Afrezza

Patient Information

AFREZZA
(uh-FREZZ-uh)
(insulin human) inhalation powder, for oral inhalation use

What is the most important information I should know about AFREZZA?

AFREZZA can cause serious side effects, including:

• Sudden lung problems (bronchospasms). Do not use AFREZZA if you have long-term (chronic) lung problems such as asthma or chronic obstructive pulmonary disease (COPD). Before starting AFREZZA, your healthcare provider will give you a breathing test to check how your lungs are working.

What is AFREZZA?

• AFREZZA is a man-made insulin that is breathed-in through your lungs (inhaled) and is used to control high blood sugar in adults with diabetes mellitus.
• AFREZZA is not for use to treat diabetic ketoacidosis. AFREZZA must be used with basal insulin in people who have type 1 diabetes mellitus.
• It is not known if AFREZZA is safe and effective for use in people who smoke. AFREZZA is not for use in people who smoke or have recently stopped smoking (less than 6 months).
• It is not known if AFREZZA is safe and effective in children under 18 years of age.

Who should not use AFREZZA?

Do not use AFREZZA if you:

• Have chronic lung problems such as asthma or COPD.
• Are allergic to regular human insulin or any of the ingredients in AFREZZA. See the end of this Medication Guide for a complete list of ingredients in AFREZZA.
• Are having an episode of low blood sugar (hypoglycemia).

What should I tell my healthcare provider before using AFREZZA?

Before using AFREZZA, tell your healthcare provider about all your medical conditions, including if you:

• Have lung problems such as asthma or COPD
• Have or have had lung cancer
• Are using any inhaled medications
• Smoke or have recently stopped smoking
• Have kidney or liver problems
• Are pregnant, planning to become pregnant, or are breastfeeding. AFREZZA may harm your unborn or breastfeeding baby.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins or herbal supplements.

Before you start using AFREZZA, talk to your healthcare provider about low blood sugar and how to manage it.

How should I use AFREZZA?

• Read the detailed Instructions for Use that comes with your AFREZZA.
• Take AFREZZA exactly as your healthcare provider tells you to. Your healthcare provider should tell you how much AFREZZA to use and when to use it.
• Know the strength of AFREZZA you use. Do not change the amount of AFREZZA you use unless your healthcare provider tells you to.
• Take AFREZZA at the beginning of your meal.
• Check your blood sugar levels. Ask your healthcare provider what your blood sugar should be and when you should check your blood sugar levels.
• Keep AFREZZA and all medicines out of the reach of children.

Your dose of AFREZZA may need to change because of:

• Change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, or because of other medicines you take.

What should I avoid while using AFREZZA?

While using AFREZZA do not:

• Drive or operate heavy machinery, until you know how AFREZZA affects you
• Drink alcohol or use over-the-counter medicines that contain alcohol
• Smoke

What are the possible side effects of AFREZZA?

AFREZZA may cause serious side effects that can lead to death, including:

See “What is the most important information I should know about AFREZZA?”

• Low blood sugar (hypoglycemia). Signs and symptoms that may indicate low blood sugar include:
  • Dizziness or light-headedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, fast heartbeat, anxiety, irritability or mood change, hunger.
• Decreased lung function. Your healthcare provider should check how your lungs are working before you start using AFREZZA, 6 months after you start using it and yearly after that.
• Lung cancer. In studies of AFREZZA in people with diabetes, lung cancer occurred in a few more people who were taking AFREZZA than in people who were taking other diabetes medications. There were too few cases to know if lung cancer was related to AFREZZA. If you have lung cancer, you and your healthcare provider should decide if you should use AFREZZA.
• Diabetic ketoacidosis. Talk to your healthcare provider if you have an illness. Your AFREZZA dose or how often you check your blood sugar may need to be changed.
• Severe allergic reaction (whole body reaction). Get medical help right away if you have any of these signs or symptoms of a severe allergic reaction:
  • A rash over your whole body, trouble breathing, a fast heartbeat, or sweating.
• Low potassium in your blood (hypokalemia).
• Heart failure. Taking certain diabetes pills called thiazolidinediones or “TZDs” with AFREZZA may cause heart failure in some people. This can happen even if you have never had heart failure or heart problems before. If you already have heart failure it may get worse while you take TZDs with AFREZZA. Your healthcare provider should monitor you closely while you are taking TZDs with AFREZZA. Tell your healthcare provider if you have any new or worse symptoms of heart failure including:
  • Shortness of breath, swelling of your ankles or feet, sudden weight gain.
• Treatment with TZDs and AFREZZA may need to be changed or stopped by your healthcare provider if you have new or worse heart failure.

