Insulin glargine + Lixisenatide


Concise Prescribing Info
Indications/Uses
Type 2 diabetes mellitus.
Dosage/Direction for Use
Adult : SC Each mL of pre-filled pen contains insulin glargine (units)/lixisenatide (mcg): 100/50 or 100/33: Dosage is individualised according to clinical response and previous antidiabetic treatment. Combined with metformin for patients who have inadequate response to oral antidiabetics or basal insulin: As 100 units/50 mcg pen: Insulin-naive patients: Initial: 10 dose steps (10 units/5 mcg) once daily. Patients previously treated with 20-<30 units of insulin glargine (100 units/mL preparation) or any other basal insulin therapy: Initial: 20 dose steps (20 units/10 mcg) once daily. Patients previously treated with insulin glargine (300 units/mL preparation) or other basal insulin given bid: Reduce by 20% the total daily dose of previous therapy used to obtain the initial dose. As 100 units/33 mcg pen: Patients naive to basal insulin or GLP-1 agonist, currently on <30 units basal insulin or on GLP-1 agonist: Initial: 15 dose steps (15 units/5 mcg) once daily. Patients previously treated with 30-60 units of insulin glargine (100 units/mL preparation) or any other basal insulin therapy: Initial: 30 dose steps (30 units/10 mcg) once daily. Patients previously treated with insulin glargine (300 units/mL preparation) or other basal insulin given bid: Reduce by 20% the total daily dose of previous therapy used to obtain the initial dose. Titrate all doses based on individual’s need for insulin (refer to detailed product guideline). Max: 60 dose steps (60 units/20 mcg) daily.
Dosage Details
Subcutaneous
Type 2 diabetes mellitus
Adult: Available preparations:
Insulin glargine 100 units and lixisenatide 50 mcg per mL solution for inj in pre-filled pen
Insulin glargine 100 units and lixisenatide 33 mcg per mL solution for inj in pre-filled pen

