Insulin Human Inhalation Powder

Name: Insulin Human Inhalation Powder

Indications

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

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 [see WARNING AND PRECAUTIONS].
  • The safety and efficacy of AFREZZA in patients who smoke has not been established. The use of AFREZZA is not recommended in patients who smoke or who have recently stopped smoking.

Side effects

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]
  • 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]
  • Hypersensitivity reactions [see WARNING AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying designs, the incidence of adverse reactions reported in one clinical trial may not be easily compared to the incidence reported in another clinical trial, and may not reflect what is observed in clinical practice.

The data described below reflect exposure of 3017 patients to AFREZZA and include 1026 patients with type 1 diabetes and 1991 patients with type 2 diabetes. The mean exposure duration was 8.17 months for the overall population and 8.16 months and 8.18 months for type 1 and 2 diabetes patients, respectively. In the overall population, 1874 were exposed to AFREZZA for 6 months and 724 for greater than one year. 620 and 1254 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). 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. 50.8% of the population were men; 82.6% were White, 1.8% were Asian, and 4.9% were Black or African American. 9.7% 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, 33.4% of the population reported peripheral neuropathy, 32.0% reported retinopathy and 19.6% had a history of cardiovascular disease. Table 1 shows 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 in Patients with Type 2 Diabetes Mellitus (excluding Hypoglycemia) Treated with AFREZZA

  Placebo*
(n = 290)
AFREZZA
(n = 1991)
Non-placebo comparators
(n=1363)
Cough 19.7% 25.6% 5.4%
Throat pain or irritation 3.8% 4.4% 0.9%
Headache 2.8% 3.1% 1.8%
Diarrhea 1.4% 2.7% 2.2%
Productive cough 1.0% 2.2% 0.9%
Fatigue 0.7% 2.0% 0.6%
Nausea 0.3% 2.0% 1.0%
*Carrier particle without insulin was used as placebo [see DESCRIPTION].

Table 2 shows 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 in Patients with Type 1 Diabetes Mellitus (excluding Hypoglycemia) Treated with AFREZZA

  Subcutaneous Insulin
(n = 835)
AFREZZA
(n=1026)
Cough 4.9% 29.4%
Throat pain or irritation 1.9% 5.5%
Headache 2.8% 4.7%
Pulmonary function test decreased 1.0% 2.8%
Bronchitis 2.0% 2.5%
Urinary tract infection 1.9% 2.3%

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 of AFREZZA versus placebo in 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

  Placebo
(N=176)
AFREZZA
(N=177)
Severe Hypoglycemia 1.7% 5.1%
Non-Severe Hypoglycemia 30% 67%

Cough

Approximately 27% of patients treated with AFREZZA reported cough, compared to approximately 5.2% of patients treated with comparator. In clinical trials, cough was the most common reason for discontinuation of AFREZZA therapy (2.8% of AFREZZA-treated patients).

Pulmonary Function Decline

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 subjects compared to 3% of comparator-treated subjects.

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

Weight Gain

Weight gain may occur 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.

Antibody Production

Increases in anti-insulin antibody concentrations have been observed in patients treated with AFREZZA. Increases in anti-insulin antibodies are observed more frequently with AFREZZA than with subcutaneously injected mealtime insulins. Presence of antibody did not correlate with reduced efficacy, as measured by HbA1c and fasting plasma glucose, or specific adverse reactions.

Warnings

Included as part of the PRECAUTIONS section.

Overdose

Excess insulin administration may cause hypoglycemia and hypokalemia [see WARNING AND PRECAUTIONS].

Mild episodes of hypoglycemia can usually be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise, may be needed.

Severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with intramuscular / subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia. Hypokalemia must be corrected appropriately.

Patient information

AFREZZA®
(uh-FREZZ-uh)
(insulin human) inhalation powder

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 in place of long-acting insulin. AFREZZA must be used with long-acting insulin in people who have type 1 diabetes mellitus.
  • AFREZZA is not for use to treat diabetic ketoacidosis.
  • 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.

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. For more information, go to www.AFREZZA.com or call sanofi-aventis 1-800-633-1610.

What are the ingredients in AFREZZA?

Active ingredient: human insulin

Inactive ingredients: fumaryl diketopiperazine, polysorbate 80

Manufactured By: MannKind Corporation, MannKind Corporation, Danbury, CT 06810. Distributed by: sanofi-aventis U.S. LLC, Bridgewater, NJ 08807, A SANOFI COMPANY

Instructions for Use

AFREZZA®
(uh-FREZZ-uh) (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.
  • 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 1-800-633-1610.

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

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.

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 the Cartridge

Throw away the used cartridge in your regular household trash.

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.

How should I store AFREZZA?

*If a foil package, blister card or strip is not refrigerated, the contents must be used within 10 days.

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

Caring for your AFREZZA inhaler:

Care Instructions

Switching between AFREZZA and injected insulin:

Contact your healthcare provider before switching insulins.

AFREZZA® is a mealtime insulin.

Do not switch from AFREZZA to a long acting insulin.

Do not switch from a long acting insulin to AFREZZA®.

This Medication Guide and Instructions for Use has been approved by the U.S. Food and Drug Administration.

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