Get emergency medical help if you have:

• Trouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion.

The most common side effects of AFREZZA include:

• Low blood sugar (hypoglycemia), cough, sore throat.

These are not all the possible side effects of AFREZZA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 (1-800-332-1088).

General information about the safe and effective use of AFREZZA.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use AFREZZA for a condition for which it was not prescribed. Do not give AFREZZA to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about AFREZZA. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about AFREZZA that is written for health professionals.

What are the ingredients in AFREZZA?

Active ingredient: human insulin

Inactive ingredients: fumaryl diketopiperazine, polysorbate 80

INSTRUCTIONS FOR USE

AFREZZA®
(uh-FREZZ-uh) (insulin human) inhalation powder, for oral inhalation use

This “Instructions for Use” contains information on how to use AFREZZA® (insulin human) Inhalation Powder.

Read this Instructions for Use before you start using AFREZZA and each time you get a new AFREZZA Inhaler. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Your healthcare provider should show you how to use your AFREZZA Inhaler the right way before you use it for the first time.

Important information about AFREZZA:

• AFREZZA comes in 3 strengths (see Figure A):
  • 4 units (blue cartridge)
  • 8 units (green cartridge)
  • 12 units (yellow cartridge)

Figure A

• If your prescribed AFREZZA dose is higher than 12 units, you will need to use more than 1 cartridge.
• If you need to use more than 1 cartridge for your dose, throw away the used cartridge before getting a new one. You can tell when a cartridge has been used, because the cup has moved to the center.
• Do not try to open the AFREZZA cartridges. The AFREZZA Inhaler opens the cartridge automatically during use.
• AFREZZA cartridges should only be used with the AFREZZA Inhaler. Do not try to breathe in the AFREZZA insulin powder in any other way. Do not put cartridges in your mouth and do not swallow cartridges.
• Use only 1 AFREZZA Inhaler at a time. The same inhaler should be used for the 4 unit, 8 unit or 12 unit cartridges.
• Store the inhaler in a clean, dry place with the mouthpiece cover on until your next dose.
• Throw away your AFREZZA Inhaler after 15 days and get a new one.

If you are having problems with your AFREZZA Inhaler or if it breaks and you need a new one, call 1-877-323-8505.

Know your AFREZZA Inhaler:

Know your AFREZZA cartridges:

How to take your dose of AFREZZA:

Always be sure you have the right number of AFREZZA cartridges for your dose available before you start. AFREZZA cartridges must only be used with the AFREZZA Inhaler.

Step 1: Select the AFREZZA cartridges for your dose

If your prescribed AFREZZA dose is more than 12 units you will need to use more than 1 cartridge to get your right dose.

Use the dosage chart below to determine the least number of AFREZZA cartridges you can use for your dose. Other cartridge combinations can be used.

Figure B

Example

Select Cartridges

Important: Use the AFREZZA dose chart above (see Figure B) to help you choose the right number of AFREZZA cartridges needed for your dose.

Open Packages

• Remove a blister card from the foil package.
• Tear along perforation to remove one strip.

Push Cartridges to Remove

Remove a cartridge from the strip by pressing on the clear side to push the cartridge out. Remove the right number of cartridges for your dose. Pushing on the cup will not damage the cartridge. AFREZZA cartridges left over in an opened strip must be used within 3 days.

Before Proceeding:

Check that you have the right AFREZZA cartridge(s) for your dose.

Use only 1 inhaler for multiple cartridges. Throw away your AFREZZA Inhaler after 15 days and get a new one.

Step 2: Loading a cartridge

Hold Inhaler

Hold the inhaler level in one (1) 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.

Before you put the AFREZZA cartridge in your inhaler, make sure it has been at room temperature for 10 minutes.

