- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.
PosologyStarting dose: dosing is initiated at 10 mcg Lyxumia once daily for 14 days.Maintenance dose: a fixed maintenance dose of 20 mcg Lyxumia once daily is started on Day 15. Lyxumia is administered once daily, within the hour prior to any meal of the day. It is preferable that the prandial injection of Lyxumia is performed before the same meal every day, when the most convenient meal has been chosen. If a dose of Lyxumia is missed, it should be injected within the hour prior to the next meal. When Lyxumia is added to existing metformin therapy, the current metformin dose can be continued unchanged.When Lyxumia is added to existing therapy of a sulphonylurea or a basal insulin, a reduction in the dose of the sulphonylurea or the basal insulin may be considered to reduce the risk of hypoglycaemia. Lyxumia should not be given in combination with basal insulin and a sulphonylurea due to increased risk of hypoglycaemia (see section 4.4).The use of Lyxumia does not require specific blood glucose monitoring. However, when used in combination with a sulphonylurea or a basal insulin, blood glucose monitoring or blood glucose self- monitoring may become necessary to adjust the doses of the sulphonylurea or the basal insulin.
ElderlyNo dose adjustment is required based on age.
Patients with renal impairmentNo dose adjustment is required for patients with mild or moderate renal impairment. There is no therapeutic experience in patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease and therefore, it is not recommended to use Lyxumia in these populations (see section 5.2).
Patients with hepatic impairmentNo dose adjustment is needed in patients with hepatic impairment (see section 5.2).
Paediatric populationThe safety and efficacy of lixisenatide in children and adolescents less than 18 years of age have not yet been established. No data are available.
Method of administrationLyxumia is to be injected subcutaneously in the thigh, abdomen or upper arm. Lyxumia should not be administered intravenously or intramuscularly.
Acute pancreatitisUse of glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with a risk of developing acute pancreatitis. There have been few reported events of acute pancreatitis with lixisenatide although a causal relationship has not been established. Patients should be informed of the characteristic symptoms of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, lixisenatide should be discontinued ; if acute pancreatitis is confirmed, lixisenatide should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Severe gastrointestinal diseaseUse of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions. Lixisenatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and therefore, the use of lixisenatide is not recommended in these patients.
Renal impairmentThere is no therapeutic experience in patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease. Use is not recommended in patients with severe renal impairment or end-stage renal disease (see sections 4.2 and 5.2).
HypoglycaemiaPatients receiving Lyxumia with a sulphonylurea or with a basal insulin may have an increased risk of hypoglycaemia. Reduction of the dose of the sulphonylurea or the basal insulin may be considered to reduce the risk of hypoglycaemia (see section 4.2). Lyxumia should not be given in combination with basal insulin and a sulphonylurea due to increased risk of hypoglycaemia.
Concomitant medicinal productsThe delay of gastric emptying with lixisenatide may reduce the rate of absorption of orally administered medicinal products. Lyxumia should be used with caution in patients receiving oral medicinal products that require rapid gastrointestinal absorption, require careful clinical monitoring or have a narrow therapeutic ratio. Specific recommendations regarding intake of such medicinal products are given in section 4.5.
Populations not studiedLixisenatide has not been studied in combination with dipeptidyl peptidase 4 (DPP-4) inhibitors.
DehydrationPatients treated with Lyxumia should be advised of the potential risk of dehydration in relation to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. Excipients This medicinal product contains metacresol, which may cause allergic reactions.
ParacetamolParacetamol was used as a model medicinal product to evaluate the effect of lixisenatide on gastric emptying. Following administration of a single dose of paracetamol 1000 mg, paracetamol AUC and t1/2 were unchanged whatever the timing of its administration (before or after the lixisenatide injection). When administered 1 or 4 hours after 10 mcg lixisenatide , Cmax of paracetamol was decreased by 29% and 31% respectively and median tmax was delayed by 2.0 and 1.75 hours respectively. A further delay in tmax and a reduced Cmax of paracetamol have been predicted with the 20 mcg maintenance dose.No effects on paracetamol Cmax and tmax were observed when paracetamol was administered 1 hour before lixisenatide.Based on these results, no dose adjustment for paracetamol is required but the delayed tmax observed when paracetamol is administered 1-4 hours after lixisenatide should be taken into account when a rapid onset of action is required for efficacy.
