Dosing & Uses
Dosage Forms & Strengths
insulin glargine/lixisenatide
subcutaneous injection
- (100units/33mcg) per mL
- Available as a 3-mL single-use pen
Type 2 Diabetes Mellitus
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Starting dose
- Discontinue basal insulin or GLP-1 agonist before initiating insulin glargine/lixisenatide
- Patients who are naïve to basal insulin or GLP-1 agonists, currently on a GLP-1 receptor agonist, or on basal insulin <30 units/day: insulin glargine 15 units/lixisenatide 5 mcg SC qDay
- Patients currently on basal insulin 30-60 units/day with or without a GLP-1 agonist: insulin glargine 30 units/lixisenatide 10 mcg SC qDay
Dose titration
- May titrate dose upwards or downwards by 2-4 units of insulin glargine every week based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal until the desired fasting plasma glucose is achieved
To minimize the risk of hypoglycemia or hyperglycemia, additional titration may be needed with the following
- Changes in physical activity, meal patterns (ie, macronutrient content or timing of food intake), or renal or hepatic function
- During acute illness
- When used with other medications
Dosage Modifications
Renal impairment
- Mild-to-moderate: No dosage adjustment required; monitor for lixisenatide related adverse effects
- Severe (eGFR 15 to <30 mL/min/1.73 m²): Closely monitor; may increase occurrence of lixisenatide-associated GI and renal adverse effects
- ESRD (eGFR <15 mL/min/1.73 m²): Not studied; use not recommended
Hepatic impairment
- Not studied
- Frequent glucose monitoring and dose adjustment may be needed
Dosing Considerations
Discontinue therapy with lixisenatide or basal insulin prior to initiation
Limitations of use
- Has not been studied in patients with a history of pancreatitis; consider other antidiabetic therapies
- Not recommended in combination with any other product containing another GLP-1 receptor agonist
- Not indicated for type 1 diabetes mellitus or treatment of diabetic ketoacidosis
- Has not been studied in patients with gastroparesis and is not recommended in patients with gastroparesis
- Has not been studied in combination with prandial insulin
<18 years: Safety and efficacy not established
Initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions
Hypoglycemia may be more difficult to recognize in elderly individuals
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (1)
- pramlintide
insulin glargine, pramlintide. Mechanism: unspecified interaction mechanism. Contraindicated. Must be administered separately.
Serious - Use Alternative (2)
- ethanol
ethanol, insulin glargine. Other (see comment). Avoid or Use Alternate Drug. Comment: Alcohol may either increase or decrease the blood glucose lowering effect of insulin; alcohol may decrease endogenous glucose production (increased hypoglycemia risk) or worsen glycemic control by adding calories.
- macimorelin
insulin glargine, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may transiently elevate growth hormone (GH) concentrations may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.
Monitor Closely (131)
- acarbose
acarbose, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- albiglutide
albiglutide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- alogliptin
alogliptin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- aripiprazole
aripiprazole, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- asenapine
asenapine, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- aspirin
aspirin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.
- atazanavir
atazanavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- azilsartan
azilsartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- benazepril
benazepril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypoglycemic effects; Monitor blood glucose.
- bexagliflozin
bexagliflozin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- bitter melon
bitter melon increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypoglycemia.
- canagliflozin
insulin glargine, canagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with canagliflozin.
canagliflozin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - candesartan
candesartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- captopril
captopril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose. Monitor blood glucose.
- chlorpropamide
chlorpropamide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- cinnamon
cinnamon increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Potential for hypoglycemia.
- ciprofibrate
ciprofibrate increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.
- clozapine
clozapine, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- dapagliflozin
insulin glargine, dapagliflozin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with dapagliflozin.
dapagliflozin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - darunavir
darunavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- deflazacort
insulin glargine and deflazacort both decrease serum potassium. Use Caution/Monitor.
- dexfenfluramine
dexfenfluramine increases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Dexfenfluramine enhances glucose uptake in peripheral tissue, increasing risk of hypoglycemia.
- dichlorphenamide
dichlorphenamide and insulin glargine both decrease serum potassium. Use Caution/Monitor.
- disopyramide
disopyramide increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and disopyramide may require insulin dosage adjustment and increased glucose monitoring.