Place Cartridge

Hold the cartridge with the cup facing down.

Line up the cartridge with the opening in the inhaler. The pointed end of the cartridge should line up with the pointed end in the inhaler.

Place the cartridge into the inhaler. Be sure that the cartridge lies flat in the inhaler.

If any of these occur, throw away the cartridge and load a new cartridge.

Close Inhaler

Lower the mouthpiece to close the inhaler (this will open the drug cartridge).

You should feel a snap when the inhaler is closed.

Step 3: Inhaling AFREZZA

Remove the Mouthpiece Cover

Important: Keep the inhaler level during and after removal of the purple mouthpiece cover.

Check that you are ready to inhale:

• Purple mouthpiece cover is removed.
• Inhaler is held level.
• Fully review the following A-B-C steps prior to beginning the inhale process.

Exhale

Hold the inhaler away from your mouth and fully blow out (exhale).

Position Inhaler in Mouth

Keeping your head level, place the mouthpiece in your mouth and tilt the inhaler down towards your chin, as shown.

Close your lips around the mouthpiece to form a seal.

Tilt the inhaler downward while keeping your head level.

Inhale Deeply and Hold Breath

With your mouth closed around the mouthpiece, inhale deeply through the inhaler.

Hold your breath for as long as comfortable and at the same time remove the inhaler from your mouth. After holding your breath, exhale and continue to breathe normally.

Step 4: Removing a used cartridge

Replace Mouthpiece Cover

Place the purple mouthpiece cover back onto the inhaler.

Open Inhaler

Open the inhaler by lifting up the white mouthpiece.

Remove Cartridge

Remove the cartridge from the purple base.

Throw away (or recycle) the Cartridge

Throw away the used cartridge in your regular household trash.

Alternatively, the used cartridge (composed of HDPE, assigned recycling number 2) can be recycled.

Multiple cartridge dosing

If you need more than one (1) AFREZZA cartridge for your dose, see the AFREZZA dosage chart above (Figure B).

Repeat steps 2 through 4 for each AFREZZA cartridge you need for your prescribed AFREZZA dose.

</table>&lt;b>How should I store AFREZZA?&amp;lt;/table&amp;amp;amp;gt;Caring for your AFREZZA Inhaler:Storage InstructionsOnce you have taken your full dose, make sure the purple mouthpiece cover has been replaced and the inhaler is closed.

• Keep the inhaler in a clean, dry place with the mouthpiece cover on until your next dose.
• May be stored refrigerated, but must be at room temperature before use.
• Never leave or store cartridges in the inhaler.
• Keep out of reach of children.

Care Instructions

• Use one inhaler at a time. The same inhaler should be used to take 4 unit, 8 unit or 12 unit cartridges. Replace the inhaler every 15 days to maintain drug delivery.
• Keep track of 15 days from when you start using the inhaler with a calendar, or use the chart on the back of the inhaler box.
• After taking your dose, powder residue in the mouthpiece is normal, this does not affect your dose.

The outside of the inhaler can be wiped with a clean, dry cloth if needed. Never wash the inhaler. Keep it dry.</table&gt;&amp;lt;b&amp;gt;Switching between AFREZZA and injected insulin:Contact your healthcare provider before switching insulins.AFREZZA is a mealtime insulin.</p&amp;gt;<br />Do not switch from AFREZZA to a long acting insulin.Do not switch from a long acting insulin to AFREZZA.This Instructions for Use has been approved by the U.S. Food and Drug Administration.</table>

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

Limitations Of Use

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Dosage And Administration

Lung Function Assessment Prior To Administration

AFREZZA is contraindicated in patients with chronic lung disease because of the risk of acute bronchospasm in these patients. Before initiating AFREZZA, perform a medical history, physical examination and spirometry (FEV₁) in all patients to identify potential lung disease [see CONTRAINDICATIONS and WARNING AND PRECAUTIONS].

