Afrezza

Name: Afrezza

Uses of Afrezza

Afrezza is a prescription medication used to control hyperglycemia (high blood sugar) in patients with type 1 and type 2 diabetes mellitus.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Side Effects of Afrezza

Serious side effects have been reported with Afrezza. See the “Afrezza Precautions” section.

The most common side effect of Afrezza is hypoglycemia, which can include the following symptoms:

  • Sweating
  • Dizziness
  • Palpitation
  • Tremor
  • Hunger
  • Restlessness
  • Tingling in the hands, feet, lips, or tongue
  • Lightheadedness
  • Decreased concentration
  • Headache
  • Drowsiness
  • Sleep disturbances
  • Anxiety
  • Blurred vision
  • Slurred speech
  • Depressed mood
  • Irritability
  • Abnormal behavior
  • Unsteady movement
  • Personality changes

Afrezza can also cause cough and throat pain or irritation.  

This is not a complete list of Afrezza side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Afrezza Precautions

Serious side effects have been reported with Afrezza including the following:

  • Hypoglycemia. Tell your healthcare provider right away if you have some or all of the following symptoms of hypoglycemia.
    • Sweating
    • Dizziness
    • Palpitation
    • Tremor
    • Hunger
    • Restlessness
    • Tingling in the hands, feet, lips, or tongue
    • Lightheadedness
    • Decreased concentration
    • Headache
    • Drowsiness
    • Sleep disturbances
    • Anxiety
    • Blurred vision
    • Slurred speech
    • Depressed mood
    • Irritability
    • Abnormal behavior
    • Unsteady movement
    • Personality changes

Hypoglycemia related to Afrezza can also cause dizziness, drowsiness, and blurred vision. Do not drive or operate heavy machinery until you know how Afrezza affects you.

  • 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 such as 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.

Do not take Afrezza if you:

  • are allergic to Afrezza or to any of its ingredients
  • are experiencing hypoglycemia
  • chronic lung disease, such as asthma, or chronic obstructive pulmonary disease

Afrezza Dosage

Use this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight (weight loss or weight gain)
  • your level of physical activity
  • your meal times and eating habits
  • increased stress
  • if you are feeling ill
 

Afrezza - Clinical Pharmacology

Mechanism of Action

Insulin lowers blood glucose levels by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in adipocytes, inhibits proteolysis, and enhances protein synthesis.

Pharmacodynamics

The pharmacodynamic profile for orally inhaled Afrezza 8 units relative to subcutaneously administered insulin lispro 8 units from a study in 12 patients with type 1 diabetes is shown in Figure 3(A). The median time to maximum effect of Afrezza (measured by the peak rate of glucose infusion) was approximately 53 minutes (standard deviation of 74 minutes) and the effect then declined to near baseline levels by about 160 minutes.

* Despite the faster absorption of insulin (PK) from Afrezza, the onset of activity (PD) was comparable to insulin lispro.
Figure 3. Baseline-Corrected Glucose Infusion Rate (A) and Baseline-Corrected Serum Insulin Concentrations (B) after Administration of Afrezza or Subcutaneous Insulin Lispro in Type 1 Diabetes Patients*

In a study of 32 healthy subjects, the pharmacodynamic effect of Afrezza, measured as area under the glucose infusion rate - time curve (AUC-GIR) from an euglycemic clamp, increased in a less than dose-proportional manner. This effect has been observed for subcutaneously administered insulins, but it is unknown if the diminishing pharmacodynamic benefit at higher dosage of Afrezza parallels that which is seen with subcutaneously administered insulin.

Pharmacokinetics

The insulin contained in Afrezza is regular human insulin. Following pulmonary absorption into systemic circulation, the metabolism and elimination are comparable to regular human insulin.

Absorption: The pharmacokinetic profiles for orally inhaled Afrezza 8 units relative to subcutaneously administered insulin lispro 8 units from a study in 12 patients with type 1 diabetes are shown in Figure 3(B). The maximum serum insulin concentration was reached by 12–15 minutes after inhalation of Afrezza 8 units and serum insulin concentrations declined to baseline by approximately 180 minutes. However, the faster absorption of insulin from Afrezza [see Figure 3(B)] did not result in a faster onset of activity compared to insulin lispro [see Figure 3(A)].

Disposition: Systemic insulin disposition (median terminal half-life) following oral inhalation of Afrezza 4 and 32 units was 28–39 minutes, and 145 minutes for subcutaneous regular human insulin 15 units.

