Afrezza

Name: Afrezza

Afrezza Drug Class

Afrezza is part of the drug class:

  • Insulins and analogues for inhalation

Afrezza Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Afrezza, there are no specific foods that you must exclude from your diet when receiving this medication.

Precautions While Using Afrezza

Your doctor will want to check your progress at regular visits, especially during the first few weeks you take this medicine. Blood and lung function tests may be needed to check for unwanted effects.

It is very important to follow carefully any instructions from your health care team about:

  • Alcohol—Drinking alcohol (including beer and wine) may cause severe low blood sugar. Discuss this with your health care team.
  • Other medicines—Do not take other medicines during the time you are taking this medicine unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.
  • Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy.
  • Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.

In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to:

  • Wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.
  • Keep an extra supply of insulin on hand in case high blood sugar occurs.
  • Keep some kind of quick-acting sugar handy to treat low blood sugar.
  • Have a glucagon kit and a syringe and needle available in case severe low blood sugar occurs. Check and replace any expired kits regularly.

Tell your doctor if you are smoking or have recently stopped smoking while using this medicine.

Too much insulin human inhaled can cause hypoglycemia (low blood sugar). Symptoms of low blood sugar include anxiety, behavior change similar to being drunk, blurred vision, cold sweats, confusion, depression, difficulty in thinking, dizziness or lightheadedness, drowsiness, excessive hunger, fast heartbeat, headache, irritability or abnormal behavior, nervousness, nightmares, restless sleep, shakiness, slurred speech, and tingling in the hands, feet, lips, or tongue.

If symptoms of low blood sugar occur, eat glucose tablets or gel to relieve the symptoms. Also, check your blood for low blood sugar. Get to a doctor or a hospital right away if the symptoms do not improve. Someone should call for emergency help immediately if severe symptoms such as convulsions (seizures) or unconsciousness occur. Have a glucagon kit available, along with a syringe and needle, and know how to use it. Members of your household also should know how to use it.

Hyperglycemia (high blood sugar) may occur if you do not take enough or skip a dose of your antidiabetic medicine, overeat or do not follow your meal plan, have a fever or infection, or do not exercise as much as usual.

Symptoms of high blood sugar include blurred vision, drowsiness, dry mouth, flushed, dry skin, fruit-like breath odor, increased urination, ketones in the urine, loss of appetite, stomachache, nausea, or vomiting, tiredness, troubled breathing (rapid and deep), unconsciousness, or unusual thirst.

If symptoms of high blood sugar occur, check your blood sugar level and then call your doctor for instructions.

This medicine may make you dizzy or drowsy. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

Check with your doctor right away if you have a cough that keeps coming back or does not go away, shortness of breath, or trouble breathing.

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have a rash, itching, swelling of the face, tongue, and throat, trouble breathing, or chest pain after you receive the medicine.

Using this medicine together with other diabetes medicine (such as pioglitazone, rosiglitazone, Actos®, Actoplus Met®, Avandia®) may cause serious heart problem or edema (fluid retention). Check with your doctor immediately if you are rapidly gaining weight, having shortness of breath, chest pain or discomfort, extreme tiredness or weakness, trouble breathing, uneven heartbeat, or excessive swelling of the hands, wrist, ankles, or feet.

What do I need to tell my doctor BEFORE I take Afrezza?

  • If you have an allergy to insulin or any other part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have low blood sugar.
  • If you have an acidic blood problem caused by diabetes.
  • If you smoke or have recently stopped smoking.
  • If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with Afrezza.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

How is this medicine (Afrezza) best taken?

Use Afrezza as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Follow how to use as you have been told by the doctor or read the package insert.
  • For breathing in only by a puffer (inhaler) into the lungs.
  • Only use the device that comes with this medicine. Do not use any other devices.
  • Use at the start of a meal as your doctor has told you.
  • Put the cap back on after you are done using your dose.
  • After a cartridge has been put in, handle the device with care. If the device has been turned upside down, held with the mouthpiece pointing down, shaken, or dropped, replace the cartridge before use.
  • Follow the diet and workout plan that your doctor told you about.
  • Be sure you know what to do if you do not eat as much as normal or if you skip a meal.

