|
Check the Pen to
make sure that it is not damaged and inspect the medicine to make sure it is
not cloudy, discolored or has particles in it.
|
Wash your hands.
|
|
Choose Your Injection Site
|
|
|
· Your
healthcare provider can help you choose the injection site that is best for
you.
· You
may inject the medicine into your stomach (abdomen) or thigh.
· Another
person may give you the injection in your upper arm.
· Change
(rotate) your injection site each week. You may use the same area of your
body, but be sure to choose a different injection site in that area.
|
|
|
|
|
|
1 Uncap the Pen
 Make sure the Pen is locked.
· Pull
the Base Cap straight off and throw it away in your household trash.
Do not put the Base Cap back on—this could damage the
needle. Do not touch the needle.
|
|
|
2 Place and Unlock
· Place
the Clear Base flat and firmly against your skin at the injection site.
 Unlock by
turning the Lock Ring.
|
|
|
3
Press and Hold
· Press
and hold the green Injection Button; you will hear a loud click.
 Continue holding the Clear Base firmly
against your skin until you hear a second click. This happens when the needle
starts retracting in about 5-10 seconds.
· Remove
the Pen from your skin.
|
You will know your injection is complete when the gray
plunger is visible.
|
|
Important Information
Disposal of Pen
Storage and Handling
Commonly Asked Questions
Other Information
Where to Learn More
|
|
Disposing of Your Used Pens
· Put
your used Pens in a FDA-cleared sharps disposal container right away after
use. Do not throw away (dispose of) Pens in your
household trash.
· If
you do not have a FDA-cleared sharps disposal container, you may use a
household container that is:
-
made of a heavy-duty plastic,
-
can be closed with a tight-fitting,
puncture-resistant lid, without sharps being able to come out,
-
upright and stable during use,
-
leak-resistant, and
-
properly labeled to warn of hazardous waste inside
the container.
· When
your sharps disposal container is almost full, you will need to follow your
community guidelines for the right way to dispose of your sharps disposal
container. There may be state or local laws about how you should throw away
used needles and syringes. For more information about safe sharps disposal,
and for specific information about sharps disposal in the state that you live
in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
· Do not recycle your used sharps disposal container.
|
|
|
|
|
Storage and Handling
|
|
· Store
your Pen in the refrigerator between 36°F to 46°F (2°C to 8°C).
· You
may store your Pen at room temperature below 86°F (30°C) for up to a total of
14 days.
· Do
not freeze your Pen. If the Pen has been frozen, throw the Pen away and use a
new Pen.
· Storage
of your Pen in the original carton is recommended. Protect your Pen from
direct heat and light.
· The
Pen has glass parts. Handle it carefully. If you drop it on a hard surface,
do not use it. Use a new Pen for your injection.
· Keep
your Trulicity Pen and all medicines out of the reach of children.
|
|
Commonly Asked Questions
|
|
What if I see an air bubble in my Pen?
Air bubbles are normal.
What if I unlock the Pen and press the green Injection
Button before pulling off the Base Cap?
Do not remove the Base Cap. Throw away the Pen and get a new Pen.
What if there is a drop of liquid on the tip of the
needle when I remove the Base Cap?
A drop of liquid on the tip of the needle is normal.
Do I need to hold the Injection Button down until the
injection is complete?
This is not necessary, but it may help you keep the Pen steady and firm
against your skin.
I heard more than 2 clicks during my injection—2 louder
clicks and 1 soft one. Did I get my complete injection?
Some patients may hear a soft click right before the second loud click. That
is the normal operation of the Pen. Do not remove the Pen from your skin
until you hear the second louder click.
What if there is a drop of liquid or blood on my skin
after my injection?
This is normal.
I am not sure if my Pen worked the right way.
Check to see if you have received your dose. Your dose was delivered the
right way if the gray plunger is visible (see
step 3). Also contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or
your healthcare provider for further instructions. Until then, store your Pen
safely to avoid an accidental needle stick.
|
|
|
|
Other Information
|
|
· If
you have vision problems, do not use your Pen without help from a person
trained to use the Trulicity Pen.
|
|
Where to Learn More
|
|
· If
you have any questions or problems with your Trulicity Single-Dose Pen,
contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare
provider.