- dulaglutide
dulaglutide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- empagliflozin
empagliflozin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.
- enalapril
enalapril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- eprosartan
eprosartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- ertugliflozin
ertugliflozin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- ethinylestradiol
ethinylestradiol decreases effects of insulin glargine by pharmacodynamic antagonism. Use Caution/Monitor. Oral contraceptives may decrease hypoglycemic effects of antidiabetics by impairing glucose tolerance. Monitor for glycemic control in diabetic patients.
- exenatide injectable solution
exenatide injectable solution, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- exenatide injectable suspension
exenatide injectable suspension, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- fenfluramine
fenfluramine increases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Fenfluramine enhances glucose uptake in peripheral tissue, increasing risk of hypoglycemia.
- fenofibrate
fenofibrate increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.
- fenofibrate micronized
fenofibrate micronized increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.
- fenofibric acid
fenofibric acid increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.
- fleroxacin
fleroxacin increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- fluoxetine
fluoxetine increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and fluoxetine may require insulin dosage adjustment and increased glucose monitoring.
- fosamprenavir
fosamprenavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- fosinopril
fosinopril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- gemfibrozil
gemfibrozil increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Hypoglycemia; increased risk in hypoalbuminemia.
- gemifloxacin
gemifloxacin increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- glimepiride
glimepiride, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- glipizide
glipizide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- glucagon
glucagon decreases effects of insulin glargine by pharmacodynamic antagonism. Use Caution/Monitor. Endogenous glucagon is a regulatory hormone that increases blood glucose levels; exogenous glucagon is often used to treat hypoglycemia in patients with diabetes mellitus.
- glucagon intranasal
glucagon intranasal decreases effects of insulin glargine by pharmacodynamic antagonism. Use Caution/Monitor. Endogenous glucagon is a regulatory hormone that increases blood glucose levels; exogenous glucagon is often used to treat hypoglycemia in patients with diabetes mellitus.
- glyburide
glyburide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- iloperidone
iloperidone, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- imidapril
imidapril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- indinavir
indinavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- irbesartan
irbesartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- isocarboxazid
isocarboxazid increases effects of insulin glargine by unknown mechanism. Use Caution/Monitor.
- ketotifen, ophthalmic
ketotifen, ophthalmic, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Combination may result in thrombocytopenia (rare). Monitor CBC.
- lanreotide
lanreotide increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.
- levofloxacin
levofloxacin increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- linagliptin
linagliptin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- linezolid
linezolid increases effects of insulin glargine by unknown mechanism. Use Caution/Monitor.
- liraglutide
liraglutide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- lisinopril
lisinopril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- lithium
lithium, insulin glargine. unspecified interaction mechanism. Use Caution/Monitor. Lithium salts may cause either hypoglycemia or hyperglycemia. Insulin dosage adjustment and increased glucose monitoring may be required.
- lixisenatide (DSC)
lixisenatide (DSC), insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypoglycemia increased when coadministered with basal insulins. Basal insulin dose reduction may be required.
- lonapegsomatropin
lonapegsomatropin decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
lonapegsomatropin decreases effects of insulin glargine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone. - lopinavir
lopinavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- losartan
losartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- lurasidone
lurasidone, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- magnesium salicylate
magnesium salicylate increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.
- marijuana
marijuana decreases effects of insulin glargine by pharmacodynamic antagonism. Use Caution/Monitor.
- mecasermin
mecasermin increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Additive hypoglycemic effects.
- metformin
metformin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- methyltestosterone
methyltestosterone increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. It is important to monitor all patients with type 2 diabetes on antidiabetic agents receiving androgens for changes in glycemic control. Potential for hypoglycemia.
- metoclopramide intranasal
metoclopramide intranasal increases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose. Monitor blood glucose and adjust insulin dosage regimen as needed.
- metreleptin
insulin glargine, metreleptin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of metreleptin with insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinide derivatives) may increase risk for hypoglycemia; may require lower dose of insulin or insulin secretagogue.
