insulin degludec/insulin aspart (Rx)

Brand and Other Names:Ryzodeg

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

prefilled pen

  • insulin degludec 70 units/insulin aspart 30 units per mL (ie, 100 units/mL for combination)

Diabetes Mellitus Types 1 & 2

Indicated to improve glycemic control in adults with diabetes mellitus

Starting dose in insulin naïve patients

  • Type 1 diabetes mellitus: ~One third to one half of the total daily insulin dose; as a general rule; the remainder of the total daily insulin dose should be administered as a short- or rapid-acting insulin divided between each daily meal; 0.2-0.4 units/kg can be used to calculate the initial total daily insulin dose in insulin-naïve patients with type 1 diabetes
  • Type 2 diabetes mellitus: 10 units SC once daily

Starting dose in patients with types 1 or 2 diabetes on a once or twice daily premix or self-mix insulin alone or as part of a regimen of multiple daily injections

  • Start insulin degludec/insulin aspart 70/30 at the same unit dose and injection schedule as the premix or self-mix insulin
  • In patients also using short- or rapid-acting insulin at mealtimes, continue the short- or rapid-acting insulin at the same dose for meals NOT covered by degludec/insulin aspart 70/30

Starting dose in patients with types 1 or 2 diabetes on a once or twice daily basal insulin alone or as part of a regimen of multiple daily injections

  • Patients with T2DM switching from regimen that includes only a once- or twice-daily basal insulin, start insulin degludec/insulin aspart 70/30 at the same unit dose and injection schedule
  • For patients switching from once-daily basal insulin to once-daily insulin degludec/insulin aspart 70/30, monitor blood glucose after starting therapy due to the rapid-acting insulin component
  • In patients switching from a multiple daily injections regimen that includes a basal and short- or rapid-acting insulin at mealtimes, start insulin degludec/insulin aspart 70/30 once daily with the main meal at the same unit dose as the basal insulin; continue the short- or rapid-acting insulin at the same dose for meals NOT covered by insulin degludec/insulin aspart 70/30

Dosing Considerations

Not recommended for treatment of diabetic ketoacidosis

Dosage Forms & Strengths

prefilled pen

  • insulin degludec 70 units/insulin aspart 30 units per mL (ie, 100 units/mL for combination)

Diabetes Mellitus Types 1 & 2

Starting dose in insulin naïve patients

  • <1 year: Not studied
  • ≥1 year:
    • Type 1 diabetes mellitus: ∼One-third to one-half of the total daily insulin dose; as a general rule; the remainder of the total daily insulin dose should be administered as a short- or rapid-acting insulin divided between each daily meal; 0.2-0.4 units/kg can be used to calculate the initial total daily insulin dose in insulin-naïve patients with type 1 diabetes

Starting dose in patients with types 1 or 2 diabetes on a once or twice-daily premix or self-mix insulin alone or as part of a regimen of multiple daily injections

  • <1 year: Not studied
  • ≥1 year
    • Start insulin degludec/insulin aspart 70/30 80% of total daily mixed insulin dose in order to minimize risk of hypoglycemia and administer once daily with main meal of the day
    • In patients also using short- or rapid-acting insulin at mealtimes continue the short- or rapid-acting insulin at same dose for meals NOT covered by insulin degludec/insulin aspart 70/30

Starting dose in patients with types 1 or 2 diabetes on a once or twice daily basal insulin alone or as part of a regimen of multiple daily injections

  • < 1 year: Not studied
  • ≥1 year:
    • Start insulin degludec/insulin aspart 70/30 at 80% of long- or intermediate-acting insulin component of daily regimen in order to minimize risk of hypoglycemia and administer once-daily with the main meal of the day
    • In patients also using short- or rapid-acting insulin at meantime continue the short- or rapid-acting insulin at the same dose for meals NOT covered by insulin degludec/insulin aspart 70/30
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Interactions

Interaction Checker

and insulin degludec/insulin aspart

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              • ethanol

                ethanol, insulin degludec/insulin aspart. Other (see comment). Avoid or Use Alternate Drug. Comment: Alcohol may either increase or decrease the blood glucose lowering effect of insulin; alcohol may decrease endogenous glucose production (increased hypoglycemia risk) or worsen glycemic control by adding calories.

              Monitor Closely (170)

              • acarbose

                acarbose, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • acebutolol

                acebutolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • albiglutide

                albiglutide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • alogliptin

                alogliptin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • aripiprazole

                aripiprazole decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • asenapine

                asenapine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • aspirin

                aspirin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • atazanavir

                atazanavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • atenolol

                atenolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • azilsartan

                azilsartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • benazepril

                benazepril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypoglycemic effects; Monitor blood glucose.

