Insulin inhalation

You should not use this medicine if you are allergic to insulin, or if you are having an episode of hypoglycemia (low blood sugar).

Insulin inhalation can cause sudden or serious lung problems. Do not use this medicine if you have:

• chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD); or

• diabetic ketoacidosis (call your doctor for treatment).

Do not use insulin inhalation if you smoke or have recently quit smoking (within the past 6 months).

In studies with insulin inhalation, lung cancer occurred in a small number of people. It is not clear whether this medicine was the actual cause of lung cancer. Your doctor will perform lung function tests before and during your treatment with insulin inhalation.

Insulin inhalation is not approved for use by anyone younger than 18 years old.

To make sure insulin inhalation is safe for you, tell your doctor if you have ever had:

• asthma, COPD, or other breathing problems;

• lung cancer;

• liver or kidney disease; or

• if you use other inhaled medicines.

Tell your doctor if you also take pioglitazone or rosiglitazone (sometimes contained in combinations with glimepiride or metformin). Taking certain oral diabetes medicines while you are using insulin may increase your risk of serious heart problems.

It is not known whether insulin inhalation will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether insulin inhalation passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Usual Adult Dose for Diabetes Type 2:

Insulin-naive :
Initial dose: 4 units via oral inhalation at each meal
Maintenance dose: Adjust dosage according to patient requirements

Switching from Subcutaneous Mealtime Insulin:
Dose conversion as follows:
4 units inhaled insulin replaces up to 4 units of subcutaneous mealtime insulin
8 units inhaled insulin replaces 5 to 8 units of subcutaneous mealtime insulin
12 units inhaled insulin replaces 9 to 12 units of subcutaneous mealtime insulin
16 units inhaled insulin replaces 13 to 16 units of subcutaneous mealtime insulin
20 units inhaled insulin replaces 17 to 20 units of subcutaneous mealtime insulin
24 units inhaled insulin replaces 21 to 24 units of subcutaneous mealtime insulin

Switching from Subcutaneous Pre-mixed insulin:
-Estimate mealtime injected dose by dividing the total daily injected pre-mixed insulin dose by one-half (half will be the total daily mealtime dose; half will be the daily basal dose)
-Divide the total daily mealtime dose equally among the 3 meals of the day and using the dose conversion table above, convert to the appropriate inhaled insulin dose.
-Give the appropriate basal insulin dose as calculated above.

Comments:
-Should only be administered via AFREZZA(R) inhaler.
-Administer at the beginning of a meal.
-Use a single inhalation per cartridge; doses exceeding 8 units will require multiple cartridges.
-After cartridge is inserted, keep inhaler level; if inhaler is turned upside down, shaken, or dropped after the cartridge has been inserted, replace the cartridge before use.
-Monitor blood glucose, especially in patients requiring high doses; if blood glucose control is not achieved with increasing doses, consider subcutaneous mealtime insulin.

Use: Adult patients with diabetes mellitus to improve glycemic control. Inhaled insulin is a rapid acting insulin and is not a substitute for long-acting insulin. In patients with type 1 diabetes mellitus, inhaled insulin should be used in combination with long-acting insulin.

Usual Adult Dose for Diabetes Type 1:

Insulin-naive :
Initial dose: 4 units via oral inhalation at each meal
Maintenance dose: Adjust dosage according to patient requirements

Switching from Subcutaneous Mealtime Insulin:
Dose conversion as follows:
4 units inhaled insulin replaces up to 4 units of subcutaneous mealtime insulin
8 units inhaled insulin replaces 5 to 8 units of subcutaneous mealtime insulin
12 units inhaled insulin replaces 9 to 12 units of subcutaneous mealtime insulin
16 units inhaled insulin replaces 13 to 16 units of subcutaneous mealtime insulin
20 units inhaled insulin replaces 17 to 20 units of subcutaneous mealtime insulin
24 units inhaled insulin replaces 21 to 24 units of subcutaneous mealtime insulin

Switching from Subcutaneous Pre-mixed insulin:
-Estimate mealtime injected dose by dividing the total daily injected pre-mixed insulin dose by one-half (half will be the total daily mealtime dose; half will be the daily basal dose)
-Divide the total daily mealtime dose equally among the 3 meals of the day and using the dose conversion table above, convert to the appropriate inhaled insulin dose.
-Give the appropriate basal insulin dose as calculated above.

Comments:
-Should only be administered via AFREZZA(R) inhaler.
-Administer at the beginning of a meal.
-Use a single inhalation per cartridge; doses exceeding 8 units will require multiple cartridges.
-After cartridge is inserted, keep inhaler level; if inhaler is turned upside down, shaken, or dropped after the cartridge has been inserted, replace the cartridge before use.
-Monitor blood glucose, especially in patients requiring high doses; if blood glucose control is not achieved with increasing doses, consider subcutaneous mealtime insulin.

Use: Adult patients with diabetes mellitus to improve glycemic control. Inhaled insulin is a rapid acting insulin and is not a substitute for long-acting insulin. In patients with type 1 diabetes mellitus, inhaled insulin should be used in combination with long-acting insulin.

Applies to insulin inhalation, rapid acting: inhalation aerosol powder

Along with its needed effects, insulin inhalation, rapid acting may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking insulin inhalation, rapid acting:

• Anxiety
• blurred vision
• chills
• cold sweats
• coma
• confusion
• cool, pale skin
• cough
• depression
• dizziness
• fast heartbeat
• headache
• increased hunger
• nausea
• nightmares
• seizures
• shakiness
• slurred speech
• unusual tiredness or weakness

• Difficulty breathing
• difficulty swallowing
• hives, itching, or skin rash
• noisy breathing
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• tightness in the chest

Some side effects of insulin inhalation, rapid acting may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• sore throat

• Weight gain

US REMS: The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Afrezza. It includes a communication plan. For additional information: www.fda.gov/REMS

US BOXED WARNINGS:
-Acute bronchospasm has been observed in patients with asthma and COPD.
-Contraindicated in patients with chronic lung disease.
-Prior to initiating treatment, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential underlying lung disease.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Data not available

Administration Advice:
-See patient instructions for use for complete administration instructions with illustrations.
-Administer at the beginning of a meal.
-Replace inhaler every 15 days.

Storage requirements:
-Inhaler may be stored refrigerated, but should be at room temperature before use; cartridges and inhaler should be at room temperature for 10 minutes prior to use.
-Cartridges should be stored in sealed foil packages in refrigerator until ready to use; blister cards and strips should not be put back in the refrigerator after being at room temperature.
-Unopened foil package, blister card, and strips stored at room temperature should be used within 10 days.
-Opened strips should be used within 3 days.

Monitoring:
-Assess pulmonary function (FEV1) prior to initiating, at 6 months, and annually; may increase monitoring as needed.
-Routine self-monitoring of blood glucose (SMBG) and regular HbA1c testing is recommended; more frequent blood glucose monitoring is recommended during periods of stress, changes in insulin regimen, and with changes to concomitant medications.
-Monitor potassium levels in patients at risk for hypokalemia.
-Monitor for fluid retention and symptoms of heart failure in patients receiving concomitant peroxisome proliferator-activated receptor (PPAR )-agonists.

Patient Advice:
-Patients should report any respiratory difficulty to their healthcare provider.
-Patients should understand the importance of diet, exercise, and blood glucose monitoring; they should be able to recognize and treat high and low blood glucose levels.
-Patients should seek medical advice promptly during periods of stress as their insulin requirements may change.
-Patients who are pregnant or planning to become pregnant should speak with their healthcare provider.