Soliqua
(insulin glargine / lixisenatide)Dosage & Administration
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Soliqua Prescribing Information
SOLIQUA 100/33 is a combination of insulin glargine and lixisenatide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Limitations of Use:
- SOLIQUA 100/33 has not been studied in patients with a history of pancreatitis [see Warnings and Precautions (5.2)]. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- SOLIQUA 100/33 is not recommended for use in combination with any other product containing a GLP-1 receptor agonist [see Warnings and Precautions (5.5)].
- SOLIQUA 100/33 is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
- SOLIQUA 100/33 has not been studied in patients with gastroparesis and is not recommended in patients with gastroparesis.
- SOLIQUA 100/33 has not been studied in combination with prandial insulin.
Important Dosage Information
- SOLIQUA 100/33 is a combination of insulin glargine and lixisenatide.
- Administer SOLIQUA 100/33 subcutaneously once a day within the hour prior to the first meal of the day.
- The SOLIQUA 100/33 pen delivers doses from 15 to 60 units in a single injection. Table 1 presents the units of insulin glargine and the micrograms of lixisenatide in each dosage of SOLIQUA 100/33 [see Dosage and Administration (2.2)].
- The maximum dose of SOLIQUA 100/33 is 60 units daily (60 units insulin glargine and 20 mcg lixisenatide) [see Warnings and Precautions (5.5)].
Recommended Starting Dose
In patients naive to basal insulin or to a GLP-1 receptor agonist, currently on a GLP-1 receptor agonist or currently on less than 30 units of basal insulin daily:
- Discontinue therapy with basal insulin or a GLP-1 receptor agonist prior to initiation of SOLIQUA 100/33.
- The recommended starting dosage of SOLIQUA 100/33 is 15 units (15 units insulin glargine and 5 mcg lixisenatide) given subcutaneously once daily.
In patients currently on 30 to 60 units of basal insulin daily, with or without a GLP-1 receptor agonist:
- Discontinue therapy with basal insulin or GLP-1 receptor agonist prior to initiation of SOLIQUA 100/33.
- The recommended starting dosage of SOLIQUA 100/33 is 30 units (30 units insulin glargine and 10 mcg lixisenatide) given subcutaneously once daily.
| SOLIQUA 100/33 (dose window display) * | Insulin glargine component dose | Lixisenatide component dose | Comment |
|---|---|---|---|
| |||
| 2 | --- | --- | Safety test dose – not for injection |
| 15 | 15 units | 5 mcg | Recommended starting dosage for patients naive to basal insulin or GLP-1 receptor agonist, currently on GLP-1 receptor agonist, or currently on less than 30 units of basal insulin daily |
| 16 | 16 units | 5.3 mcg | |
| 17 | 17 units | 5.7 mcg | |
| 18 | 18 units | 6 mcg | |
| 19 | 19 units | 6.3 mcg | |
| 20 | 20 units | 6.7 mcg | |
| 21 | 21 units | 7 mcg | |
| 22 | 22 units | 7.3 mcg | |
| 23 | 23 units | 7.7 mcg | |
| 24 | 24 units | 8 mcg | |
| 25 | 25 units | 8.3 mcg | |
| 26 | 26 units | 8.7 mcg | |
| 27 | 27 units | 9 mcg | |
| 28 | 28 units | 9.3 mcg | |
| 29 | 29 units | 9.7 mcg | |
| 30 | 30 units | 10 mcg | Recommended starting dosage for patients currently on 30 to 60 units of basal insulin daily, with or without a GLP-1 receptor agonist: |
| 31 | 31 units | 10.3 mcg | |
| 32 | 32 units | 10.7 mcg | |
| 33 | 33 units | 11 mcg | |
| 34 | 34 units | 11.3 mcg | |
| 35 | 35 units | 11.7 mcg | |
| 36 | 36 units | 12 mcg | |
| 37 | 37 units | 12.3 mcg | |
| 38 | 38 units | 12.7 mcg | |
| 39 | 39 units | 13 mcg | |
| 40 | 40 units | 13.3 mcg | |
| 41 | 41 units | 13.7 mcg | |
| 42 | 42 units | 14 mcg | |