              • bendroflumethiazide

                bendroflumethiazide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • betamethasone

                betamethasone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • betaxolol

                betaxolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • bexagliflozin

                bexagliflozin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.

              • bisoprolol

                bisoprolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • bumetanide

                bumetanide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • canagliflozin

                canagliflozin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • candesartan

                candesartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • captopril

                captopril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose. Monitor blood glucose.

              • cariprazine

                cariprazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • carvedilol

                carvedilol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • chlorothiazide

                chlorothiazide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • chlorpromazine

                chlorpromazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • chlorpropamide

                chlorpropamide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • chlorthalidone

                chlorthalidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • chromium

                chromium, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • clonidine

                clonidine, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.

              • clozapine

                clozapine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • conjugated estrogens

                conjugated estrogens decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • corticotropin

                corticotropin decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • cortisone

                cortisone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • danazol

                danazol decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Danazol may cause insulin resistance.

              • dapagliflozin

                dapagliflozin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • darunavir

                darunavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • dexamethasone

                dexamethasone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • diazoxide

                diazoxide decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Diazoxide increases blood glucose by inhibiting pancreatic insulin release and stimulating catecholamines release.

              • dichlorphenamide

                dichlorphenamide and insulin degludec/insulin aspart both decrease serum potassium. Use Caution/Monitor.

              • dienogest/estradiol valerate

                dienogest/estradiol valerate decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens and progesterones may impair glucose tolerance.

              • disopyramide

                disopyramide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • droxidopa

                droxidopa decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • dulaglutide

                dulaglutide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • empagliflozin

                empagliflozin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with SGLT2 inhibitors.

              • enalapril

                enalapril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • ephedrine

                ephedrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • epinephrine

                epinephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • eprosartan

                eprosartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • erythromycin base

                erythromycin base, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • esmolol

                esmolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • estradiol

                estradiol decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • estrogens conjugated synthetic

                estrogens conjugated synthetic decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • ethacrynic acid

                ethacrynic acid decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • ethinylestradiol

                ethinylestradiol decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • etonogestrel

                etonogestrel decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • exenatide injectable solution

                exenatide injectable solution, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • exenatide injectable suspension

                exenatide injectable suspension, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • fenofibrate

                fenofibrate, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • fenofibrate micronized

                fenofibrate micronized, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • fenofibric acid

                fenofibric acid, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • fludrocortisone

                fludrocortisone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • fluoxetine

                fluoxetine, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • fluphenazine

                fluphenazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • fosamprenavir

                fosamprenavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • fosinopril

                fosinopril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • furosemide

                furosemide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • gemfibrozil

                gemfibrozil, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • glimepiride

                glimepiride, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • glipizide

                glipizide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • glucagon

                glucagon decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Endogenous glucagon is a regulatory hormone that increases blood glucose levels; exogenous glucagon is often used to treat hypoglycemia in patients with diabetes mellitus.

              • glucagon intranasal

                glucagon intranasal decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Endogenous glucagon is a regulatory hormone that increases blood glucose levels; exogenous glucagon is often used to treat hypoglycemia in patients with diabetes mellitus.

              • glyburide

                glyburide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • hydrochlorothiazide

                hydrochlorothiazide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • hydrocortisone

                hydrocortisone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • hydroxyprogesterone caproate (DSC)

                hydroxyprogesterone caproate (DSC) decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • iloperidone

                iloperidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • indapamide

                indapamide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • indinavir

                indinavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • irbesartan

                irbesartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • isocarboxazid

                isocarboxazid, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • isoniazid

                isoniazid decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Isoniazid may increase blood glucose (rare).

              • labetalol

                labetalol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • lanreotide

                lanreotide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • levonorgestrel intrauterine

                levonorgestrel intrauterine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • levonorgestrel oral

                levonorgestrel oral decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • levothyroxine

                levothyroxine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • linagliptin

                linagliptin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • liothyronine

                liothyronine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • liotrix

                liotrix decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • liraglutide

                liraglutide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • lisinopril

                lisinopril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • lithium

                lithium, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Lithium may either increase or decrease the blood glucose lowering effect of antidiabetic agents.

              • lonapegsomatropin

                lonapegsomatropin decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.

              • losartan

                losartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • lurasidone

                lurasidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • magnesium salicylate

                magnesium salicylate, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • mecasermin

                mecasermin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • medroxyprogesterone

                medroxyprogesterone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • megestrol

                megestrol decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • metformin

                metformin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • methyclothiazide

                methyclothiazide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • methylprednisolone

                methylprednisolone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • metolazone

                metolazone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • metoprolol

                metoprolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • miglitol

                miglitol, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • moexipril

                moexipril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • nadolol

                nadolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • nateglinide

                nateglinide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • nebivolol

                nebivolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • nelfinavir

                nelfinavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • niacin

                niacin decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Niacin interferes with glucose metabolism and can result in hyperglycemia.

