SOLIQUA 100/33 VIDEO

    NARRATOR:

    SOLIQUA 100/33 insulin glargine and lixisenatide injection 100 Units per mL and 33 mcg per mL is a combination of a long-acting human insulin analog with a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

    Limitations of Use:

    • Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
    • Not recommended for use in combination with any other product containing a GLP-1 receptor agonist.
    • Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
    • Not recommended for use in patients with gastroparesis.
    • Has not been studied in combination with prandial insulin.

    SOLIQUA 100/33 is contraindicated:

    • During episodes of hypoglycemia.
    • In patients with known hypersensitivity to the active substance(s) or to any of the product components.

    CHAPTER ONE: EPIDEMIOLOGY
    SUPER:
    CHAPTER ONE:
     EPIDEMIOLOGY
    CHAPTER TWO: PIVOTAL AND POST HOC EFFICACY
    CHAPTER THREE: SAFETY
    CHAPTER FOUR: TITRATION
    CHAPTER FIVE: SUMMARY
    CHAPTER SIX: IMPORTANT SAFETY INFORMATION
    DR. JEREMY PETTUS:
    Hello, I’m Dr. Jeremy Pettus and I’m excited to share with you results from a clinical trial that provide compelling evidence for the use of SOLIQUA 100/33 in adult type 2 diabetes patients, including those with an A1C greater than or equal to 9 percent.
    ON-SCREEN TEXT:
    Jeremy Pettus, MD
    Assistant Professor of Medicine
    Division of Endocrinology
    University of California, San Diego
    DR. JEREMY PETTUS:
    SOLIQUA 100/33 was approved to treat patients uncontrolled on basal insulin or lixisenatide as an adjunct to diet and exercise—and was shown to provide effective A1C lowering with a single daily injection.
    In 2019, the SOLIQUA 100/33 label was updated to include an expanded indication as an adjunct to diet and exercise. This label expansion could support the use of SOLIQUA 100/33 as a first injectable.
    So, let’s begin with an interesting statistic.
    Despite the current clinical recommendations and growing number of treatment options for type 2 diabetes, 8.2 million adult patients have an A1C that’s 9 percent or higher.
    Used individually, GLP-1 RA or basal insulin, even in combination with metformin, may not be enough to get patients to goal.
    ON-SCREEN TEXT:
    THE CURRENT AACE/ACE AND ADA GUIDELINES RECOMMEND EARLY COMBINATION THERAPY BE CONSIDERED IN PATIENTS WITH A1C ≥9% OR 1.5%-2% ABOVE TARGET, RESPECTIVELY
    CHAPTER TWO: PIVOTAL AND POST HOC EFFICACY
    ON-SCREEN TEXT:
    Do you consider a simultaneous treatment like SOLIQUA 100/33 after OADs for appropriate patients?
    Yes
    No
    SOLIQUA 100/33 is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
    DR. JEREMY PETTUS:
    Let’s take a look at the SOLIQUA 100/33 data to see how it may help these patients.
    The LixiLan-O trial was designed to evaluate the effect of SOLIQUA 100/33 in a population of insulin-naive patients uncontrolled on metformin with or without another OAD, including those with A1C greater than 9 percent.
    In this study, eligible adult patients with type 2 diabetes were enrolled in a run-in period, during which they stopped taking any OADs beyond metformin, and they were titrated to a daily metformin dose of 2 thousand milligrams or the maximum tolerated dose. At the end of the run-in period, 1170 patients still inadequately controlled were randomized to either SOLIQUA 100/33, Lantus, or the GLP-1 RA lixisenatide (while they continued taking metformin). Mean A1C at baseline was 8.1% and the primary endpoint was mean change in A1C from baseline to Week 30. The maximum dose of insulin glargine allowed in the study was 60 Units for both the SOLIQUA 100/33 and Lantus groups. The trial was designed to show the contribution of the GLP-1 component to glycemic lowering, and the insulin glargine dose and the dosing algorithm were selected to isolate the effect of the GLP-1 component.