<h4>Important Administration And Discard Instructions&lt;/h4&amp;gt;<p>Onl&amp;lt;/p&gt;

y administer AFREZZA via oral inhalation using the AFREZZA Inhaler. Administer AFREZZA at the beginning of each meal. Administer AFREZZA using a single inhalation per cartridge (if the dose is greater than the contents of a single cartridge, more than one cartridge is needed) [see DOSAGE AND ADMINISTRATION]. For additional administration instructions on how to use the AFREZZA Inhaler [see DOSAGE AND ADMINISTRATION</b>] and see the Instructions for Use.

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.

Recommended Starting Mealtime Dosage

<p&gt;For insulin naïve patients, start on 4 units of AFREZZA at the beginning of each meal.For patients using subcutaneous, mealtime (prandial) insulin:

• Determine the appropriate AFREZZA dose for each meal by converting from the injected insulin dose using Figure 1.
• When switching from another insulin to AFREZZA, a different insulin dose may be needed requiring increased frequency of blood glucose monitoring [see WARNING AND PRECAUTIONS].

For patients using subcutaneous, pre-mixed insulin:</p>

• Estimate the mealtime injected dose by dividing half of the total daily injected pre-mixed insulin dose equally among the three meals of the day. When switching from another insulin to AFREZZA, a different insulin dose may be needed. When switching a patient’s insulin regimen, increase the frequency of blood glucose monitoring [see WARNING AND PRECAUTIONS].
• Convert each estimated injected mealtime dose to an appropriate AFREZZA dose using Figure 1.
• Administer half of the total daily injected pre-mixed dose as an injected basal insulin dose.&lt;/li&gt;

For AFREZZA doses exceeding the contents of a single cartridge at mealtime, inhalations from more than one cartridge are necessary. To achieve the required total mealtime dose, use a combination of 4 unit, 8 unit, and 12 unit cartridges. Examples of cartridge combinations for doses of up to 24 units are shown in Figure 1. For doses above 24 units, use combinations of different multiple cartridges.

n=”center”>&lt;b>Figure 1: Mealtime AFREZZA Starting Dose Conversion Table

Mealtime Dosage Modification

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Modify the AFREZZA dosage based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal.

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            • • Dosage modifications may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see WARNING AND PRECAUTIONS an

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    • Carefully monitor blood glucose control in patients requiring high AFREZZA doses. If blood glucose control is not achieved with increased AFREZZA doses in these patients, consider discontinuing AFREZZA.

  Dosage Modifications For Drug Interactions

  Dosage modification may be needed when:&lt;/p>

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        • • • • AFREZZA is used concomitantly with certain drugs that increase and/or decrease the glucose lowering effect [see <b>DRUG INTERACTIONS].

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  Administration Instructions

  Refer patients to the Instructions for Use for detailed instructions and visuals on how to prepare, administer, and store AFREZZA; use the AFREZZA cartridges; and use the AFREZZA inhaler. Critical administration instructions are as follows:

  • • • • • • • Keep the inhaler level with the white mouthpiece on top and purple base on the bottom after a cartridge has been inserted into the inhaler. Loss of drug effect can occur if the inhaler is turned upside down, held with the mouthpiece pointing down, shaken, or dropped after the cartridge has been inserted but before the dose has been administered. If any of the above occur, replace the cartridge before use.
              • Hold the inhaler away from the mouth and fully exhale.</li>
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              • ter the inhaler is placed in the mouth and the lips form a seal, tilt the inhaler down towards the chin while keeping the head level.
              • With the mouth closed around the mouthpiece, inhale deeply through the inhaler.
              • Hold the breath for as long as comfortable and at the same time remove the inhaler from the mouth.
              • After holding the breath, exhale and continue to breathe normally.

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    How Supplied

    Dosage Forms And Strengths</h4>

     

    Inhalation Powder: single-use cartridges containing 4 units, 8 units or 12 units of insulin human as white powder to be administered via oral inhalation with the AFREZZA inhaler only [see HOW SUPPLIED/Storage And Handling].

    Storage And Handling

    AFREZZA (insulin human) Inhalation Powder is available as 4 unit, 8 unit and 12 unit single-use cartridges. Three cartridges are contained in a single cavity of a blister strip. Each card contains 5 blister strips (each containing three cartridges) separated by perforations for a total of 15 cartridges. Two cards of the same cartridge strength are packaged in a foil laminate overwrap (30 cartridges per foil package).