              • norepinephrine

                norepinephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • norethindrone

                norethindrone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • norethindrone acetate

                norethindrone acetate decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • norethindrone transdermal

                norethindrone transdermal decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • octreotide

                octreotide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • olanzapine

                olanzapine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • olmesartan

                olmesartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • paliperidone

                paliperidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • pasireotide

                pasireotide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • penbutolol

                penbutolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • pentamidine

                pentamidine, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Pentamidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

              • pentoxifylline

                pentoxifylline, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • perindopril

                perindopril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • perphenazine

                perphenazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • phenelzine

                phenelzine, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • phenylephrine

                phenylephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • pindolol

                pindolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • pioglitazone

                pioglitazone, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • pramlintide

                pramlintide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Pramlintide is indicated to be used in combination with insulin; however, pamlintide increases risk of insulin-induced hypoglycemia; reduce prandial insulin dose when initiating pramlintide.

              • prednisolone

                prednisolone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • prednisone

                prednisone decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Endogneous cortisol is a regulatory hormone that increases blood glucose levels; exogenous systemic corticosteroids have been associated with hyperglycemia and may cause diabetes with chronic, high dose use; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • prochlorperazine

                prochlorperazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • progesterone intravaginal gel

                progesterone intravaginal gel decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • progesterone micronized

                progesterone micronized decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • propranolol

                propranolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • pseudoephedrine

                pseudoephedrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

              • quetiapine

                quetiapine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • quinapril

                quinapril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • ramipril

                ramipril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • risperidone

                risperidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • ritonavir

                ritonavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • rosiglitazone

                rosiglitazone, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • sacubitril/valsartan

                sacubitril/valsartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • salsalate

                salsalate, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • saquinavir

                saquinavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • saxagliptin

                saxagliptin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • sitagliptin

                sitagliptin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • somatropin

                somatropin decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Growth hormone decreases insulin sensitivity by opposing the effects of insulin on carbohydrate metabolism.

              • sotagliflozin

                sotagliflozin increases effects of insulin degludec/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Hypoglycemia risk increased. Lower dose of insulin may be required.

              • sotalol

                sotalol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • sulfadiazine

                sulfadiazine, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • sulfisoxazole

                sulfisoxazole, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • telmisartan

                telmisartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • testosterone

                testosterone increases effects of insulin degludec/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • testosterone buccal system

                testosterone buccal system increases effects of insulin degludec/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • testosterone intranasal

                testosterone intranasal increases effects of insulin degludec/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • testosterone topical

                testosterone topical increases effects of insulin degludec/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of antidiabetic medication.

              • thioridazine

                thioridazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • thyroid desiccated

                thyroid desiccated decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Thyroid hormones regulate carbohydrate metabolism, gluconeogenesis, and glycogen stores mobilization; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              • timolol

                timolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

              • tipranavir

                tipranavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

              • tolazamide

                tolazamide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • tolbutamide

                tolbutamide, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Antidiabetic agents are often used in combination; dosage adjustments may be required when initiating or discontinuing antidiabetic agents.

              • torsemide

                torsemide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

              • trandolapril

                trandolapril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • tranylcypromine

                tranylcypromine, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • triamcinolone acetonide injectable suspension

                triamcinolone acetonide injectable suspension decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Corticosteroids may diminish hypoglycemic effect of antidiabetic agents. Monitor blood glucose levels carefully.

              • trifluoperazine

                trifluoperazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • valsartan

                valsartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • ziprasidone

                ziprasidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Atypical antipsychotics have been associated with hyperglycemia that may alter blood glucose control; dose of antidiabetic agents may need adjustment and increased frequency of glucose monitoring may be required.

              Minor (1)

              • stevia

                stevia increases effects of insulin degludec/insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

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              Adverse Effects

              >10%

              Nasopharyngitis (11.1-24.6%)

              Severe hypoglycemia (0.4-13.3%)

              1-10%

              Headache (5.6-9.7%)

              URT infection (5.7-9.1%)

              Influenza (6.9%)

              Peripheral edema (1.8-2.2%)

              Injection site reaction (2%)

              <1%

              Allergic reaction

              Lipodystrophy

              Postmarketing reports

              Localized cutaneous amyloidosis at injection site

              Hypersensitivity

              Hypokalemia

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              Warnings

              Contraindications

              During episodes of hypoglycemia

              Documented hypersensitivity

              Cautions

              Do not share, even if the needle is changed; sharing poses a risk for transmission of blood-borne pathogens