Oral contraceptivesFollowing administration of a single dose of an oral contraceptive medicinal product (ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg) 1 hour before or 11 hours after 10 mcg lixisenatide, the Cmax, AUC, t1/2 and tmax of ethinylestradiol and levonorgestrel were unchanged.Administration of the oral contraceptive 1 hour or 4 hours after lixisenatide did not affect AUC and t1/2 of ethinylestradiol and levonorgestrel, whereas Cmax of ethinylestradiol was decreased by 52% and 39% respectively and Cmax of levonorgestrel was decreased by 46% and 20%, respectively and median tmax was delayed by 1 to 3 hours.The reduction in Cmax is of limited clinical relevance and no dose adjustment for oral contraceptives is required.
AtorvastatinWhen lixisenatide 20 mcg and atorvastatin 40 mg were co-administered in the morning for 6 days, the exposure to atorvastatin was not affected, while Cmax was decreased by 31% and tmax was delayed by 3.25 hours. No such increase for tmax was observed when atorvastatin was administered in the evening and lixisenatide in the morning but the AUC and Cmax of atorvastatin were increased by 27% and 66% respectively. These changes are not clinically relevant and therefore, no dose adjustment for atorvastatin is required when co-administered with lixisenatide.
Warfarin and other coumarin derivativesAfter concomitant administration of warfarin 25 mg with repeated dosing of lixisenatide 20 mcg, there were no effects on AUC or INR (International Normalised Ratio) while Cmax was reduced by 19% and tmax was delayed by 7 hours. Based on these results, no dose adjustment for warfarin is required when co-administered with lixisenatide; however, frequent monitoring of INR in patients on warfarin and/or coumarin derivatives is recommended at the time of initiation or ending of lixisenatide treatment.
DigoxinAfter concomitant administration of lixisenatide 20 mcg and digoxin 0.25 mg at steady state, the AUC of digoxin was not affected. The tmax of digoxin was delayed by 1.5 hour and the Cmax was reduced by 26%. Based on these results, no dose adjustment for digoxin is required when co-administered with lixisenatide.
RamiprilAfter concomitant administration of lixisenatide 20 mcg and ramipril 5 mg during 6 days, the AUC of ramipril was increased by 21% while the Cmax was decreased by 63%.The AUC and Cmax of the active metabolite (ramiprilat) were not affected. The tmax of ramipril and ramiprilat were delayed by approximately 2.5 hours. Based on these results, no dose adjustment for ramipril is required when co-administered with lixisenatide.
Women of childbearing potentialLyxumia is not recommended in women of childbearing potential not using contraception.
PregnancyThere are no adequate data from the use of Lyxumia in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Lyxumia should not be used during pregnancy. The use of insulin is recommended instead. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Lyxumia should be discontinued.
Breast-feedingIt is unknown if Lyxumia is excreted in human milk. Lyxumia should not be used during breast-feeding.
FertilityAnimal studies do not indicate direct harmful effects with respect to fertility.
Summary of the safety profileOver 2,600 patients have received Lyxumia either alone or in combination with metformin, a sulphonylurea (with or without metformin) or a basal insulin (with or without metformin, or with or without a sulphonylurea) in 8 large placebo- or active-controlled phase III studies. The most frequently reported adverse reactions during clinical studies were nausea, vomiting and diarrhoea. These reactions were mostly mild and transient. In addition, hypoglycaemia (when Lyxumia was used in combination with a sulphonylurea and/or a basal insulin) and headache occurred. Allergic reactions have been reported in 0.4% of Lyxumia patients.