Carrier Particles

Clinical pharmacology studies showed that carrier particles [see Description (11)] are not metabolized and are eliminated unchanged in the urine following the lung absorption. Following oral inhalation of Afrezza, a mean of 39% of the inhaled dose of carrier particles was distributed to the lungs and a mean of 7% of the dose was swallowed. The swallowed fraction was not absorbed from the GI tract and was eliminated unchanged in the feces.

Drug Interaction: Bronchodilators and Inhaled Steroids

Albuterol increased the AUC insulin administered by Afrezza by 25% in patients with asthma. Effect of fluticasone on insulin exposures following Afrezza administration has not been evaluated in patients with asthma; however, no significant change in insulin exposure was observed in a study in healthy volunteers. Frequent glucose monitoring and dose reduction may be necessary for Afrezza if it is co-administered with albuterol.

How Supplied/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 separated by perforations for a total of 15 cartridges. For convenience, the perforation allows users to remove a single strip containing 3 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 is available in the following configurations:

  • NDC 47918-874-90, Afrezza (insulin human) Inhalation Powder: 90 − 4 unit cartridges and 2 inhalers
  • NDC 47918-878-90, Afrezza (insulin human) Inhalation Powder: 90 − 8 unit cartridges and 2 inhalers
  • NDC 47918-891-90, Afrezza (insulin human) Inhalation Powder: 90 − 12 unit cartridges and 2 inhalers
  • NDC 47918-884-63, Afrezza (insulin human) Inhalation Powder: 90 cartridges; 60 – 4 unit cartridges and 30 − 8 unit cartridges and 2 inhalers
  • NDC 47918-882-36, Afrezza (insulin human) Inhalation Powder: 90 cartridges; 30 – 4 unit cartridges and 60 − 8 unit cartridges and 2 inhalers
  • NDC 47918-894-63, Afrezza (insulin human) Inhalation Powder: 90 cartridges; 60 – 8 unit cartridges and 30 - 12 unit cartridges and 2 inhalers
  • NDC 47918-880-18, Afrezza (insulin human) Inhalation Powder: 180 cartridges; 90 – 4 unit cartridges and 90 - 8 unit cartridges and 2 inhalers (Titration Pack)
  • NDC 47918-902-18, Afrezza (insulin human) Inhalation Powder; 180 cartridges; 60 – 4 unit cartridges, 60 – 8 unit cartridges and 60 – 12 unit cartridges and 2 inhalers (Titration Pack)

Storage

Not in Use: Refrigerated Storage 2–8ºC (36–46ºF)

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

In Use: Room Temperature Storage 25ºC (77ºF), excursions permitted 15–30ºC (59–86ºF)

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 at 2–25ºC (36–77ºF); 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.

PRINCIPAL DISPLAY PANEL - 90 -8 Unit KitCarton

NDC 47918-878-90
Rx ONLY

For FPO Only

Afrezza®
(insulin human)
Inhalation Powder

Each green cartridge
approximates 8 units
of injected insulin

MannKind Corporation

8
units per
cartridge

90 cartridges

FOR ORAL INHALATION ONLY

Carton Contains:
90 – 8 unit Cartridges + 2 Inhalers

Dispense the enclosed Medication Guide
to each patient

PRINCIPAL DISPLAY PANEL - 60 – 4 Unit/30 – 8 Unit Kit Carton

NDC 47918-884-63
Rx ONLY

For FPO Only

Afrezza®
(insulin human)
Inhalation Powder

Each blue cartridge
approximates 4 units
of injected insulin

Each green cartridge
approximates 8 units
of injected insulin

MannKind Corporation

4
units per
cartridge

8
units per
cartridge

90 cartridges

FOR ORAL INHALATION ONLY

Carton Contains:
60 – 4 unit Cartridges | + 2 Inhalers
30 – 8 unit Cartridges

Dispense the enclosed
Medication Guide
to each patient

PRINCIPAL DISPLAY PANEL - 60 – 8 Unit/30 – 12 Unit Kit Carton

NDC 47918-894-63
Rx ONLY

For FPO Only

Afrezza®
(insulin human)
Inhalation Powder

Each green cartridge
approximates 8 units
of injected insulin

Each yellow cartridge
approximates 12 units
of injected insulin

MannKind Corporation

8
units per
cartridge

12
units per
cartridge

90 cartridges

FOR ORAL INHALATION ONLY

Carton Contains:
60 – 8 unit Cartridges | + 2 Inhalers
30 – 12 unit Cartridges

Dispense the enclosed
Medication Guide
to each patient

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