insulin degludec (Rx)

Brand and Other Names:Tresiba
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution (prefilled pen, FlexTouch)

  • 100 units/mL
  • 200 units/mL

Type 1 Diabetes Mellitus

Long-acting basal insulin indicated to improve glycemic control in patients with diabetes mellitus

Initial dose

  • For insulin-naïve patients
    • Start ~1/3 to 1/2 of the total daily insulin dose; use remaining of total daily insulin dose on short-acting insulin and divided between each daily meal
    • Usual initial dose range: 0.2-0.4 units/kg
    • See Dosing Consideration and Administration

Type 2 Diabetes Mellitus

Long-acting basal insulin indicated to improve glycemic control in adults with type 2 diabetes mellitus

Initial dose

  • For insulin-naïve patients
    • Start 10 units SC qDay
    • See Dosing Consideration and Administration

Dosage Modifications

Hepatic impairment

  • No difference in the pharmacokinetics of insulin degludec was identified in a study comparing healthy subjects and subjects with hepatic impairment (mild, moderate, and severe hepatic impairment)

Renal impairment

  • No clinically relevant difference in the pharmacokinetics of insulin degludec was identified in a study comparing healthy subjects and subjects with renal impairment including subjects with end stage renal disease

Dosing Considerations

Use insulin degludec with caution in patients with visual impairment that may rely on audible clicks to dial their dose

Starting dose in patients already on insulin therapy

  • Type 1 or 2 diabetes mellitus: Start insulin degludec at the same unit dose as the total daily long or intermediate-acting insulin unit dose

Limitation of use

  • Not indicated for diabetic ketoacidosis

Dosage Forms & Strengths

injectable solution (prefilled pen, FlexTouch)

  • 100 units/mL
  • 200 units/mL

Type 1 Diabetes Mellitus

Long-acting basal insulin indicated to improve glycemic control in children and adolescents aged 1-17 yr with type 1 diabetes mellitus

<1 year: Safety and efficacy not established

Children and adolescents aged 1-17 years

  • Starting dose in insulin naïve patients
    • Start ~1/3 to 1/2 of the total daily insulin dose; use remaining of total daily insulin dose on short-acting insulin and divided between each daily meal
    • Usual initial dose range: 0.2-0.4 units/kg
    • See Dosing Consideration and Administration

Type 2 Diabetes Mellitus

Long-acting basal insulin indicated to improve glycemic control in children and adolescents aged 1-17 yr with type 2 diabetes mellitus

<1 year: Safety and efficacy not established

Children and adolescents aged 1-17 years

  • Starting dose in insulin naïve patients
    • 10 units SC qDay
    • See Dosing Consideration and Administration

Dosing Considerations

Limitations of use

  • Not indicated for diabetic ketoacidosis
  • Not recommended for pediatric patients requiring <5 units of insulin degludec
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Interactions

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              • ethanol

                ethanol, insulin degludec. 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.

              • macimorelin

                insulin degludec, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may transiently elevate growth hormone (GH) concentrations may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.

              Monitor Closely (175)

              • acarbose

                acarbose, insulin degludec. 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. 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. 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. 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 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 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 increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

              • atazanavir

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

                azilsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • benazepril

                benazepril, insulin degludec. 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 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 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. 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).

              • bisoprolol

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

                candesartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • captopril

                captopril, insulin degludec. 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 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. 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 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 by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • chlorpropamide

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

              • clonidine

                clonidine, insulin degludec. 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 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 by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • corticotropin

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

              • dapagliflozin

                dapagliflozin, insulin degludec. 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 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.

              • deflazacort

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

              • dexamethasone

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

              • dichlorphenamide

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

              • dienogest/estradiol valerate

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

              • disopyramide

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

                disopyramide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and disopyramide may require insulin dosage adjustment and increased glucose monitoring.

              • droxidopa

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

              • ephedrine

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

                eprosartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • ertugliflozin

                ertugliflozin, insulin degludec. 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 ertugliflozin.

              • erythromycin base

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

              • esmolol

                esmolol, insulin degludec. 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 by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may impair glucose tolerance.