Tabulated list of adverse reactionsAdverse reactions reported from placebo- and active-controlled phase III studies over the entire treatment period are presented in Table 1. The table presents adverse reactions that occurred with an incidence >5% if the frequency was higher among Lyxumia treated patients than patients treated with all comparators. The table also includes adverse reactions with a frequency ≥1% in the Lyxumia group if the frequency was greater than 2 times the frequency for all comparators group. Frequencies of adverse reactions are defined as: 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).Within each system organ class, adverse reactions are presented in order of decreasing frequency. Table 1: Adverse reactions reported in placebo- and active-controlled phase III studies during the entire treatment period (including the period beyond the main 24-week treatment period in studies with ≥76 weeks of total treatment).
|System Organ Class||Frequency of occurrence|
|Infections and infestations||Influenza Upper respiratory tract infectionCystitis Viral infection|
|Immune system disorders||Anaphylactic reaction|
|Metabolism and nutrition disorders||Hypoglycaemia (in combination with a sulphonylurea and / or a basal insulin)||Hypoglycaemia (in combination with metformin alone)|
|Nervous system disorders||Headache||DizzinessSomnolence|
|Skin and subcutaneous tissue disorders||Urticaria|
|Musculoskeletal and connective tissue disorders||Back pain|
|General disorders and administration site conditions||Injection site pruritus|
Description of selected adverse reactions
HypoglycaemiaIn patients taking Lyxumia in monotherapy, symptomatic hypoglycaemia occurred in 1.7% of lixisenatide treated patients and in 1.6% of placebo treated patients. When Lyxumia is used in combination with metformin alone, symptomatic hypoglycaemia occurred in 7.0% of lixisenatide patients and in 4.8% of placebo patients during the entire treatment period.In patients taking Lyxumia in combination with a sulphonylurea and metformin, symptomatic hypoglycaemia occurred in 22.0% of lixisenatide treated patients and in 18.4% of placebo treated patients during the entire treatment period (3.6% absolute difference). When Lyxumia is used in combination with a basal insulin with or without metformin, symptomatic hypoglycaemia occurred in 42.1% of lixisenatide patients and in 38.9% of placebo patients during the entire treatment period (3.2% absolute difference).During the entire treatment period, when Lyxumia was given with a sulphonylurea alone, symptomatic hypoglycaemia occurred in 22.7% of lixisenatide treated patients versus 15.2% with placebo (7.5% absolute difference). When Lyxumia was given with a sulphonylurea and a basal insulin, symptomatic hypoglycaemia occurred in 47.2% of lixisenatide treated patients compared to 21.6% with placebo (25.6% absolute difference).Overall, the incidence of severe symptomatic hypoglycaemia was uncommon (0.4% in lixisenatide patients and 0.2% in placebo patients) during the entire treatment period of the Phase III placebo-controlled studies.
Gastrointestinal disordersNausea and vomiting were the most frequently reported adverse reactions during the main 24-week treatment period. The incidence of nausea was higher in the lixisenatide group (26.1%) compared to the placebo group (6.2%) and the incidence of vomiting was higher in the lixisenatide group (10.5%) than in the placebo group (1.8%). They were mostly mild and transient and occured during the first 3 weeks after starting treatment. Thereafter, they progressively decreased during the following weeks.
Injection site reactionsInjections site reactions were reported in 3.9% of the patients receiving Lyxumia while they were reported in 1.4% of patients receiving placebo during the main 24-week treatment period. The majority of reactions were mild in intensity and usually did not result in discontinuation of the treatment.
ImmunogenicityConsistent with the potentially immunogenic properties of medicinal products containing proteins or peptides, patients may develop anti-lixisenatide antibodies following treatment with Lyxumia and, at the end of the main 24-week treatment period in placebo-controlled studies, 69.8% of lixisenatide patients had a positive antibody status. The percentage of patients who were antibody positive was similar at the end of the entire 76-week treatment period. At the end of the main 24-week treatment period, 32.2% of the patients having a positive antibody status had an antibody concentration above the lower limit of quantification, and at the end of the entire 76-week treatment period, 44.7% of the patients had an antibody concentration above the lower limit of quantification. After stopping the treatment, few antibody positive patients were followed up for antibody status; the percentage decreased to approximately 90% within 3 months and 30% at 6 months or beyond. The change in HbA1c from baseline was similar regardless of the antibody status (positive or negative).Of lixisenatide-treated patients with HbA1c measurement, 79.3% had either a negative antibody status or an antibody concentration below the lower limit of quantification and the other 20.7% of patients had a quantified antibody concentration. In the subset of patients (5.2%) with the highest antibody concentrations, the mean improvement in HbA1c at Week 24 and at Week 76 was in a clinically relevant range; however there was variability in the glycaemic response and 1.9% had no decrease in HbA1c. The antibody status (positive or negative) is not predictive of the reduction of HbA1c for an individual patient. There was no difference in the overall safety profile in patients regardless of the antibody status with the exception of an increase of the incidence of injection site reactions (4.7%in antibody positive patients compared to 2.5% in antibody negative patients during the entire treatment period). The majority of injection site reactions were mild, regardless of antibody status.There was no cross-reactivity versus either native glucagon or endogenous GLP-1.