    Now, here’s where it gets interesting.
    Study results from this pivotal trial showed that SOLIQUA 100/33 significantly reduced A1C over 30 weeks.
    SOLIQUA 100/33 lowered A1C from a mean baseline of 8.1% to 6.5%, compared to only 7.3% with the GLP-1 RA lixisenatide and 6.8% with Lantus, showing statistical significance with a p-value of ≤0.0001. Of note, the final mean basal insulin dose was similar between SOLIQUA 100/33 and Lantus, 39.8 Units and 40.5 Units respectively, determined by the FPG titration.
    Note, results observed in this trial may not reflect the effect that will be observed in the care setting.
    What I also find interesting are the results of a post hoc subgroup analysis of patients with a baseline A1C of 9 percent or greater.|
    The A1C reduction seen with SOLIQUA 100/33 suggests it can be an option for patients with high A1C and could be considered as an option versus a stepwise approach of a GLP-1 RA with basal insulin added sequentially, or vice versa.
    ON-SCREEN TEXT:
    SOLIQUA 100/33 demonstrated efficacy for patients with high A1C (≥9%) 
    and can be considered after OADs for appropriate patients
    DR. JEREMY PETTUS:
    In this subgroup of patients with high A1C, SOLIQUA 100/33 reduced A1C by 2.9%, vs 1.7% with the GLP-1 RA lixisenatide and 2.5% with Lantus. This post hoc subgroup analysis of the LixiLan-O clinical trial evaluated patients with a baseline A1C between 9% and 10.4%. Doses were similar between SOLIQUA 100/33 (45 Units) and Lantus (44 Units).
    This study was not designed or powered to detect differences between treatments within this subgroup. Analysis included limited sample size, N=134. P-values are for descriptive purposes only without multiplicity adjustments. Results observed in this trial may not reflect the effect that will be observed in the care setting.
    How did this A1C lowering translate into helping high A1C patients get to goal? Let’s see.
    In the same post hoc analysis of patients with A1C of 9 percent or greater, SOLIQUA 100/33 helped 73.5% get to goal, compared with 47.3% of those taking Lantus and 0% of patients taking the GLP-1 RA lixisenatide. That is nearly 3 out of 4 patients. Please note the analysis limitations we just mentioned.
    These figures support the use of injectable combination therapy, such as SOLIQUA 100/33, in patients with high A1C uncontrolled on 2 or more OADs.
    ON-SCREEN TEXT:
    Are you SOLIQUA 100/33 SMART?
    In post-hoc analysis, what was the reduction in A1C for SOLIQUA 100/33 in patients with A1C ≥9%?
    A. 1.5%
    B. 2.9%
    C. 3.5%
    B. 2.9% is the correct answer
    Study was not designed or powered to detect differences between treatments within this subgroup.
    CHAPTER THREE: SAFETY
    DR. JEREMY PETTUS:
    In my practice, I continually monitor and adjust therapy until my patients achieve a target A1C of less than 7 percent, and I frequently prescribe SOLIQUA 100/33 to appropriate patients when 2 OADs are insufficient in getting patients to goal.
    One of the key obstacles in getting patients with high A1C to goal can be the adverse events associated with antidiabetic treatments. Let’s take a look at the SOLIQUA 100/33 safety data.
    SOLIQUA 100/33 demonstrated safety and tolerability in patients uncontrolled on OADs. In the pivotal study, the incidence of severe hypoglycemia was 0% with SOLIQUA 100/33 and the incidence of symptomatic hypoglycemia – defined as plasma glucose less than 54 milligrams per deciliter — was 8.1%.
    Hypoglycemia is the most common adverse event with insulin-containing therapy.
    ON-SCREEN TEXT:
    Severe symptomatic hypoglycemia defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
    Hypoglycemia defined as self-monitored plasma glucose <54 mg/dl.
