DOSING & TITRATION

Afrezza is a prandial insulin treatment with an innovative inhaled delivery method. 

Afrezza has a unique time-action profile that mimics physiologic insulin, and delivers ultra-rapid absorption in the blood in less than 1 minute.1,7

Due to the unique characteristics of Afrezza, Afrezza units are different than injectable insulin units.

Jason

FLEXIBLE DOSING

Afrezza is an ultra-rapid acting inhaled insulin used at the beginning of a meal with an oral inhaler and one or more single-use cartridges. Afrezza comes in 4, 8 and 12-unit color-coded cartridges. Patients can mix and match cartridges for their prescribed dose. For example, two 12-unit cartridges provide a dose of 24 units of Afrezza. 

Inhaler Cartridges
Afrezza mealtime control is possible with individualized dosing.1
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EFFECTIVE DOSING

Like all insulin therapy, monitor therapeutic effect of Afrezza and adjust dosing as needed to achieve optimal glycemic control 1

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CONVERSION CONSIDERATIONS

Based on clinical trials, consider a ~1.5x conversion from injectable insulin units to Afrezza units to achieve a comparable glucose effect 2,9,14

12 24 Units Icon 3

TYPICAL DOSING AT MEALTIME

In clinical trials, most patients received 12-24 Afrezza insulin units per meal2,9,10

Afrezza is dispensed in monthly packages to meet your patients' mealtime insulin needs 1

Rx

EXAMPLE AFREZZA PRESCRIPTION:

Afrezza Titration Pack (1,440 units)

1 pack of 180 cartridges, #2 packs

4-Unit, 8-Unit, 12-Unit Cartridges

Inhale 12-24 units by mouth at mealtime and additional units as needed for glucose control.

Total daily dose 36-84 units daily. 


NDC 47918-874-90

Afrezza 4-Unit Cartridges

Contains 90 Cartridges

01

[90] 4-Unit Cartridges

Inheler

[2] Inhalers

Includes 360 Total Afrezza Insulin Units

NDC 47918-878-90

Afrezza 8-Unit Cartridges

Contains 90 Cartridges

02

[90] 8-Unit Cartridges

Inheler

[2] Inhalers

Includes 720 Total Afrezza Insulin Units

NDC 47918-891-90

Afrezza 12-Unit Cartridges

Contains 90 Cartridges

03

[90] 12-Unit Cartridges

Inheler

[2] Inhalers

Includes 1080 Total Afrezza Insulin Units

NDC 47918-880-18

Afrezza Titration Pack

Contains 180 Cartridges

04

[90] 4-Unit Cartridges
[90] 8-Unit Cartridges

Inheler

[2] Inhalers

Includes 1080 Total Afrezza Insulin Units

NDC 47918-902-18

Afrezza Titration Pack

Contains 180 Cartridges

05

[60] 4-Unit Cartridges
[60] 8-Unit Cartridges
[60] 12-Unit Cartridges

Inheler

[2] Inhalers

Includes 1440 Total Afrezza Insulin Units

NDC 47918-898-18

Afrezza 8 and 12-Unit Combo Pack

Contains 180 cartridges

06

[90] 8-Unit Cartridges
[90] 12-Unit Cartridges

Inheler

[2] Inhalers

Includes 1800 Total Afrezza Units
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LET'S TALK ABOUT TITRATION FOR

INSULIN EXPERIENCED PATIENTS

Converting from multiple daily injections in type 1 or type 2 diabetes.

Initiate prandial Afrezza at 1.5 Afrezza units for every 1 injectable insulin unit

Adjust mealtime doses by 4-unit increments every 3 days based on 2 hour PPG > 160 mg/dL (3 day average)

Dosing Pic 1 V2

Example of initiating Afrezza: 

8 units subcutaneous injection per meal

8 units x 1.5 = 12 units Afrezza inhalation per meal

Example of adjusting Afrezza: 

Increase mealtime dose by 4 unit increments every 3 days until PPG controlled (additional cartridges maybe required)

Dosing Pic 2

LET'S TALK ABOUT TITRATION FOR 

PRANDIAL INSULIN NAIVE PATIENTS

Example Afrezza dosing for prandial naive patients. 

Days: 1 - 3
4 Afrezza Units

4 Afrezza Units

Given with each meal for 3 days (total of 12 Afrezza units per day).

DOSE FOR 3 DAYS

Dose adjusted to 8 units with each meal based on 2 hr PPG x 3 days (PPG > 160 mg/dL).

Days: 4 - 6
8 Afrezza Units

8 Afrezza Units

Given with each meal for 3 days (total of  24 Afrezza units per day).

TITRATE UP TO 3 DAYS

Dose adjusted to 12 units with each meal based on 2 hr PPG x 3 days (PPG > 160 mg/dL).

Days: 7 - 9
12 Afrezza Units

12 Afrezza Units

Given with each meal for 3 days (total of 36 Afrezza units per day).

TITRATE TO EFFECT

Dose adjusted to 16 units with each meal based on 2 hr PPG x 3 days (PPG > 160 mg/dL).

