Xultophy

/ Novo Nordisk

One dose step contains 1 unit of insulin degludec and 0.036 mg of liraglutide. This formulation is given once daily by subcutaneous administration can be administered at any time of the day, preferably at the same time of the day. The dosage should be adjusted in accordance with the individual patient’s needs. It is recommended to optimise glycaemic control via dose adjustment based on fasting plasma glucose. Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness. Patients who forget a dose are advised to take it upon discovery and then resume their usual once-daily dosing schedule. A minimum of 8 hours between injections should always be ensured. This also applies when administration at the same time of the day is not possible. The drug administered as dose steps. One dose step contains 1 unit of insulin degludec and 0.036 mg of liraglutide. The pre-filled pen can provide from 1 up to 50 dose steps in one injection in increments of one dose step. The maximum daily dose is 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). The dose counter on the pen shows the number of dose steps.
Add-on to oral glucose-lowering medicinal products: The recommended starting doseis 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide). The drug can be added to existing oral anti-diabetic treatment. When this drug is added to sulfonylurea therapy, a reduction in the dose of sulfonylurea should be considered.
Transfer from GLP-1 receptor agonist: Therapy with GLP-1 receptor agonists should be discontinued prior to initiation of this drug. When transferring from a GLP-1 receptor agonist, the recommended starting dose of the drug is 16 dose steps (16 units  insulin degludec and 0.6 mg liraglutide). The recommended starting dose should not be exceeded. If transferring from a long-acting GLP-1 receptor agonist (e.g. once-weekly dosing), the prolonged action should be considered. Treatment with this drug should be initiated at the moment the next dose of the long-acting GLP-1 receptor agonist would have been taken. Close glucose monitoring is recommended during the transfer and in the following weeks.
Transfer from basal insulin: Therapy with basal insulin should be discontinued prior to initiation of this drug.
When transferring from basal insulin therapy, the recommended starting dose: is 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide). The recommended starting dose should not be exceeded. Close glucose monitoring is recommended during the transfer and in the following weeks.
Transfer from basal insulin: Therapy with basal insulin should be discontinued prior to initiation of this formulation. When transferring from basal insulin therapy, the recommended starting dose of this drug is 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide). The recommended starting dose should not be exceeded. Close glucose monitoring is recommended during the transfer and in the following weeks.
Special populations
Elderly patients (≥65 years old): The drug can be used in elderly patients. Glucose monitoring is to be intensified and the dose adjusted on an individual basis. The therapeutic experience in patients ≥75 years of age is limited.
Renal impairment: When this drug is used in patients with mild or moderate renal impairment, glucose monitoring is to be intensified and the dose adjusted on an individual basis. This formulation cannot be recommended for use in patients with severe renal impairment including patients with end-stage renal disease.
Hepatic impairment: The drug can be used in patients with mild or moderate hepatic impairment. Glucose monitoring is to be intensified and the dose adjusted on an individual basis. Due to the liraglutide component, this drug is not recommended for use in patients with severe hepatic impairment.
See prescribing information for full details.

Treatment of adults with type 2 diabetes mellitus to improve glycaemic control in combination with oral glucose-lowering medicinal products when these alone or combined with a GLP-1 receptor agonist or basal insulin do not provide adequate glycaemic control.

Hypersensitivity to either or both active substances or to any of the excipients.

Hypoglycemia: Hypoglycemia may occur if the dose of this drug  is higher than required. Omission of a meal or unplanned strenuous physical exercise may lead to hypoglycemia. In combination with sulfonylurea, the risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea.
Hyperglycaemia: Inadequate dosing and/or discontinuation of anti-diabetic treatment may lead to hyperglycaemia and potentially to hyperosmolar coma. In case of discontinuation of this drug, ensure that instruction for initiation of alternative anti-diabetic medication is followed. Furthermore, concomitant illness.
Combination of pioglitazone and insulin medicinal products: Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin medicinal products, especially in patients with risk factors for development of cardiac failure. This should be kept in mind if treatment with the combination of pioglitazone and this formulation  is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and edema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.
Eye disorder: Intensification of therapy with insulin, a component of this drug with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy, while long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.
Antibody formation: This formulation  may cause formation of antibodies against insulin degludec and/or liraglutide. In rare cases, the presence of such antibodies may necessitate adjustment of the this drug dose in order to correct a tendency to hyper- or hypoglycaemia.
Acute pancreatitis: Use of GLP-1 receptor agonists including liraglutide, a component of this drug  has been associated with a risk of developing acute pancreatitis. There have been few reported events of acute pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, the treatment should be discontinued; if acute pancreatitis is confirmed, the drug should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Thyroid adverse events: Thyroid adverse events, including increased blood calcitonin, goitre and thyroid neoplasm have been reported in clinical trials with GLP-1 receptor agonists including liraglutide, a component of Xultophy®, in particular in patients with pre-existing thyroid disease, and Xultophy® should therefore be used with caution in these patients.
Inflammatory bowel disease and diabetic gastroparesis: There is no experience with Xultophy® in patients with inflammatory bowel disease and diabetic gastroparesis. Xultophy® is therefore not recommended in these patients.
Dehydration: Signs and symptoms of dehydration, including renal impairment and acute renal failure have been reported in clinical trials with GLP-1 receptor agonists including liraglutide, a component of this drug Patients should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion.
Avoidance of medication errors: Patients must be instructed to always check the pen label before each injection to avoid accidental mix-ups between this formulation and other injectable diabetes medicinal products.
See prescribing information for full details.

Hypoglycemia, decreased appetite, Nausea, diarrhea, vomiting, constipation, dyspepsia, gastritis, abdominal pain, gastro esophageal reflux disease, abdominal distension, Injection site reaction  increased lipase, amylase.
See prescribing information for full details.

Interaction studies with this drug  have not been performed. A number of substances affect glucose metabolism and may require dose adjustment of this drug.
The following substances may reduce this drug requirement: Anti-diabetic medicinal products, monoamine oxidase inhibitors (MAOI), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulfonamides.
The following substances may increase this drug requirement:  Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormones and danazol. Beta-blockers may mask the symptoms of hypoglycaemia. Octreotide/lanreotide may either increase or decrease this drug requirement. Alcohol may intensify or reduce the hypoglycaemic effect of this drug.
See prescribing information for full details.

Pregnancy: There is no clinical experience with use of this formulation, insulin degludec or liraglutide in pregnant women. If a patient wishes to become pregnant, or pregnancy occurs, the treatment should be discontinued.
Lactation: There is no clinical experience with use of this drug  during breast-feeding. Because of lack of experience, this drug should not be used during breast-feeding.
See prescribing information for full details.

Limited data are available with regard to overdose with this drug. Hypoglycaemia may develop if a patient is dosed more than required: Mild hypoglycaemic episodes can be treated by oral administration of glucose or other products containing sugar. It is therefore recommended that the patient always carries sugar-containing products. Severe hypoglycaemic episodes, where the patient is not able to treat himself, can be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a trained person, or with glucose given intravenously by a healthcare professional. Glucose must be given intravenously if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrates is recommended for the patient in order to prevent a relapse.

Storage: Before first opening: Store in a refrigerator (2°C – 8°C). Keep away from the freezing element. Do not freeze. Keep the cap on the pre-filled pen in order to protect from light. After first opening: Store at a maximum of 30°C or store in a refrigerator (2°C – 8°C). Do not freeze. Keep the cap on the pre-filled pen in order to protect from light.
Compatibility: Substances added to this formulation may cause degradation of the active substances. The drug must not be added to infusion fluids. This medicinal product must not be mixed with other medicinal products.