Xultophy 100/3.6

What is Xultophy 100/3.6?

11 DESCRIPTION Insulin degludec Insulin degludec is a long-acting basal human insulin analog. Insulin degludec is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification. Insulin degludec differs from human insulin in that the amino acid threonine in position B30 has been omitted and a side-chain consisting of glutamic acid and a C16 fatty acid has been attached (chemical name: LysB29(Nε-hexadecandioyl-γ-Glu) des(B30) human insulin). Insulin degludec has a molecular formula of C 274 H 411 N 65 O 81 S 6 and a molecular weight of 6.104 kDa. It has the following structure: Figure 1. Structural Formula of Insulin degludec Liraglutide Liraglutide is an analog of human GLP-1 and acts as a GLP-1 receptor agonist. The peptide precursor of liraglutide, produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae , has been engineered to be 97% homologous to native human GLP-1 by substituting arginine for lysine at position 34. Liraglutide is made by attaching a C16 fatty acid (palmitic acid) with a glutamic acid spacer on the remaining lysine residue at position 26 of the peptide precurs

Uses of Xultophy 100/3.6

Established uses

• 1 INDICATIONS AND USAGE XULTOPHY 100/3.6 is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Limitations of Use: • XULTOPHY 100/3.6 contains liraglutide.
• Coadministration with any other product containing liraglutide or another glucagon-like peptide-1 (GLP-1) receptor agonist is not recommended [see Warnings and Precautions ( 5.5 )].
• XULTOPHY 100/3.6 is not recommended for the treatment of diabetic ketoacidosis.
• XULTOPHY 100/3.6 has not been studied in combination with prandial insulin.
• 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.

How Xultophy 100/3.6 works

In more detail: 12.1 Mechanism of Action XULTOPHY 100/3.6 XULTOPHY 100/3.6 is a combination product consisting of insulin degludec and liraglutide. Insulin degludec The primary activity of insulin degludec is the regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis. Liraglutide Liraglutide is a GLP-1 receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying.

How to take Xultophy 100/3.6

2 DOSAGE AND ADMINISTRATION • Administer once-daily at same time each day with or without food. ( 2.1 ) • XULTOPHY 100/3.6 pen delivers doses from 10 to 50 units with each injection ( 2.1 , 2.2 ); each XULTOPHY 100/3.6 dosage unit contains 1 unit of insulin degludec and 0.036 mg of liraglutide. ( 2.1 ) • Maximum daily dosage is 50 units (50 units of insulin degludec and 1.8 mg of liraglutide). ( 2.1 ) • Recommended starting dosage in patients naïve to basal insulin or GLP-1 receptor agonist is 10 units (10 units of insulin degludec and 0.36 mg of liraglutide) injected subcutaneously once-daily. (2.2 ) • Discontinue therapy with liraglutide or basal insulin prior to initiation of XULTOPHY 100/3.6. ( 2.2 ) • Recommended starting dosage in patients currently on basal insulin or GLP-1 receptor agonist is 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) injected subcutaneously once-daily. ( 2.2 ) • See Full Prescribing Information for titration recommendations. ( 2.3 ) • Inject XULTOPHY 100/3.6 subcutaneously into the thigh, upper arm, or abdomen. ( 2.5 ) • Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.5 ) • Do not admi

Dosage

Follow the dose prescribed by your doctor or pharmacist. The ranges below are general information, not a personal prescription.

Adults

2 DOSAGE AND ADMINISTRATION • Administer once-daily at same time each day with or without food. ( 2.1 ) • XULTOPHY 100/3.6 pen delivers doses from 10 to 50 units with each injection ( 2.1 , 2.2 ); each XULTOPHY 100/3.6 dosage unit contains 1 unit of insulin degludec and 0.036 mg of liraglutide. ( 2.1 ) • Maximum daily dosage is 50 units (50 units of insulin degludec and 1.8 mg of liraglutide). ( 2.1 ) • Recommended starting dosage in patients naïve to basal insulin or GLP-1 receptor agonist is 10 units (10 units of insulin degludec and 0.36 mg of liraglutide) injected subcutaneously once-daily. (2.2 ) • Discontinue therapy with liraglutide or basal insulin prior to initiation of XULTOPHY 100/3.6. ( 2.2 ) • Recommended starting dosage in patients currently on basal insulin or GLP-1 receptor agonist is 16 units (16 units of insulin degludec and 0.58 mg of liraglutide) injected subcutaneously once-daily. ( 2.2 ) • See Full Prescribing Information for titration recommendations. ( 2.3 ) • Inject XULTOPHY 100/3.6 subcutaneously into the thigh, upper arm, or abdomen. ( 2.5 ) • Rotate injection sites to reduce risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.5 ) • Do not admi

Side effects of Xultophy 100/3.6

Common

• 6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-cell Tumors [see Warnings and Precautions ( 5.1 )] • Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] • Hypoglycemia [see Warnings and Precautions ( 5.6 )] • Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.7 )] • Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.8 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] • Acute Gallbladder Disease [see Warnings and Precautions ( 5.10 )] • Hypokalemia [see Warnings and Precautions ( 5.11 )] • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.13 )] • Most common adverse reactions (incidence ≥5%) in clinical trials are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection.
• ( 6 ) • Immunogenicity-related events, including urticaria, were more common among liraglutide-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials.
• ( 12.6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk

Warnings and who should not take it

Who should NOT take Xultophy 100/3.6?

• 4 CONTRAINDICATIONS XULTOPHY 100/3.6 is contraindicated: • In patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions ( 5.1 )] .
• During episodes of hypoglycemia [see Warnings and Precautions ( 5.6 )] .
• In patients with hypersensitivity to insulin degludec, liraglutide, or any of the excipients in XULTOPHY 100/3.6.
• Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide, one of the components of XULTOPHY 100/3.6 [see Warnings and Precautions ( 5.9 )].
• Patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 ( 4 ) • During episodes of hypoglycemia ( 4 ) • Patients with a serious hypersensitivity reaction to insulin degludec, liraglutide, or any of the excipients in XULTOPHY 100/3.6 ( 4 )

Overdose

10 OVERDOSAGE Hypoglycemia (from insulin and liraglutide) and gastrointestinal adverse reactions (from liraglutide) may develop if a patient is dosed with more XULTOPHY 100/3.6 than required. An excess of insulin-containing products like XULTOPHY 100/3.6 relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.6 , 5.10 )] . Mild episodes of hypoglycemia usually can be treated with oral glucose. Lowering the drug dosage, and adjustments in meal patterns, or exercise may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon for emergency use or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid reoccurrence of hypoglycemia. Hypokalemia must be corrected appropriately. Overdoses have been reported in clinical trials and postmarketing use of liraglutide, one of the components of XULTOPHY 100/3.6. Effects have included severe nausea and severe vomiting. In

Safety at a glance

Children and elderly

Interactions

Medicine and medicine

• 7 DRUG INTERACTIONS • Drugs that affect glucose metabolism : Adjustment of XULTOPHY 100/3.6 dosage may be needed;
• closely monitor blood glucose.
• ( 7.1 ) • Anti-Adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Hypoglycemia signs and symptoms may be reduced or absent.
• ( 7.1 ) • Effects of delayed gastric emptying on oral medications : May impact absorption of concomitantly administered oral medications.
• ( 7.2 ) 7.1 Medications that Can Affect Glucose Metabolism A number of medications affect glucose metabolism and may require dose adjustment of XULTOPHY 100/3.6 and particularly close monitoring [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.6 )].
• Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when XULTOPHY 100/3.6 is coadministered with these drugs.

Frequently asked questions