What do I do if I miss a dose?

  • Be sure you know what to do if you forget to take a dose
  • If you are not sure what to do if you miss a dose, call your doctor.

Afrezza Dosage and Administration

Route of Administration

Afrezza should only be administered via oral inhalation using the Afrezza Inhaler. Afrezza is administered using a single inhalation per cartridge.

Dosage Information

Administer Afrezza at the beginning of the meal.

Dosage adjustment may be needed when switching from another insulin to Afrezza [see Warnings and Precautions (5.2)].

Starting Mealtime Dose:

  • Insulin Naïve Individuals: Start on 4 units of Afrezza at each meal.
  • Individuals Using Subcutaneous Mealtime (Prandial) Insulin: Determine the appropriate Afrezza dose for each meal by converting from the injected dose using Figure 1.
  • Individuals 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. 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.

Figure 1. Mealtime Afrezza Dose Conversion Table

Mealtime Dose Adjustment

Adjust the dosage of Afrezza based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.

Dosage adjustments 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 doses of Afrezza. If, in these patients, blood glucose control is not achieved with increased Afrezza doses, consider use of subcutaneous mealtime insulin.

Afrezza Administration for Doses Exceeding 12 units

For Afrezza doses exceeding 12 units, inhalations from multiple cartridges are necessary. To achieve the required total mealtime dose, patients should 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, combinations of different multiple cartridges can be used.

Dosage Adjustment due to Drug Interactions

Dosage adjustment may be needed when Afrezza is coadministered with certain drugs [see Drug Interactions (7)].

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 Instructions

See Patient Instructions for Use for complete administration instructions with illustrations.

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, the cartridge should be replaced before use.

Adverse Reactions

The following serious adverse reactions are described below and elsewhere in the labeling:

  • Acute bronchospasm in patients with chronic lung disease [see Warnings and Precautions (5.1)]
  • Hypoglycemia [see Warnings and Precautions (5.3)]
  • Decline in pulmonary function [see Warnings and Precautions (5.4)]
  • Lung cancer [see Warnings and Precautions (5.5)]
  • Diabetic ketoacidosis [see Warnings and Precautions (5.6)]
  • Hypersensitivity reactions [see Warnings and Precautions (5.7)]

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, 4.9% were Black or African American and 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* Afrezza Non-placebo comparators
(n = 290) (n = 1991) (n=1363)
* Carrier particle without insulin was used as placebo
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%

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 Warnings and Precautions (5.3)]. 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 (14.3)], 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.

Afrezza Description

Afrezza Cartridges

Afrezza consists of single-use plastic cartridges filled with a white powder containing insulin (human), which is administered via oral inhalation using the Afrezza Inhaler only.

Afrezza cartridges contain human insulin produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Chemically, human insulin has the empirical formula C257H383N65O77S6 and a molecular weight of 5808. Human insulin has the following primary amino acid sequence:

Insulin is adsorbed onto carrier particles consisting of fumaryl diketopiperazine (FDKP) and polysorbate 80.

Afrezza Inhalation Powder is a dry powder supplied as 4 unit, 8 unit or 12 unit cartridges. The 4 unit cartridge contains 0.35 mg of insulin. The 8 unit cartridge contains 0.7 mg of insulin. The 12 unit cartridge contains 1 mg of insulin.

Afrezza Inhaler

The Afrezza Inhaler is breath-powered by the patient. When the patient inhales through the device, the powder is aerosolized and delivered to the lung. The amount of Afrezza delivered to the lung will depend on individual patient factors.

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

NDC 47918-882-36
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:
30 – 4 unit Cartridges | + 2 Inhalers
60 – 8 unit Cartridges

Dispense the enclosed
Medication Guide
to each patient

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