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Most common AEs with AFREZZA (≥2%), excluding hypoglycemia1
Table comparing the incidence of the two most common adverse events—cough and throat pain or irritation—with SC insulin, placebo, and AFREZZA.
These adverse reactions, which exclude hypoglycemia, were not present at baseline, occurred more commonly on AFREZZA than placebo and/or comparator, and occurred in at least 2% of patients treated with AFREZZA in the pool of active-controlled and placebo-controlled trials in patients with T1D or T2D, respectively.1
Cough was generally mild, and declined with use2,3
Incidence of Cough in Pooled Safety Population2,3
Bar chart showing how mild cough, the most common AE associated with AFREZZA, declined with use. Three percent of patients discontinued due to cough.
3% of patients discontinued due to cough1
Pooled data from 13 phase 2/3 clinical studies in 5,505 patients with T1DM or T2DM treated with AFREZZA, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events. Study sample size reduced over time: from 3,017 (AFREZZA) and 2,198 (comparators) at Week 1 to 2,563 (AFREZZA) and 2,034 (comparators) by Week 12.2,3
  • 93.2% of cough episodes were characterized as intermittent or single defined episodes3
Safety—lung function1
Monitor lung function with AFREZZA1
  • Measure FEV1 before starting patients on AFREZZA, then again at 6 months, and annually thereafter1
  • In clinical trials excluding patients with chronic lung disease and lasting up to 2 years, AFREZZA-treated patients experienced a small [40 mL (95% CI: -80, -1)] but greater FEV1 decline than comparator-treated patients1
  • In healthy individuals, total lung capacity is about 4,200-6,000 mL4
    — The 40 mL average difference between AFREZZA-and comparator-treated patients represents about 1% decline in total lung capacity
    — In clinical trials lasting up to 2 years, differences manifested in the first few months of exposure and were non-progressive5
Icon of lungs with callout: Upper respiratory infection did not impact the absorption or action of AFREZZA.
Upper respiratory infection did not impact the absorption or action of AFREZZA6
Icon of plate, fork and spoon with plate featuring clock hands.
FEV1 test provided when patients start on AFREZZA
  • The FEV1 test is one of the tools that can be used to establish a baseline assessment before initiating AFREZZA; monitor lung function after 6 months of therapy and annually thereafter1
Request information about an FEV1 kit for HCP office use
Electronic peak flow meter, or FEV1 test, alongside packaging
Conducting a FEV1 test7
STEP 1
Insert mouthpiece and switch device on
Three-step process for conducting an FEV1 test: Insert mouthpiece and switch on device, instruct patient to exhale 3 times, record best result.
STEP 2
Instruct patient to exhale 3 times
Three-step process for conducting an FEV1 test: Insert mouthpiece and switch on device, instruct patient to exhale 3 times, record best result.
STEP 3
Record best FEV1 result
Three-step process for conducting an FEV1 test: Insert mouthpiece and switch on device, instruct patient to exhale 3 times, record best result.

AE=adverse event; FEV1=forced expiratory volume in 1 second; T1D=type 1 diabetes; T2D=type 2 diabetes.

References: 1. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation. 2. Data on file. MannKind Corporation. 3. McGill JB, Peters A, Buse JB, et al. Comprehensive pulmonary safety review of inhaled Technosphere® insulin in patients with diabetes mellitus. Clin Drug Investig. 2020;40(10):973-983. 4. Oches M, O’Brodovich H. 5 – The Structural and Physiologic Basis of Respiratory Disease, In: Kendig & Chernick’s Disorders of the Respiratory Tract in Children. 8 ed. W.B. Saunders; 2012: 35-74 5. Raskin P, Heller S, Honka M, et al. Pulmonary function over 2 years in diabetic patients treated with prandial inhaled Technosphere Insulin or usual antidiabetes treatment: a randomized trial. Diabet Obes Metab. 2012;14(2):163-173. 6. Levin PA, Heinemann L, Boss A, Rosenblit PD. Impact of symptomatic upper respiratory tract infections on insulin absorption and action of Technosphere inhaled insulin. BMJ Open Diabetes Res Care. 2016;4(1):e000228. 7. Sonmol PEF. User manual. 2023.

© MannKind Corporation January, 2025. US-AFR-2599

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.