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insulin glargine

A10A - Insulins and analogues ATC A10AD05 Protein approved 2000 Parenteral

JFDA label: Novomix Penfill Cart.

Mechanism of Action

Agonist of Insulin receptor — Insulin receptor agonist

TargetActionGene / class
Insulin receptor efficacy AGONIST INSR

Indications

Approved

  • Diabetes mellitus, types 1 and 2

Contraindications

Source: Lexicomp

  • Hypersensitivity to insulin glargine or any component of the formulation Absolute
  • during episodes of hypoglycemia Documentation of allergenic cross-reactivity for insulin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (3)

Very Common Hypertension · peripheral edema

Common Retinal vascular disease

Nervous system disorders (2)

Very Common Depression

Common Headache

Renal and urinary disorders (1)

Very Common Urinary tract infection

Immune system disorders (1)

Very Common Antibody development

Metabolism and nutrition disorders (2)

Very Common Hypoglycemia

Not Known Sodium retention

Gastrointestinal disorders (1)

Very Common Diarrhea

Musculoskeletal and connective tissue disorders (3)

Very Common Arthralgia · back pain · limb pain

Eye disorders (2)

Very Common Cataract · retinopathy

Infections and infestations (2)

Very Common infection · Influenza

General disorders and administration site conditions (6)

Common Accidental injury · Pain at injection site

Not Known Erythema at injection site · itching at injection site · localized edema · swelling at injection site

Respiratory, thoracic and mediastinal disorders (7)

Very Common bronchitis · cough · nasopharyngitis · sinusitis · Upper respiratory tract infection

Common Pharyngitis · rhinitis

Dosing

Source: Lexicomp

Note: Insulin glargine is a long-acting insulin administered by SubQ injection. Insulin glargine is approximately equipotent to human insulin, but has a slower onset, no pronounced peak, and a longer duration of activity. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision. Diabetes mellitus, type 1: SubQ: Insulin glargine-specific dosing: Initial dose: Approximately one-third to one-half of the total daily insulin requirement administered once daily. A rapid-acting or short-acting insulin should also be used to complete the balance (~1/2 to 2/3) of the total daily insulin requirement. Adjust dosage according to patient response. Conversion to insulin glargine from other insulin therapies: Converting from once-daily NPH insulin to insulin glargine: May be substituted on an equivalent unit-per-unit basis Converting from twice-daily NPH insulin to insulin glargine: Initial dose: Use 80% of the total daily dose of NPH (eg, 20% reduction); administer once daily; adjust dosage according to patient response Conversion between Toujeo, Lantus, and Basaglar: Conversion from once-daily Toujeo to once-daily Lantus or once-daily Basaglar: Initial dose: Use 80% of the dose of Toujeo (eg, 20% reduction); adjust dosage according to patient blood glucose response. Conversion from once-daily Lantus to once-daily Toujeo or once-daily Basaglar: Initial dose: May be substituted on an equivalent unit-per-unit basis; however, generally a higher daily dosage of Toujeo will be required to achieve the same level of glycemic control as with Lantus. General insulin dosing (off-label): Type 1: SubQ: Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations used. Insulin glargine must be used in combination with a rapid- or short-acting insulin. Initial total insulin dose: 0.2 to 0.6 units/kg/day in divided doses. Conservative initial doses of 0.2 to 0.4 units/kg/day are often recommended to avoid the potential for hypoglycemia. Usual maintenance range: 0.5 to 1 units/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows: Nonobese: 0.4 to 0.6 units/kg/day Obese: 0.8 to 1.2 units/kg/day Division of daily insulin requirement ("conventional therapy"): Generally, 50% to 75% of the total daily dose (TDD) is given as an intermediate-acting or a long-acting form of insulin (eg, insulin glargine) (in 1 to 2 daily injections). The remaining portion of the TDD is then divided and administered before or at mealtimes (depending on the formulation) as a rapid-acting (eg, lispro, aspart, glulisine) or short-acting (regular) form of insulin. Division of daily insulin requirement ("intensive therapy"): Basal insulin delivery with 1 or 2 doses of intermediate-acting or long-acting insu
(For additional information see "Insulin glargine: Pediatric drug information") Insulin glargine is a long-acting insulin administered by SubQ injection. Insulin glargine is approximately equipotent to human insulin, but has a slower onset, no pronounced peak, and a longer duration of activity. Changing the basal insulin component from another insulin to insulin glargine can be done on a unit-to-unit basis. Insulin requirements vary dramatically between patients and dictates frequent monitoring and close medical supervision. See Insulin Regular for additional information. Insulin glargine-specific dosing: Type 1 diabetes mellitus: Children ≥6 years and Adolescents: SubQ: Initial dose: Approximately one-third of the total daily insulin requirement; a rapid-acting or short-acting insulin should also be used. Type 1 or type 2 diabetes; previously receiving basal insulin plus bolus insulin (eg, NPH + regular insulin): Children Children ≥6 years: SubQ: Converting from once-daily NPH insulin: May be substituted on an equivalent unit-per-unit basis Converting from twice-daily NPH insulin: Initial dose: Use 80% of the total daily dose of NPH (eg, 20% reduction); administer once daily; adjust dosage according to patient response General insulin dosing (off-label): Type 1 diabetes mellitus: Children and Adolescents: Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations used. Insulin glargine must be used in combination with a short-acting insulin. Usual maintenance range: SubQ: 0.5-1 unit/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows: Nonobese: 0.4 to 0.6 units/kg/day Obese: 0.8 to 1.2 units/kg/day Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day (IDF/ISPAD, 2011) Dosage adjustment: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose to maintain premeal and bedtime glucose in target range. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component.
Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.
There are no dosage adjustments provided in the manufacturer’s labeling; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.