- miglitol
miglitol, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- moexipril
moexipril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- moxifloxacin
moxifloxacin increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- nadolol
nadolol, insulin glargine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers delay recovery of normoglycemia after insulin induced hypoglycemia; however, they also inhibit insulin secretion, so long term beta blocker Tx may result in reduced glucose tolerance. Insulin induced hypoglycemia may induce hypertension during non selective beta blocker Tx.
- nateglinide
nateglinide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- nelfinavir
nelfinavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- niacin
niacin decreases effects of insulin glargine by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant use of insulin and niacin may require insulin dosage adjustment and increased glucose monitoring.
- octreotide
octreotide increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.
- ofloxacin
ofloxacin increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Quinolone antibiotic administration may result in hyper- or hypoglycemia. Gatifloxacin is most likely to produce dysglycemia; moxifloxacin is least likely.
- olanzapine
olanzapine, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- olmesartan
olmesartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- opuntia ficus indica
opuntia ficus indica increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- paliperidone
paliperidone, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- pasireotide
pasireotide increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.
- pentamidine
pentamidine, insulin glargine. unspecified interaction mechanism. Use Caution/Monitor. Pentamidine may cause either hypoglycemia or hyperglycemia followed by the opposing effect. Insulin dosage adjustment and increased glucose monitoring may be required.
- perindopril
perindopril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- phenelzine
phenelzine increases effects of insulin glargine by unknown mechanism. Use Caution/Monitor.
- pindolol
pindolol, insulin glargine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers delay recovery of normoglycemia after insulin induced hypoglycemia; however, they also inhibit insulin secretion, so long term beta blocker Tx may result in reduced glucose tolerance. Insulin induced hypoglycemia may induce hypertension during non selective beta blocker Tx.
- pioglitazone
insulin glargine increases toxicity of pioglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists).
pioglitazone, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - procarbazine
procarbazine increases effects of insulin glargine by unknown mechanism. Use Caution/Monitor.
- propranolol
propranolol, insulin glargine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers delay recovery of normoglycemia after insulin induced hypoglycemia; however, they also inhibit insulin secretion, so long term beta blocker Tx may result in reduced glucose tolerance. Insulin induced hypoglycemia may induce hypertension during non selective beta blocker Tx.
- pseudoephedrine
pseudoephedrine decreases effects of insulin glargine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.
- quetiapine
quetiapine, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- quinapril
quinapril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- ramipril
ramipril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- rasagiline
rasagiline increases effects of insulin glargine by unknown mechanism. Use Caution/Monitor.
- risperidone
risperidone, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
- ritonavir
ritonavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- rosiglitazone
insulin glargine increases toxicity of rosiglitazone by unknown mechanism. Use Caution/Monitor. Insulin may increase the fluid retention associated with thiazolidinediones (peroxisome proliferator-activated receptor [PPAR]-gamma agonists).
rosiglitazone, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents. - sacubitril/valsartan
sacubitril/valsartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- salsalate
salsalate increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.
- saquinavir
saquinavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- saxagliptin
saxagliptin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- selegiline
selegiline increases effects of insulin glargine by unknown mechanism. Use Caution/Monitor.
- semaglutide
semaglutide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin dose may reduce hypoglycemia risk.
- shark cartilage
shark cartilage increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor. Theoretical interaction.
- sitagliptin
sitagliptin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol
insulin glargine and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- somapacitan
somapacitan decreases effects of insulin glargine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatrogon
somatrogon decreases effects of insulin glargine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatropin
somatropin decreases effects of insulin glargine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- sotagliflozin
sotagliflozin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Hypoglycemia risk increased. Lower dose of insulin may be required.
- sulfadiazine
sulfadiazine increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and sulfonamide antibiotics may require insulin dosage adjustment and increased glucose monitoring.
- sulfamethoxypyridazine
sulfamethoxypyridazine increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Risk of hypoglycemia.
- sulfisoxazole
sulfisoxazole increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and sulfonamide antibiotics may require insulin dosage adjustment and increased glucose monitoring.
- telmisartan
telmisartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- testosterone intranasal
testosterone intranasal increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.
- timolol
timolol, insulin glargine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Non selective beta blockers delay recovery of normoglycemia after insulin induced hypoglycemia; however, they also inhibit insulin secretion, so long term beta blocker Tx may result in reduced glucose tolerance. Insulin induced hypoglycemia may induce hypertension during non selective beta blocker Tx.
