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Closely mimics
physiologic insulin1,2
Lungs are well-suited for
ultra-rapid delivery1,2
AFREZZA is absorbed through the lungs without having to change molecular structure, pass through SC tissue, or undergo first-pass metabolism, thereby facilitating ultra-rapid absorption (<1 minute) and ultra-rapid onset1,3,4
When inhaled, these microparticles are appropriately sized to reach and deposit in the deep lung5
Anatomical illustration of man inhaling AFREZZA and the movement of microparticles through the lungs, where insulin is released, rapidly reaching systemic circulation. Anatomical illustration of man inhaling AFREZZA and the movement of microparticles through the lungs, where insulin is released, rapidly reaching systemic circulation.
The pH in the lungs will cause dissolution of the microspheres, releasing insulin which rapidly reaches systemic circulation and attains maximum concentration within 15 minutes6
More rapid onset and shorter duration of action compared with SC RAIs1,7
Comparative chart showing how pulmonary delivery is closer to physiological insulin than subcutaneous delivery in terms of onset and duration of action.
*Data shown are for the 12-unit doses. The 48-unit doses have a time to peak effect of 55 minutes and time for effect to return to baseline of 270 minutes.8
Insulin secretion data obtained from a study in healthy subjects (n=10) to estimate insulin sensitivity based on a MGTT.4,10,11 Delivery data obtained from the prescribing information for inhaled and SC insulin therapies4,10,11 and a quantitative comparison of GIR profiles for AFREZZA and lispro.3
  • AFREZZA can be taken at the start of a meal since it mimics physiologic insulin: no pre-bolus required4
Insulin in healthy adults: Time to peak concentration ~45 minutes8
Line graph showing that in healthy adults, physiologic insulin reaches peak concentration in about 45 minutes.
AVERAGE INSULIN CONCENTRATION DURING Meal Glucose Tolerance Test IN HEALTHY ADULTS8
AFREZZA: Time to peak effect ~45 minutes3,4,9
Line graph showing that time to peak effect with AFREZZA is about 45 minutes and with subcutaneous RAIs, about 90 minutes.
TIME-ACTION PROFILES OF AFREZZA AND SC RAI COMPARATOR3,9
Data from an open-label, randomized, controlled, cross-over study that compared the area under the glucose infusion rate versus time curve (GIR AUC) of AFREZZA (12 units) with SC RAI lispro in 30 patients with T1D. Each volunteer received 3 different doses of each treatment over a series of 6 euglycemic clamps.3,9 The time course of insulin action may vary considerably in different individuals or within the same individual.

AUC=area under curve; GIR=glucose infusion rate; MGTT=mean glucose tolerance test; PK=pharmacokinetics; PD=pharmacodynamics; RAI=rapid-acting insulin; SC RAI=subcutaneous rapid-acting insulin; T1D=type 1 diabetes.

References: 1. Heinemann L, Baughman R, Boss A, Hompesch M. Pharmacokinetic and pharmacodynamic properties of a novel inhaled insulin. J Diabetes Sci Technol. 2017;11(1):148-156. 2. Heinemann L, Parkin CG. Rethinking the viability and utility of inhaled insulin in clinical practice. J Diabetes Res. 2018;:4568903. 3. Data on file. MannKind Corporation. 4. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation. 5. Leone-Bay A, Baughman R, Smutney C, Kocinsky J. Innovation in drug delivery by inhalation. OnDrugDelivery Magazine. 2010;4-8. 6. Sarala N, Bengalorkar G, Bhuvana K. Technosphere: new drug delivery system for inhaled insulin. Fut Prescriber. 2012;13:14-16. 7. Rave K, Heise T, Heinemann L, Boss AH. Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with type 2 diabetes. J Diabetes Sci Technol. 2008;2(2):205-212. 8. Caumo A, Bergman RN, Cobelli C. Insulin sensitivity from meal tolerance tests in normal subjects: a minimal model index. J Clin Endocrinol Metab. 2000;85(11):4396-4402 9. Grant M, Heise T, Baughman R. Comparison of pharmacokinetics and pharmacodynamics of inhaled Technosphere insulin and subcutaneous insulin lispro in the treatment of type 1 diabetes mellitus. Clin Pharmacokinet. 2022;61(3):413-422. 10. Fiasp (insulin aspart injection) Prescribing Information. Novo Nordisk. 11. Lyumjev (insulin lispro-aabc injection) Prescribing Information. Eli Lilly and Company.

© MannKind Corporation June, 2024. US-AFR-2502

Indications and Usage

Afrezza® (insulin human) Inhalation Powder is a rapid acting inhaled human insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis, not recommended in patients who smoke or have recently stopped smoking.

