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 (4) and Warnings and Precautions (5.1)].

Important Administration and Discard Instructions

Only 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 (2.3)]. For additional administration instructions on how to use the AFREZZA Inhaler [see Dosage and Administration (2.6)] 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

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 Warnings and Precautions (5.2)].

For patients using subcutaneous, pre-mixed insulin:

• 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 Warnings and Precautions (5.2)].
• 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.

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.

Figure 1. Mealtime AFREZZA Starting Dose Conversion Table

Mealtime Dosage Modification

• Modify the AFREZZA dosage based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
• 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 Warnings and Precautions (5.3) and Use in Specific Populations (8.6, 8.7)].
• 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:

• AFREZZA is used concomitantly with certain drugs that increase and/or decrease the glucose lowering effect [see Drug Interactions (7.1, 7.2, 7.3)].
• Switching from another insulin to AFREZZA [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)]

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.
• After 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.