insulin inhaled (Rx)

Brand and Other Names:Afrezza
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

orally inhaled powder

  • Available as single-use cartridges
  • 4 units/cartridge
  • 8 units/cartridge
  • 12 units/cartridge

Diabetes Mellitus (Types 1 and 2)

Orally inhaled rapid-acting insulin indicated to improve glycemic control in adults with diabetes mellitus

Dosing must be individualized

Starting mealtime dose

  • Insulin naïve: 4 units at each meal initially
  • Converting from SC mealtime (prandial) insulin: Determine the appropriate inhaled insulin dose for each meal by converting from the injected dose (see Mealtime dose conversion)
  • Using SC premixed insulin: Estimate the mealtime injected dose by dividing half of the total daily injected premixed insulin dose equally among the 3 meals of the day; convert each estimated injected mealtime dose to an appropriate inhaled insulin dose (see Mealtime dose conversion); administer half of the total daily injected premixed dose as an injected basal insulin dose

Mealtime dose conversion

  • Dosage adjustment may be needed when switching from insulin to inhaled insulin
  • Up to 4 units SC = 4 units inhaled
  • 5-8 units SC = 8 units inhaled
  • 9-12 units SC = 12 units inhaled
  • 13-16 units SC = 16 units inhaled
  • 17-20 units SC = 20 units inhaled
  • 21-24 units SC = 24 units inhaled

Dose adjustment

  • Adjust the inhaled insulin dosage based on the individual's metabolic needs, blood glucose monitoring results, and glycemic control goal
  • Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (ie, macronutrient content or timing of food intake), and changes in renal or hepatic function or during acute illness
  • Carefully monitor blood glucose control in patients requiring high doses; if blood glucose control is not achieved with increased inhaled insulin doses, consider use of SC mealtime insulin

Dosing Considerations

Before initiating, perform a detailed medical history, physical examination, and spirometry (FEV1) in all patients to identify potential lung disease

Limitations of use

  • Not a substitute for long-acting insulin; must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus
  • Not recommended for treatment of diabetic ketoacidosis
  • Safety and efficacy not established in patients who smoke and is not recommended in patients who smoke or who have recently stopped smoking

<18 years: Safety and efficacy not established

See adult dosing

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Interactions

Interaction Checker

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              • ethanol

                ethanol, insulin inhaled. 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 inhaled, 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 (174)

              • acarbose

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

                azilsartan increases effects of insulin inhaled 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 inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypoglycemic effects; Monitor blood glucose.

              • bendroflumethiazide

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

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

              • chlorpropamide

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

              • clonidine

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

              • corticotropin

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

              • dapagliflozin

                dapagliflozin, insulin inhaled. 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 inhaled 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 inhaled and deflazacort both decrease serum potassium. Use Caution/Monitor.

              • dexamethasone

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

              • dichlorphenamide

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

              • dienogest/estradiol valerate

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

              • disopyramide

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

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

              • ephedrine

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

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

              • esmolol

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

              • estrogens conjugated synthetic

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

              • ethacrynic acid

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

              • etonogestrel

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

              • exenatide injectable solution

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

              • fenofibrate micronized

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

              • fenofibric acid

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

              • fludrocortisone

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

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

              • fosamprenavir

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

              • furosemide

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

              • glimepiride

                glimepiride, insulin inhaled. 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 inhaled. 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 inhaled 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 inhaled 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 inhaled. 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 inhaled 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 inhaled 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 inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • iloperidone

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

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

              • isoniazid

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

              • labetalol

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

                lanreotide increases effects of insulin inhaled 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 inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • levonorgestrel oral

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

              • levothyroxine

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

              • lithium

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

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

              • losartan

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

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

              • medroxyprogesterone

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

              • megestrol

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

              • metformin

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

              • nadolol

                nadolol, insulin inhaled. 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 inhaled. 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 inhaled. 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 inhaled 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 inhaled 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 inhaled 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 inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Progestins may impair glucose tolerance.

              • norethindrone acetate

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

              • norethindrone transdermal

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

              • octreotide

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

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

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

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

              • perindopril

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

              • perphenazine

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

              • phenelzine

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

              • phenylephrine

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

              • progesterone intravaginal gel

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

              • progesterone micronized

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

              • propranolol

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

              • ramipril

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

              • risperidone

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

                sacubitril/valsartan increases effects of insulin inhaled 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 inhaled 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 inhaled 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 inhaled. 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 inhaled. 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 inhaled. 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 inhaled 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 inhaled 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 inhaled 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 inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Growth hormone decreases insulin sensitivity by opposing the effects of insulin on carbohydrate metabolism.