    The cartridges are color-coded, blue for 4 units, green for 8 units and yellow for 12 units. Each cartridge is marked with “afrezza” and “4 units”, “8 units” or “12 units”.

    The AFREZZA Inhaler is individually packaged in a clear overwrap. The inhaler is fully assembled with a removable mouthpiece cover. 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.

    AFREZZA (insulin human) Inhalation Powder is available in the following configurations:

    NDC	Cartridge Strength	Quantity of Cartridges per Strength	Total Quantity of Cartridges per Kit	Total Units in Kit	Number of Inhalers
    47918-874-90	4 units	90	90	360 Units	2
    47918-878-90	8 units	90	90	720 Units	2
    47918-891-90	12 units	90	90	1080 Units	2
    47918-898-18	8 units, 12 units	90	180	1800 Units	2
    47918-880-18 (Titration Pack)	4 units, 8 units	90	180	1080 Units	2
    47918-902-18 (Titration Pack)	4 units, 8 units, 12 units	60	180	1440 Units	2

    Storage

    Not in Use: Refrigerated Storage 2-8°C (36-46°F)

    Sealed (Unopened) Foil Package	May be stored until the Expiration Date*
    Sealed (Unopened) Blister Cards + Strips	Must be used within 1 month*
    * If a foil package, blister card or strip is not refrigerated, the contents must be used within 10 days.

    In Use: Room Temperature Storage 25°C (77°F), excursions permitted 15-30°C (59-86°F)

    Sealed (Unopened) Blister Cards + Strips	Must be used within 10 days
    Opened Strips	Must be used within 3 days

    Do not put a blister card or strip back into the refrigerator after being stored at room temperature.

    Inhaler Storage

    Store refrigerated or at room temperature 2-25°C (36-77°F); excursions permitted. Inhaler may be stored refrigerated, but should be at room temperature before use.

    Handling

    Before use, cartridges should be at room temperature for 10 minutes.

    Manufactured by: MannKind Corporation, Danbury, CT 06810. Revised: Feb 2023

The following serious adverse reactions are described below and elsewhere in the labeling:

• • • Acute bronchospasm in patients with chronic lung disease [see WARNING AND PRECAUTIONS]

  <li>Hypoglycemia [see

 WARNING AND PRECAUTIONS

• • ]
    • Decline in pulmonary function [see WARNING AND PRECAUTIONS]
    • Lung cancer [see WARNING AND PRECAUTIONS]
    • Diabetic ketoacidosis [see WARNING AND PRECAUTIONS</b>]

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Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure of 3,017 patients to AFREZZA and include 1,026 patients with type 1 diabetes and 1,991 patients with type 2 diabetes. The mean exposure duration was 8.2 months for patients with type 1 diabetes and those with type 2 diabetes. In the overall population:

• 1,874 patients were exposed to AFREZZA for 6 months and 724 patients for greater than one year.
• 620 and 1,254 patients with type 1 and type 2 diabetes, respectively, were exposed to AFREZZA for up to 6 months.
• 238 and 486 patients with type 1 and type 2 diabetes, respectively, were exposed to AFREZZA for greater than one year (median exposure = 1.8 years).</li>

AFREZZA was studied in placebo and active-controlled trials (n = 3 and n = 10, respectively).

The mean age of the population was 50.2 years and 20 patients were older than 75 years of age; 51% of the population were males; 83% were White, 5% were Black or African American, and 2% were Asian; 10% were Hispanic. At baseline, the type 1 diabetes population had diabetes for an average of 16.6 years and had a mean HbA1c of 8.3%, and the type 2 diabetes population had diabetes for an average of 10.7 years and had a mean HbA1c of 8.8%. At baseline, 33% of the population reported peripheral neuropathy, 32% reported retinopathy and 20% had a history of cardiovascular disease.

Table 1 shows the frequency of common adverse reactions, excluding hypoglycemia, associated with the use of AFREZZA in the pool of controlled trials in type 2 diabetes patients. These adverse reactions were not present at baseline, occurred more commonly on AFREZZA than on placebo and/or comparator and occurred in at least 2% of patients treated with AFREZZA.