Warnings & Precautions

Source: Lexicomp

Hypersensitivity

Severe, life-threatening allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy.

Hypoglycemia

The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin detemir, insulin glargine, insulin degludec) may delay recovery from hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.

Hypokalemia

Insulin (especially IV insulin) causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium and supplement potassium when necessary. Disease-related concerns:

Hepatic impairment

Use with caution in patients with hepatic impairment. Dosage requirements may be reduced.

Renal impairment

Use with caution in patients with renal impairment. Dosage requirements may be reduced. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Hospitalized patients with diabetes

Exclusive use of a sliding scale insulin regimen (insulin regular) in the inpatient hospital setting is strongly discouraged. In the critical care setting, continuous IV insulin infusion (insulin regular) has been shown to best achieve glycemic targets. In noncritically ill patients with either poor oral intake or taking nothing by mouth, basal insulin or basal plus bolus is preferred. In noncritically ill patients with adequate nutritional intake, a combination of basal insulin, nutritional, and correction components is preferred. An effective insulin regimen will achieve the goal glucose range without the risk of severe hypoglycemia. A blood glucose value Dosage form specific issues:

Multiple dose injection pens

According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012). Other warnings/precautions:

Administration

Insulin glargine is a clear solution, but it is NOT intended for IV or IM administration or via an insulin pump.

Appropriate use

Diabetes mellitus: The general objective of exogenous insulin therapy is to approximate the physiologic pattern of insulin secretion which is characterized by two distinct phases. Phase 1 insulin secretion suppresses hepatic glucose production and phase 2 insulin secretion occurs in response to carbohydrate ingestion; therefore, exogenous insulin therapy may consist of basal insulin (eg, intermediate- or long-acting insulin), insulin administered via continuous subcutaneous insulin infusion [CSII]) and/or preprandial insulin (eg, short- or rapid-acting insulin) (see Related Information: Insulin Products). Patients with type 1 diabetes do not produce endogenous insulin; therefore, these patients require both basal and preprandial insulin administration. Patients with type 2 diabetes retain some beta-cell function in the early stages of their disease; however, as the disease progresses, phase 1 insulin secretion may become completely impaired and phase 2 insulin secretion becomes delayed and/or inadequate in response to meals. Therefore, patients with type 2 diabetes may be treated with oral antidiabetic agents, basal insulin, and/or preprandial insulin depending on the stage of disease and current glycemic control. Since treatment regimens often consist of multiple agents, dosage adjustments must address the specific phase of insulin release that is primarily contributing to the patient’s impaired glycemic control. Treatment and monitoring regimens must be individualized.

Patient education

Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.

Pregnancy & Lactation

Pregnancy

FDA category B

Safe

Drug of choice for diabetes in pregnancy. Tight glucose control reduces congenital malformations, macrosomia, stillbirth. Monitor glucose closely — requirements change by trimester

Lactation

In a study using insulin glargine, both exogenous and endogenous insulin were present in breast milk (Whitmore 2012). Breastfeeding is encouraged for all women, including those with type 1, type 2, or GDM (ACOG 2005; ADA 2018c; Blumer 2013; Metzger 2007). A small snack (such as milk) before breastfeeding may help decrease the risk of hypoglycemia in women with pregestational diabetes (ACOG 2005; Reader 2004). The manufacturer considers the use of insulin glargine to be compatible with breastfeed

Monitoring

EfficacyFasting blood glucose (target 80–130 mg/dL); HbA1c every 3 months until target then every 6 months
ToxicityHypoglycaemia; injection site reactions (lipohypertrophy/lipoatrophy from fixed-site injections); hypokalaemia
Clinical pearlLong-acting insulins should not be mixed with other insulin types in the same syringe. Rotate injection sites to prevent lipohypertrophy.
CounselingRotate injection sites. Always keep fast-acting glucose available. Check blood glucose more frequently during illness, unusual physical activity, or changes in diet.

