The first FDA-approved, interchangeable insulin glargine
SEMGLEE® (insulin glargine-yfgn) injection
Switch your adult and pediatric patients with Type 1 diabetes and your adult patients with Type 2 diabetes patients from LANTUS® to SEMGLEE or Insulin Glargine (insulin glargine-yfgn) injection, the first FDA-approved, interchangeable biosimilar insulin glargine.
Indicated to improve glycemic control in adults and pediatric patients from 6 years old with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.
It is not known if SEMGLEE is safe and effective in children less than 6 years of age with type 1 diabetes.
What is SEMGLEE?1
- SEMGLEE is a once-daily long-acting insulin analog (100 units/ml) that is FDA-approved as interchangeable for LANTUS in adults and pediatric patients with type 1 diabetes and in adults with type 2 diabetes.
- SEMGLEE offers highly similar clinical benefits compared with LANTUS including duration of action, rate of hypoglycemia and effect on changes HbA1c and fasting plasma glucose from baseline when used as directed.
- SEMGLEE is biosimilar to, and depending on state pharmacy laws, can be substituted for, its reference product LANTUS, a long-acting insulin analog.
- SEMGLEE is available as a solution for injection in 10ml multiple dose vials or in 3ml single-patient-use prefilled injector pens.
What does “Interchangeable” mean?
According to the FDA, an interchangeable product is a biological product that is approved based on data demonstrating that it is highly similar to an FDA-approved reference product and that there are no clinically meaningful differences between the products. The interchangeable product can be expected to produce the same clinical result as the reference product in any given patient. Further, if the interchangeable product is administered more than once to a patient, the risk in terms of safety or diminished efficacy from alternating or switching between use of the reference product and interchangeable product is not greater than that from the reference product without such alternation or switch.
Interchangeability of SEMGLEE has been demonstrated for the condition(s) of use, strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information.
An interchangeable biologic product is a biosimilar that meets additional requirements and may be substituted for the reference product at the pharmacy, depending on state pharmacy laws.
How does SEMGLEE work?1
SEMGLEE (insulin glargine-yfgn) injection is a sterile solution for subcutaneous use. Insulin glargine is a recombinant human long-acting insulin analog. The primary activity of insulin, including SEMGLEE, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis and enhances protein synthesis. Insulin glargine is metabolized into 2 active metabolites M1 and M2.
Pharmacodynamic Profile
The pharmacodynamic profile for SEMGLEE was determined after subcutaneous administration of a single 0.5 U/kg dose in a euglycemic clamp study conducted in 116 type 1 diabetes patients.
The median time to maximum effect of SEMGLEE (measured by the peak rate of glucose infusion) was approximately 11.3 hours. The pharmacodynamic profile of SEMGLEE following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak. The arithmetic mean area under the glucose infusion rate curves (AUC GIR 0-24h) and maximum glucose infusion rate were 1423 mg/kg and 1.8 mg/kg/min, respectively.
The time course of action of insulin may vary considerably in different individuals or within the same individual.
Pharmacokinetics
After subcutaneous injection of a single 0.5 U/kg dose of SEMGLEE in a euglycemic clamp study conducted in 116 type 1 diabetes patients, the M1 active metabolite plasma concentration profile indicated a prolonged absorption and a relatively constant concentration/time profile over 24 hours.
The median time to maximum M1 plasma concentration was 12 hours after injection. The mean plasma observed area under the concentration-time curve for M1 from time zero to 24 hours and peak plasma concentration were 10.5 ng*hr/mL and 0.64 ng/mL, respectively.
Elimination
A metabolism study in humans indicates that insulin glargine is partly metabolized at the carboxyl terminus of the B chain in the subcutaneous depot to form two active metabolites with in vitro activity similar to that of human insulin, M1 (21A-Gly-insulin) and M2 (21A-Gly-des30B-Thr-insulin). Unchanged drug and these degradation products are also present in the circulation.
Specific Population
Age, Race, and Gender
Effect of age, race, and gender on the pharmacokinetics of SEMGLEE has not been evaluated.
Obesity
Effect of Body Mass Index (BMI) on the pharmacokinetics of SEMGLEE has not been evaluated.
References:
- SEMGLEE® (insulin glargine-yfgn) injection. Prescribing Information. 2021. Mylan Pharmaceuticals Inc. Morgantown, WV.
Adverse Events Reporting
This medicine is subject to additional monitoring. This will allow quick identification of new safety information. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare providers are asked to report any suspected adverse reactions. Reporting forms and information can be found at http://www.mhra.gov.uk/yellowcard. In order to support effective tracking and traceability of biologics including biosimilars, it is recommended that the brand name and batch number are recorded and used when reporting adverse events. You can also report adverse events direct to the marketing authorisation holder at ukpharmacovigilance@mylan.com.