              • sotalol

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

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

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

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

              • thyroid desiccated

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

              • tranylcypromine

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

              • valsartan

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

                valsartan increases effects of insulin inhaled 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 inhaled 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 (0)

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                Adverse Effects

                >10%

                Nonsevere hypoglycemia (67%)

                Cough (25.6-29.4%)

                1-10%

                Throat pain or irritation (4.4-5.5%)

                Severe hypoglycemia (5.1%)

                Headache (3.1-4.7%)

                Pulmonary function test decreased (2.8%)

                Diarrhea (2.7%)

                Bronchitis (2.5%)

                Urinary tract infection (2.3%)

                Productive cough (2.2%)

                Fatigue (2%)

                Nausea (2%)

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                Warnings

                Black Box Warnings

                Acute bronchospasm reported in patients with asthma and COPD using inhaled insulin

                Contraindicated in patients with chronic lung disease

                Before initiating, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients

                Contraindications

                During episodes of hypoglycemia

                Chronic lung disease (eg, asthma, COPD), because of the risk of acute bronchospasm

                Hypersensitivity to regular human insulin or any inhaled insulin excipients

                Cautions

                Acute bronchospasm observed in patients with asthma and COPD; before initiating, perform spirometry (FEV1) in all patients; do not use in patients with chronic lung disease

                Change insulin regimen under close medical supervision and increase frequency of blood glucose monitoring

                Hypoglycemia reported and may be life-threatening; increase frequency of glucose monitoring with changes to insulin dosage, coadministered glucose-lowering medications, meal pattern, and physical activity; and in patients with renal or hepatic impairment and hypoglycemia unawareness

                Assess pulmonary function (eg, spirometry) before initiating, after 6 months of therapy, and annually, even in the absence of pulmonary symptoms

                Two cases (2 in 2750 patient-years exposure) of lung cancer reported during clinical trials, both were in patients with history of heavy smoking; 2 additional cases of lung cancer (squamous cell and lung blastoma) occurred in nonsmokers were reported by investigators after clinical trial completion; in patients with active lung cancer, a prior history of lung cancer, or those at risk for lung cancer, consider whether the benefits of use outweigh this potential risk

                More patients using inhaled insulin (0.43%) experienced diabetic ketoacidosis in clinical trials compared with comparators (0.14%); monitor and change to alternate route of insulin delivery, if indicated

                Hypersensitivity reactions, including severe, life-threatening, generalized allergy, and anaphylaxis can occur with insulin products

                Hypokalemia may occur, including life-threatening low serum levels; monitor potassium levels in patients at risk

                Monitor for fluid retention and heart failure with concomitant use of thiazolidinediones; consider dosage reduction or discontinuation if heart failure occurs

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                Pregnancy & Lactation

                Pregnancy

                Limited available data with in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes; available information from published studies with human insulin use during pregnancy has not reported a clear association with human insulin and adverse developmental outcomes; there are risks to mother and fetus associated with poorly controlled diabetes in pregnancy; in animal reproduction studies, there were no adverse developmental outcomes with subcutaneous administration of carrier particles (vehicle without insulin) to pregnant rats during organogenesis at doses 14-21 times the maximum recommended daily dose

                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 the presence in human milk, effects on breastfed infant, or on milk production; one small published study reported that exogenous insulin was present in human milk; no adverse effects in infants were noted; carrier particles are present in rat milk; potential adverse effects that are related to inhalational administration are unlikely to be associated with potential exposure through breast milk; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant 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

                Recombinant regular human insulin administered as a powder for oral inhalation

                Lowers blood glucose levels by stimulating peripheral glucose uptake by skeletal muscle and fat and by inhibiting hepatic glucose production

                Inhibits lipolysis in adipocytes, inhibits proteolysis, and enhances protein synthesis

                Pharmacokinetics

                Peak plasma time: 12-15 minutes

                Median time to maximum effect: ~53 minutes (SD: 74 minutes)

                Return to baseline levels: 160 minutes

                39% of dose distributed to the lungs

                7% of dose swallowed

                Half-life: 28-39 minutes

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                Administration

                Inhaled Administration

                Administer via oral inhalation only at the beginning of a meal

                Administer using a single inhalation per cartridge

                Keep inhaler level and white mouthpiece on top and purple base on the bottom after a cartridge has been inserted into the inhaler

                Loss of drug effect can occur if the inhaler is turned upside down, held with the mouthpiece pointing down, or shaken (or dropped) after the cartridge has been inserted but before the dose has been administered

                If any of the above occurs, the cartridge should be replaced before use

                The inhaler can be used for up to 15 days from the date of first use; after 15 days of use, the inhaler must be discarded and replaced with a new inhaler

                See complete illustrated administration instructions provided in packaging

                Inhaled insulin doses >12 units

                • Doses >12 units require inhalations from multiple cartridges
                • To achieve the required total mealtime dose, patients should use a combination of 4-unit, 8-unit, and 12-unit cartridges
                • For doses >24 units, combinations of different multiple cartridges can be used

                Storage

                Before use, cartridges and inhaler should be at room temperature for 10 minutes

                Cartridges not in use

                • Sealed [unopened] cartridges in foil package
                • Refrigerate at 2-8ºC (36-46ºF)
                • If foil package is not refrigerated, must use within 10 days

                Cartridges in use

                • Store at room temperature (25ºC [77ºF]), excursions permitted 15-30ºC (59-86ºF)
                • Sealed [unopened] blister cards and strips: Must be used within 10 days
                • Opened strips: Must be used within 3 days

                Inhaler

                • May be refrigerated, but should be at room temperature before use
                • Store between 2-25ºC (36-77ºF); excursions permitted
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                Images

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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.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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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.