· For
more information about Trulicity Single-Dose Pen, visit our website at:
www.Trulicity.com.
|
|
This Instructions
for Use has been approved by the U.S. Food and Drug Administration.
Eli Lilly and Company
Indianapolis,IN46285,USA
Trulicity is a trademark of Eli Lilly and Company.
Copyright © 2014, 2016, Eli Lilly and Company. All rights reserved.
The Trulicity Pen meets the current dose accuracy and functional requirements
of ISO 11608-1:2012 and 11608-5:2012.
Revised: OCT 13, 2016
|
TRULOAI-0001-IFU-SES-20161013
|
Instructions for Use
|
|
Trulicity® (Trū-li-si-tee)
(dulaglutide)
injection, for subcutaneous use
1.5 mg/0.5 mL Single-Dose Pen
once weekly
|
|
BREAK
SEAL
|
|
BREAK
SEAL
|
|
|
|
|
|
|
|
Information About Trulicity Single-Dose Pen
Please read this Instructions for Use and the Medication
Guide carefully and completely before using your Trulicity Single-Dose Pen.
Talk to your healthcare provider about how to inject Trulicity the right way.
· Trulicity
Single-Dose Pen (Pen) is a disposable, prefilled medicine delivery device.
Each Pen contains 1 dose of Trulicity (1.5 mg/0.5 mL). Each Pen
should only be used 1 time.
· Trulicity is used 1 time each week. You may want to mark your calendar
to remind you when to take your next dose.
|
|
Before You Get Started
|
|
|
|
|
|
|
Remove
|
Check
|
Inspect
|
Prepare
|
|
Remove the Pen
from the refrigerator.
|
Check the Pen
label to make sure you have the right medicine and it has not expired.
|
Check the Pen to
make sure that it is not damaged and inspect the medicine to make sure it is
not cloudy, discolored or has particles in it.
|
Wash your hands.
|
|
Choose Your Injection Site
|
|
|
· Your
healthcare provider can help you choose the injection site that is best for
you.
· You
may inject the medicine into your stomach (abdomen) or thigh.
· Another
person may give you the injection in your upper arm.
· Change
(rotate) your injection site each week. You may use the same area of your
body, but be sure to choose a different injection site in that area.
|
|
|
|
|
|
|
|
|
|
|
|
1 Uncap the Pen
 Make sure the Pen is locked.
· Pull
the Base Cap straight off and throw it away in your household trash.
Do not put the Base Cap back on—this could damage the
needle. Do not touch the needle.
|
|
|
2 Place and Unlock
· Place
the Clear Base flat and firmly against your skin at the injection site.
 Unlock by
turning the Lock Ring.
|
|
|
3 Press and Hold
· Press
and hold the green Injection Button; you will hear a loud click.
 Continue holding the Clear Base firmly
against your skin until you hear a second click. This happens when the needle
starts retracting in about 5-10 seconds.
· Remove
the Pen from your skin.
|
You will know your injection is complete when the gray
plunger is visible.
|
|
Important Information
Disposal of Pen
Storage and Handling
Commonly Asked Questions
Other Information
Where to Learn More
|
|
Disposing of Your Used Pens
· Put
your used Pens in a FDA-cleared sharps disposal container right away after
use. Do not throw away (dispose of) Pens in your
household trash.
· If
you do not have a FDA-cleared sharps disposal container, you may use a
household container that is:
-
made of a heavy-duty plastic,
-
can be closed with a tight-fitting,
puncture-resistant lid, without sharps being able to come out,
-
upright and stable during use,
-
leak-resistant, and
-
properly labeled to warn of hazardous waste inside
the container.
· When
your sharps disposal container is almost full, you will need to follow your
community guidelines for the right way to dispose of your sharps disposal
container. There may be state or local laws about how you should throw away
used needles and syringes. For more information about safe sharps disposal,
and for specific information about sharps disposal in the state that you live
in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
· Do not recycle your used sharps disposal container.
|
|
|
Storage and Handling
|
|
· Store
your Pen in the refrigerator between 36°F to 46°F (2°C to 8°C).
· You
may store your Pen at room temperature below 86°F (30°C) for up to a total of
14 days.
· Do
not freeze your Pen. If the Pen has been frozen, throw the Pen away and use a
new Pen.