| 43 | 43 units | 14.3 mcg | |
| 44 | 44 units | 14.7 mcg | |
| 45 | 45 units | 15 mcg | |
| 46 | 46 units | 15.3 mcg | |
| 47 | 47 units | 15.7 mcg | |
| 48 | 48 units | 16 mcg | |
| 49 | 49 units | 16.3 mcg | |
| 50 | 50 units | 16.7 mcg | |
| 51 | 51 units | 17 mcg | |
| 52 | 52 units | 17.3 mcg | |
| 53 | 53 units | 17.7 mcg | |
| 54 | 54 units | 18 mcg | |
| 55 | 55 units | 18.3 mcg | |
| 56 | 56 units | 18.7 mcg | |
| 57 | 57 units | 19 mcg | |
| 58 | 58 units | 19.3 mcg | |
| 59 | 59 units | 19.7 mcg | |
| 60 | 60 units | 20 mcg | Maximum daily dosage [see Warnings and Precautions (5.5)] |
Titration of SOLIQUA 100/33
- After starting with the recommended dosage of SOLIQUA 100/33, [see Dosage and Administration (2.2)], titrate the dosage upwards or downwards by two to four units (see Table 2) 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 changes in physical activity, meal patterns (i.e., macronutrient content or timing of food intake), or renal or hepatic function; during acute illness; or when used with other medications [see Warnings and Precautions (5.4) and Drug Interactions (7)].
| Self-Monitored Fasting Plasma Glucose | SOLIQUA 100/33 Dosage Adjustment |
|---|---|
| |
| Above target range | +2 units (2 units of insulin glargine and 0.66 mcg of lixisenatide) to +4 units (4 units of insulin glargine and 1.32 mcg of lixisenatide) |
| Within target range | 0 units |
| Below target range | -2 units (2 units of insulin glargine and 0.66 mcg of lixisenatide) to -4 units (4 units of insulin glargine and 1.32 mcg of lixisenatide) |
Missed Doses
Instruct patients who miss a dose of SOLIQUA 100/33 to 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 dose.
Important Administration Instructions
- The SOLIQUA 100/33 prefilled pen is for single-patient-use only [see Warnings and Precautions (5.3)].
- Train patients on proper use and injection technique before initiating SOLIQUA 100/33.
- Always check the SOLIQUA 100/33 label before administration [see Warnings and Precautions (5.5)].
- Visually inspect for particulate matter and discoloration prior to administration. Only use SOLIQUA 100/33 if the solution is clear and colorless to almost colorless.
- Inject SOLIQUA 100/33 subcutaneously into the abdominal area, thigh, or upper arm.
- Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions (5.2), Adverse Reactions (6)].
- During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions (5.4)].
- Do not administer intravenously or via an insulin pump.
- Use SOLIQUA 100/33 with caution in patients with visual impairment who may rely on audible clicks to dial their dose.
- The SOLIQUA 100/33 pen dials in 1-unit increments.
- Do not dilute or mix SOLIQUA 100/33 with any other insulin or solution.
- Do not split the dose of SOLIQUA 100/33.
SOLIQUA 100/33 is a clear, colorless to almost colorless solution available as:
Injection: 100 units of insulin glargine and 33 mcg of lixisenatide per mL in a 3 mL prefilled, disposable, single-patient-use SoloStar® pen.
Pregnancy
Risk Summary
Based on animal reproduction studies, there may be risks to the fetus from exposure to lixisenatide, a component of SOLIQUA 100/33, during pregnancy. SOLIQUA 100/33 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
The limited available data with SOLIQUA 100/33 and lixisenatide in pregnant women is not sufficient to inform a drug-associated risk of major birth defects and miscarriage. Published studies with insulin glargine use during pregnancy have not reported a clear association with insulin glargine and major birth defect or miscarriage risk [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations].