              • estrogens conjugated synthetic

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

              • ethacrynic acid

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

              • etonogestrel

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

              • exenatide injectable solution

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

              • fenofibrate micronized

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

              • fenofibric acid

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

              • fludrocortisone

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

                fluoxetine increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and fluoxetine may require insulin dosage adjustment and increased glucose monitoring.

              • fluphenazine

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

              • fosamprenavir

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

              • furosemide

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

              • glimepiride

                glimepiride, insulin degludec. 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. 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 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 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. 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 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 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

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

              • iloperidone

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

                irbesartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • isocarboxazid

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

              • isoniazid

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

              • labetalol

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

                lanreotide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.

              • levonorgestrel intrauterine

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

              • levonorgestrel oral

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

              • levothyroxine

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

              • lithium

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

                lithium, insulin degludec. unspecified interaction mechanism. Use Caution/Monitor. Lithium salts may cause either hypoglycemia or hyperglycemia. Insulin dosage adjustment and increased glucose monitoring may be required.

              • lixisenatide

                lixisenatide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of hypoglycemia increased when coadministered with basal insulins. Basal insulin dose reduction may be required.

              • losartan

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

                losartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • lurasidone

                lurasidone decreases effects of insulin degludec 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 increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

              • mecasermin

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

              • medroxyprogesterone

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

              • megestrol

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

              • metformin

                metformin, insulin degludec. 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 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 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.

              • metoclopramide intranasal

                metoclopramide intranasal increases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Increased GI motility by metoclopramide may increase delivery of food to the intestines and increase blood glucose. Monitor blood glucose and adjust insulin dosage regimen as needed.

              • metolazone

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

              • nadolol

                nadolol, insulin degludec. 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. 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. 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 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 by pharmacodynamic antagonism. Use Caution/Monitor. Concomitant use of insulin and niacin may require insulin dosage adjustment and increased glucose monitoring.

              • norepinephrine

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

              • norethindrone acetate

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

              • norethindrone transdermal

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

              • octreotide

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

                octreotide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.

              • olanzapine

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

                olmesartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • paliperidone

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

                pasireotide increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and somatostatin analogs may require insulin dosage adjustment and increased glucose monitoring.

              • penbutolol

                penbutolol, insulin degludec. 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. 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.

                pentamidine, insulin degludec. unspecified interaction mechanism. Use Caution/Monitor. Pentamidine may cause either hypoglycemia or hyperglycemia followed by the opposing effect. Insulin dosage adjustment and increased glucose monitoring may be required.

              • pentoxifylline

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

              • perindopril

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

              • perphenazine

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

              • phenelzine

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

              • phenylephrine

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

              • progesterone micronized

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

              • propranolol

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

              • ramipril

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

              • risperidone

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

                sacubitril/valsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • salsalate

                salsalate increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

              • saquinavir

                saquinavir decreases effects of insulin degludec 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. 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.

              • semaglutide

                semaglutide, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with GLP-1 agonists may increase hypoglycemia risk. Lowering the insulin dose may reduce hypoglycemia risk.

              • sitagliptin

                sitagliptin, insulin degludec. 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.

              • sodium sulfate/?magnesium sulfate/potassium chloride

                sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              • sodium sulfate/potassium sulfate/magnesium sulfate

                sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              • somapacitan

                somapacitan decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating somapacitan. .

              • somatropin

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

              • sotalol

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

                sulfadiazine increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and sulfonamide antibiotics may require insulin dosage adjustment and increased glucose monitoring.

              • sulfisoxazole

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

                sulfisoxazole increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and sulfonamide antibiotics may require insulin dosage adjustment and increased glucose monitoring.

              • telmisartan

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

                telmisartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • testosterone

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

              • thyroid desiccated

                thyroid desiccated decreases effects of insulin degludec 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. 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 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. 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. 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 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. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              • tranylcypromine

                tranylcypromine, insulin degludec. 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 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 by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

              • valsartan

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

                valsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              • ziprasidone

                ziprasidone decreases effects of insulin degludec 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 by pharmacodynamic synergism. Minor/Significance Unknown.

