Insulin (Oral Inhalation)
Medically reviewed by Drugs.com. Last updated on Oct 15, 2020.
(IN soo lin)
- Inhaled Insulin
- Technosphere Insulin (TI)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Afrezza: 4 units (90 ea); 8 units (90 ea); 12 units (90 ea); 4 units & 8 units (90 ea [DSC], 180 ea); 8 units & 12 units (90 ea [DSC]); 90 x 8 UNIT & 90x12 UNIT (180 ea); 4 units & 8 units & 12 units (180 ea) [contains polysorbate 80]
Brand Names: U.S.
- Insulin, Rapid-Acting
Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. Target organs for insulin include the liver, skeletal muscle, and adipose tissue.
Within the liver, insulin stimulates hepatic glycogen synthesis. Insulin promotes hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. Skeletal muscle effects of insulin include increased protein synthesis and increased glycogen synthesis. Within adipose tissue, insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes; also directly inhibits the hydrolysis of triglycerides. In addition, insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.
Normally secreted by the pancreas, insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae. Inhaled human insulin has an identical structure to that of native human insulin and is adsorbed onto carrier particles which dissolve within the lungs after inhalation leading to rapid absorption of insulin in the systemic circulation. Insulins are categorized based on the onset, peak, and duration of effect (eg, rapid-, short-, intermediate-, and long-acting insulin). Inhaled insulin is an ultra-rapid acting insulin.
Onset of Action
~12 minutes; Peak effect: ~35 to 55 minutes
Time to Peak
10 to 20 minutes
Duration of Action
~90 to 270 minutes (proportional to dose)
120 to 206 minutes (apparent terminal half-life)
Use: Labeled Indications
Diabetes mellitus, type 1 or type 2, treatment: Treatment of type 1 diabetes mellitus and type 2 diabetes mellitus to improve glycemic control.
Hypersensitivity to regular insulin or any component of the formulation; during episodes of hypoglycemia; chronic lung disease such as asthma or COPD, due to risk of bronchospasm.
Documentation of allergenic cross-reactivity for insulin is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Diabetes mellitus, types 1 and 2, treatment: Note: Insulin requirements vary dramatically between patients and therapy requires dosage adjustments with careful medical supervision. Inhaled insulin must be used concomitantly with long-acting (basal) insulin in patients with type 1 diabetes. In patients with type 2 diabetes, rapid-acting insulins (including inhaled insulin) are typically added at one or more meals if adequate glycemic control is not achieved with basal insulin alone (ADA 2020).
Insulin-naive patients: 4 units at each meal.
Patients previously on SubQ mealtime (prandial) insulin:
≤4 units injected dose per meal: 4 units inhalation dose per meal.
5 to 8 units injected dose per meal: 8 units inhalation dose per meal.
9 to 12 units injected dose per meal: 12 units inhalation dose per meal.
13 to 16 units injected dose per meal: 16 units inhalation dose per meal.
17 to 20 units injected dose per meal: 20 units inhalation dose per meal.
21 to 24 units injected dose per meal: 24 units inhalation dose per meal.
Patients previously on SubQ premixed insulin:
To replace the basal insulin component, administer half of the total daily injected premixed dose as an injected basal insulin dose.
To replace the mealtime insulin component with inhaled insulin, first estimate the mealtime injected dose by dividing half of the total daily injected premixed insulin dose equally among the three meals of the day. Then, convert each estimated injected mealtime dose to a mealtime inhalation dose based upon the following scale:
Estimated ≤4 units injected dose per meal: 4 units inhalation dose per meal.
Estimated 5 to 8 units injected dose per meal: 8 units inhalation dose per meal.
Estimated 9 to 12 units injected dose per meal: 12 units inhalation dose per meal.
Estimated 13 to 16 units injected dose per meal: 16 units inhalation dose per meal.
Estimated 17 to 20 units injected dose per meal: 20 units inhalation dose per meal.
Estimated 21 to 24 units injected dose per meal: 24 units inhalation dose per meal.
Adjustment of dose: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Adjust dose based on metabolic needs, blood glucose monitoring results and glycemic control goal. Carefully monitor blood glucose control in patients requiring high inhalation doses. If blood glucose control is not achieved with increased inhalation doses, consider the use of SubQ mealtime insulin. Treatment and monitoring regimens must be individualized.
Inhaled insulin is adjusted in 4-unit increments. The following dosage adjustments for injectable prandial insulin are recommended in patients with type 2 diabetes (ADA 2020):
To reach self-monitoring glucose target: Adjust dose by 10% to 15%.
For hypoglycemia: If no clear reason for hypoglycemia, decrease dose by 10% to 20%; for severe hypoglycemia (ie, requiring assistance from another person or blood glucose <40 mg/dL) reduce dose by 20% to 40%.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Refer to adult dosing.
