Afrezza

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is likely Afrezza is excreted in human breast milk. A decision should be made whether to discontinue nursing orsuspend use of the drug since Afrezza has not been studied in lactating women.

Inhalational:

WARNING: RISK OF ACUTE BRONCHOSPASM IN PATIENTS WITH CHRONIC LUNG DISEASE

Acute bronchospasm has been observed in patients with asthma and COPD using AFREZZA.

Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD.

Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients

• Follow how to store closely. Read the package insert that comes with this medicine. If you have questions about how to store Afrezza, talk with your pharmacist.
• Be sure you know how long you can store this medicine before you need to throw it away.
• Throw away the inhaler 15 days after first use and get a new one.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Afrezza is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Afrezza or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Afrezza (insulin (oral inhalation)). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

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 (5.6)].
• 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.

Afrezza is contraindicated in patients with the following:

• During episodes of hypoglycemia
• Chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD), because of the risk of acute bronchospasm [see Warnings and Precautions (5.1)]
• Hypersensitivity to regular human insulin or any of the Afrezza excipients [see Warnings and Precautions (5.7)]

Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions (5.3, 5.8)].

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 104 week carcinogenicity study, rats were given doses up to 46 mg/kg/day of the carrier and up to 1.23 mg/kg/day of insulin, by nose-only inhalation. No increased incidence of tumors was observed at systemic exposures equivalent to the insulin at a maximum daily Afrezza dose of 99 mg based on a comparison of relative body surface areas across species.

No increased incidence of tumors was observed in a 26 week carcinogenicity study in transgenic mice (Tg-ras-H2) given doses up to 75 mg/kg/day of carrier and up to 5 mg/kg/day of Afrezza.

Afrezza was not genotoxic in Ames bacterial mutagenicity assay and in the chromosome aberration assay, using human peripheral lymphocytes with or without metabolic activation. The carrier alone was not genotoxic in the in vivo mouse micronucleus assay.

In female rats given subcutaneous doses of 10, 30, and 100 mg/kg/day of carrier (vehicle without insulin) beginning 2 weeks prior to mating until gestation day 7, there were no adverse effects on male fertility at doses up to 100 mg/kg/day (a systemic exposure 14–21 times that following the maximum daily Afrezza dose of 99 mg based on AUC). In female rats there was increased pre- and post-implantation loss at 100 mg/kg/day but not at 30 mg/kg/day (14–21 times higher systemic exposure than the maximum daily Afrezza dose of 99 mg based on AUC).

See FDA-approved patient labeling (Medication Guide)

Instructions

Instruct patients to read the Medication Guide before starting Afrezza therapy and to reread it each time the prescription is renewed, because information may change. Instruct patients to inform their healthcare provider or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens.

Inform patients of the potential risks and benefits of Afrezza and of alternative modes of therapy. Inform patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and HbA1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications. Advise patients to seek medical advice promptly during periods of stress such as fever, trauma, infection, or surgery, as medication requirements may change.

Instruct patients to use Afrezza only with the Afrezza inhaler.

Inform patients that the most common adverse reactions associated with the use of Afrezza are hypoglycemia, cough, and throat pain or irritation.

Advise women with diabetes to inform their physician if they are pregnant or are planning to become pregnant while using Afrezza.

Acute Bronchospasm in Patients with Chronic Lung Disease

Advise patients to inform their physicians if they have a history of lung disease, because Afrezza should not be used in patients with chronic lung disease (e.g., asthma, COPD, or other chronic lung disease(s)) [see Contraindications (4) and Warnings and Precautions (5.1)].

Advise patients that if they experience any respiratory difficulty after inhalation of Afrezza, they should report it to their physician immediately for assessment.

Hypoglycemia

Instruct patients on self-management procedures including glucose monitoring, proper inhalation technique, and management of hypoglycemia and hyperglycemia especially at initiation of Afrezza therapy. Instruct patients on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals.

Instruct patients on the management of hypoglycemia. Inform patients that their ability to concentrate and react may be impaired as a result of hypoglycemia. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery [see Warnings and Precautions (5.3)].

Decline in Pulmonary Function and Monitoring

Inform patients that Afrezza can cause a decline in lung function and their lung function will be evaluated by spirometry before initiation of Afrezza treatment [see Warnings and Precautions (5.4)].

Lung Cancer

Inform patients to promptly report any signs or symptoms potentially related to lung cancer [see Warnings and Precautions (5.5)].

Diabetic Ketoacidosis

Instruct patients to carefully monitor their blood glucose during illness, infection, and other risk situations for diabetic ketoacidosis and to contact their healthcare provider if their blood glucose control worsens [see Warnings and Precautions (5.6)].

Hypersensitivity Reactions

Advise patients that hypersensitivity reactions can occur with insulin therapy including Afrezza. Inform patients on the symptoms of hypersensitivity reactions [see Warnings and Precautions (5.7)].

Afrezza is a registered trademark owned by MannKind Corporation
Patented: http://www.mannkindcorp.com/research-development/patent-notices

MannKind Corporation
Danbury, CT 06810

NDC 47918-874-90
Rx ONLY

For FPO Only

Afrezza®
(insulin human)
Inhalation Powder

Each blue cartridge
approximates 4 units
of injected insulin

MannKind Corporation

4
units per
cartridge

90 cartridges

FOR ORAL INHALATION ONLY

Carton Contains:
90 – 4 unit Cartridges + 2 Inhalers

Dispense the enclosed Medication Guide
to each patient