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              Adverse Effects

              >10%

              Nasopharyngitis (12.9-23.9%)

              Severe hypoglycemic episode (0.3-12.3%)

              Upper respiratory tract infection (8.4-11.9%)

              Headache (8.8-11.8%)

              1-10%

              Diarrhea (6.3%)

              Sinusitis (5.1%)

              Gastroenteritis (5.1%)

              Injection site reactions (3.8%)

              Peripheral edema (0.9-3%)

              <1%

              Lipodystrophy

              Postmarketing Reports

              Localized cutaneous amyloidosis at the injection

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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

              To avoid dosing errors and potential overdose, never use a syringe to remove drug from pen injector into a syringe

              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

              Drug interactions overview

              • Thiazolidinediones are peroxisome proliferator-activated receptor (PPAR)-gamma agonists and can cause dose-related fluid retention, particularly when used in combination with insulin; fluid retention may lead to or exacerbate heart failure; monitor for signs and symptoms of heart failure, treat accordingly, and consider discontinuing thiazolidinediones
              • Coadministration with these drugs (eg, antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs [eg, octreotide], sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors) may increase the risk of hypoglycemia
              • Coadministration with these drugs (eg, atypical antipsychotics [eg, olanzapine and clozapine], corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens [eg, oral contraceptives], protease inhibitors, somatropin, sympathomimetic agents [eg, albuterol, epinephrine, terbutaline], and thyroid hormones) may decrease the risk of hypoglycemia
              • Concomitant use of alcohol, beta-blockers, clonidine, and lithium salts with insulin degludec may increase or decrease blood glucose lowering effect of insulin glargine
              • Pentamidine may cause hypoglycemia, which may sometimes be followed with hyperglycemia
              • Coadministration with beta-blockers, clonidine, guanethidine, or reserpine may blunt signs and symptoms of hypoglycemia
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              Pregnancy

              Pregnancy

              There are no available data with insulin degludec in pregnant women to inform a drug-associated risk for major birth defects and miscarriage

              There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy

              Animal studies

              • The effect of insulin degludec was consistent with those observed with human insulin as both caused preimplantation and postimplantation losses and visceral/skeletal abnormalities in rats at an insulin degludec dose of 21 U/kg/day (~5 times the human exposure [AUC] at a human SC dose of 0.75 U/kg/day) and in rabbits at a dose of 3.3 U/kg/day (~10 times the AUC at a human SC dose of 0.75 U/kg/day)
              • The effects are probably secondary to maternal hypoglycemia

              Lactation

              There are no data on the presence of insulin degludec in human milk, the effects on the breastfed infant, or the effects on milk production

              Insulin degludec is present in rat milk

              Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the 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

              Once-daily basal insulin analogue

              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

              Peak plasma time: 9 hr

              Peak plasma concentration: 4472 pmol/L

              Steady state: 3-4 days

              Distribution

              Protein bound: >99% to albumin

              Metabolism

              Metabolites: Inactive

              Elimination

              Half-life: ~25 hr

              Clearance: 0.03 L/kg

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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 daily at any time of day

              Inject SC into the thigh, upper arm, or abdomen

              Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy

              Do not administer IV, IM, or in an insulin infusion pump

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

              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

              Instruct patients who miss a dose to inject their daily dose during waking hours upon discovering the missed dose

              Instruct patients to ensure that at least 8 hr have elapsed between consecutive insulin degludec injections

              DO NOT perform dose conversion when using the insulin degludec U-100 or U-200 FlexTouch pens; the dose window for both the U-100 and U-200 FlexTouch pens shows the number of insulin units to be delivered and NO conversion is needed

              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

              • Refrigerate at 36-46°F (2-8°C) or store at room temperature (<86°F [30°C]) for up to 56 days (8 wk)
              • Do not freeze
              • Keep away from direct heat and light
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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              Tresiba U-100 Insulin subcutaneous
              -
              100 unit/mL vial
              Tresiba FlexTouch U-100 subcutaneous
              -
              100 unit/mL (3 mL) insulin pen
              Tresiba FlexTouch U-200 subcutaneous
              -
              200 unit/mL (3 mL) insulin pen

              Copyright © 2010 First DataBank, Inc.

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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.
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              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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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.