AFREZZA

AFREZZA is an FDA-registered drug product whose active ingredient is INSULIN HUMAN. It is labelled by Mannkind Corporation taken by respiratory (inhalation) and marketed as a human prescription drug product. Identifiers on file: NDC 47918-874, application BLA022472, label effective 20260530. It is one of 5 FDA drug label records sharing the active ingredient INSULIN HUMAN. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing INSULIN HUMAN are most often described in connection with: indicated improve, glycemic control, pediatric patients, years age, diabetes mellitus, treatment diabetic, ketoacidosis dka, recently stopped. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE AFREZZA ® is indicated to improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus. AFREZZA ® is a rapid acting inhaled human insulin indicated to improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus. ( 1 ) Limitations of Use : Not recommended for the treatment of diabetic ketoacidosis (DKA) ( 1 ) Not recommended in patients who smoke or who have recently stopped smoking ( 1 ) Limitations of Use: AFREZZA is not recommended for the treatment of diabetic ketoacidosis (DKA) [see Warnings and Precautions ( 5.6 )] . The safety and effectiveness of AFREZZA in patients who smoke have not been established. The use of AFREZZA is not recommended in patients who smoke or who have recently stopped smoking [see Warnings and Precautions ( 5.5 )].

2 DOSAGE AND ADMINISTRATION Only administer via oral inhalation using the AFREZZA inhaler ( 2.2 ) Administer at the beginning of each meal ( 2.2 ) See full prescribing information for the recommended starting mealtime dosage in insulin-naïve patients and patients who are using subcutaneous mealtime insulin, or pre-mixed insulin ( 2.3 ) Modify the mealtime AFREZZA dosage based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal ( 2.4 ) If blood glucose control is not achieved with increased AFREZZA dosages, consider discontinuing AFREZZA ( 2.4 ) 2.1 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 (FEV 1 ) in all patients to identify potential lung disease [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )]. 2.2 Important Administration Information Prior to initiation, train patients and/or their caregiver(s) on proper administration of AFREZZA. After training, adult and pediatric patients aged 10 and older may self-administer AFREZZA if the healthcare provider determines that it is appropriate. 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. 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 ), Dosage Forms and Strengths ( 3 )]. To administer AFREZZA: 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. The AFREZZA Inhaler can be used for up to 15 days from the date of first use. After 15 days of use, discard the inhaler and replace it with a new inhaler. 2.3 Recommended Starting Mealtime Dosage of AFREZZA Insulin naïve patients The initial dosage of AFREZZA is 4 units inhaled at the beginning of each meal. Switching from Other Mealtime (prandial) Insulin Regimens to AFREZZA When switching from another insulin to AFREZZA, a different insulin dosage may be needed and increased frequency of blood glucose monitoring and monitoring for signs and symptoms of hypoglycemia may be needed [see Warnings and Precautions ( 5.2 , 5.3 ), Clinical Pharmacology ( 12.2 , 12.3 )]. Subcutaneous, Mealtime (prandial) Insulin: Follow the recommendations in Table 1 to convert each injected mealtime insulin dosage (or bolus dosage for patients using insulin pumps) to the recommended mealtime dosage of AFREZZA. Subcutaneous, Pre-Mixed Insulin: Refer to the prescribing information for the pre-mixed insulin to estimate the mealtime subcutaneous insulin dosage based on the product’s pharmacokinetic and pharmacodynamic properties. Follow the recommendations in Table 1 to convert each estimated injected mealtime dosage to an AFREZZA mealtime dose. If basal insulin is clinically indicated, refer to the prescribing information for the chosen basal insulin for dosage recommendations. Table 1. Recommended Starting Mealtime Dosage of AFREZZA when Switching from Other Mealtime Insulin Regimens Current Subcutaneous Mealtime Insulin Dosage Starting Dosage of AFREZZA Up to 3 units 4 units 4 to 5 units 8 units 6 to 7 units 12 units 8 or more units 16 units * For AFREZZA doses exceeding the contents of a single cartridge at mealtime, use more than one cartridge. To achieve the required total mealtime dosage, use a combination of 4 unit, 8 unit, and 12 unit cartridges. When titrating dosages above 16 units after the initial conversion dosage, use combinations of different cartridges [see Dosage and Administration ( 2.4 ), Dosage Forms and Strengths ( 3 ), How Supplied/Storage and Handling ( 16 )]. 2.4 Mealtime AFREZZA Dosage Modification Modify the mealtime 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 )]. Increase the frequency of blood glucose monitoring during titration of AFREZZA. If blood glucose control is not achieved with increased AFREZZA dosages, consider discontinuing AFREZZA. 2.5 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 )]. Switching from another insulin to AFREZZA [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.2 )]

