Adlyxin

Name: Adlyxin

Adlyxin Side Effects

Common Side Effects of Adlyxin

Tell your doctor if any of the following side effects become severe or don't go away:

  • Nausea
  • Vomiting
  • Diarrhea
  • Headache
  • Dizziness

Serious Side Effects of Adlyxin

Tell your doctor right away if you experience any of the symptoms listed in the Adlyxin Warnings section above, or the following serious side effects:

  • Severe pain in your stomach area (with or without vomiting)
  • Pain in your abdomen that spreads to your back
  • Signs of anaphylaxis, which may include rash, itching, rapid heartbeat, fainting, difficulty breathing or swallowing, or swelling of the face, lips, tongue, or throat

What is lixisenatide?

Lixisenatide is an injectable diabetes medicine that helps control blood sugar levels. This medication helps your pancreas produce insulin more efficiently.

Lixisenatide is used together with diet and exercise to improve blood sugar control in adults with type 2 diabetes. Lixisenatide is not for treating type 1 diabetes.

Lixisenatide may also be used for purposes not listed in this medication guide.

How should I use lixisenatide?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Lixisenatide is injected under the skin. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Lixisenatide comes in a prefilled injection pen that contains 14 pre-set doses. Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Lixisenatide is usually injected once per day. Use lixisenatide within 60 minutes (1 hour) before your first meal of the day. Try to use the medicine at the same time each day.

Your care provider will show you the best places on your body to inject lixisenatide. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

Never share an injection pen, cartridge, or syringe with another person, even if the needle has been changed. Sharing these devices can allow infections or disease to pass from one person to another.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.

Use a disposable needle only once. Follow any state or local laws about throwing away used needles. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Lixisenatide is only part of a complete treatment program that may also include diet, exercise, weight control, regular blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Storing unopened (not in use) lixisenatide: Refrigerate and protect from light. Take the injection pen out of the refrigerator and allow it to reach room temperature before using.

Do not freeze lixisenatide, and throw away the medicine if it has been frozen.

Storing opened (in use) lixisenatide: Store at room temperature with the pen cap attached, and use within 14 days. Do not store the injection pen with a needle attached.

What happens if I miss a dose?

Wait until your next meal and use the medicine within 1 hour before you eat. Then go back to your regular injection schedule the next day. Do not use extra medicine to make up the missed dose.

Cautions for Adlyxin

Contraindications

Hypersensitivity to lixisenatide or any product components. Hypersensitivity reactions including anaphylaxis have occurred with lixisenatide. 1

Warnings/Precautions

Anaphylaxis and Serious Hypersensitivity Reactions

In clinical trials of lixisenatide, there have been cases of anaphylaxis determined to be related to lixisenatide (frequency of 0.1% or 10 cases per 10,000 patient-years). Other serious hypersensitivity reactions including angioedema also occurred.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 lixisenatide. Lixisenatide is contraindicated in patients with known hypersensitivity to lixisenatide. If a hypersensitivity reaction occurs, the patient should discontinue lixisenatide and promptly seek medical attention. 1

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. 1

After initiation of lixisenatide, 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 lixisenatide and initiate appropriate management. If pancreatitis is confirmed, do not restart lixisenatide. Consider antidiabetic therapies other than lixisenatide in patients with a history of pancreatitis.1

Never Share Lixisenatide Pen Between Patients

Lixisenatide pens should never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.1

Hypoglycemia with Concomitant Use of Sulfonylureas or Basal Insulin

Patients receiving lixisenatide in combination with basal insulin or a sulfonylurea have an increased risk of hypoglycemia. In patients receiving sulfonylurea with or without metformin, 14.5% patients on lixisenatide reported symptomatic hypoglycemia compared to 10.6% for those on placebo. In patients receiving basal insulin with or without metformin, 28.3% of patients on lixisenatide reported symptomatic hypoglycemia compared to 23.0% for those on placebo. In patients receiving basal insulin with sulfonylurea, 47.2% of patients on lixisenatide reported symptomatic hypoglycemia compared to 21.6% for those on placebo. Reduction in the dose of sulfonylurea or basal insulin may be necessary.1

Acute Kidney Injury

Acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, has been reported postmarketing in patients treated with GLP-1 receptor agonists. 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. 1

Monitor renal function when initiating or escalating doses of lixisenatide in patients with renal impairment and in patients reporting severe gastrointestinal reactions. Lixisenatide is not recommended in patients with end stage renal disease.1

Immunogenicity

Patients may develop antibodies to lixisenatide following treatment with lixisenatide. 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.1

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.1

Macrovascular Outcomes

Clinical studies have not shown macrovascular risk reduction with lixisenatide or any other antidiabetic drug.1

Specific Populations

Pregnancy

Risk Summary: The limited available data with lixisenatide in pregnant women are not sufficient to inform a drug-associated risk of major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.1 Based on animal reproduction studies, there may be risks to the fetus from exposure to lixisenatide during pregnancy. Lixisenatide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.1 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 clinical dose, respectively, based on plasma AUC. 1 The estimated background risk of major birth defects is 6–10% in women with pre-gestational 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.1

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, stillbirth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.1

Animal Data

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 ≥5 mcg/kg/day, 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%.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 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.1

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, 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/m2.1

Lactation

There is no information regarding the presence of lixisenatide in human milk, the effects on the breastfed infant, or the effects on milk production. However, lixisenatide is present in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lixisenatide and any potential adverse effects on the breastfed infant from lixisenatide or from the underlying maternal condition.1

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 peptide in the gastric contents of weaning offspring.1

Pediatric Use

Safety and effectiveness of lixisenatide have not been established in pediatric patients below 18 years of age. 1

Geriatric Use

In phase 2 and 3 controlled clinical studies of lixisenatide, a total of 1837 (25%) of the patients exposed to the study medication were 65 years of age and over and 288 (4%) were 75 years of age and over. No overall differences were observed in safety or effectiveness between these patients and younger patients, but individual sensitivity cannot be ruled out. 1

Renal Impairment

In patients with mild renal impairment (eGFR: 60–89 mL/min/1.73 m2), no dose adjustment is required but close monitoring for lixisenatide related adverse reactions and for changes in renal function is recommended because a higher incidence of hypoglycemia, nausea and vomiting was observed in these patients.1

In a cardiovascular outcome study, 655 (22%) lixisenatide treated patients had moderate renal impairment (eGFR: 30 to less than 60 mL/min/1.73 m2). No dosing adjustment is recommended in patients with moderate renal impairment, but close monitoring for lixisenatide related adverse gastrointestinal reactions and for changes in renal function is recommended because these may lead to dehydration and acute renal failure and worsening of chronic renal failure in these patients.1

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. Patients with severe renal impairment exposed to lixisenatide should be closely monitored for occurrence of gastrointestinal adverse reactions and for changes in renal function.1

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 lixisenatide in this population.1

Patients with Gastroparesis

Lixisenatide slows gastric emptying. Patients with preexisting gastroparesis were excluded from clinical trials of lixisenatide. Lixisenatide should not be initiated in patients with severe gastroparesis.1

Common Adverse Effects

The most common adverse reactions (≥5%) in patients treated with lixisenatide are nausea, vomiting, headache, diarrhea, dizziness, and hypoglycemia.1

Adlyxin Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Anxiety
  • bloating
  • bluish or pale skin
  • blurred vision
  • chills
  • cold sweats
  • confusion
  • constipation
  • cough
  • darkened urine
  • depression
  • difficulty swallowing
  • dizziness
  • fainting
  • fast heartbeat
  • fever
  • headache
  • hives, itching, redness, skin rash
  • increased hunger
  • indigestion
  • loss of appetite
  • nausea
  • nervousness
  • nightmares
  • pains in the stomach, side, or abdomen, possibly radiating to the back
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • seizures
  • shakiness
  • shortness of breath
  • slurred speech
  • tightness in the chest
  • troubled breathing
  • unusual tiredness or weakness
  • vomiting
  • yellow eyes or skin
Incidence not known
  • Agitation
  • decreased urine output
  • hostility
  • irritability
  • lethargy
  • muscle twitching
  • rapid weight gain
  • stupor
  • swelling of the face, ankles, or hands

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose
  • Diarrhea
  • loss of appetite
  • nausea or vomiting
  • stomach pain, fullness, or discomfort
  • indigestion
  • passing of gas

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Diarrhea
Less common
  • Acid or sour stomach
  • belching
  • bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
  • heartburn
  • pressure in the stomach
  • stomach discomfort, upset, or pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What are some things I need to know or do while I take Adlyxin?

  • Tell all of your health care providers that you take Adlyxin. This includes your doctors, nurses, pharmacists, and dentists.
  • Follow the diet and workout plan that your doctor told you about.
  • Wear disease medical alert ID (identification).
  • Do not drive if your blood sugar has been low. There is a greater chance of you having a crash.
  • Check your blood sugar as you have been told by your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • It may be harder to control your blood sugar during times of stress like when you have a fever, an infection, an injury, or surgery. A change in level of physical activity or exercise and a change in diet may also affect your blood sugar. Talk with your doctor.
  • Talk with your doctor before you drink alcohol.
  • Kidney problems have happened with this medicine. Sometimes, kidney problems may need to be treated in the hospital. Dialysis may also be needed. Talk with your doctor.
  • If you cannot drink liquids by mouth or if you have upset stomach, throwing up, or diarrhea that does not go away, you need to avoid getting dehydrated. Contact your doctor to find out what to do. Dehydration may lead to new or worse kidney problems.
  • This medicine may prevent other drugs taken by mouth from getting into the body. If you take other drugs by mouth, you may need to take them at some other time than Adlyxin. Talk with your doctor.
  • Birth control taken by mouth may not work as well to prevent pregnancy if taken at the same time as this medicine. If you are taking birth control by mouth, take it at least 1 hour before or 11 hours after Adlyxin.
  • Do not share pen or cartridge devices with another person even if the needle has been changed. Sharing these devices may pass infections from one person to another. This includes infections you may not know you have.
  • A very bad and sometimes deadly pancreas problem (pancreatitis) has happened with other drugs like this one. Talk with your doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Dosing & Uses

Dosage Forms & Strengths

SC solution in prefilled pen

  • Starter dose (green pen)
    • 50mcg/mL in 3mL prefilled pen (provides 14 doses of 10mcg/dose)
  • Maintenance dose (burgundy pen)
    • 100mcg/mL in 3 mL prefilled pen (provides 14 doses of 20mcg/dose)

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: 10 mcg SC qDay for 14 days

Maintenance: Increase dose to 20 mcg SC qDay starting on Day 15

Dosage Modifications

Renal impairment

  • Mild (CrCl 60-89 mL/min): No dosage adjustment required; monitoring for changes in renal function recommended because of a higher incidence of hypoglycemia, nausea, and vomiting observed in these patients during clinical trials
  • Moderate (CrCl 30 to <60 mL/min): No dosage adjustment required; closely monitoring for adverse GI adverse effects and for changes in renal function is recommended because these symptoms may lead to dehydration and acute renal failure and worsening of chronic failure in these patients
  • Severe (CrCl 15 to <30 mL/min): Data are limited; there were only 5 patients with severe renal impairment in all controlled studies; lixisenatide exposure was higher in these patients; closely monitor for GI adverse effects and for changes in renal function
  • End-stage renal disease (CrCl <15 mL/min): Not recommended; no therapeutic experience

Dosing Considerations

Limitations of use

  • Has not been studied in patients with chronic pancreatitis or a history of unexplained pancreatitis; consider other antidiabetic treatment options
  • Not a substitute for insulin
  • Not indicated for patients with type 1 DM
  • Not indicated for treatment of ketoacidosis
  • Concurrent use with short-acting insulin has not been studied and is not recommended
  • Has not been studied with gastroparesis and is not recommended in patients with gastroparesis

Safety and efficacy not established

Warnings

Contraindications

Documented hypersensitivity; hypersensitivity reactions, including anaphylaxis, have occurred with lixisenatide

Cautions

Anaphylaxis (0.1%) and other hypersensitivity reactions, including angioedema, have been reported; if hypersensitivity occurs, discontinue drug and promptly seek medical attention (see Contraindications)

Acute pancreatitis, including fatal, and nonfatal hemorrhagic or necrotizing pancreatitis reported postmarketing in patients treated with GLP-1 receptor agonists; observe for signs and symptoms (eg, persistent severe abdominal pain that sometimes radiates to the back which may or may not be accompanied by vomiting); promptly discontinue if suspected; if pancreatitis confirmed, do not restart drug

Do not share pen between patients, even if the needle is changed; pen-sharing poses risk for transmission of blood-borne pathogens

Risk for hypoglycemia increased if coadministered with a sulfonylurea or basal insulin

Acute kidney injury and worsening of chronic renal failure (sometimes requiring hemodialysis); some reports were in patients without known underlying renal disease; most of the reports described patients who had experienced nausea, vomiting, diarrhea, or dehydration

Antibody development to lixisenatide occurred in 70% of patients by week 24; a subset of patients (2.4%) with the highest antibody concentrations (ie, >100 nmol/L) showed an attenuated glycemic response; a higher incidence of allergic reactions and injection site reactions occurred in antibody-positive patients

Clinical studies have NOT shown macrovascular risk reduction with lixisenatide or any other antidiabetic drug

Drug interaction overview

  • Lixisenatide delays gastric emptying, which may affect absorption of concomitantly administered oral medications
  • Caution if coadministered with drugs that have a narrow therapeutic index or drugs that require careful clinical monitoring; if these medications are to be administered with food, patients should take them with a meal or snack when lixisenatide is not being administered
  • Oral medications that are particularly dependent on minimum serum concentrations (eg, antibiotics) or medications in which a delayed effect may be undesirable (pain medications) should be administered 1 hr before lixisenatide
  • Oral contraceptives should be taken at least 1 hr before lixisenatide administration or 11 hr after lixisenatide
  • Risk of hypoglycemia when coadministered with sulfonylurea or basal insulin; dose reduction of sulfonylurea or basal insulin may be required

How should I use Adlyxin?

Use Adlyxin exactly as prescribed. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Adlyxin is injected under the skin. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes.

Adlyxin comes in a prefilled injection pen that contains 14 pre-set doses. Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Adlyxin is usually injected once per day. Use this medicine within 60 minutes (1 hour) before your first meal of the day. Try to use the medicine at the same time each day.

Your care provider will show you the best places on your body to inject Adlyxin. Use a different place each time you give an injection. Do not inject into the same place two times in a row.

Never share an injection pen, cartridge, or syringe with another person, even if the needle has been changed. Sharing these devices can allow infections or disease to pass from one person to another.

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky. To quickly treat low blood sugar, always keep a fast-acting source of sugar with you such as fruit juice, hard candy, crackers, raisins, or non-diet soda.

Your doctor can prescribe a glucagon emergency injection kit to use in case you have severe hypoglycemia and cannot eat or drink. Be sure your family and close friends know how to give you this injection in an emergency.

Also watch for signs of high blood sugar (hyperglycemia) such as increased thirst or urination, blurred vision, headache, and tiredness.

Blood sugar levels can be affected by stress, illness, surgery, exercise, alcohol use, or skipping meals. Ask your doctor before changing your dose or medication schedule.

Use a disposable needle only once. Follow any state or local laws about throwing away used needles. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Adlyxin is only part of a complete treatment program that may also include diet, exercise, weight control, regular blood sugar testing, and special medical care. Follow your doctor's instructions very closely.

Storing unopened (not in use) Adlyxin: Refrigerate and protect from light. Take the injection pen out of the refrigerator and allow it to reach room temperature before using.

Do not freeze this medicine. Throw away the medicine vials if the have been frozen.

Storing opened (in use) Adlyxin: Store at room temperature with the pen cap attached, and use within 14 days. Do not store the injection pen with a needle attached.