Lixisenatide administered to pregnant rats and rabbits during organogenesis was associated with visceral closure and skeletal defects at systemic exposures that decreased maternal food intake and weight gain during gestation, and that are 1-time and 6-times higher than the 20 mcg/day highest clinical dose, respectively, based on plasma AUC [see Data].
The estimated background risk of major birth defects is 6%–10% in women with pregestational diabetes with a HbA1c >7 and has been reported to be as high as 20%–25% in women with a HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.
Clinical considerations
Disease-associated maternal and/or embryo/fetal risk
Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.
Data
Human data
Insulin glargine
Published data do not report a clear association with insulin glargine and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin glargine is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations including small sample size and some lacking comparator groups.
Animal data
Animal reproduction studies were not conducted with the combined products in SOLIQUA 100/33. The following data are based on studies conducted with the individual components of SOLIQUA 100/33.
Lixisenatide
In pregnant rats receiving twice daily subcutaneous doses of 2.5, 35, or 500 mcg/kg during organogenesis (gestation day 6 to 17), fetuses were present with visceral closure defects (e.g., microphthalmia, bilateral anophthalmia, diaphragmatic hernia) and stunted growth. Impaired ossification associated with skeletal malformations (e.g., bent limbs, scapula, clavicle, and pelvis) were observed at ≥2.5 mcg/kg/dose, resulting in systemic exposure that is 1-time the 20 mcg/day clinical dose, based on plasma AUC. Decreases in maternal body weight, food consumption, and motor activity were observed concurrent with the adverse fetal findings, which confounds the interpretation of relevance of these malformations to the human risk assessment. Placental transfer of lixisenatide to developing rat fetuses is low with a concentration ratio in fetal/maternal plasma of 0.1%.
In pregnant rabbits receiving twice daily subcutaneous doses of 2.5, 25, 250 mcg/kg during organogenesis (gestation day 6 to 18), fetuses were present with multiple visceral and skeletal malformations, including closure defects, at ≥5 mcg/kg/day or systemic exposures that are 6-times the 20 mcg/day highest clinical dose, based on plasma AUC. Decreases in maternal body weight, food consumption, and motor activity were observed concurrent with the fetal findings, which confounds the interpretation of relevance of these malformations to the human risk assessment. Placental transfer of lixisenatide to developing rabbit fetuses is low with a concentration ratio in fetal/maternal plasma of ≤0.3%. In a second study in pregnant rabbits, no drug-related malformations were observed from twice daily subcutaneous doses of 0.15, 1.0, and 2.5 mcg/kg administered during organogenesis, resulting in systemic exposures up to 9-times the clinical exposure at 20 mcg/day, based on plasma AUC.
In pregnant rats given twice daily subcutaneous doses of 2, 20, or 200 mcg/kg from gestation day 6 through lactation, decreases in maternal body weight, food consumption, and motor activity were observed at all doses. Skeletal malformations and increased pup mortality were observed at 400 mcg/kg/day, which is approximately 200-times the 20 mcg/day clinical dose based on mcg/m2.
Insulin glargine
Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. Insulin glargine was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 2-times the recommended human subcutaneous high dose of 60 units/day (0.0364 mg/kg/day), based on mg/m2. In rabbits, doses up to 0.072 mg/kg/day, which is approximately 1-time the maximum recommended human subcutaneous dose of 60 units/day (0.0364 mg/kg/day), based on mg/m2, were administered during organogenesis. The effects of insulin glargine did not generally differ from those observed with regular human insulin in rats or rabbits. However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal.
Lactation
Risk Summary
There is no information regarding the presence of lixisenatide and insulin glargine in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous insulin is present in human milk. Lixisenatide is present in rat milk [see Data].
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SOLIQUA 100/33 and any potential adverse effects on the breastfed child from SOLIQUA 100/33 or from the underlying maternal condition.