Semglee® (Insulin glargine) 100 units/ml solution for injection in pre-filled pen
Prescribing information
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
Indication: Semglee® is indicated in the treatment of diabetes mellitus in adults, adolescents and children aged 2 years and above. Presentation: Each ml contains 100 units insulin glargine* (equivalent to 3.64 mg). Each pen contains 3 ml of solution for injection, equivalent to 300 units. Dosage and administration: Semglee® (insulin glargine) has a prolonged duration of action. It should be administered once daily at any time but at the same time each day. The pre filled pen delivers insulin in increments of 1 unit up to a maximum single dose of 80 units. The dose regimen (dose and timing) should be individually adjusted. In patients with type 2 diabetes mellitus, Semglee® can also be given together with orally active antidiabetic medicinal products. The potency of Semglee® is stated in units and these units are exclusive to Semglee®. Special population: Elderly population (≤ 65 years old): progressive deterioration of renal function may lead to a steady decrease in insulin requirements. Renal impairment: insulin requirements may be diminished due to reduced insulin metabolism. Hepatic impairment: insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism. Paediatric population: For adolescents and children aged 2 years and older patients, the dose regimen (dose and timing) should be individually adjusted. For children below 2 years of age the safety and efficacy of Semglee® have not been established. No data are available. Switch from other insulins to Semglee® When switching from a treatment regimen with an intermediate or long acting insulin to a regimen with Semglee®, a change of the dose of the basal insulin may be required and the concomitant antidiabetic treatment may need to be adjusted (dose and timing of additional regular insulins or fast acting insulin analogues or the dose of oral antidiabetic medicinal products). Switch from twice daily NPH insulin to Semglee®: To reduce the risk of nocturnal and early morning hypoglycaemia, daily dose of once daily basal insulin should be reduced by 20-30% during the first weeks of treatment. Switch from insulin glargine 300 units/ml to Semglee®: Semglee® and insulin glargine 300 units/ml are not bioequivalent and are not directly interchangeable. To reduce the risk of hypoglycemia in this group, Semglee® dose should be reduced by approximately 20%. During the first weeks increase mealtime insulin, after this period the regimen should be adjusted individually. Close metabolic monitoring is recommended during the switch and in the initial weeks thereafter. A further adjustment in dose regimen may become necessary with improved metabolic control, change of timing of insulin, patient weight or life style changes. Patients with high insulin doses because of antibodies to human insulin may experience an improved insulin response with Semglee®. Method of administration Semglee® is administered subcutaneously only. Injection sites must be rotated within a given injection area from one injection to the next. Semglee® must not be mixed with any other insulin or diluted. Before using the pre filled pen, the instructions for use included in the package leaflet must be read carefully (see section 6.6). Contraindications: Known hypersensitivity to the active substances or to any of the excipients. Warnings and precautions: Warnings: Semglee® is not the insulin of choice for the treatment of diabetic ketoacidosis. In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered. Changes in insulin strength, manufacturer, type, origin, method of manufacture and/or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment. Hypoglycaemia Due to more sustained basal insulin supply with Semglee®, less nocturnal but more early morning hypoglycaemia can be expected. Intercurrent illness In many cases urine tests for ketones are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often increased. Patients with type 1 diabetes must continue to consume at least a small amount of carbohydrates on a regular basis, even if they are able to eat only little or no food or are vomiting etc. and they must never omit insulin entirely. Insulin antibodies Rare chance of antibodies formation, may require insulin dose adjustment to avoid hyper- or hypoglycaemia. Handling of the pen Before using Semglee® pen, the instructions for use included in the package leaflet must be read carefully. Semglee® pen has to be used as recommended in the instructions for use. Medication errors Insulin label must always be checked before each injection to avoid medication errors between insulin glargine and other insulins. Interaction with other medicinal products: Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs when used with Semglee®. Substances that may enhance the blood glucose lowering effect include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase (MAO) inhibitors, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics. Substances that may reduce the blood glucose lowering effect include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, oestrogens and progestogens, phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, atypical antipsychotic medicinal products (e.g. clozapine and olanzapine) and protease inhibitors. Beta blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood glucose lowering effect of insulin. Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia. Pregnancy and lactation: Pregnancy For insulin glargine no clinical data on exposed pregnancies from controlled clinical studies are available. A large amount of data on pregnant women (more than 1000 pregnancy outcomes) indicate no specific adverse effects of insulin glargine on pregnancy and no specific malformative nor feto/neonatal toxicity of insulin glargine. Animal data do not indicate reproductive toxicity. The use of Semglee® may be considered during pregnancy, if clinically needed. The use of Semglee® may be considered during pregnancy, if clinically needed. Careful monitoring of glucose control is essential. Breast feeding It is unknown whether insulin glargine is excreted in human milk. Women may require adjustments in insulin dose and diet. Effects on ability to drive and use machines: The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment. Undesirable effects: Very common: Hypoglycaemia. Common: Lipohypertrophy, Injection site reactions Uncommon: Lipoatrophy. For rare and very rare undesirable effects, please refer to SmPC. Name and Address of Marketing Authorisation Holder: Mylan S.A.S., 117 allée des Parcs, 69800 Saint Priest, France. Marketing Authorisation Number: EU/1/18/1270/003 Basic NHS price: 3ml x 5 pens=£29.99 Legal Category: POM Date of Last Revision: October 2018
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu. and from Mylan Medical Information, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9BW, phone no. 01707 853000, Email: info@mylan.co.uk
This medicine is subject to additional monitoring. This will allow quick identification of new safety information. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare providers are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. In order to support effective tracking and traceability of biologics including biosimilars, it is recommended that the brand name and batch number are recorded and used when reporting adverse events. Adverse events should be reported to Pharmacovigilance, Mylan, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL, on phone no. 0800 121 8267, Email: ukpharmacovigilance@mylan.com
Prescribing Information
Please select from the following:
