Insulin glargine and lixisenatide

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Insulin glargine and lixisenatide is injected under the skin, usually injected once per day. Use the injection within 60 minutes (1 hour) before your first meal of the day. Try to use the medicine at the same time each day.

This medicine comes in a prefilled injection pen that contains 14 pre-set doses. You will 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.

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

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

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.

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.

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.

Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. Becoming dehydrated while using this medicine can lead to kidney failure.

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) insulin glargine and lixisenatide: Refrigerate and protect from light.

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

Storing opened (in use) insulin glargine and lixisenatide: Store at room temperature with the pen cap attached, and use within 14 days.

Do not store an injection pen with the needle attached.

Do not use the medicine if it looks cloudy, has changed colors, or has any particles in it. Call your pharmacist for new medicine.

• Tell all of your health care providers that you take insulin glargine and lixisenatide. This includes your doctors, nurses, pharmacists, and dentists.
• Allergic reactions have happened with this medicine. Rarely, some reactions can be very bad or life-threatening. Talk with the doctor.
• Low blood sugar may happen with insulin glargine and lixisenatide. Very low blood sugar can lead to seizures, passing out, long lasting brain damage, and sometimes death. Talk with the doctor.
• Low blood potassium may happen with this medicine. If not treated, this can lead to a heartbeat that is not normal, very bad breathing problems, and sometimes death. Talk with the doctor.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how insulin glargine and lixisenatide affects you.
• Some diabetes drugs like pioglitazone or rosiglitazone may cause heart failure or make it worse in people who already have it. Using insulin with these drugs may increase this risk. If you also take one of these drugs, 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.
• 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.
• Talk with your doctor before you drink alcohol.
• A very bad and sometimes deadly pancreas problem (pancreatitis) has happened with other drugs like this one. Talk with your doctor.
• 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.
• Birth control taken by mouth may not work as well to prevent pregnancy if taken at the same time as insulin glargine and lixisenatide. If you are taking birth control by mouth, take it at least 1 hour before or 11 hours after this medicine.
• If you are 65 or older, use insulin glargine and lixisenatide with care. You could have more side effects.
• 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.

Use insulin glargine and lixisenatide as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin on the top of the thigh, belly area, or upper arm.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Follow how to use as you have been told by the doctor or read the package insert.
• Check the pen label closely each time you use this medicine. Be sure that you know how to measure and get your dose ready. If you have any questions, call your doctor or pharmacist.
• Take insulin glargine and lixisenatide within the hour before the first meal every day.
• Wash your hands before and after use.
• Move site where you give the shot each time.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• Put the cap back on after you are done using your dose.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.
• Attach new needle before each dose.
• Do not mix with other liquids.
• Do not move this medicine from the pen to a syringe or mix with other types of insulin.
• Follow the diet and workout plan that your doctor told you about.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• 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 insulin glargine and lixisenatide. Talk with your doctor.
• 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.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Hard stools (constipation).
• Belly pain.
• Gas.
• Not hungry.
• Nose or throat irritation.
• Signs of a common cold.
• Headache.
• Weight gain.
• Irritation where the shot is given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Refer to individual agents.

Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (<60 units daily) or lixisenatide

eGFR ≥15 mL/minute/1.73 m2 to <90 mL/minute/1.73 m2: There are no specific dosage adjustments provided in the manufacturer’s labeling for the combination product; insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely. Limited data indicates lixisenatide exposure is increased in patients with severe impairment (eGFR <30 mL/minute/1.73 m2). Also refer to individual monographs.

eGFR <15 mL/minute/1.73 m2: Use is not recommended (has not been studied).

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Insulin. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Contraceptives (Estrogens): Lixisenatide may decrease the serum concentration of Contraceptives (Estrogens). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification

Contraceptives (Progestins): Lixisenatide may decrease the serum concentration of Contraceptives (Progestins). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification

DPP-IV Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

GLP-1 Agonists: May enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Exceptions: Liraglutide. Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulin: GLP-1 Agonists may enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification

Liraglutide: May enhance the hypoglycemic effect of Insulin. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Insulin. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pioglitazone: May enhance the adverse/toxic effect of Insulin. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. Consider therapy modification

Pramlintide: May enhance the hypoglycemic effect of Insulin. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Rosiglitazone: Insulin may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

SGLT2 Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Sulfonylureas: GLP-1 Agonists may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Data not available

Benefit should outweigh risk US FDA pregnancy category: Not Assigned Risk Summary: Based on animal studies, there may be a risk to the fetus from exposure to lixisenatide. Comment: There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy; insulin therapy is considered a drug of choice during pregnancy.

Animal studies with lixisenatide 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. Published studies with insulin glargine have not reported a clear association with major birth defects or miscarriage risk. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth, and macrosomia related morbidity. There are no controlled data in human pregnancy. Patients with diabetes or a history of gestational diabetes should maintain good metabolic control before conception and during pregnancy. Insulin requirements may decrease during the first trimester; generally, increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential. 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.