Data
Lixisenatide
A study in lactating rats showed low (9.4%) transfer of lixisenatide and its metabolites into milk and negligible (0.01%) levels of unchanged lixisenatide protein in the gastric contents of weaning offspring.
Pediatric Use
Safety and effectiveness of SOLIQUA 100/33 have not been established in pediatric patients.
Geriatric Use
Of the total number of subjects (n=834) in controlled clinical studies of patients with type 2 diabetes, who were treated with SOLIQUA 100/33, 25.2% (n=210) were ≥65 years of age and 4% (n=33) were ≥75 years of age. No overall differences in effectiveness and safety were observed in the subgroup analyses across the age groups.
Nevertheless, caution should be exercised when SOLIQUA 100/33 is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly.
Renal Impairment
Frequent glucose monitoring and dose adjustment may be necessary for SOLIQUA 100/33 in patients with renal impairment [see Warnings and Precautions (5.7)].
Insulin Glargine
Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure.
Lixisenatide
In patients with mild and moderate renal impairment no dose adjustment is required but close monitoring for lixisenatide related adverse reactions and for changes in renal function is recommended because of higher incidences of hypoglycemia, nausea and vomiting that were observed in these patients. Increased gastrointestinal adverse reactions may lead to dehydration and acute renal failure and worsening of chronic failure in these patients.
Clinical experience in patients with severe renal impairment is limited as there were only 5 patients with severe renal impairment (eGFR 15 to less than 30 mL/min/1.73 m2) exposed to lixisenatide in all controlled studies. Lixisenatide exposure was higher in these patients [see Clinical Pharmacology (12.3)]. Patients with severe renal impairment exposed to lixisenatide should be closely monitored for occurrence of gastrointestinal adverse reactions and for changes in renal function.
There is no therapeutic experience in patients with end-stage renal disease (eGFR <15 mL/min/1.73 m2), and it is not recommended to use SOLIQUA 100/33 in this population.
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of SOLIQUA 100/33 has not been studied. Frequent glucose monitoring and dose adjustment may be necessary for SOLIQUA 100/33 in patients with hepatic impairment [see Warnings and Precautions (5.6)].
Patients with Gastroparesis
Lixisenatide slows gastric emptying. Patients with preexisting gastroparesis were excluded from clinical trials of SOLIQUA 100/33. SOLIQUA 100/33 is not recommended in patients with severe gastroparesis.
SOLIQUA 100/33 is contraindicated:
- During episodes of hypoglycemia [see Warnings and Precautions (5.6)].
- In patients with serious hypersensitivity to insulin glargine, lixisenatide, or any of the excipients in SOLIQUA 100/33. Hypersensitivity reactions including anaphylaxis have occurred with both lixisenatide and insulin glargine [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
Anaphylaxis and Serious Hypersensitivity Reactions
In clinical trials of lixisenatide there have been cases of anaphylaxis (frequency of 0.1% or 10 cases per 10,000 patient-years) and other serious hypersensitivity reactions including angioedema. Severe, life-threatening, generalized allergic reactions, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock can occur with insulins, including insulin glargine. There have been postmarketing reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33 [see Adverse Reactions (6.1)].
Inform and closely monitor patients with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist for allergic reactions, because it is unknown whether such patients will be predisposed to anaphylaxis with SOLIQUA 100/33. SOLIQUA 100/33 is contraindicated in patients with known serious hypersensitivity to lixisenatide or insulin glargine [see Contraindications (4)]. If a hypersensitivity reaction occurs, the patient should discontinue SOLIQUA 100/33 and promptly seek medical attention.
Pancreatitis
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been reported postmarketing in patients treated with GLP-1 receptor agonists. In clinical trials of lixisenatide there were 21 cases of pancreatitis among lixisenatide-treated patients and 14 cases in comparator-treated patients (incidence rate of 21 vs 17 per 10,000 patient-years). Lixisenatide cases were reported as acute pancreatitis (n=3), pancreatitis (n=12), chronic pancreatitis (n=5), and edematous pancreatitis (n=1). Some patients had risk factors for pancreatitis, such as a history of cholelithiasis or alcohol abuse.