· Storage
of your Pen in the original carton is recommended. Protect your Pen from direct
heat and light.
· The
Pen has glass parts. Handle it carefully. If you drop it on a hard surface,
do not use it. Use a new Pen for your injection.
· Keep
your Trulicity Pen and all medicines out of the reach of children.
|
|
Commonly Asked Questions
|
|
What if I see an air bubble in my Pen?
Air bubbles are normal.
What if I unlock the Pen and press the green Injection
Button before pulling off the Base Cap?
Do not remove the Base Cap. Throw away the Pen and get a new Pen.
What if there is a drop of liquid on the tip of the
needle when I remove the Base Cap?
A drop of liquid on the tip of the needle is normal.
Do I need to hold the Injection Button down until the
injection is complete?
This is not necessary, but it may help you keep the Pen steady and firm
against your skin.
I heard more than 2 clicks during my injection—2 louder
clicks and 1 soft one. Did I get my complete injection?
Some patients may hear a soft click right before the second loud click. That
is the normal operation of the Pen. Do not remove the Pen from your skin
until you hear the second louder click.
What if there is a drop of liquid or blood on my skin
after my injection?
This is normal.
I am not sure if my Pen worked the right way.
Check to see if you have received your dose. Your dose was delivered the
right way if the gray plunger is visible (see
step 3). Also contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or
your healthcare provider for further instructions. Until then, store your Pen
safely to avoid an accidental needle stick.
|
|
|
|
Other Information
|
|
· If
you have vision problems, do not use your Pen without help from a person
trained to use the Trulicity Pen.
|
|
|
|
Where to Learn More
|
|
· If
you have any questions or problems with your Trulicity Single-Dose Pen,
contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare
provider.
· For
more information about Trulicity Single-Dose Pen, visit our website at:
www.Trulicity.com.
|
|
|
SCAN THIS CODE TO LAUNCH
www.Trulicity.com
|
|
|
|
|
|
This Instructions
for Use has been approved by the U.S. Food and Drug Administration.
Eli Lilly and Company
Indianapolis,IN46285,USA
Trulicity is a trademark of Eli Lilly and Company.
Copyright © 2014, 2017 Eli Lilly and Company. All rights reserved.
The Trulicity Pen meets the current dose accuracy and functional requirements
of ISO 11608-1:2012 and 11608-5:2012.
Revised: June 22, 2017
TRUHIAI-0002-IFU-20170622
|
|
|
|
BREAK
|
Instructions for Use
|
BREAK
|
|
SEAL
|
Trulicity® (Trū-li-si-tee)
(dulaglutide)
injection, for subcutaneous use
1.5 mg/0.5 mL Single-Dose Pen
once weekly
|
SEAL
|
|
|
|
|
|
Information About Trulicity Single-Dose Pen
Please read this Instructions for Use and the Medication
Guide carefully and completely before using your Trulicity Single-Dose Pen.
Talk to your healthcare provider about how to inject Trulicity the right way.
• Trulicity Single-Dose Pen (Pen) is a disposable, prefilled medicine
delivery device. Each Pen contains 1 dose of Trulicity
(1.5 mg/0.5 mL). Each Pen should only be used 1 time.
• Trulicity is used 1 time each week. You
may want to mark your calendar to remind you when to take your next dose.
|
|
Before You Get Started
|
|
|
|
|
|
|
Remove
|
Check
|
Inspect
|
Prepare
|
|
Remove the Pen
from the refrigerator.
|
Check the Pen
label to make sure you have the right medicine and it has not expired.
|
Check the Pen to
make sure that it is not damaged and inspect the medicine to make sure it is
not cloudy, discolored or has particles in it.
|
Wash your hands.
|
|
Choose Your Injection Site
|
|
|
· Your
healthcare provider can help you choose the injection site that is best for
you.
· You
may inject the medicine into your stomach (abdomen) or thigh.
· Another
person may give you the injection in your upper arm.
· Change
(rotate) your injection site each week. You may use the same area of your
body, but be sure to choose a different injection site in that area.
|
|
|
|
|
|
|
|
|
1 Uncap the Pen
 Make sure the Pen is locked.
· Pull
the Base Cap straight off and throw it away in your household trash.