- tipranavir
tipranavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .
- tolazamide
tolazamide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- tolbutamide
tolbutamide, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.
- trandolapril
trandolapril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.
- tranylcypromine
tranylcypromine increases effects of insulin glargine by unknown mechanism. Use Caution/Monitor.
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension decreases effects of insulin glargine by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.
- valsartan
valsartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.
- xipamide
xipamide decreases levels of insulin glargine by increasing renal clearance. Use Caution/Monitor.
- ziprasidone
ziprasidone, insulin glargine. Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; monitor glucose levels closely.
Minor (76)
- agrimony
agrimony increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- American ginseng
American ginseng increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- amitriptyline
amitriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- amoxapine
amoxapine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- anamu
anamu increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.
- balsalazide
balsalazide increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.
- bendroflumethiazide
bendroflumethiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- bexarotene
bexarotene increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- budesonide
budesonide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- chlorothiazide
chlorothiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- chlorthalidone
chlorthalidone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- chromium
chromium increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- clomipramine
clomipramine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- clonidine
clonidine, insulin glargine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
clonidine decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. - coenzyme Q10
coenzyme Q10 increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Monitor insulin requirements.
- cornsilk
cornsilk increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- cortisone
cortisone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- cyclopenthiazide
cyclopenthiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- damiana
damiana decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.
- danazol
danazol increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- deflazacort
deflazacort decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- desipramine
desipramine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- devil's claw
devil's claw increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- dexamethasone
dexamethasone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- diflunisal
diflunisal increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.
- doxepin
doxepin increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- elderberry
elderberry increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (in vitro research).
- eucalyptus
eucalyptus increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.
- fludrocortisone
fludrocortisone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- fluoxymesterone
fluoxymesterone increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- fo-ti
fo-ti increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- forskolin
forskolin increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Colenol, a compound found in Coleus root, may stimulate insulin release.
- gotu kola
gotu kola increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
- guanfacine
guanfacine, insulin glargine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
guanfacine decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. - gymnema
gymnema increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- horse chestnut seed
horse chestnut seed increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- hydrochlorothiazide
hydrochlorothiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- hydrocortisone
hydrocortisone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- imipramine
imipramine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- indapamide
indapamide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- isoniazid
isoniazid decreases effects of insulin glargine by unspecified interaction mechanism. Minor/Significance Unknown.
- juniper
juniper increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- lofepramine
lofepramine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- lycopus
lycopus increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (theoretical interaction).
- maitake
maitake increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of hypoglycemia (animal research).
- maprotiline
maprotiline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- mesalamine
mesalamine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.
- mesterolone
mesterolone increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- methylprednisolone
methylprednisolone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- metolazone
metolazone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
- nettle
nettle increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction).
- nortriptyline
nortriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- ofloxacin
ofloxacin, insulin glargine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Potential dysglycemia.
- oxandrolone
oxandrolone increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- oxymetholone
oxymetholone increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- panax ginseng
panax ginseng increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- pegvisomant
pegvisomant increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- potassium acid phosphate
potassium acid phosphate increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- potassium chloride
potassium chloride increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- potassium citrate
potassium citrate increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Interaction especially seen in the treatment of hypokalemia.
- prednisolone
prednisolone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- prednisone
prednisone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown.
- protriptyline
protriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- sage
sage increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- salicylates (non-asa)
salicylates (non-asa) increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.
- Siberian ginseng
Siberian ginseng increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- sulfasalazine
sulfasalazine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.
- testosterone
testosterone increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- testosterone buccal system
testosterone buccal system increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- testosterone topical
testosterone topical increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- tongkat ali
tongkat ali increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypoglycemia.
- trazodone
trazodone increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- trimipramine
trimipramine increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- vanadium
vanadium increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.
- willow bark
willow bark increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.