Allergic reactionsAllergic reactions possibly associated with lixisenatide (such as anaphylactic reaction, angioedema and urticaria) have been reported in 0.4% of lixisenatide patients while possibly associated allergic reactions occurred in less than 0.1% of placebo patients during the main 24-week treatment period. Anaphylactic reactions were reported in 0.2% of the lixisenatide treated patients vs. none in the placebo group. Most of these reported allergic reactions were mild in severity. One case of anaphylactoid reaction was reported during clinical trials with lixisenatide.
Heart rateIn a study in healthy volunteers, a transient rise in heart rate has been observed after administration of lixisenatide 20 mcg. Cardiac arrhythmias particularly tachycardia (0.8% vs <0.1%) and palpitations (1.5% vs 0.8%) have been reported in lixisenatide patients compared to placebo treated patients.
WithdrawalThe incidence of treatment discontinuation due to adverse events was 7.4% for Lyxumia compared to 3.2% in the placebo group during the main 24-week treatment period. The most common adverse reactions which led to treatment discontinuation in the lixisenatide group were nausea (3.1%) and vomiting (1.2%). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Mechanism of actionLixisenatide is a selective GLP-1 receptor agonist. The GLP-1 receptor is the target for native GLP-1, an endogenous incretin hormone that potentiates glucose-dependent insulin secretion from the pancreatic beta cells.Lixisenatide action is mediated via a specific interaction with GLP-1 receptors, leading to an increase in intracellular cyclic adenosine monophosphate (cAMP). Lixisenatide stimulates insulin secretion when blood glucose is increased but not at normoglycaemia, which limits the risk of hypoglycaemia. In parallel, glucagon secretion is suppressed. In case of hypoglycaemia, the rescue mechanism of glucagon secretion is preserved. Lixisenatide slows gastric emptying thereby reducing the rate at which meal-derived glucose appears in the circulation. Pharmacodynamic effectsWhen administered once daily, lixisenatide improves glycaemic control through the immediate and sustained effects of lowering both post-prandial and fasting glucose concentrations in patients with type 2 diabetes. This effect on post-prandial glucose was confirmed in a 4-week study versus liraglutide 1.8 mg once a day in combination with metformin. Reduction from baseline in the AUC0:30-4:30 h of plasma glucose after a test meal was: -12.61 h*mmol/L (-227.25 h*mg/dl) in the lixisenatide group and -4.04 h*mmol/L (-72.83 h*mg/dl) in the liraglutide group. This was also confirmed in an 8-week study versus liraglutide, administered before breakfast, in combination with insulin glargine with or without metformin.
Clinical efficacy and safetyThe clinical efficacy and safety of Lyxumia were evaluated in nine randomised doubleblind, placebocontrolled clinical studies including 4,508 patients with type 2 diabetes (2,869 patients randomised to lixisenatide, 47.5% men and 52.5% women, and 517 were ≥65 years of age). Efficacy of Lyxumia was also assessed in two randomised, open-label, activecontrolled study (versus exenatide or versus insulin glulisine) and in a meal time study (in total 1,067 patients randomised to lixisenatide).Efficacy and safety of Lyxumia in patients older than 70 years was addressed in a specifically dedicated placebo-controlled study (176 patients randomised to lixisenatide, including 62 patients ≥75 years of age).In addition, a double-blind, placebo-controlled cardiovascular outcome study (ELIXA) enrolled 6,068 type 2 diabetes patients with previous acute coronary syndrome (3,034 randomised to lixisenatide, including 198 patients ≥75 years of age and 655 patients with moderate renal impairment).In the completed Phase III studies, it was observed that approximately 90% of the patients were able to remain on the once daily maintenance dose of 20 mcg Lyxumia at the end of the main 24week treatment period. • Glycaemic control Add-on combination therapy with oral antidiabeticsLyxumia in combination with metformin, a sulphonylurea, pioglitazone or a combination of these agents showed statistically significant reductions in HbA1c, in fasting plasma glucose and in 2-hour post-prandial glucose after a test-meal compared to placebo at the end of the main 24-week treatment period (tables 2 and 3). The HbA1c reduction was significant with once daily administration, whether administered morning or evening.This effect on HbA1c was sustained in long term studies for up to 76 weeks.