Adlyxin side effects

Get emergency medical help if you have signs of an allergic reaction to Adlyxin: hives, itching, severe rash; rapid heartbeats; trouble swallowing; difficult breathing; feeling light-headed; swelling of your face, lips, tongue, or throat.

Stop using this medicine and call your doctor at once if you have:

  • pancreatitis - severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

  • low blood sugar - headache, hunger, sweating, irritability, dizziness, nausea, fast heart rate, and feeling anxious or shaky; or

  • kidney problems - little or no urination, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath.

Common Adlyxin side effects may include:

  • nausea, vomiting, diarrhea;

  • headache;

  • dizziness; or

  • low blood sugar.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For Healthcare Professionals

Applies to lixisenatide: subcutaneous kit, subcutaneous solution

General

The most frequently reported adverse reactions were nausea, vomiting, headache, diarrhea, dizziness, and hypoglycemia.[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 26.5%), vomiting (up to 10.5%)
Common (1% to 10%): Dyspepsia, diarrhea, constipation, abdominal distension, abdominal pain, upper abdominal pain
Frequency not reported: Pancreatitis[Ref]

Gastrointestinal adverse reactions including nausea and vomiting were responsible for discontinuation of treatment in 4.3% of patients. During clinical trials, the severity of gastrointestinal adverse reactions were graded as mild, moderate or severe in 64.2%, 32.3%, and 3.5% of cases, respectively. The majority of reactions occurred during the first 3 weeks of treatment.

During clinical trials, 21 cases of pancreatitis were reported including acute pancreatitis (n=3), pancreatitis (n=12), chronic pancreatitis (n=5), and edematous pancreatitis (n=1). Of these cases, some had risk factors such as a history of cholelithiasis or alcohol abuse. Fourteen cases of pancreatitis were reported in the comparator-treated.[Ref]

Immunologic

Very common (10% or more): Development of anti-lixisenatide (the active ingredient contained in Adlyxin) antibodies (69.8%)[Ref]

Pooled analysis of drug-treated patients has found that almost 70% were antibody positive at 24 weeks. Of the antibody positive patients, those with the highest antibody concentrations (greater than 100 nmol/L) had attenuated glycemic responses. Additionally, a higher incidence of allergic reactions and injection site reactions occurred in antibody positive patients.[Ref]

Metabolic

Very common (10% or more): Hypoglycemia (in combination with a sulfonylurea and/or a basal insulin)
Common (1% to 10%): Hypoglycemia (in combination with metformin alone)[Ref]

Nervous system

Very common (10% or more): Headache
Common (1% to 10%): Dizziness, somnolence[Ref]

Cardiovascular

Common (1% to 10%): Palpitations
Uncommon (0.1% to 1%): Tachycardia[Ref]

Genitourinary

Common (1% to 10%): Cystitis[Ref]

Local

Common (1% to 10%): Injection site reactions including pain, pruritus, erythema[Ref]

Musculoskeletal

Common (1% to 10%): Back pain[Ref]

Other

Common (1% to 10%): Viral infection[Ref]

Respiratory

Common (1% to 10%): Influenza, upper respiratory tract infection[Ref]

Dermatologic

Uncommon (0.1% to 1%): Urticaria[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Anaphylactic reaction, angioedema, pruritus[Ref]

Some side effects of Adlyxin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Lixisenatide Pregnancy Warnings

Animal studies have shown reproductive toxicity. Studies in pregnant rats and rabbits at doses of 1 and 6 times the recommended human dose, respectively, were associated with visceral closure and skeletal defects. There are no controlled data in human pregnancy. In humans, poorly controlled diabetes during pregnancy increases fetal risk for major birth defects, still birth, and macrosomia related mortality. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Use should be avoided. AU TGA pregnancy category: B3 US FDA pregnancy category: Not Assigned Risk Summary: There is no enough available data in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Comments: -Insulin is generally considered the drug of choice during pregnancy. -Use of adequate methods of contraception should be encouraged in women of childbearing potential; if a patient wishes to become pregnant, or pregnancy occurs, this drug should be discontinued. -Administration times for oral contraceptives should be at least 1 hour before or 11 hours after dosing of this drug.

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