Continue to adjust dose by 4 unit increments every 3 days until PPG controlled. 12-24 units was the typical mealtime dose in clinical trials 9,10

LET'S TALK ABOUT

CONSIDERING THE PATIENT

Sia

Meet Sarah, a patient living with type 1 diabetes

• On basal insulin and injects insulin aspart before meals
• Has an A1C of 8.2 and is concerned about hypoglycemia
• Tired of scheduling meals around injections
• Anxious about frequency of CGM alerts
• She hasn’t found what would help her achieve her target goal

Give patients like Sarah improved mealtime control with Afrezza

• Afrezza delivers an ultra-rapid insulin response with absorption in the blood in <1 minute1,7
• Patients inhale Afrezza at mealtime, when they are ready to eat, with no needlesticks1
• Afrezza was proven to be non-inferior to SC rapid-acting insulin in clinical trials9


Afrezza may be right for a patient with type 1 diabetes struggling to maintain glycemic control.

Jason

Meet Jason, a patient living with type 2 diabetes

• Diagnosed with type 2 diabetes 6 years ago
• On daily regimen of multiple oral agents (OAs), weekly GLP 1 injection, and just started using CGM
• Has an A1C over 9.0 and wants to achieve glycemic target
• Doesn't want to deal with daily injections

Give patients like Jason improved mealtime control with Afrezza

• Afrezza delivers an ultra-rapid insulin response with absorption in the blood in <1 minute1,7
• Patients inhale Afrezza at mealtime, when they are ready to eat, with no needlesticks1
• One out of three patients with type 2 diabetes treated with OAs plus Afrezza achieved A1C 7% versus OAs alone10


Afrezza may be right for a patient with type 2 diabetes struggling to maintain glycemic control.

Learn about Afrezza and lung function

EFFICACY & SAFETY

See if Afrezza is right for your patients

Request samples, learn about FEV1, or schedule a representative to come visit your office.

REQUEST A REP VISIT

References

1. Afrezza (insulin human) Inhalation Powder Prescribing Information. MannKind Corporation.

2. Data on file. MannKind Corporation.

3. Akturk HK, Snell-Bergeon JK, Rewers A, et al. Improved postprandial glucose with inhaled Technosphere insulin compared with insulin aspart in patients with type 1 diabetes on multiple daily injections: the STAT study. Diabetes Technol Ther. 2018;20(10):639--647.

4. Peyrot M, Rubin RR, Kruger DF, et al. Correlates of insulin injection omission. Diabetes Care. 2010;33(2):240–245.

5. Lasalle JR, Berria R. Insulin therapy in type 2 diabetes mellitus: a practical approach for primary care physicians and other health care professionals. J Am Osteopath Assoc. 2013;113(3):152–162.

6. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients. Diabetes Care. 2003;26(3):881-885.

7. Rave K, Heise T, Heinemann L, et al. 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. Rossetti P, Porcellati F. Prevention of hypoglycemia while achieving good glycemic control in type 1 diabetes. Diabetes Care. 2008;31(2):S113–S120.

9. Bode BW, McGill JB, Lorber DL, et al. Inhaled Technosphere insulin compared with injected prandial insulin in type 1 diabetes: a randomized 24-week trial. Diabetes Care. 2015;38(12):2266–2273.

10. Rosenstock J, Franco D, Korpachev V, et al. Inhaled Technosphere insulin versus inhaled Technosphere placebo in insulin-naive subjects with type 2 diabetes inadequately controlled on oral antidiabetes agent. Diabetes Care. 2015;38(12):2274–2281.

11. Oldham PD. Decline of FEV1. Adapted from NHANES III equations. Thorax. 1987;42:161–164.

12. Lange P, Groth S, Mortensen J, et al. Diabetes mellitus and ventilatory capacity: a five year follow-up study. Eur Resp J. 1990;3(3):288–292.

13. Levin PA, Heinemann L, Boss A, et al. Impact of symptomatic upper respiratory tract infections on insulin absorption and action of Technosphere inhaled insulin. BMJ Open Diabetes Res Care. 2016;4:e000228.

14. 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.

Important Safety Information

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

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. 


Limitations of Use

  • AFREZZA is not a substitute for long-acting insulin. AFREZZA must be used in combination with long-acting insulin in patients with type 1 diabetes mellitus.
  • AFREZZA is not recommended for the treatment of diabetic ketoacidosis.
  • The safety and efficacy of AFREZZA in patients who smoke have not been established. The use of AFREZZA is not recommended in patients who smoke or who have recently stopped smoking (less than 6 months). 

Contraindications
AFREZZA is contraindicated in patients: 

  • During episodes of hypoglycemia
  • With chronic lung disease (such as asthma or chronic obstructive pulmonary disease [COPD]) because of the risk of acute bronchospasm
  • With hypersensitivity to regular human insulin or any of the AFREZZA excipients

Warnings and Precautions
Acute Bronchospasm: Before initiating therapy, evaluate patients with a medical history, physical examination and spirometry (FEV1) to identify potential underlying lung disease. Acute bronchospasm has been observed following AFREZZA dosing in patients with asthma and patients with COPD. The long-term safety and efficacy of AFREZZA in patients with chronic lung disease have not been established.


Changes 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 to help mitigate the risk of hypoglycemia or hyperglycemia.

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 mitigating the risks associated with hypoglycemia. Increased frequency of blood glucose monitoring is recommended for patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of 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. 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. 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 outweigh the risks.

Diabetic Ketoacidosis (DKA): 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 with insulin products, including AFREZZA. If hypersensitivity reactions occur, discontinue AFREZZA, treat per standard of care and monitor if indicated.

Hypokalemia: 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, manage according to current standards and consider TZD dose reduction or discontinuation.

Adverse Reactions
The most common adverse reactions associated with AFREZZA (2% or greater incidence) are hypoglycemia, cough, and throat pain or irritation. 

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, please see Full Prescribing Information.