    DR. JEREMY PETTUS:
    Overall, treatment-emergent adverse events with a frequency 5% or greater included nausea, diarrhea, upper respiratory tract infection, nasopharyngitis, and headache.
    We know that with the GLP-1 RAs in particular, GI adverse events can be problematic, so let’s take a closer look at the GI numbers and see how SOLIQUA 100/33 compared with the GLP-1 RA lixisenatide.
    As you can see here, patients were 5 times less likely to discontinue SOLIQUA 100/33 due to GI side effects vs the GLP-1 RA lixisenatide. 0.9% of patients discontinued SOLIQUA 100/33 due to GI side effects vs 5.2% for the GLP-1 RA lixisenatide. The incidence of nausea was less than 10% with SOLIQUA 100/33 compared to 24% with the GLP-1 RA lixisenatide. The incidence of diarrhea was the same and the incidence of vomiting was 3.2% with SOLIQUA 100/33 compared to 6.4% with the GLP-1 RA lixisenatide. These data suggest that SOLIQUA 100/33 offers a tolerable GI profile.
    CHAPTER FOUR: TITRATION
    ON-SCREEN TEXT:
    Are you SOLIQUA 100/33 SMART?
    In the pivotal study, what did gradual titration of both basal insulin and GLP-1 RA potentially offer?
    A. Mitigation of GI adverse events
    B. Lower discontinuation due to GI adverse events
    C. Both A & B
    C. Both A & B is the correct answer
    DR. JEREMY PETTUS:
    The administration of SOLIQUA 100/33 is different from the GLP-1 RA lixisenatide and allows for the gradual titration of the GLP-1 RA along with the basal insulin. Using small increments—as small as three-tenths of a microgram—to titrate the GLP-1 RA may help mitigate the risk of GI adverse events. With GLP-1 RAs, there’s only 2 or 3 dose steps, so it’s challenging to slowly titrate GLP-1 RA therapy to help mitigate GI side effects.
    CHAPTER FIVE: SUMMARY
    DR. JEREMY PETTUS:
    In summary, here are the key trial results that we reviewed.
    In patients with A1C of 9 percent or higher, uncontrolled on oral therapy, SOLIQUA 100/33 offers effective A1C lowering to help get patients to goal. In a pivotal trial of patients uncontrolled on oral therapy, 74% of patients got to goal (below 7 percent) with SOLIQUA 100/33, vs 33% with GLP-1 RA lixisenatide and 59% with Lantus. In a post hoc subgroup analysis of patients with high A1C between 9 percent and 10.4 percent, SOLIQUA 100/33 was shown to reduce A1C by 2.9%. This analysis (N=134) was not powered to detect the differences between treatment arms. From a tolerability perspective, patients were 5 times less likely to discontinue SOLIQUA 100/33 due to GI side effects vs the GLP-1 RA lixisenatide. 0.9% of patients discontinued SOLIQUA 100/33 due to GI side effects vs 5.2% of the GLP-1 RA lixisenatide. The most common GI side effects include nausea (9.6%), diarrhea (9.0%), and vomiting (3.2%). The incidence of severe symptomatic hypoglycemia was 0%; hypoglycemia was 8.1%. These data support the use of initial injectable therapy with SOLIQUA 100/33 in patients with high A1C. In addition to A1C lowering proven to help get patients to goal, SOLIQUA 100/33 has a demonstrated safety and tolerability profile.
    To learn more about SOLIQUA 100/33 in patients with high A1C, visit SOLIQUAPRO.com or talk to your Sanofi representative.
    ON-SCREEN TEXT:
    ADULT PATIENTS WITH A1C ≥9% UNCONTROLLED ON OAD THERAPY
    CHOOSE SOLIQUA 100/33 FOR THE POWER TO GET TO GOAL
    Are you SOLIQUA 100/33 SMART?
    Based on the clinical data you just saw, would you consider SOLIQUA 100/33 as the FIRST injectable for patients with A1C ≥9%?
    Yes
    No
    Thank you.
    For full clinical profile of SOLIQUA 100/33, please visit SOLIQUAPRO.com
    CHAPTER SIX: IMPORTANT SAFETY INFORMATION
    NARRATOR:
    SOLIQUA 100/33 is a combination of a long-acting human insulin analog with a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
    Limitations of Use:

    • Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
    • Not recommended for use in combination with any other product containing a GLP-1 receptor agonist.
    • Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
    • Not recommended for use in patients with gastroparesis.
    • Has not been studied in combination with prandial insulin.

    Important Safety Information for SOLIQUA® 100/33 (insulin glargine and lixisenatide injection) 100 Units/mL and 33 mcg/mL
    Contraindications

    • During episodes of hypoglycemia.
    • In patients with known hypersensitivity to the active substance(s) or to any of the product components.

    Warnings and Precautions

    • Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, life-threatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.
    • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.
    • Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.
    • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed.

      Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.

    • Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.
    • Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.
    • Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with GLP-1 RAs, such as lixisenatide. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.
    • Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.
    • Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.
    • Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.
    • Macrovascular Outcomes: Clinical studies have not shown macrovascular risk reduction with SOLIQUA 100/33.

    Most Common Adverse Reactions

    The most common adverse reactions reported in ≥5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache.

    Drug Interactions

    • Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
    • The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta-blockers, clonidine, guanethidine, and reserpine).
    • The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
    • Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
    • Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.

    ON-SCREEN TEXT:
    Please click the button to the right for full Prescribing Information.
    References

    1. Davies MJ, Russell-Jones D, Barber TM, et al. Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial. Diabetes Obes Metab. 2019;21:1967-1972. doi:10.1111/dom.13791.

    2. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2017.

    3. HEDIS Measures and Technical Resources. Comprehensive Diabetes Care National Committee for Quality Assurance. 2019. Washington, DC. Available at https://www.ncqa.org/hedis/measures/comprehensive-diabetes-care. Accessed June 4, 2019.

    4. Singhal M, Unni S, Schauerhamer M, et al. Real-world glycemic control from GLP-1 RA therapy with and without concurrent insulin in patients with type 2 diabetes.J Manag Care Spec Pharm. 2017;23(3):267-275.

    5. Mocarski M, Yeaw J, Divino V, et al. Slow titration and delayed intensification of basal insulin among patients with type 2 diabetes. J Manag Care Spec Pharm. 2018;24(4):390-400.

    6. American Diabetes Association. Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl 1): S1-S193. doi:10.2337/dc19-S009.

    7. SOLIQUA 100/33 Prescribing Information.

    8. Rosenstock J, Aronson R, Grunberger G, et al. Benefits of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide, vs insulin glargine and lixisenatide monocomponents in type 2 diabetes inadequately controlled on oral agents: the Lixilan-O randomized trial. Diabetes Care. 2016;39(11):2026-2035. doi:10.2337/dc16-0917.

    9. Data on file. CSR 12404. Sanofi US.

    SOLIQUAPRO.com
    MAT-US-2016065-v1.0-10/2020

SOLIQUA 100/33 dosing guide

SOLIQUA 100/33 samples

SOLIQUA 100/33 is a combination of a long-acting human insulin analog with a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Limitations of Use:

  • Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • Not recommended for use in combination with any other product containing a GLP-1 receptor agonist.
  • Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
  • Not recommended for use in patients with gastroparesis.
  • Has not been studied in combination with prandial insulin.

Important Safety Information

Important Safety Information

Important Safety Information for SOLIQUA 100/33 (insulin glargine and lixisenatide) injection 100 Units/mL and 33 mcg/mL

Contraindications

  • During episodes of hypoglycemia.
  • In patients with known serious hypersensitivity to insulin glargine, lixisenatide, or to any of the product components.

Warnings and Precautions

  • Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, lifethreatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine. There have been reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.
  • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.
  • Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.
  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously, and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed.
    Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.
  • Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.
  • Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.
  • Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.
  • Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.
  • Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.
  • Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.

Most Common Adverse Reactions
The most common adverse reactions reported in ≥ 5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache.

Drug Interactions

  • Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
  • The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta- blockers, clonidine, guanethidine, and reserpine).
  • The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
  • Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
  • Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.

Important Safety Information

Important Safety Information

Important Safety Information for SOLIQUA 100/33 (insulin glargine and lixisenatide) injection 100 Units/mL and 33 mcg/mL

Contraindications

  • During episodes of hypoglycemia.
  • In patients with known serious hypersensitivity to insulin glargine, lixisenatide, or to any of the product components.

Warnings and Precautions

  • Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, lifethreatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine. There have been reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.
  • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.
  • Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.
  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously, and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed.
    Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.
  • Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.
  • Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.
  • Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.
  • Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.
  • Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.
  • Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.

Most Common Adverse Reactions
The most common adverse reactions reported in ≥ 5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache.

Drug Interactions

  • Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
  • The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta- blockers, clonidine, guanethidine, and reserpine).
  • The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
  • Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
  • Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.