Dosage is individualised according to clinical response and previous antidiabetic treatment. Combined with metformin for patients who have inadequate response to oral antidiabetics or basal insulin: As 100 units/50 mcg pen: Insulin-naive patients: Initially, 10 dose steps (10 units/5 mcg) once daily. Patients previously treated with 20-<30 units of insulin glargine (100 units/mL preparation) or any other basal insulin therapy: Initially, 20 dose steps (20 units/10 mcg) once daily. Patients previously treated with insulin glargine (300 units/mL preparation) or other basal insulin given bid: Reduce by 20% the total daily dose of previous therapy used to obtain the initial dose. As 100 units/33 mcg pen: Patients naive to basal insulin or GLP-1 agonist, currently on <30 units basal insulin or on GLP-1 agonist: Initially, 15 dose steps (15 units/5 mcg) once daily. Patients previously treated with 30-60 units of insulin glargine (100 units/mL preparation) or any other basal insulin therapy: Initially, 30 dose steps (30 units/10 mcg) once daily. Patients previously treated with insulin glargine (300 units/mL preparation) or other basal insulin given bid: Reduce by 20% the total daily dose of previous therapy used to obtain the initial dose. Titrate all doses based on individual’s need for insulin (refer to detailed product guideline). Max: 60 dose steps (60 units/20 mcg) daily. All doses are given 1 hour prior to a meal. Discontinue treatment with basal insulin or other oral antidiabetics prior to initiation of therapy.
Renal Impairment
Mild to moderate: Dose adjustment may be necessary. Severe or ESRD: Not recommended.
Hepatic Impairment
Dose adjustment may be necessary.
Contraindications
Hypersensitivity. Episodes of hypoglycaemia.
Special Precautions
Patients with risk factors for hypoglycaemia, including changes in meal pattern, level of physical activity, and insulin regimen (e.g. insulin type, strength, brand, inj site, method of administration), intercurrent illness (e.g. vomiting, diarrhoea), improved insulin sensitivity (e.g. removal of stress factors), alcohol consumption, certain uncompensated endocrine disorders (e.g. hypothyroidism, adrenocortical or anterior pituitary insufficiency); history of pancreatitis, at risk for hypokalaemia (e.g. taking loop diuretics); undergoing bariatric surgery. Not recommended in patients with severe gastrointestinal disease (e.g. severe gastroparesis), severe renal impairment or ESRD. Not indicated for use in type 1 diabetes mellitus and diabetic ketoacidosis. Hepatic and mild to moderate renal impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Hypoglycaemia, dehydration, antibody formation, hypokalaemia, acute kidney injury, worsening of chronic renal failure.
Gastrointestinal disorders: Nausea, diarrhoea, vomiting, dyspepsia, abdominal pain.
General disorders and administration site conditions: Fatigue, inj site reactions (e.g. erythema, local oedema, pruritus).
Nervous system disorders: Dizziness, headache.
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, upper respiratory tract infection.
Skin and subcutaneous tissue disorders: Urticaria, lipodystrophy, cutaneous amyloidosis.
Potentially Fatal: Acute pancreatitis, including haemorrhagic and necrotising pancreatitis; serious hypersensitivity reactions (e.g. anaphylaxis, angioedema); severe and prolonged hypoglycaemia, untreated hypokalaemia.
Patient Counseling Information
This drug may impair your ability to concentrate and react due to hypoglycaemia, if affected, do not drive or operate machinery. Rotate inj sites within the same region to reduce the risk of lipodystrophy.
MonitoringParameters
Monitor blood glucose, HbA1c (at least twice a year in patients with stable glycaemic control; quarterly in patients not meeting treatment goals), renal and hepatic function, weight, electrolytes, serum K (as necessary in at risk patients); signs and symptoms of pancreatitis, hypersensitivity reactions, and hypoglycaemia regularly.
Overdosage
Symptoms: Hypoglycaemia, hypokalaemia, gastrointestinal effects; hypoglycaemia with coma, seizure, neurologic impairment. Management: Supportive treatment. May give oral carbohydrates for mild episodes of hypoglycaemia; adjustments in the dose, meal patterns, or physical activities may be necessary. Administer IM/SC glucagon or concentrated IV glucose for severe cases; close observation and sustained carbohydrate intake may be necessary.
Drug Interactions
May increase risk of hypoglycaemia with other antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, pentoxifylline, propoxyphene, salicylates and sulphonamide antibiotics. May reduce hypoglycaemic effect with corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, somatropin, sympathomimetic agents (e.g. epinephrine, salbutamol, terbutaline), phenothiazines, atypical antipsychotics (e.g. clozapine, olanzapine), thyroid hormones, and protease inhibitors. Signs and symptoms of hypoglycaemia may be masked by β-blockers, clonidine, guanethidine and reserpine. Increased risk of fluid retention and heart failure with peroxisome proliferator-activated receptor (PPAR)-γ agonists (e.g. thiazolidinediones).
Insulin glargine: Hypoglycaemic effect may either be increased or decreased by β-blockers, clonidine, lithium salts, and pentamidine.
Lixisenatide: May reduce the rate of absorption of paracetamol, warfarin and other coumarin derivatives, digoxin and ramipril.
Food Interaction
May increase risk of hypoglycaemia with alcohol.
Action
Description: Insulin glargine is a long-acting human insulin analogue that stimulates peripheral glucose uptake (particularly by skeletal muscle and fat) and blocks hepatic glucose production, resulting in lower blood glucose levels.
Lixisenatide is a synthetic, short-acting glucagon-like peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin secretion from β cells and inhibits glucagon release from α cells in the pancreas.
Onset: Insulin glargine: Approx 1.1 hours (100 unit/mL preparation); approx 6 hours (300 unit/mL preparation).
Duration: Insulin glargine: Approx 24 hours (100 unit/mL preparation); approx 36 hours (300 unit/mL preparation).
Pharmacokinetics:
Absorption: Insulin glargine: Slowly absorbed from SC tissue after inj.
Lixisenatide: Rapidly absorbed from SC tissue after inj. Time to peak plasma concentration: 1-3.5 hours.
Distribution: Insulin glargine: Volume of distribution: 1,700 L.
Lixisenatide: Volume of distribution: 100 L. Plasma protein binding: 55%.
Metabolism: Insulin glargine: Partially metabolised in SC tissue depot at the carboxyl terminus of the B chain to form 2 active metabolites, M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin).
Lixisenatide: May undergo elimination via glomerular filtration and proteolytic degradation into smaller peptides and amino acids that are reintroduced in the protein metabolism. Not metabolised by CYP450 isoenzymes.
Excretion: Lixisenatide: Terminal elimination half-life: Approx 3 hours.
Chemical Structure

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Storage
Unopened pen: Store between 2-8°C. Do not freeze. Protect from light. Opened (in-use) pen: Store below 25°C. Do not refrigerate or freeze. Protect from direct heat or light.
MIMS Class
ATC Classification
A10AE54 - insulin glargine and lixisenatide ; Belongs to the class of long-acting insulins and analogues for injection. Used in the treatment of diabetes.
Disclaimer: This information is independently developed by MIMS based on Insulin glargine + Lixisenatide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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