Adverse Effects
>10%
Documented symptomatic hypoglycemia (25.6-40%)
1-10%
Nausea (10%)
Nasopharyngitis (7%)
Diarrhea (7%)
Upper respiratory tract infection (5.5%)
Headache (5.4%)
Severe symptomatic hypoglycemia (1.1%)
Injection site reactions (1.7%)
<1%
Anaphylaxis
Frequency Not Defined
Lipodystrophy
Peripheral edema
Weight gain
Immunogenicity
Localized cutaneous amyloidosis at the injection site
Hepatobiliary: Cholecystitis, cholelithiasis requiring cholecystectomy
Warnings
Contraindications
During episodes of hypoglycemia
Hypersensitivity to either of the active drugs or any excipients
Cautions
Anaphylaxis reported; severe, life-threatening, generalized allergic reactions, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock reported; inform and closely monitor patients with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist for allergic reactions; unknown whether such patients will be predisposed to anaphylaxis
Acute events of gallbladder disease such as cholelithiasis or cholecystitis reported in GLP-1 receptor agonist trials and postmarketing; if cholelithiasis suspected, gallbladder studies and appropriate clinical follow-up are indicated
Do not share insulin pens between patients
Caution when changing dosage regimens; increase frequency of blood glucose monitoring to detect hypoglycemia or hyperglycemia
Do not exceed maximum dose or use with other GLP-1 agonists or basal insulins
No clinical studies have established conclusive evidence of macrovascular risk reduction with any antidiabetic drugs
Kidney injury
- Acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, has been reported post marketing in patients treated with the 100/33 formulation
- Some of these events were reported in patients without known underlying renal disease; majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration
- Monitor renal function when initiating or escalating doses of the 100/33 formulation in patients with renal impairment and in patients reporting severe gastrointestinal reactions
- Advise patients of potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid fluid depletion; the 100/33 formulation is not recommended in patients with end-stage renal disease
Medication errors
- The 100/33 formulation contains two drugs: insulin glargine and lixisenatide; daily administration of more than 60 units of the 100/33 formulation can result in overdose of the lixisenatide component
- Do not exceed the 20-mcg maximum recommended dose of lixisenatide or use with other glucagonlike peptide-1 receptor agonists
- Accidental mix-ups between insulin products reported; to avoid medication errors between the 100/33 formulation and other insulins, instruct patients to always check the insulin label before each injection
Immunogenicity
- Patients may develop antibodies to insulin and lixisenatide following treatment
- Attenuated glycemic response reported in patients with the highest antibody concentrations (>100 nmol/L); a higher incidence of allergic reactions and injection-site reactions reported in antibody positive patients
- Consider alternative antidiabetic therapy if there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection-site reactions or allergic reactions
Pancreatitis
- Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, reported postmarketing
- After initiation therapy, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting)
- If pancreatitis suspected, promptly discontinue therapy and initiate appropriate management; if confirmed, restarting drug not recommended; consider antidiabetic therapies other than this drug in patients with a history of pancreatitis
Hypokalemia
- All insulin-containing products, including the 100/33 formulation, cause a shift in potassium from extracellular to intracellular space, possibly leading to hypokalemia
- Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death; monitor potassium levels in patients at risk for hypokalemia if indicated (eg, patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations)
Fluid retention
- Increased risk of fluid retention and CHF with coadministration of peroxisome proliferator-activated receptor (PPAR)-gamma agonists (eg, thiazolidinediones)
- Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin-containing products
- Fluid retention may lead to or exacerbate heart failure; patients treated with the 100/33 formulation and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure
- If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered
Hyperglycemia or hypoglycemia with changes in insulin regimen
- Changes in insulin, insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia
- Hypoglycemia is the most common adverse effect of insulin; self-monitoring of blood glucose is essential to prevent and manage hypoglycemia
- Severe hypoglycemia can cause seizures, may be life-threatening or cause death
- Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (eg, driving or operating other machinery
- Changes should be made cautiously and only under close medical supervision and frequency of blood glucose monitoring should be increased
- Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis reported to result in hyperglycemia; a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia
- Insulin, should not be used during episodes of hypoglycemia; hypoglycemia can happen suddenly, and symptoms may differ in each individual and change over time in the same individual
- Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring
- Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, or in patients who experience recurrent hypoglycemia
- Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change injection site to unaffected areas and closely monitor for hypoglycemia
- Risk of hypoglycemia generally increases with intensity of glycemic control; risk of hypoglycemia after an injection is related to duration of action of insulin and, in general, is highest when glucose lowering effect of insulin is maximal
- As with all insulin-containing preparations, the glucose lowering effect time course of the 100/33 formulation may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection-site blood supply and temperature
- Other factors which may increase the risk of hypoglycemia include changes in meal pattern (eg, macronutrient content or timing of meals), changes in level of physical activity, or changes to coadministered medication; patients with renal or hepatic impairment may be at higher risk of hypoglycemia
- Patients and caregivers must be educated to recognize and manage hypoglycemia; self-monitoring of blood glucose plays an essential role in prevention and management of hypoglycemia; in patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring recommended
- The long-acting effect of insulin glargine may delay recovery from hypoglycemia
- For patients with type 2 diabetes, dosage adjustments in concomitant oral antidiabetic treatment may be needed
Drug interaction overview
-
Drugs that may increase hypoglycemia risk
- May require dose reduction and increased glucose monitoring frequency if coadministered with drugs that cause hypoglycemia
- Examples include antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (eg, octreotide), and sulfonamide antibiotics
-
Drug that may decrease blood glucose-lowering effect of lixisenatide/insulin glargine
- May require dose increase and increased glucose monitoring frequency if coadministered with drugs that increase blood glucose
- Examples include atypical antipsychotics (eg, olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (eg, in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (eg, albuterol, epinephrine, terbutaline), and thyroid hormones
-
Drugs that may increase or decrease the blood glucose-lowering effects of lixisenatide/insulin glargine
- Dose adjustment in increased blood glucose monitoring may be required
- Examples include alcohol, beta-blockers, clonidine, and lithium salts; pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia
-
Drugs that may blunt signs and symptoms of hypoglycemia
- Increase frequency of blood glucose monitoring
- Examples include beta-blockers, clonidine, guanethidine, and reserpine
Pregnancy
Pregnancy
Based on animal reproduction studies, there may be risks to the fetus from exposure to lixisenatide during pregnancy
Use during pregnancy only if the potential benefit justifies the potential risk to the fetus
There are no available data with use in pregnant women to inform a drug-associated risk for major birth defects or miscarriage
There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Lixisenatide: Incretin mimetic; analogue of human glucagonlike peptide-1 (GLP-1); acts as GLP-1 receptor agonist to augment glucose-dependent insulin secretion, decreases glucagon secretion, and slows gastric emptying
Insulin glargine: Basal insulin analog; insulin lowers 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; targets include skeletal muscle, liver, and adipose tissue
Absorption
Peak plasma time (lixisenatide): 2.5-3 hr
Distribution
Protein bound (lixisenatide): 55%
Metabolism
Insulin glargine: Partly metabolized at the carboxyl terminus of the B chain in the subcutaneous depot to form 2 active metabolites with in vitro activity similar to that of human insulin
Lixisenatide: Presumed to be eliminated through glomerular filtration and proteolytic degradation
Elimination
Half-life (lixisenatide): 3 hr
Clearance (lixisenatide): 35 L/hr
Administration
SC Administration
The pen delivers 15-60 units of insulin glargine with each injection
Administer SC once daily within 1 hr prior to the first meal of the day
Inject SC in thigh, upper arm, or abdomen
Rotate injection site within the same region from 1 injection to the next to reduce lipodystrophy risk
Do not administer IV, IM, or by infusion pump
Do not dilute or mix with any other insulin products or solutions
Do not split the dose
Missed doses
- Resume the once-daily regimen as prescribed with the next scheduled dose
- Do not administer an extra dose or increase the dose to make up for the missed dos
Storage
Prior to first use
- Refrigerate between 36-46°F (2-8°C)
- Do not freeze; discard if it has been frozen
- Protect from light
After first use
- Store at room temperature below 86°F (30°C)
- Replace the pen cap after each use to protect from light
- Discard pen 14 days after first use
- Always remove the needle after each injection and store the pen without a needle attached; this prevents contamination and/or infection, or leakage of the pen, and ensures accurate dosing
- Always use a new needle for each injection to prevent contamination
Images
Formulary
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