ITY 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)].
8.7 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). No overall differences in safety or effectiveness were observed relative to patients with normal renal function, though conclusions are limited due to small numbers. 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 [see Clinical Pharmacology (12.3)].
There is limited clinical experience in patients with severe renal impairment or ESRD. TRULICITY should be used with caution, and if these patients experience adverse gastrointestinal side effects, renal function should be closely monitored [see Dosage and Administration (2.3), Warning and Precautions (5.5), Clinical Pharmacology (12.3)].
8.8 Gastroparesis
Dulaglutide slows gastric emptying. TRULICITY has not been studied in patients with preexisting gastroparesis.
10 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.
11 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 or prefilled syringe 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.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism 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-surfac |
