Trulicity

HOS-096840 · has-adverse-reaction-information · PDF-Seite 8

Summary of safety profile In the completed phase 2 and phase 3 studies to support the initial registration of dulaglutide 0.75 mg and 1.5 mg, 4,006 patients were exposed to dulaglutide alone or in combination with other glucose lowering medicinal products. The most frequently reported adverse reactions in clinical trials were gastrointestinal, including nausea, vomiting and diarrhoea. In general, these reactions were mild or moderate in severity and transient in nature. Results from the long-term cardiovascular outcome study with 4,949 patients randomised to dulaglutide and followed for a median of 5.4 years were consistent with these findings. Tabulated list of adverse reactions The following adverse reactions have been identified based on evaluation of the full duration of the phase 2 and phase 3 clinical studies, the long-term cardiovascular outcome study and post-marketing reports. The adverse reactions are listed in Table 1 as MedDRA preferred term by system organ class and in order of decreasing incidence (very common: ≥ 1/10; common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1,000 to < 1/100; rare: ≥ 1/10,000 to < 1/1,000; very rare: < 1/10,000 and not known: cannot be estimated from available data). Within each incidence grouping, adverse reactions are presented in order of decreasing frequency. Frequencies for events have been calculated based on their incidence in the phase 2 and phase 3 registration studies. Table 1. The frequency of adverse reactions of dulaglutide System organ Very common Common Uncommon Rare Not class known Immune system Hypersensitivity Anaphylactic disorders reaction# Metabolism Hypoglycaemia* Hypoglycaemia* Dehydration and nutrition (when used in (when used as disorders combination monotherapy or with insulin, in combination glimepiride, with metformin metformin† or plus metformin plus pioglitazone) glimepiride) 8  Nervous system Dysgeusia disorders Gastrointestinal Nausea,

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HOS-096836 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-096835 · has-indication-information · PDF-Seite 3

Type 2 Diabetes Mellitus Trulicity is indicated for the treatment of patients 10 years and above with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise • as monotherapy when metformin is considered inappropriate due to intolerance or contraindications • in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1.

HOS-096838 · has-interaction-information · PDF-Seite 6

Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. In the clinical pharmacology studies described below, dulaglutide doses up to 1.5 mg did not affect the absorption of the orally administered medicinal products tested to any clinically relevant degree. For the 4.5 mg dose, absence of major clinically relevant interactions was predicted by physiologically-based pharmacokinetic (PBPK) modelling simulations. For patients receiving dulaglutide in combination with oral medicinal products with rapid gastrointestinal absorption or prolonged release, there is a potential for altered medicinal product exposure, particularly at the time of dulaglutide treatment initiation. Sitagliptin Sitagliptin exposure was unaffected when coadministered with a single 1.5 mg dose of dulaglutide. Following coadministration with 2 consecutive 1.5 mg doses of dulaglutide, sitagliptin AUC(0-τ) and Cmax decreased by approximately 7.4 % and 23.1 %, respectively. Sitagliptin tmax increased approximately 0.5 hours following coadministration with dulaglutide compared to sitagliptin alone. Sitagliptin can produce up to 80 % inhibition of DPP-4 over a 24-hour period. Dulaglutide (1.5 mg) coadministration with sitagliptin increased dulaglutide exposure and Cmax by approximately 38 % and 27 %, respectively, and median tmax increased approximately 24 hours. Therefore, dulaglutide does have a high degree of protection against DPP-4 inactivation (see section 5.1, Mechanism of action). The increased exposure may enhance the effects of dulaglutide on blood glucose levels. Paracetamol Following a first dose of 1 and 3 mg dulaglutide, paracetamol Cmax was reduced by 36 % and 50 %, respectively, and the median tmax occurred later (3 and 4 hours, respectively). After coadministration with up to 3 mg of dulaglutide at steady state, there were no statistically significant differences on AUC(0-12), Cmax or tmax of paracetamol. No dose adjustment of paracetamol is necessary when administered with dulaglutide. Atorvastatin Coadministration of 1.5 mg of dulaglutide with atorvastatin decreased Cmax and AUC(0-∞) up to 70 % and 21 %, respectively, for atorvastatin and its major metabolite o-hydroxyatorvastatin. The mean t1/2 of atorvastatin and o-hydroxyatorvastatin were increased by 17 % and 41 %, respectively, following dulaglutide administration. These observations are not clinically relevant. No dose adju

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HOS-096839 · has-pregnancy-information · PDF-Seite 7

Pregnancy There are no or limited amount of data from the use of dulaglutide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Therefore, the use of dulaglutide is not recommended during pregnancy. Breast-feeding It is unknown whether dulaglutide is excreted in human milk. A risk to newborns/infants cannot be excluded. Dulaglutide should not be used during breast-feeding. 7 Fertility The effect of dulaglutide on fertility in humans is unknown. In the rat, there was no direct effect on mating or fertility following treatment with dulaglutide (see section 5.3).

HOS-096837 · has-warning-information · PDF-Seite 4

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered medicinal product should be clearly recorded. Type 1 diabetes mellitus or diabetic ketoacidosis 4 Dulaglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Dulaglutide is not a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dose reduction of insulin (see section 4.2). Severe gastrointestinal disease Dulaglutide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients. Events related to impaired gastric emptying, including severe gastroparesis, have been reported. Monitor and consider dose modification or discontinuation in patients who develop severe gastrointestinal symptoms while on treatment. Aspiration in association with general anaesthesia or deep sedation Cases of pulmonary aspiration have been reported in patients receiving GLP-1 receptor agonists undergoing general anaesthesia or deep sedation. Therefore, the increased risk of residual gastric content due to delayed gastric emptying (see section 4.8) should be considered prior to performing procedures with general anaesthesia or deep sedation. Dehydration Dehydration, sometimes leading to acute renal failure or worsening renal impairment, has been reported in patients treated with dulaglutide, especially at the initiation of treatment. Many of the reported adverse renal events occurred in patients who had experienced nausea, vomiting, diarrhoea, or dehydration. Patients treated with dulaglutide should be advised of the potential risk of dehydration, particularly in relation to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. Acute pancreatitis Use of GLP-1 receptor agonists has been associated with a risk of developing acute pancreatitis. In clinical trials, acute pancreatitis has been reported in association with dulaglutide (see section 4.8). Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, dulaglutide should be discontinued. If pancreatitis is confirmed, dulaglutide should not be restarted. In the absence of other signs and symptoms of acute pancreatitis, elevations in

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