              Changes in insulin, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia; these changes should be made cautiously and only under medical supervision, and the frequency of blood glucose monitoring should be increased

              Severe, life-threatening, generalized allergy, including anaphylaxis, can occur

              All insulin products cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia; monitor potassium levels in patients at risk for hypokalemia including patients using potassium-lowering medications or those taking medications sensitive to serum potassium concentrations; treat if indicated

              Thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists can cause dose-related fluid retention, particularly when used in combination with insulin; this may lead to or exacerbate heart failure

              Hyperglycemia or hypoglycemia with changes in insulin regimen

              • Hypoglycemia is the most common adverse effect and can happen suddenly; severe hypoglycemia can cause seizures, may be life-threatening, or cause death
              • Hypoglycemia can impair concentration ability and reaction time and place an individual and others at risk in situations where these abilities are important (eg, driving or operating other machinery)
              • Risk increases with intensity of glycemic control and is related to the duration of action of the insulin
              • Other factors that may increase the risk of hypoglycemia include changes in meal pattern (eg, macronutrient content or timing of meals), changes in level of physical activity, or changes to coadministered medication
              • Renal or hepatic impairment may increase hypoglycemia risk
              • In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended
              • Accidental mix-ups between basal insulin products and other insulins, particularly rapid-insulins, have been reported
              • Do not transfer insulin degludec from the prefilled pen to a syringe; the markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia
              • Changes in insulin, insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia
              • Changes should be made cautiously and only under close medical supervision and frequency of blood glucose monitoring should be increased
              • Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis reported to result in hyperglycemia; a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia
              • Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring
              • Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change injection site to unaffected areas and closely monitor for hypoglycemia
              • For patients with type 2 diabetes, dosage adjustments in concomitant oral antidiabetic treatment may be needed
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              Pregnancy

              Pregnancy

              There are no available data in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; available data from one unpublished trial and the published literature with insulin degludec use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

              Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes; poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity

              Lactation

              There are no data on presence of drug in human milk, effects on breastfed infant, or effect on milk production; insulin degludec is present in rat milk; one small published study reported that exogenous insulin, including insulin aspart, was present in human milk; however, there is insufficient information to determine effects on the breastfed infant and no available information on effects on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for insulin, potential adverse effects on breastfed child therapy or from underlying maternal condition

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Insulin degludec: Long-acting basal insulin

              Insulin aspart: Rapid-acting insulin

              Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production; insulin inhibits lipolysis and proteolysis and enhances protein synthesis; targets include skeletal muscle, liver, and adipose tissue

              Absorption

              Onset of action (insulin aspart): 14 min

              Peak plasma time: 9 hr insulin degludec; 72 min insulin aspart

              Steady state (insulin degludec): 3-4 days

              Distribution

              Protein bound: >99% to albumin insulin degludec; <10% insulin aspart

              Metabolism

              Metabolites: Inactive

              Elimination

              Half-life: ~25 hr insulin degludec

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              Administration

              Preparation

              Inspect visually for particulate matter and discoloration; only use if the solution appears clear and colorless

              Do not dilute or mix with any other insulin products or solutions

              Do not transfer drug from the insulin degludec pen into a syringe for administration

              SC Administration

              Inject SC once or twice daily with any main meal and in pediatric patients once daily with any main meal

              Administer a rapid- or a short-acting insulin at other meals if needed

              Patients with type 1 diabetes, will generally require a rapid- or short-acting insulin at meals when insulin degludec/insulin aspart 70/30 is not administered for optimal glucose control

              Individualize and titrate the dose based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal

              Adjust dose according to blood glucose measurements before breakfast (fasting)

              Inject SC into the thigh, upper arm, or abdomen

              The recommended days between dose increases is 3-4 days

              Dose adjustments may be needed with changes in physical activity, changes in meal patterns (ie, macronutrient content or timing of food intake), changes in renal or hepatic function, or during acute illness to minimize the risk of hypoglycemia or hyperglycemia

              If a dose of insulin degludec/insulin aspart 70/30 is missed, the next dose should be taken with the next main meal of that day and thereafter resume the usual dosing schedule; patients should not take an extra dose to make up for a missed dose

              Storage

              Unopened (not in-use) prefilled pen

              • Refrigerate at 36-46°F (2-8°C)
              • Do not store in the freezer or directly adjacent to the refrigerator cooling element
              • Do not freeze
              • Do not use if it has been frozen

              Open (in-use) prefilled pen

              • Should NOT be refrigerated but should be kept at room temperature (<86°F [30°C])
              • Keep away from direct heat and light
              • The opened pen may be used for up to 28 days (4 wk) after being opened, if it is kept at room temperature
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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.