Important Safety Information for Afrezza® (insulin human) Inhalation Powder

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE. Acute bronchospasm has been observed in patients with asthma and COPD using AFREZZA. AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD. Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.

Indications and Usage:

AFREZZA® (insulin human) Inhalation Powder is a rapid acting inhaled human insulin indicated to improve glycemic control in adult patients with diabetes mellitus.

Limitations of Use: Not recommended for the treatment of diabetic ketoacidosis, not recommended in patients who smoke or have recently stopped smoking.

Important Safety Information

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE

  • Acute bronchospasm has been observed in AFREZZA-treated patients with asthma and COPD.
  • AFREZZA is contraindicated in patients with chronic lung disease such as asthma or COPD.
  • Before initiating AFREZZA, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients.

Contraindications

AFREZZA is contraindicated: during episodes of hypoglycemia, in patients with chronic lung disease (such as asthma or chronic obstructive pulmonary disease [COPD]) because of the risk of acute bronchospasm, and in patients with hypersensitivity to regular human insulin or any of the excipients in AFREZZA.

Warnings and Precautions

Acute Bronchospasm: In a study of patients with asthma whose bronchodilators were temporarily withheld for assessment, bronchoconstriction and wheezing following AFREZZA dosing was reported. Before initiating therapy, evaluate all patients with a medical history, physical examination, and spirometry (FEV1) to identify potential underlying lung disease. Do not use in patients with chronic lung disease such as asthma or COPD.

Hypoglycemia or Hyperglycemia with Changes in Insulin Regimen: Glucose monitoring is essential for patients receiving insulin therapy. Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. These changes should be made under close medical supervision and the frequency of blood glucose monitoring should be increased. For patients with type 2 diabetes, dosage modifications of concomitant oral antidiabetic treatment may be needed.

Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulins, including AFREZZA. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly, and symptoms may differ across patients and change over time in the same patient. Patients and caregivers should be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia.

Decline in Pulmonary Function: AFREZZA causes a decline in lung pulmonary function over time as measured by FEV1. In clinical trials excluding patients with chronic lung disease and lasting up to 2 years, AFREZZA-treated patients experienced a small (40 mL) but greater FEV1 decline than comparator-treated patients. Assess pulmonary function with spirometry at baseline, after the first 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. In patients who have a decline of ≥20% in FEV1 from baseline, consider discontinuing AFREZZA. Consider more frequent lung function assessment in patients with pulmonary symptoms, e.g., wheezing, bronchospasm, breathing difficulties, or persistent or recurring cough. If symptoms persist, discontinue AFREZZA.

Lung Cancer: In clinical trials, 2 cases of lung cancer were observed in patients exposed to AFREZZA while no cases were reported for the comparators. In both cases, a prior history of heavy tobacco use was identified as a risk factor for lung cancer. Two additional cases of lung cancer (squamous cell and lung blastoma) were reported in non-smokers exposed to AFREZZA after the trial completion. These data are insufficient to determine whether AFREZZA has an effect on lung or respiratory tract tumors. In patients with active lung cancer, a prior history of lung cancer, or in patients at risk of lung cancer, consider whether the benefits of AFREZZA use outweigh this potential risk.

Diabetic Ketoacidosis (DKA): In clinical trials enrolling patients with type 1 diabetes, diabetic ketoacidosis (DKA) was more common in AFREZZA-treated patients (0.43%; n=13) than in comparator-treated patients (0.14%; n=3). Patients with type 1 diabetes should always use AFREZZA in combination with basal insulin. In patients at risk for DKA, such as those with an acute illness or infection, increase the frequency of glucose monitoring and consider discontinuing AFREZZA and giving insulin using an alternate route of administration.

Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including AFREZZA. If hypersensitivity reactions occur, discontinue AFREZZA, treat per standard of care and monitor until symptoms and signs resolve.

Hypokalemia: All insulin products, including AFREZZA, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

Fluid Retention and Heart Failure with Concomitant Use of Thiazolidinediones (TZDs): Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of TZDs and insulin. Observe these patients for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the TZD should be considered.

Drug Interactions

Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia, or decreasing or increasing the blood glucose lowering effect of AFREZZA. Dose adjustment and increased frequency of blood glucose monitoring may be required. Co-administration of beta-blockers, clonidine, guanethidine, and reserpine with AFREZZA may reduce the signs and symptoms of hypoglycemia. For full list, see Prescribing Information.

Adverse Reactions

The most common adverse reactions associated with AFREZZA are hypoglycemia, cough, and throat pain or irritation.

To report SUSPECTED ADVERSE REACTIONS, contact MannKind Corporation at 1-877-323-8505 or FDA at www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088).

Please see full Prescribing Information, including BOXED WARNING for AFREZZA.