USAGE GUIDE

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. 

In clinical trials, the typical Afrezza dose per meal was 12-24 units.2,9,10

Product
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INSTRUCTIONAL VIDEO

Please see full Prescribing Information, including BOXED WARNING, Medication Guide, and Instructions for Use.

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STEP-BY-STEP GUIDE

Healthcare providers will provide direction on how to take Afrezza, but as a reminder, patients can follow this step-by-step guide. 

Step 1: Select cartridge for the right dose

  • 4 Units: If the Afrezza dose is 4 units, use 1 blue cartridge.
  • 8 Units: If the Afrezza dose is 8 units, use 1 green cartridge.
  • 12 Units: If the Afrezza dose is 12 units, use 1 yellow cartridge.

If the prescribed Afrezza dose is more than 12 units, patient will need to use more than 1 cartridge to get the right dose. Multiple inhalations will be necessary.

3 Cartridges

Step 2: Load cartridge

  • Hold Inhaler: Hold the inhaler level in one hand with the white mouthpiece on the top and purple base on the bottom.
  • Open Inhaler: Open the inhaler by lifting the white mouthpiece to a vertical position.
  • Place Cartridge: Hold the cartridge with the cup facing down. The pointed end of the cartridge should line up with the pointed end in the inhaler. Place cartridge into the inhaler, making sure it lies flat in inhaler.
  • Keep Level: Now that the cartridge is loaded, keep the inhaler level from this point forward to avoid loss of drug powder. Do not turn it upside down, shake, or drop, as this could cause a loss of drug powder.
  • Close Inhaler: Lower the mouthpiece to close the inhaler (this will open the drug cartridge). A snap should be felt when the inhaler is closed.
Setp2 Insertcartridge

Step 3: Inhale insulin

  • Remove Cover: Remove the mouthpiece cover. Keep the inhaler level.
  • Exhale: Hold the inhaler away from mouth and exhale fully.
  • Position Inhaler: Keeping head and inhaler level, place the mouthpiece in mouth. Close lips around the mouthpiece to form a seal. Tilt the inhaler downward while keeping head level as shown.
  • Inhale Deeply and Hold Breath: With mouth closed around the mouthpiece, inhale deeply through the inhaler. Hold breath for as long as comfortable and at the same time remove the inhaler from mouth. Exhale and breathe normally.
Step3 Tilt Inhale 3Illustrations

Step 4: Remove cartridge and discard

  • Replace Cover: Put the mouthpiece cover back onto the inhaler.
  • Open Inhaler: Open the inhaler by lifting the white mouthpiece.
  • Remove Cartridge: Remove the cartridge from the purple base.
  • Discard: Throw away the cartridge in regular household trash.

Repeat steps 2 through 4 for each Afrezza cartridge needed for dose.

Step4 Illustrations

CARE INSTRUCTIONS

AFREZZA INHALER

Once the full dose is taken, the purple mouthpiece cover must be replaced and the inhaler closed.

• The Afrezza inhaler can be used for up to 15 days from the date of first use. After 15 days of use, the inhaler must be discarded and replaced with a new inhaler.
• The inhaler should be kept in a clean, dry place with the mouthpiece cover on until the next dose.
• May be stored refrigerated, but must be at room temperature before use.
• Cartridges should never be left or stored in the inhaler.
• Keep out of reach of children.


Tips for Use

Patients can keep track of 15 days from the first use of the inhaler with a calendar, or use the chart on the back of the Afrezza box.

Hcp Inhaler Ifu With Labels

AFREZZA INSULIN CARTRIDGES

Afrezza insulin comes in 4, 8 and 12 unit color-coded cartridges. Cartridges containing the ultra-rapid acting insulin are sealed in foil packages containing 2 blister cards with 15 cartridges each. Cards are perforated so they can be easily removed 3 cartridges at a time.

It's important not to mix new and used cartridges. New cartridges should be kept in the foil pack until right before use. Used cartridges should be discarded right away.


Tips for Use

New cartridges have the cup positioned forward near the point. Used cartridges will have the cup positioned in the center.

New And Used Cartridges
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* If a foil package, blister card, or strip is not refrigerated, the content must be used within 10 days.

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.