For oral inhalation only. Administer at the beginning of the meal. Remove the amount/strength of cartridges needed for a single dose from packaging; multiple cartridges may be needed to achieve the correct dose. Allow cartridges to sit at room temperature for 10 minutes. Insert cartridge into the inhaler and snap to close. Keep inhaler level with mouthpiece on top and base on the bottom. Loss of drug may occur if inhaler is inverted, held with mouthpiece pointing down, shaken or dropped after cartridge is inserted but prior to dose administration. If any of these actions occur, a new cartridge must be loaded into the inhaler. Exhale fully. Close lips tightly around mouthpiece; do not exhale into inhaler. Tilt inhaler downward while keeping head level and inhale (rapidly, steadily and deeply). Hold breath for as long as comfortable at the same time removing the inhaler from the mouth. Exhale and continue to breathe normally. Throw away empty cartridge by removing it from the base; do not leave in inhaler. Repeat the steps for each cartridge needed for the correct total dose; use only one inhaler for multiple cartridges. Replace the inhaler every 15 days to maintain accurate drug delivery.
Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.
Prior to use (sealed package): Store at 2ºC to 8ºC (36°F to 46°F). If foil package is not refrigerated, contents must be used within 10 days.
In use: Once foil package has been opened, store blister cards and strips at room temperature 25ºC (77ºF); excursions are permitted between 15°C and 30°C (59°F and 86°F). Unopened blister cards and strips must be used within 10 days; opened strips must be used within 3 days. Inhaler may be stored refrigerated, but should be at room temperature prior to use. Cartridges should also be at room temperature for 10 minutes before administration.
Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulins. Monitor therapy
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Insulins. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Liraglutide: May enhance the hypoglycemic effect of Insulins. Management: Consider reducing the liraglutide dose if coadministered with insulin. Prescribing information for the Saxenda brand of liraglutide recommends a dose decrease of 50%. Monitor blood glucose for hypoglycemia. Consider therapy modification
Macimorelin: Insulins may diminish the diagnostic effect of Macimorelin. Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Metreleptin: May enhance the hypoglycemic effect of Insulins. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs and symptoms of hypoglycemia. Consider therapy modification
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Pioglitazone: May enhance the adverse/toxic effect of Insulins. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, consider insulin dose reductions to avoid hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure, and consider pioglitazone dose reduction or discontinuation if heart failure occurs Consider therapy modification
Pramlintide: May enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Rosiglitazone: Insulins may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Endocrine & metabolic: Hypoglycemia (67%)
Respiratory: Acute bronchospasm (patients with asthma: 29%), cough (26% to 29%)
1% to 10%:
Central nervous system: Headache (5%), fatigue (2%)
Endocrine & metabolic: Severe hypoglycemia (5%)
Gastrointestinal: Sore throat (≤6%), diarrhea (3%), nausea (2%)
Genitourinary: Urinary tract infection (2%)
Respiratory: Reduced forced expiratory volume (6%; ≥15% decline), throat irritation (≤6%), bronchitis (3%), decreased lung function (3%), productive cough (2%)
<1%, postmarketing, and/or case reports: Antibody development (drug efficacy not affected), diabetic ketoacidosis (diabetes mellitus, type 1), hypersensitivity reaction, hypokalemia
ALERT: U.S. Boxed WarningRisk of Acute Bronchospasm in Patients with Chronic Lung Disease
Acute bronchospasm has been observed in patients with asthma and COPD using inhaled insulin. Use is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating inhaled insulin, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.
Concerns related to adverse effects:
• Diabetic ketoacidosis: In clinical trials involving type 1 diabetic patients, diabetic ketoacidosis (DKA) was observed more commonly with inhaled insulin than with comparators; increase glucose monitoring in patients at risk of DKA (eg, acute illness, infection) and if necessary, consider an alternative route of insulin administration. Inhaled insulin is not recommended for treatment of DKA.
• Hypersensitivity: Severe, life-threatening, generalized allergic reactions, including anaphylaxis, may occur. If hypersensitivity reactions occur, discontinue therapy, treat the patient with supportive care and monitor until signs and symptoms resolve.
• Hypoglycemia: The most common adverse effect of insulin is hypoglycemia. The timing of hypoglycemia differs among various insulin formulations. Hypoglycemia may result from increased work or exercise without eating; use of long-acting insulin preparations (eg, insulin degludec, insulin detemir, insulin glargine) may delay recovery from hypoglycemia. Profound and prolonged episodes of hypoglycemia may result in convulsions, unconsciousness, temporary or permanent brain damage, or even death. Insulin requirements may be altered during illness, emotional disturbances, or other stressors. Instruct patients to use caution with ethanol; may increase risk of hypoglycemia.