After initiation of SOLIQUA 100/33, 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 is suspected, promptly discontinue SOLIQUA 100/33 and initiate appropriate management. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended. Consider antidiabetic therapies other than SOLIQUA 100/33 in patients with a history of pancreatitis.
Never Share a SOLIQUA 100/33 Prefilled Pen Between Patients
SOLIQUA 100/33 prefilled pens must never be shared between patients, even if the needle is changed. Sharing of the pen poses a risk for transmission of blood-borne pathogens.
Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen
Changes in insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.6)] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions (6)].
Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant oral antidiabetic treatment may be needed. When converting from basal insulin therapy or a GLP-1 receptor agonist to SOLIQUA 100/33 follow dosing recommendations [see Dosage and Administration (2.2, 2.3)].
Overdose Due to Medication Errors
SOLIQUA 100/33 contains two drugs: insulin glargine and lixisenatide. Administration of more than 60 units of SOLIQUA 100/33 daily can result in overdose of the lixisenatide component. Do not exceed the 20-mcg maximum recommended dose of lixisenatide or use with other glucagon-like peptide-1 receptor agonists.
Accidental mix-ups between insulin products have been reported. To avoid medication errors between SOLIQUA 100/33 and other insulins, instruct patients to always check the insulin label before each injection.
Hypoglycemia
Hypoglycemia is the most common adverse reaction associated with insulin-containing products, including SOLIQUA 100/33 [see Adverse Reactions (6.1)]. 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 (e.g., driving or operating other machinery). SOLIQUA 100/33 (an insulin-containing product), or any insulin, should not be used during episodes of hypoglycemia [see Contraindications (4)].
Hypoglycemia can happen suddenly, and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7.1)], or in patients who experience recurrent hypoglycemia.
Risk Factors for Hypoglycemia
The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin-containing preparations, the glucose lowering effect time course of SOLIQUA 100/33 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 [see Clinical Pharmacology (12.2)].
Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to coadministered medication [see Drug Interactions (7.1)]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6, 8.7)].
Risk Mitigation Strategies for Hypoglycemia
Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the 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 is recommended.
The long-acting effect of insulin glargine may delay recovery from hypoglycemia.
Acute 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 SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration.
Monitor renal function when initiating or escalating doses of SOLIQUA 100/33 in patients with renal impairment and in patients reporting severe gastrointestinal reactions. Advise patients of the potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease [see Use in Specific Populations (8.6)].
Immunogenicity
Patients may develop antibodies to insulin and lixisenatide following treatment. A pooled analysis of studies of lixisenatide-treated patients showed that 70% were antibody positive at Week 24. In the subset of patients (2.4%) with the highest antibody concentrations (>100 nmol/L), an attenuated glycemic response was observed. A higher incidence of allergic reactions and injection-site reactions occurred in antibody positive patients [see Warnings and Precautions (5.1), Adverse Reactions (6.2)].
If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection-site reactions or allergic reactions, alternative antidiabetic therapy should be considered.
Hypokalemia
All insulin-containing products, including SOLIQUA 100/33, cause a shift in potassium from the 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 (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists
Thiazoidinediones (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, including SOLIQUA 100/33. Fluid retention may lead to or exacerbate heart failure. Patients treated with SOLIQUA 100/33 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.
Acute Gallbladder Disease
Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In a cardiovascular outcomes trial, cholelithiasis occurred in 0.4% of lixisenatide-treated patients versus 0.2% in placebo-treated patients and acute cholecystitis in 0.3% of lixisenatide-treated patients versus 0.2% in placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
Pulmonary Aspiration During General Anesthesia or Deep Sedation
SOLIQUA 100/33 delays gastric emptying [see Clinical Pharmacology (12.1)]. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.
Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking SOLIQUA 100/33, including whether modifying preoperative fasting recommendations or temporarily discontinuing SOLIQUA 100/33 could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking SOLIQUA 100/33.