Do not put the Base Cap back on—this could damage the
needle. Do not touch the needle.
|
|
|
2 Place and Unlock
· Place
the Clear Base flat and firmly against your skin at the injection site.
 Unlock by
turning the Lock Ring.
|
|
|
3
Press and Hold
· Press
and hold the green Injection Button; you will hear a loud click.
 Continue holding the Clear Base firmly
against your skin until you hear a second click. This happens when the needle
starts retracting in about 5-10 seconds.
· Remove
the Pen from your skin.
|
You will know your injection is complete when the gray
plunger is visible.
|
|
Important Information
Disposal of Pen
Storage and Handling
Commonly Asked Questions
Other Information
Where to Learn More
|
|
Disposing of Your Used Pens
· Put
your used Pens in a FDA-cleared sharps disposal container right away after
use. Do not throw away (dispose of) Pens in your
household trash.
· If
you do not have a FDA-cleared sharps disposal container, you may use a
household container that is:
-
made of a heavy-duty plastic,
-
can be closed with a tight-fitting,
puncture-resistant lid, without sharps being able to come out,
-
upright and stable during use,
-
leak-resistant, and
-
properly labeled to warn of hazardous waste inside
the container.
· When
your sharps disposal container is almost full, you will need to follow your
community guidelines for the right way to dispose of your sharps disposal
container. There may be state or local laws about how you should throw away
used needles and syringes. For more information about safe sharps disposal,
and for specific information about sharps disposal in the state that you live
in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.
· Do not recycle your used sharps disposal container.
|
|
|
Storage and Handling
|
|
· Store
your Pen in the refrigerator between 36°F to 46°F (2°C to 8°C).
· You
may store your Pen at room temperature below 86°F (30°C) for up to a total of
14 days.
· Do
not freeze your Pen. If the Pen has been frozen, throw the Pen away and use a
new Pen.
· Storage
of your Pen in the original carton is recommended. Protect your Pen from
direct heat and light.
· The
Pen has glass parts. Handle it carefully. If you drop it on a hard surface,
do not use it. Use a new Pen for your injection.
· Keep
your Trulicity Pen and all medicines out of the reach of children.
|
|
Commonly Asked Questions
|
|
What if I see an air bubble in my Pen?
Air bubbles are normal.
What if I unlock the Pen and press the green Injection
Button before pulling off the Base Cap?
Do not remove the Base Cap. Throw away the Pen and get a new Pen.
What if there is a drop of liquid on the tip of the
needle when I remove the Base Cap?
A drop of liquid on the tip of the needle is normal.
Do I need to hold the Injection Button down until the
injection is complete?
This is not necessary, but it may help you keep the Pen steady and firm
against your skin.
I heard more than 2 clicks during my injection—2 louder
clicks and 1 soft one. Did I get my complete injection?
Some patients may hear a soft click right before the second loud click. That
is the normal operation of the Pen. Do not remove the Pen from your skin
until you hear the second louder click.
What if there is a drop of liquid or blood on my skin
after my injection?
This is normal.
I am not sure if my Pen worked the right way.
Check to see if you have received your dose. Your dose was delivered the
right way if the gray plunger is visible (see
step 3). Also contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or
your healthcare provider for further instructions. Until then, store your Pen
safely to avoid an accidental needle stick.
|
|
Other Information
|
|
· If
you have vision problems, do not use your Pen without help from a person
trained to use the Trulicity Pen.
|
|
Where to Learn More
|
|
· If
you have any questions or problems with your Trulicity Single-Dose Pen,
contact Lilly at 1-800-Lilly-Rx (1-800-545-5979) or call your healthcare
provider.
· For
more information about Trulicity Single-Dose Pen, visit our website at:
www.Trulicity.com.
|
|
|
SCAN THIS CODE TO LAUNCH
www.Trulicity.com
|
|
|
This Instructions
for Use has been approved by the U.S. Food and Drug Administration.
Eli Lilly and Company
Indianapolis, IN 46285, USA
Trulicity is a trademark of Eli Lilly and Company.
Copyright © 2014, 2016, Eli Lilly and Company. All rights reserved.
The Trulicity Pen meets the current dose accuracy and functional requirements
of ISO 11608-1:2012 and 11608-5:2012.
