Xultophy (insulin degludec and liraglutide injection)

Xultophy 100/3.6 is a combination of insulin degludec, a long-acting human insulin analog, and liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (less than 50 units daily) or liraglutide (less than or equal to 1.8 mg daily).

WARNING

Possible thyroid tumors, including cancer

Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rats and mice, liraglutide, one of the components of Xultophy 100/3.6, and medicines that work like liraglutide caused thyroid tumors, including thyroid cancer.

It is not known if Xultophy 100/3.6 will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people. • Do not use Xultophy 100/3.6 if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Common Side Effects

The most common side effects of Xultophy 100/3.6 include stuffy or runny nose, sore throat, headache, nausea, diarrhea, increased blood levels of lipase, and upper respiratory tract infection. Talk to your healthcare provider about any side effect that bothers you or does not go away.

Stop using Xultophy 100/3.6 and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.

Low blood sugar (hypoglycemia)

Your risk for getting low blood sugar may be higher if you use Xultophy 100/3.6 with another medicine that can cause low blood sugar.

Signs and symptoms of low blood sugar may include:

• dizziness or light-headedness
• sweating
• confusion or drowsiness
• headache
• blurred vision
• slurred speech
• shakiness
• fast heartbeat
• anxiety, irritability, or mood changes
• hunger
• weakness
• feeling jittery

Kidney problems (kidney failure)

Worsening of kidney failure and sudden kidney failure have happened in people with kidney problems and in people without kidney problems, who have taken liraglutide, one of the ingredients in Xultophy 100/3.6.

Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems to get worse. Tell your healthcare provider if you have diarrhea, nausea, or vomiting. Drink plenty of fluids to help reduce your risk of dehydration during treatment with Xultophy 100/3.6.

Serious allergic reactions

Stop using Xultophy 100/3.6 and get medical help right away, if you have any symptoms of a serious allergic reaction including:
• hives
• rash
• itching
• fast heartbeat
• fainting or feeling dizzy
• swelling of your face, lips, tongue, or throat
• problems breathing or swallowing
• sudden coughing
• chest pain or tightness

Gallbladder problems

Gallbladder problems have happened in some people who take liraglutide, an ingredient in Xultophy 100/3.6. Tell your healthcare provider right away if you get symptoms of gallbladder problems which may include:

• pain in the right or middle upper stomach area
• fever
• nausea and vomiting
• your skin or the white part of your eyes turns yellow

Low potassium in your blood (hypokalemia)

Heart failure

Taking certain diabetes pills called thiazolidinediones or TZDs with Xultophy 100/3.6 may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure, it may get worse while you take TZDs with Xultophy 100/3.6. Your healthcare provider should monitor you closely while you are taking TZDs with Xultophy 100/3.6.

Tell your healthcare provider if you have any new or worse symptoms of heart failure including shortness of breath, tiredness, swelling of your ankles or feet and sudden weight gain. Treatment with TZDs and Xultophy 100/3.6 may need to be adjusted or stopped by your healthcare provider if you have new or worsening heart failure.

• Discontinue therapy with liraglutide or basal insulin prior to initiation of Xultophy 100/3.6.
• Recommended starting dosage is 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) given subcutaneously once daily.
• Administer once daily at same time each day with or without food.
• Maximum daily dosage is 50 units (50 units of insulin degludec and 1.8 mg of liraglutide).
• Xultophy 100/3.6 pen delivers doses from 10 to 50 units with each injection; each Xultophy 100/3.6 dosage unit contains 1 unit of insulin degludec and 0.036 mg of liraglutide.
• Use alternative antidiabetic products if patients require a Xultophy 100/3.6 daily dosage:
  • o Persistently below 16 units, or
  • o Over 50 units
• Inject subcutaneously in thigh, upper arm or abdomen.
• Do not administer intravenously, intramuscularly, or by an infusion pump.
• Do not dilute or mix with any other insulin products or solutions

Drugs that affect glucose metabolism

Adjustment of Xultophy 100/3.6 dosage may be needed; closely monitor blood glucose.

Anti-Adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine)

Hypoglycemia signs and symptoms may be reduced.

Effects of delayed gastric emptying on oral medications

May impact absorption of concomitantly administered oral medications

Based on animal reproduction studies, there may be risks to the fetus from exposure to liraglutide during pregnancy. Xultophy 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There are no available data with Xultophy 100/3.6, insulin degludec or liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage.

There are no data on the presence of liraglutide or insulin degludec in human milk, the effects on the breastfed infant, or the effects on milk production. In lactating rats, insulin degludec and liraglutide, the two components of Xultophy 100/3.6, were present in milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Xultophy 100/3.6 and any potential adverse effects on the breastfed infant from Xultophy 100/3.6 or from the underlying maternal condition.