Add-on treatment to metformin aloneTable 2: Placebo-controlled studies in combination with metformin (24-week results).
|Metformin as background therapy|
|Lixisenatide 20 mcg (N= 160)||Placebo (N= 159)||Lixisenatide 20 mcg||Placebo (N= 170)|
|Morning (N= 255)||Evening (N= 255)|
|Mean HbA1c (%)|
|LS mean change from baseline||-0.92||-0.42||-0.87||-0.75||-0.38|
|Patients (%) achieving HbA1c <7.0%||47.4||24.1||43.0||40.6||22.0|
|Mean body weight (kg)|
|LS mean change from baseline||-2.63||-1.63||-2.01||-2.02||-1.64|
Add-on treatment to a sulphonylurea alone or in combination with metforminTable 3: Placebo-controlled study in combination with a sulphonylurea (24-week results)
|Sulphonylurea as background therapy with or without metformin|
|Lixisenatide 20 mcg (N= 570)||Placebo (N= 286)|
|Mean HbA1c (%)|
|LS mean change from baseline||-0.85||-0.10|
|Patients (%) achieving HbA1c <7.0%||36.4||13.5|
|Mean body weight (kg)|
|LS mean change from baseline||-1.76||-0.93|
Add-on treatment to pioglitazone alone or in combination with metforminIn a clinical study, the addition of lixisenatide to pioglitazone with or without metformin, in patients not adequately controlled with pioglitazone, resulted in an HbA1c decrease from baseline of 0.90%, compared to a decrease from baseline of 0.34% in the placebo group at the end of the 24-week main treatment period. At the end of the 24-week main treatment period, 52.3% of the lixisenatide patients achieved an HbA1c less than 7 % compared to 26.4% in the placebo group. During the 24-week main treatment period, nausea was reported in 23.5% in the lixisenatide group compared to 10.6% in the placebo group and symptomatic hypoglycaemia was reported in 3.4% of the lixisenatide patients compared to 1.2% in the placebo group. Add-on combination therapy with a basal insulin Lyxumia given with a basal insulin alone, or with a combination of a basal insulin and metformin, or a combination of a basal insulin and a sulphonylurea resulted in statistically significant reductions in HbA1c and in 2-hour post-prandial glucose after a test- meal compared to placebo. Table 4: Placebo-controlled studies in combination with a basal insulin (24-week results)
|Basal insulin as background therapy Alone or in combination with metformin||Basal insulin as background therapy Alone or in combination with a sulphonylurea *|
|Lixisenatide 20 mcg||Placebo||Lixisenatide 20 mcg||Placebo|
|(N= 327)||(N= 166)||(N= 154)||(N= 157)|
|Mean HbA1c (%)|
|LS mean change from baseline||-0.74||-0.38||-0.77||0.11|
|Patients (%) achieving HbA1c <7.0%||28.3||12.0||35.6||5.2|
|Mean duration of treatment with basal insulin at baseline (years)||3.06||3.2||2.94||3.01|
|Mean change in basal insulin dose (U)|
|LS mean change from baseline||-5.62||-1.93||-1.39||-0.11|
|Mean body weight (kg)|
|LS mean change from baseline||-1.80||-0.52||-0.38||0.06|
|Lixisenatide||Insulin glulisine QD||Insulin glulisine TID|
|Mean HbA1c (%) LS change from baseline LS mean difference (SE) of lixisenatide versus 95% CI||N = 297 -0.63|| N = 298
(-0.170 to 0.064)
| N = 295
(0.095 to 0.328)
|Mean body weight LS change from baseline LS mean difference (SE) of lixisenatide versus 95% CI||N = 297 -0.63|| N = 298
(-2.257 to -1.062)
| N = 295
(-2.593 to -1.396)*
People aged ≥70 yearsThe efficacy and safety of lixisenatide in people aged ≥70 years with type 2 diabetes was evaluated in a double-blind, placebo-controlled study of 24 weeks duration. Frail patients, including patients at risk for malnutrition, patients with recent cardiovascular events and patients with moderate to severe cognitive impairment were excluded. A total of 350 patients were randomized (randomization ratio 1:1). Overall, 37% of the patients were ≥75 years old (N=131) and 31% had moderate renal impairment (N=107). Patients received stable dose(s) of oral antidiabetic drug(s) (OAD) and/or basal insulin as background therapy. Sulfonylureas or glinides were not used with basal insulin as background therapy. Lixisenatide provided significant improvements in HbA1c (-0.64% change compared to placebo; 95% CI: -0.810% to -0.464%; p<0.0001), from a mean baseline HbA1c of 8.0%.