Table 1:Common Adverse Reactions That Occurred in ≥ 2% in Patients with Type 2 Diabetes Mellitus (excluding Hypoglycemia) Treated with AFREZZA

<td>Fatigue2.0%0.7%0.6%<td align=”center”>0.3%ign=”center”>2.2%<tr>Nausea</td><td align=”center”>2.0%1.0%</td></tr>

>	idth=”25%”>AFREZZA (n = 1,991)	Placebo* (n = 290)	Non-placebo comparators (n=1,363)
Cough	25.6%	19.7%	5.4%
Throat pain or irritation	4.4%	gn=”center”>3.8%	0.9%
Headache	3.1%	2.8%	1.8%</td>
Diarrhea	2.7%	1.4%</td></td>	al
Productive cough	2.2%	1.0%	0.9%
an=”4″>*Carrier particle without insulin was used as placebo [see DESCRIPTION].

Table 2 shows the frequency of common adverse reactions, excluding hypoglycemia, associated with the use of AFREZZA in the pool of active-controlled trials in type 1 diabetes patients. These adverse reactions were not present at baseline, occurred more commonly on AFREZZA than on comparator, and occurred in at least 2% of patients treated with AFREZZA.

Table 2: Common Adverse Reactions That Occurred in ≥ 2% in Patients with Type 1 Diabetes Mellitus (excluding Hypoglycemia) Treated with AFREZZA

>	idth=”25%”>AFREZZA (n=1026)	Subcutaneous Insulin (n = 835)
Cough	29.4%	4.9%
Throat pain or irritation	5.5%	1.9%
Headache	4.7%	2.8%
Pulmonary function test decreased	ss=”yoast-text-mark”>n=”center”>2.8%	1.0%
Bronchitis	2.5%	2.0%
Urinary tract infection	2.3%	1.9%

Hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including AFREZZA [see WARNING AND PRECAUTIONS]. The incidence of severe and non-severe hypoglycemia in AFREZZA-treated patients versus placebo-treated patients with type 2 diabetes is shown in Table 3. A hypoglycemic episode was recorded if a patient-reported symptoms of hypoglycemia with or without a blood glucose value consistent with hypoglycemia. Severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose value consistent with hypoglycemia or prompt recovery after treatment for hypoglycemia.

Table 3: Incidence of Severe and Non-Severe Hypoglycemia in a Placebo-Controlled Study of Patients with Type 2 Diabetes

</tr><td class=”EmphTd”>th=”25%”>Placebo(N=176)

>	idth=”25%”>AFREZZA />(N=177)
Severe Hypoglycemia	5.1%	1.7%
Non-Severe Hypoglycemia	67%</td></td><td>ign=”center”>30%

Cough

Approximately 27% of patients treated with AFREZZA reported cough, compared to approximately 5% of patients treated with comparator. In clinical trials, cough was the most common reason for discontinuation of AFREZZA therapy (3% of AFREZZA-treated patients).

Pulmonary Function Decline</h5>

In clinical trials lasting up to 2 years, excluding patients with chronic lung disease, patients treated with AFREZZA had a 40 mL (95% CI: -80, -1) greater decline from baseline in forced expiratory volume in one second (FEV₁) compared to patients treated with comparator anti-diabetes treatments. The decline occurred during the first 3 months of therapy and persisted over 2 years (Figure 2). A decline in FEV₁ of ≥ 15% occurred in 6% of AFREZZA-treated patients compared to 3% of comparator-treated patients [see WARNING AND PRECAUTIONS].

Figure 2: Mean (+/-SE) Change in FEV₁ (Liters) from Baseline for Type 1 and Type 2 Diabetes Patients

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Weight Gain

Weight gain has occurred with some insulin therapies, including AFREZZA. Weight gain has been attributed to the anabolic effects of insulin and the decrease in glycosuria. In a clinical trial of patients with type 2 diabetes [see Clinical Studies], there was a mean 0.49 kg weight gain among AFREZZA-treated patients compared with a mean 1.13 kg weight loss among placebo-treated patients.

Postmarketing Experience

The following adverse reaction has been identified during post approval use of AFREZZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: bronchospasm.