Revised: OCT 13, 2016
TRUHIAI-0001-IFU-SES-20161013
|
PACKAGE
LABEL – Trulicity
®, 0.75 mg/0.5 mL, Single-Dose Pens (Indianapolis)
NDC 0002-1433-80
4 Single-Dose Pens
Each pen delivers a 0.75 mg
dose.
Use one pen every week.
trulilcity®
(dulaglutide) injection
0.75 mg/0.5 mL
once weekly
Rx only
For subcutaneous use only
Single-Dose Only
Dispense the accompanying
Medication Guide to each patient.
www.Trulicity.com
Lilly
PACKAGE
LABEL – Trulicity
®, 0.75 mg/0.5 mL, Single-Dose Pens (Sesto)
NDC 0002-1433-80
4 Single-Dose Pens
Each pen delivers a 0.75 mg
dose.
Use one pen every week.
trulilcity®
(dulaglutide) injection
0.75 mg/0.5 mL
once weekly
Rx only
For subcutaneous use only
Single-Dose Only
Dispense the accompanying
Medication Guide to each patient.
www.Trulicity.com
Lilly
PACKAGE
LABEL – Trulicity
®, 1.5 mg/0.5 mL, Single-Dose Pens (Indianapolis)
NDC 0002-1434-80
4 Single-Dose Pens
Each pen delivers a 1.5 mg
dose.
Use one pen every week.
Trulicity®
(dulaglutide) injection
1.5 mg/0.5 mL
once weekly
Rx only
For subcutaneous use only
Single-Dose Only
Dispense the accompanying
Medication Guide to each patient.
www.Trulicity.com
Lilly
PACKAGE
LABEL – Trulicity
®, 1.5 mg/0.5 mL, Single-Dose Pens (Sesto)
NDC 0002-1434-80
4 Single-Dose Pens
Each pen delivers a 1.5 mg
dose.
Use one pen every week.
Trulicity®
(dulaglutide) injection
1.5 mg/0.5 mL
once weekly
Rx only
For subcutaneous use only
Single-Dose Only
Dispense the accompanying
Medication Guide to each patient.
www.Trulicity.com
Lilly
|
Trulicity dulaglutide
injection, solution
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0002-1433
|
|
Route of
Administration
|
SUBCUTANEOUS
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Dulaglutide (Dulaglutide)
|
Dulaglutide
|
0.75 mg
in 0.5 mL
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Trisodium
Citrate Dihydrate
|
1.37 mg
in 0.5 mL
|
|
Anhydrous
Citric Acid
|
0.07 mg
in 0.5 mL
|
|
Mannitol
|
23.2 mg
in 0.5 mL
|
|
Polysorbate
80
|
0.10 mg
in 0.5 mL
|
|
Water
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0002-1433-80
|
4 SYRINGE in 1
CARTON
|
|
|
1
|
NDC:0002-1433-01
|
0.5 mL in 1
SYRINGE
|
|
|
2
|
NDC:0002-1433-61
|
2 SYRINGE in 1
CARTON
|
|
|
2
|
|
0.5 mL in 1
SYRINGE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing Start
Date
|
Marketing
End Date
|
|
BLA
|
BLA125469
|
09/18/2014
|
|
|
|
Trulicity dulaglutide
injection, solution
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0002-1434
|
|
Route of
Administration
|
SUBCUTANEOUS
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
Dulaglutide (Dulaglutide)
|
Dulaglutide
|
1.5 mg
in 0.5 mL
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
Trisodium
Citrate Dihydrate
|
1.37 mg
in 0.5 mL
|
|
Anhydrous
Citric Acid
|
0.07 mg
in 0.5 mL
|
|
Mannitol
|
23.2 mg
in 0.5 mL
|
|
Polysorbate
80
|
0.10 mg
in 0.5 mL
|
|
Water
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0002-1434-80
|
4 SYRINGE in 1
CARTON
|
|
|
1
|
NDC:0002-1434-01
|
0.5 mL in 1
SYRINGE
|
|
|
2
|
NDC:0002-1434-61
|
2 SYRINGE in 1
CARTON
|
|
|
2
|
|
0.5 mL in 1
SYRINGE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
BLA
|
BLA125469
|
09/18/2014
|
|
|
|
Labeler - Eli Lilly and Company (006421325)
|
Eli Lilly and Company