Paediatric populationThe European Medicines Agency has deferred the obligation to submit the results of studies with Lyxumia in one or more subsets of the paediatric population in type 2 diabetes mellitus (see section 4.2 for information on paediatric use).
AbsorptionFollowing subcutaneous administration to patients with type 2 diabetes, the rate of lixisenatide absorption is rapid and not influenced by the dose administered. Irrespective of the dose and whether lixisenatide was administered as single or multiple doses, the median tmax is 1 to 3.5 hours in patients with type 2 diabetes. There are no clinically relevant differences in the rate of absorption when lixisenatide is administered subcutaneously in the abdomen, thigh, or arm.
DistributionLixisenatide has a moderate level of binding (55%) to human proteins.The apparent volume of distribution after subcutaneous administration of lixisenatide (Vz/F) is approximately 100 L.
Biotransformation and eliminationAs a peptide, lixisenatide is eliminated through glomerular filtration, followed by tubular reabsorption and subsequent metabolic degradation, resulting in smaller peptides and amino acids, which are reintroduced in the protein metabolism. After multiple dose administration in patients with type 2 diabetes, mean terminal half-life was approximately 3 hours and the mean apparent clearance (CL/F) about 35 L/h.
Patients with renal impairmentIn subjects with mild (creatinine clearance calculated by the Cockcroft-Gault formula 60-90 ml/min), moderate (creatinine clearance 30-60 ml/min) and severe renal impairment (creatinine clearance 15-30 ml/min) AUC was increased by 46%, 51% and 87%, respectively.
Patients with hepatic impairmentAs lixisenatide is cleared primarily by the kidney, no pharmacokinetic study has been performed in patients with acute or chronic hepatic impairment. Hepatic dysfunction is not expected to affect the pharmacokinetics of lixisenatide.
GenderGender has no clinically relevant effect on the pharmacokinetics of lixisenatide.
RaceEthnic origin had no clinically relevant effect on the pharmacokinetics of lixisenatide based on the results of pharmacokinetic studies in Caucasian, Japanese and Chinese subjects.
ElderlyAge has no clinically relevant effect on the pharmacokinetics of lixisenatide.In a pharmacokinetic study in elderly non diabetic subjects, administration of lixisenatide 20 mcg resulted in a mean increase of lixisenatide AUC by 29% in the elderly population (11 subjects aged 65 to 74 years and 7 subjects aged ≥75 years) compared to 18 subjects aged 18 to 45 years, likely related to reduced renal function in the older age group.
Body weightBody weight has no clinically relevant effect on lixisenatide AUC.
After first useStore below 30°C. Do not freeze.Do not store with attached needle. Keep the cap on the pen in order to protect from light.
Treatment initiation packType I glass cartridge with a (bromobutyl) rubber plunger, flanged caps (aluminium) with inserted laminated sealing disks (bromobutyl rubber on the product side and polyisoprene on the outside). Each cartridge is assembled into a disposable pen. Pack containing 1 green pre-filled pen of Lyxumia 10 mcg and 1 purple pre-filled pen of Lyxumia 20 mcg.Each green pre-filled pen contains 3 ml solution, delivering 14 doses of 10 mcg.Each purple pre-filled pen contains 3 ml solution, delivering 14 doses of 20 mcg.
1 Onslow Street, Guildford, Surrey, GU1 4YS, UK
+44 (0)1483 535 432
+44 (0)1483 505 515
+44 (0)845 372 7101