Chemistry & Properties

2D structure
CAS160337-95-1
PubChem CID118984454
SMILESCCC(C)C1C(=O)NC2CSSCC(C(=O)NC(CSSCC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)NCC(=O)O)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NCC(=O)NC(CC5=CC=CC=C5)C(=O)NC(CC6=CC=CC=C6)C(=O)NC(CC7=CC=C(C=C7)O)C(=O)NC(C(C)O)C(=O)N8CCCC8C(=O)NC(CCCCN)C(=O)NC(C(C)O)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCNC(=N)N)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)C(CC(C)C)NC(=O)C(CC2=CNC=N2)NC(=O)C(CCC(=O)N)NC(=O)C(CC(=O)N)NC(=O)C(C(C)C)NC(=O)C(CC2=CC=CC=C2)N)C(=O)NC(C(=O)NC(C(=O)N1)CO)C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(CCC(=O)O)NC(=O)C(C(C)C)NC(=O)C(C(C)CC)NC(=O)CN

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability70.0%
Half-life13.28 h
Volume of distribution0.133 L/kg
Protein binding-77.5%
BBB penetrantNo

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drugSeverityManagement
Cinoxacin major
Ciprofloxacin major
Delafloxacin major
Enoxacin major
Gatifloxacin major
Gemifloxacin major
Grepafloxacin major
Levofloxacin major
Lomefloxacin major
Moxifloxacin major
Nalidixic acid major
Norfloxacin major
Ofloxacin major
Sparfloxacin major
Trovafloxacin major
Acebutolol moderate
Acetazolamide moderate
Acetohexamide moderate
Acetylsalicylic acid moderate
Albiglutide moderate
Alimemazine moderate
Aloe Vera Leaf moderate
Alogliptin moderate
Alpelisib moderate
Amprenavir moderate
Aripiprazole moderate
Asenapine moderate
Asparaginase Erwinia chrysanthemi moderate
Asparaginase Escherichia coli moderate
Atazanavir moderate
Atenolol moderate
Azilsartan medoxomil moderate
Benazepril moderate
Bendroflumethiazide moderate
Benzphetamine moderate
Benzthiazide moderate
Betamethasone moderate
Betaxolol moderate
Betaxolol (ophthalmic) moderate
Bexarotene moderate

Showing 40 of 100+.

Registered Products (21)

BrandForm / strengthPackAgentCitizen (JOD)
NovoRapid 100IU/ml Solution for Injection vial Injection 100 IU/ml 10 ml Khoury Drug Store 17.660
NovoRapid Flexpen Pre-filled Pen 100 IU/ml 3 ml Khoury Drug Store 24.490
Humalog Cartridge 100iu/ml Cartridge 100 IU/ml 3 ml THE ARAB DRUG STORE P.S.C 27.410
Humalog Mix 25/ 100IU/ml Solution 25 %, 75 % 3 ml THE ARAB DRUG STORE P.S.C 27.410
Humalog Mix 50 Injection 100 IU/ml 3 ml THE ARAB DRUG STORE P.S.C 27.410
NovoRapid Penfills Injection 100 IU/ml 3 ml Khoury Drug Store 28.210
Novomix Penfill Cart. Cartridge 100 IU/ml 3 ml Khoury Drug Store 28.210
Novomix 30 flexpen Injection 100 IU/ml 3 ml Khoury Drug Store 32.420
Semglee Pre-filled Pen 100 UNT/1 ml 3 ml Sabbagh Drug Store 32.640
Apidra Solostar 100IU/ml Solution for Injection Injection 100 IU/ml 3 ml Ulfa Pharma Co. 34.230
Novomix 50 flexpen Injection 100 IU/ml 3 ml Khoury Drug Store 36.550
Levemir Flexpen 100IU/ml solution for injection Injection 14.2 mg/ml 3 ml Khoury Drug Store 39.020
Levemir Penfill Cartridge 100 IU/ml 3 ml Khoury Drug Store 39.690
Toujeo 300 IU/ml Solution for Inj in PFP Injection 300 IU/ml 1.5 ml pack varies Ulfa Pharma Co. 43.960
Tresiba Penfill 100 iu/ml Cartridge 100 IU/ml 3 ml Khoury Drug Store 49.290
Lantus Solostar Pre-filled Pen 100 IU/ml 3 ml Ulfa Pharma Co. 49.810
Tresiba Flextouch 100IU/ML Pre-filled Pen 100 IU/ml 3 ml Khoury Drug Store 51.160
Ryzodeg 100 IU/ml Flextouch solution for injection Powder for Injection 30 %, 70 % 3 ml Khoury Drug Store 59.910
Tresiba Flextouch 200IU ,3 X 3 Pre-filled Pen 200 IU/ml 3 ml Khoury Drug Store 61.040
Toujeo 300 IU/ml Solution for Inj in PFP Injection 300 IU/ml 1.5 ml pack varies Ulfa Pharma Co. 66.460
Ryzodeg Penfill 100IU/ml Cartridge 180 nmol, 420 nmol 3 ml Khoury Drug Store 72.940