THE ULTRA RAPID-ACTING INSULIN

Afrezza® is a one-of-a-kind insulin purposefully engineered for ultra-rapid delivery of
human insulin1,2

Dry-powder formulation of monomeric human insulin for oral inhalation1

TIME TO APPEARANCE IN CIRCULATION1,3-8

ultra-rapid-insulin
  • The proprietary Technosphere® system allows Afrezza to dissolve immediately on contact with the lung surface and insulin to be rapidly absorbed into the systemic circulation9
  • Monomeric insulin administered by oral inhalation enables ultra-rapid delivery, with time to appearance in systemic circulation of <1 minute1,3
  • 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 onset (i.e., time to reach peak effect)1-3
filling your afrezza® prescription

See the Afrezza formulation and delivery in action

Afrezza is an ultra rapid-acting inhaled insulin that uses a unique formulation to deliver insulin into the bloodstream via the lungs in <1 minute3

FAST IN, FAST EFFECT, FAST OUT

Afrezza closely mimics physiologic insulin2,10,11

  • Afrezza achieves blood insulin concentrations within 12 minutes and produces maximal glucose lowering in about 45 minutes with a short duration of action (about 3 hours)1,9
  • Allows for early suppression of endogenous glucose production3,9

MEASURABLE EFFECTS OF ENDOGENOUS AND EXOGENOUS INSULIN1,3,12-14*

Insulin Parameters

Time to measurable effect

Time to peak effect

Time for effect to return to baseline

Physiologic Insulin

*Data shown are for the 12-unit doses. The 48-unit doses of Afrezza have a time to peak effect of 55 minutes and time for effect to return to baseline of 270 minutes.1

Insulin secretion data from a study in healthy subjects (n=10) to estimate insulin sensitivity based on an oral glucose tolerance test or a meal glucose tolerance test (MGTT).12
Delivery data obtained from the prescribing information for inhaled and SC insulin therapies1,13,14 and a quantitative comparison of glucose infusion rate (GIR) profiles for Afrezza and lispro.3 Comparisons of efficacy and safety should not be made in the absence of head-to-head studies.

Afrezza approximates the time-action profile of endogenous insulin1,2,10,11

AVERAGE INSULIN CONCENTRATION
DURING MGTT IN HEALTHY ADULTS12

Average Insulin Concentration

Data from a study in healthy subjects (n=10) that estimated insulin sensitivity during a MGTT.12

TIME-ACTION PROFILES OF AFREZZA
AND SC RAI COMPARATOR3

Time Action Profiles

Data from a randomized, controlled, 6-treatment crossover, dose-response study that compared Afrezza with the SC RAI lispro, in 30 patients with T1D. On average the pharmacodynamic (PD) effect of Afrezza, measured as area under the glucose infusion rate time curve (AUC GIR), increased linearly with doses up to 48 units.3 The time course of insulin action may vary considerably in different individuals or within the same individual.

*The clinical significance of the differences in PD parameters has not been established.

MEALTIME SPONTANEITY

The onset and offset of Afrezza closely mimics
physiologic insulin1,2,10,11

  • Ultra-rapid onset
  • Short time to peak effect
  • Time to return to baseline similar to
    physiologic insulin

Actual Afrezza User

References: 1. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation 2. 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. 3. Data on file. MannKind Corporation. 4. Holleman F, Hoekstra JB. Insulin lispro. N Engl J Med. 1997;337(3):176-183. 5. Heise T, Hövelmann U, Brøndsted L, Adrian CL, Nosek L, Haahr H. Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart. Diabetes Obes Metab. 2015;17(7):682-688. 6. Heise T, Stender-Petersen K, Hövelmann U, Bonde Jacobsen J, Nosek L, Zijlstra E, et al. Pharmacokinetic and pharmacodynamic properties of faster-acting insulin aspart versus insulin aspart across a clinically relevant dose range in subjects with type 1 diabetes mellitus. Clin Pharmacokinet. 2017;56(6):649-660. 7. Heise T, Pieber TR, Danne T, Erichsen L, Haahr H. A pooled analysis of clinical pharmacology trials investigating the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in adults with type 1 diabetes. Clin Pharmacokinet. 2017;56(5):551-559. 8. Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Di Vincenzo A, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000;49(12):2142-2148. 9. Rosenstock J, Lorber DL, Gnudi L, et al. Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial. Lancet. 2010;375(9733):2244-2253. 10. 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. 11. Boss AH, Petrucci R, Lorber D. Coverage of prandial insulin requirements by means of an ultra-rapid-acting inhaled insulin. J Diabetes Sci Technol. 2012;6(4):773-779. 12. 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. 13. Fiasp (insulin aspart injection) Prescribing Information. Novo Nordisk. 14. Lyumjev (insulin lispro-aabc injection) Prescribing Information. Eli Lilly and Company.

US-AFR-1669

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.

Important Safety Information

Indications and Usage:

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

Limitations of Use: Patients with type 1 diabetes must use with a long-acting insulin, not recommended for the treatment of diabetic ketoacidosis, not recommended in patients who smoke.

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.

 

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 AFREZZA excipients.

Warnings and Precautions
Acute Bronchospasm: Acute bronchospasm has been observed following AFREZZA dosing in patients with asthma and COPD. Prior to initiating therapy, evaluate patients with a medical history, physical examination, and spirometry (FEV1) to identify potential underlying lung disease. Do not use in patients with COPD.

Change in Insulin Regimen: Monitor blood glucose in all patients treated with insulin. Modify insulin regimen and dose cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type, or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant oral antidiabetic treatment.

Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin therapy, including AFREZZA, and may be serious and life-threatening. Educate patients and caregivers on recognizing symptoms and mitigating the risks associated with hypoglycemia.

Decline in Pulmonary Function: AFREZZA has been shown to cause a decrease in lung function as measured by FEV1. In clinical trials 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 initial 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 reported in patients exposed to AFREZZA while no cases were reported for the comparators. 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 outweigh the risks.

Diabetic Ketoacidosis (DKA): In clinical trials enrolling subjects with type 1 diabetes, diabetic ketoacidosis (DKA) was more common in subjects receiving AFREZZA (0.43%; n=13) than in subjects receiving comparators (0.14%; n=3). Increase the frequency of glucose monitoring and consider an alternate route of administration of insulin in patients at risk for DKA.

Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue AFREZZA, monitor, and treat if indicated.

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 occurs, consider dose reduction or discontinuation of TZD.

Drug Interactions
Certain drugs may affect glucose metabolism, increasing the risk of hypoglycemia or decreasing 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 include hypoglycemia, cough, and throat pain or irritation.

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

AFREZZA, MANNKIND, and the Afrezza and MannKind logos are registered trademarks, and AFREZZAASSIST, AfrezzaAssist and logo are mark applications, all owned by MannKind Corporation. © MannKind Corporation 2021. This site is intended for use by US healthcare professionals only.

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