Insulin Glargine-Lixisenatide

Insulin Glargine-Lixisenatide is a prescription medication used to treat the symptoms of Type 2 Diabetes Mellitus. 

• Insulin Glargine-Lixisenatide is available under the following different brand names: Soliqua 100/33

Common side effects of Insulin Glargine-Lixisenatide include:

• body aches,
• pain,
• diarrhea,
• ear congestion,
• loss of voice
• muscle aches,
• sneezing,
• sore throat,
• stuffy or runny nose, and
• blistering, bleeding, burning, coldness, discoloration of the skin, feeling of pressure, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site

Serious side effects of Insulin Glargine-Lixisenatide include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• abdominal or stomach pain,
• agitation,
• bloating,
• blurred vision,
• increased urination,
• indigestion,
• irregular heartbeat,
• irritability,
• chills,
• cold sweats,
• clammy skin,
• coma,
• fatigue,
• light-headedness,
• loss of consciousness,
• confusion,
• constipation,
• convulsions,
• muscle pain or cramps,
• loss of appetite,
• cool or pale skin,
• cough,
• muscle twitching,
• nausea,
• vomiting,
• nightmares,
• little or no urination,
• difficulty swallowing,
• dizziness,
• noisy breathing,
• numbness or tingling in the hands, feet, or lips,
• light-headedness,
• abdominal pain radiating to the back,
• fast or weak heartbeat,
• dry mouth,
• fever,
• flushed, dry skin,
• fruit-like breath odor,
• headache,
• itching,
• rash,
• hostility,
• increased thirst,
• increased hunger,
• swelling of the eyelids or around the eyes, face, lips, or tongue,
• rapid weight gain,
• slurred speech,
• stupor,
• sweating,
• tightness in the chest,
• trouble breathing,
• unexplained weight loss,
• tiredness,
• weakness, and
• yellowing of the skin or eyes (jaundice)

Rare side effects of Insulin Glargine-Lixisenatide include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Subcutaneous injection

• (100 units/33 mcg) per mL
• Available as a 3 -mL single-use pen

Type 2 Diabetes Mellitus

Adult dosage

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 basal insulin below 30 units/day: insulin Glargine 15 units/lixisenatide 5 mcg subcutaneous once a day
• Patients currently on basal insulin 30-60 units/day with or without a GLP-1 agonist: insulin Glargine 30 units/lixisenatide 10 mcg subcutaneous once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Insulin Glargine-Lixisenatide has severe interactions with the following drug:
  • pramlintide
• Insulin Glargine-Lixisenatide has serious interactions with the following drugs:
  • ethanol
  • macimorelin
• Insulin Glargine-Lixisenatide has moderate interactions with at least 138 other drugs.
• Insulin Glargine-Lixisenatide has minor interactions with at least 76 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• During episodes of hypoglycemia
• Hypersensitivity to either of the active drugs or any excipients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Insulin Glargine-Lixisenatide?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Insulin Glargine-Lixisenatide?”

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 are reported in GLP-1 receptor agonist trials and post-marketing; if cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
• Do not share insulin pens between patients
• Caution when changing dosage regimens; increase the frequency of blood glucose monitoring to detect hypoglycemia or hyperglycemia
• Do not exceed the 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, have been reported postmarketing in patients treated with the 100/33 formulation
  • Some of these events were reported in patients without known underlying renal disease; most 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 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; 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 an 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 were 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
  • The attenuated glycaemic response was reported in patients with the highest antibody concentrations (above 100 nmol/L); a higher incidence of allergic reactions and injection-site reactions was reported in antibody-positive patients
  • Consider alternative antidiabetic therapy if there is worsening glycaemic control or failure to achieve targeted glycaemic control, significant injection-site reactions, or allergic reactions
• Pancreatitis
  • Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, was reported post-marketing
  • After initiation therapy, observe patients 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 therapy, and initiate appropriate management; if confirmed, restarting the drug is 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 hypokalaemia
  • Untreated hypokalaemia may cause respiratory paralysis, ventricular arrhythmia, and death; monitor potassium levels in patients at risk for hypokalaemia if indicated (.g, 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 (.g, 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 (.g, driving or operating other machinery
• Changes should be made cautiously and only under close medical supervision and the frequency of blood glucose monitoring should be increased
• Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis are reported to result in hyperglycemia; a sudden change in the injection site (to an 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
• The risk of hypoglycemia generally increases with the intensity of glycemic control; the risk of hypoglycemia after an injection is related to the duration of action of insulin and, in general, is highest when the 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 the 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 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 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 (.g, octreotide), and sulfonamide antibiotics
  • A 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 (.g, olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (.g, in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (.g, 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 and Lactation

• 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 on 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 the underlying maternal condition