• Hypokalemia: Insulin causes a shift of potassium from the extracellular space to the intracellular space, possibly producing hypokalemia. If left untreated, hypokalemia may result in respiratory paralysis, ventricular arrhythmia and even death. Use with caution in patients at risk for hypokalemia (eg, loop diuretic use). Monitor serum potassium in patients at risk for hypoglycemia.
• Lung cancer: Rare cases of cancer have been reported. In clinical trials, 2 cases were reported in patients with a history of heavy tobacco use; after clinical trial completion, 2 additional cases were reported in nonsmokers. The effect of inhalation powder on the development of lung or respiratory tract tumors is unknown. Use caution in patients with active lung cancer, a prior history of lung cancer, or in patients at risk for lung cancer.
• Pulmonary lung function decline: May cause a decline in lung function (measured by FEV1) over time; decline was observed within the first 3 months of therapy and persisted, but did not worsen, for therapy duration, up to 2 years. Assess PFTs at baseline, after the first 6 months of therapy and yearly thereafter, even in the absence of pulmonary symptoms. If FEV1 decline of ≥20% is observed, consider discontinuation. Frequently monitor patients with wheezing, persistent or recurring cough, bronchospasm, or breathing difficulties. If symptoms persist, discontinue the product.
• Bariatric surgery:
– Type 2 diabetes, hypoglycemia: Closely monitor insulin dose requirement throughout active weight loss with a goal of eliminating antidiabetic therapy or transitioning to agents without hypoglycemic potential; hypoglycemia after gastric bypass, sleeve gastrectomy, and gastric band may occur (Mechanick 2013). Insulin secretion and sensitivity may be partially or completely restored after these procedures (Korner 2009; Peterli 2012). Rates and timing of type 2 diabetes improvement and resolution vary widely by patient. Insulin dose reduction of at least 75% has been suggested after gastric bypass for patients without severe β-cell failure (fasting c-peptide <0.3 nmol/L) (Cruijsen 2014). Avoid the use of bolus insulin injections or dose conservatively with close clinical monitoring in the early phases after surgery.
– Weight gain: Insulin therapy is preferred if antidiabetic therapy is required during the perioperative period (Mechanick 2019). Evaluate risk versus benefit of long-term post-operative use and consider alternative therapy due to potential for insulin-induced weight gain (Apovian 2015).
• Cardiac disease: Concurrent use with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones may cause dose-related fluid retention and lead to or exacerbate heart failure, particularly when used in combination with insulin. If PPAR-gamma agonists are prescribed, monitor for signs and symptoms of heart failure. If heart failure develops, consider PPAR-gamma agonist dosage reduction or therapy discontinuation.
• Chronic lung disease: [US Boxed Warning]: Acute bronchospasm has been observed in patients with asthma and chronic obstructive pulmonary disease (COPD) using inhaled insulin. Use is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating inhaled insulin, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.
• Hepatic impairment: Use with caution in patients with hepatic impairment (has not been studied). Dosage requirements may be reduced and patients may require more frequent glucose monitoring.
• Renal impairment: Use with caution in patients with renal impairment (has not been studied). Dosage requirements may be reduced and patients may require more frequent glucose monitoring.
• Smokers: Use is not recommended in smokers or patients who have recently stopped smoking (safety and efficacy has not been established).
• Appropriate use: Inhaled insulin is not a substitute for long-acting insulin and must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus.
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
Plasma glucose, electrolytes, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2020]); renal function; hepatic function, weight; pulmonary function tests at baseline, after the first 6 months of therapy and yearly thereafter. Frequently monitor patients with wheezing, persistent or recurring cough, bronchospasm, or breathing difficulties. In patients at risk for Diabetic ketoacidosis (eg, acute illness or infection), increase glucose monitoring frequency.
Information specific to the use of inhaled insulin during pregnancy is limited (Makam 2009).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).
Due to pregnancy-induced physiologic changes, insulin requirements tend to increase as pregnancy progresses, requiring frequent monitoring and dosage adjustments. Following delivery, insulin requirements decrease rapidly (ACOG 201 2018; ADA 2020).
Insulin is the preferred treatment of type 1 and type 2 diabetes mellitus in pregnancy, as well as gestational diabetes mellitus when pharmacologic therapy is needed. Agents other than inhaled insulin are currently preferred (ACOG 190 2018; ACOG 201 2018; ADA 2020).
Refer to the Insulin Regular monograph for additional information related to the use of insulin in pregnancy.
What is this drug used for?
• It is used to lower blood sugar in patients with high blood sugar (diabetes).
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Weight gain
• Throat pain
• Sore throat
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
• Severe fatigue
• Trouble breathing
• Vision changes
• Passing out
• Mood changes
• Slurred speech
• Persistent cough
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
More about insulin inhalation, rapid acting
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Interactions
- En Español
- 34 Reviews
- Drug class: insulin
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