Trulicity❅ 0.75 mg solution for injection in pre-filled pen.
Trulicity 1.5 mg solution for injection in pre-filled pen.
Trulicity 0.75 mg solution for injection in pre-filled syringe.
Trulicity 1.5 mg solution for injection in pre-filled syringe.
Pre-filled pen
Trulicity 0.75 mg solution for injection
Each pre-filled pen contains 0.75 mg of dulaglutide* in 0.5 ml solution.
Trulicity 1.5 mg solution for injection
Each pre-filled pen contains 1.5 mg of dulaglutide* in 0.5 ml solution.
Pre-filled syringe
Trulicity 0.75 mg solution for injection
Each pre-filled syringe contains 0.75 mg of dulaglutide* in 0.5 ml solution.
Trulicity 1.5 mg solution for injection
Each pre-filled syringe contains 1.5 mg of dulaglutide* in 0.5 ml solution.
*Produced in CHO cells by recombinant DNA technology.
For the full list of excipients, see section 6.1.
Solution for injection (injection).
Clear, colourless solution.
Trulicity is indicated in adults with type 2 diabetes mellitus to improve glycaemic control as:
Monotherapy
When diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications.
Add-on therapy
In combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control (see section 5.1 for data with respect to different combinations).
Posology
Monotherapy
The recommended dose is 0.75 mg once weekly.
Add-on therapy
The recommended dose is 1.5 mg once weekly.
For potentially vulnerable populations, such as patients ≥ 75 years, 0.75 mg once weekly can be considered as a starting dose.
When Trulicity is added to existing metformin and/or pioglitazone therapy, the current dose of metformin and/or pioglitazone can be continued. When it is added to existing therapy of a sulphonylurea or prandial insulin, a reduction in the dose of sulphonylurea or insulin may be considered to reduce the risk of hypoglycaemia (see sections 4.4 and 4.8).
The use of Trulicity does not require blood glucose self-monitoring. Self-monitoring may be necessary to adjust the dose of sulphonylurea or prandial insulin.
Elderly
No dose adjustment is required based on age (see section 5.2). However, the therapeutic experience in patients ≥ 75 years is very limited (see section 5.1), and in these patients 0.75 mg once weekly can be considered as a starting dose.
Renal impairment
No dosage adjustment is required in patients with mild or moderate renal impairment.
There is very limited experience in patients with severe renal impairment (eGFR [by CKD-EPI] < 30 ml/min/1.73 m2) or end stage renal disease, therefore Trulicity is not recommended in this population (see section 5.2).
Hepatic impairment
No dosage adjustment is required in patients with hepatic impairment.
Paediatric population
The safety and efficacy of dulaglutide in children aged less than 18 years have not yet been established. No data are available.
Method of administration
Trulicity is to be injected subcutaneously in the abdomen, thigh or upper arm. It should not be administered intravenously or intramuscularly.
The dose can be administered at any time of day, with or without meals.
If a dose is missed, it should be administered as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days (72 hours) remain before the next scheduled dose, the missed dose should be skipped and the next dose should be administered 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 (72 hours) before.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Dulaglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions. This should be considered when treating patients with impaired renal function since these events, i.e. nausea, vomiting, and/or diarrhoea, may cause dehydration which could cause a deterioration of renal function. Dulaglutide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.
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 pancreatic enzymes alone are not predictive of acute pancreatitis (see section 4.8).
Hypoglycaemia
Patients receiving dulaglutide in combination with sulphonylurea or insulin may have an increased risk of hypoglycaemia. The risk of hypoglycaemia may be lowered by a reduction in the dose of sulphonylurea or insulin (see sections 4.2 and 4.8).
Populations not studied
There is limited experience in patients with congestive heart failure.
Sodium content
This medicinal product contains less than 1 mmol sodium (23 mg) per 1.5 mg dose, i.e. essentially 'sodium- free'.
Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. Dulaglutide should be used with caution in patients receiving oral medicinal products that require rapid gastrointestinal absorption. For some prolonged release formulations, an increased release due to an extended gastric residence time may slightly increase drug exposure.
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 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 adjustment of atorvastatin is necessary when administered with dulaglutide.
Digoxin
After coadministration of steady state digoxin with 2 consecutive doses of dulaglutide, overall exposure (AUC
) and tmax of digoxin were unchanged; and Cmax decreased by up to 22 %. This change is not expected to have clinical consequences. No dose adjustment is required for digoxin when administered with dulaglutide.
Anti-hypertensives
Coadministration of multiple dulaglutide doses with steady state lisinopril caused no clinically relevant changes in the AUC or Cmax of lisinopril. Statistically significant delays in lisinopril tmax of approximately 1 hour were observed on Days 3 and 24 of the study. When a single dose of dulaglutide and metoprolol were coadministered, the AUC and Cmax of metoprolol increased by19 % and 32 %, respectively. While metoprolol tmax was delayed by 1 hour, this change was not statistically significant. These changes were not clinically relevant; therefore no dose adjustment of lisinopril or metoprolol is necessary when administered with dulaglutide.
Warfarin
Following dulaglutide coadministration, S- and R-warfarin exposure and R-warfarin Cmax were unaffected, and S-warfarin Cmax decreased by 22 %. AUCINR increased by 2 %, which is unlikely to be clinically significant, and there was no effect on maximum international normalised ratio response (INRmax). The time of international normalised ratio response (tINRmax) was delayed by 6 hours, consistent with delays in tmax of approximately 4 and 6 hours for S- and R-warfarin, respectively. These changes are not clinically relevant. No dose adjustment for warfarin is necessary when given together with dulaglutide.
Oral contraceptives
Coadministration of dulaglutide with an oral contraceptive (norgestimate 0.18 mg/ethinyl estradiol 0.025 mg) did not affect the overall exposure to norelgestromin and ethinyl estradiol. Statistically significant reductions in Cmax of 26 % and 13 % and delays in tmax of 2 and 0.30 hours were observed for norelgestromin and ethinyl estradiol, respectively. These observations are not clinically relevant. No dose adjustment for oral contraceptives is required when given together with dulaglutide.
Metformin
Following coadministration of multiple dose dulaglutide with steady state metformin (immediate release formula [IR]), metformin AUC increased up to 15 % and Cmax decreased up to 12 %, respectively, with no changes in tmax. These changes are consistent with the gastric emptying delay of dulaglutide and within the pharmacokinetic variability of metformin and thus are not clinically relevant. No dose adjustment for metformin IR is recommended when given with dulaglutide.
Sitagliptin
Sitagliptin exposure was unaffected when coadministered with a single dose of dulaglutide. Following coadministration with 2 consecutive doses of dulaglutide, sitagliptin AUC(0-) 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 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). The increased exposure may enhance the effects of dulaglutide on blood glucose levels.
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.
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).
Trulicity has no or negligible influence on the ability to drive or use machines. When it is used in combination with a sulphonylurea or prandial insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines (see section 4.4).
Summary of safety profile
In the phase II and phase III studies conducted, 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.
Tabulated list of adverse reactions
The following adverse reactions have been identified based on eva luation of the full duration of the phase II and phase III clinical studies and 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.
Table 1: The frequency of adverse reactions of dulaglutide
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System Organ Class
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Very common
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Common
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Uncommon
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Rare
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Metabolism and nutrition disorders
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Hypoglycaemia* (when used in combination with prandial insulin, metformin† or metformin plus glimepiride)
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| 以下是“全球医药”详细资料 |
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