XULTOPHY 100/3.6 Dosage & Rx Info

Xultophy 100/3.6 Generic Name & Formulations

Legal Class

General Description

Insulin degludec 100 Units/mL, liraglutide 3.6mg/mL; soln for SC inj.

Pharmacological Class

Human insulin analog + glucagon-like peptide-1 (GLP-1) receptor agonist.

How Supplied

Prefilled pen (3mL)—5

Manufacturer

Novo Nordisk

Generic Availability

Mechanism of Action

The primary activity of insulin degludec is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibit lipolysis and proteolysis, and enhance protein synthesis. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin release, decreases glucagon secretion, and slows gastric emptying.

Xultophy 100/3.6 Indications

Indications

As adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Limitations of Use

Not recommended as first-line treatment for patients inadequately controlled on diet and exercise. Not for use with other liraglutide- or GLP-1 receptor agonist-containing products. Not for treating type 1 diabetes mellitus or diabetic ketoacidosis. Not studied in combination with prandial insulin.

Xultophy 100/3.6 Dosage and Administration

Adult

Give by SC inj once daily at the same time each day into thigh, upper arm or abdomen; rotate inj sites. Individualize; monitor and adjust as needed. Naive to basal insulin or GLP-1 agonist: initially 10 Units once daily. Currently on basal insulin or GLP-1 agonist: discontinue basal insulin or liraglutide prior to initiation; initially 16 Units once daily. Both: titrate dose by 2 Units every 3–4 days until desired FPG achieved; max 50 Units daily.

Children

Not established.

Xultophy 100/3.6 Contraindications

Contraindications

History (personal or family) of medullary thyroid carcinoma. Multiple endocrine neoplasia syndrome type 2. During episodes of hypoglycemia.

Xultophy 100/3.6 Boxed Warnings

Boxed Warning

Risk of thyroid C-cell tumors.

Xultophy 100/3.6 Warnings/Precautions

Warnings/Precautions

Risk of thyroid C-cell tumors; inform patients of potential risk and symptoms. Monitor for pancreatitis; discontinue if suspected; do not restart if confirmed. History of pancreatitis. Instruct patients on diet, exercise, blood testing, proper administration of insulin, and management of hypoglycemia. Do not reuse or share pens or needles between patients, even if the needle is changed. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis. Increased risk of hyperglycemia or hypoglycemia if changes in physical activity, meal patterns, renal or hepatic function, insulin regimen, administration site, and if acute illness occurs: monitor glucose more frequently and may need to adjust dose. Monitor potassium levels in patients at risk for hypokalemia (eg, concomitant K⁺-lowering or K⁺-sensitive drugs). Discontinue if hypersensitivity reactions occur. History of anaphylaxis or angioedema with another GLP-1 agonist; monitor closely. Acute gallbladder disease (eg, cholelithiasis, cholecystitis). Perform gallbladder studies and clinical follow-up if cholelithiasis is suspected. Pre-existing gastroparesis. Visual impairment. Renal impairment or GI adverse reactions: monitor and avoid fluid depletion. Elderly. Pregnancy. Nursing mothers.

REMS

YES

Xultophy 100/3.6 Pharmacokinetics

Absorption

After reaching the maximum daily dose of Xultophy 100/3.6, the estimated mean steady-state exposure (AUC 0-24h) of insulin degludec was 113 h*nmol/L and of liraglutide 1227 h*ng/mL. The maximum concentrations were 5196 pmol/L for insulin degludec and 55 ng/mL for liraglutide. Steady state concentrations of insulin degludec and liraglutide are reached after 2–3 days of daily administration.

Distribution

Plasma protein bound: >99% (insulin degludec); >98% (liraglutide).

Metabolism

Degradation of insulin degludec is similar to that of human insulin.

Liraglutide is endogenously metabolized in a similar manner to large proteins without a specific organ as a major route of elimination.

Elimination

Half-life: ~25 hours (insulin degludec); ~13 hours (liraglutide).

Xultophy 100/3.6 Interactions

Interactions

Do not mix or dilute with other insulins or solutions. Concomitant peroxisome proliferator-activated receptor (PPAR)-gamma agonists may cause fluid retention and heart failure; consider dose reduction or discontinue PPAR-gamma agonists. Increased risk of hypoglycemia with concomitant antidiabetics, ACE inhibitors, ARBs, disopyramide, fibrates, fluoxetine, MAOIs, pentoxifylline, pramlintide, salicylates, somatostatin analogs, sulfonamide antibiotics. Reduced efficacy with concomitant atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens, protease inhibitors, somatropin, sympathomimetics, thyroid hormones. Variable effects with β-blockers, clonidine, lithium salts, alcohol, pentamidine. Concomitant β-blockers, clonidine, guanethidine, reserpine may blunt hypoglycemia. May affect absorption of oral drugs (delayed gastric emptying).

Xultophy 100/3.6 Adverse Reactions

Adverse Reactions

Nasopharyngitis, headache, nausea, diarrhea, increased lipase, upper respiratory tract infection; hypoglycemia, hypokalemia, lipodystrophy, acute kidney injury; rare: pancreatitis, anaphylactic reactions, angioedema.

Xultophy 100/3.6 Clinical Trials

See Literature

Xultophy 100/3.6 Note

Not Applicable

Xultophy 100/3.6 Patient Counseling