4 CONTRAINDICATIONS AFREZZA is contraindicated: During episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )]. In patients with chronic lung disease, such as asthma or COPD, because of the risk of acute bronchospasm [see Warnings and Precautions ( 5.1 )]. In patients with a previous severe hypersensitivity reaction to any regular human insulin product or any of the inactive ingredients in AFREZZA. Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with AFREZZA [see Warnings and Precautions ( 5.7 )]. During episodes of hypoglycemia ( 4 ) Chronic lung disease, such as asthma, or COPD ( 4 ) Hypersensitivity to any regular human insulin product or any of the inactive ingredients in AFREZZA ( 4 )

6 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 )] The most common adverse reactions associated with AFREZZA (2% or greater incidence) are hypoglycemia, cough, and throat pain or irritation ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact MannKind at 1-877-323-8505 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials in Adults with Type 1 or Type 2 Diabetes Mellitus The data described below reflect exposure of 3,017 adult patients to AFREZZA and include 1,026 patients with type 1 diabetes mellitus and 1,991 patients with type 2 diabetes mellitus. The mean exposure duration was 8.2 months for patients with type 1 diabetes mellitus and those with type 2 diabetes mellitus [see Clinical Studies ( 14.2 , 14.3 )] . In the overall population: 1,874 patients with type 1 or type 2 diabetes mellitus were exposed to AFREZZA for 6 months and 724 patients for greater than one year. 620 and 1,254 patients with type 1 or type 2 diabetes mellitus, respectively, were exposed to AFREZZA for up to 6 months. 238 and 486 patients with type 1 or type 2 diabetes mellitus, respectively, were exposed to AFREZZA for greater than one year (median exposure was 1.8 years). AFREZZA was studied in placebo and active-controlled adult trials (n = 3 and n = 10, respectively). The mean age of the adult population was 50 years and 20 patients were older than 75 years of age; 51% of the population were males; 83% were White, 5% were Black or African American, and 2% were Asian; 10% were Hispanic or Latino ethnicity. At baseline, the type 1 diabetes mellitus population had diabetes mellitus for an average of 17 years and had a mean HbA1c of 8.3%, and the type 2 diabetes mellitus population had diabetes mellitus for an average of 11 years and had a mean HbA1c of 8.8%. At baseline, 33% of the population reported peripheral neuropathy, 32% reported retinopathy and 20% had a history of cardiovascular disease. Table 2 shows the frequency of common adverse reactions, excluding hypoglycemia, associated with the use of AFREZZA in the pool of controlled trials in adults with type 2 diabetes mellitus patients that occurred more commonly on AFREZZA than on placebo and/or comparator and occurred in at least 2% of patients treated with AFREZZA. Table 2. Common Adverse Reactions That Occurred in ≥ 2% in Adult Patients with Type 2 Diabetes Mellitus (excluding Hypoglycemia) Treated with AFREZZA Adverse Reaction AFREZZA (n = 1,991) % Placebo a (n = 290) % Non-placebo comparators (n=1,363) % Cough 26 20 5 Throat pain or irritation 4 4 1 Headache 3 3 2 Diarrhea 3 1 2 Productive cough 2 1 1 Fatigue 2 1 1 Nausea 2 0.3 1 a Carrier particle without insulin was used as placebo [see Description ( 11.1 )]. Table 3 shows the frequency of common adverse reactions, excluding hypoglycemia, associated with the use of AFREZZA in the pool of active-controlled trials in adults with type 1 diabetes mellitus. These adverse reactions occurred more commonly on AFREZZA than on comparator and occurred in at least 2% of patients treated with AFREZZA. Table 3. Common Adverse Reactions That Occurred in ≥ 2% in Adult Patients with Type 1 Diabetes Mellitus (excluding Hypoglycemia) Treated with AFREZZA Adverse Reaction AFREZZA (n=1,026) % Subcutaneous Insulin (n = 835) % Cough 29 5 Throat pain or irritation 6 2 Headache 5 3 Pulmonary function test decreased 3 1 Bronchitis 3 2 Urinary tract infection 2 2 Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in patients treated with AFREZZA [see Warnings and Precautions ( 5.3 )] . The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia across clinical trials of AFREZZA or with the incidence of hypoglycemia for other insulin products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice. The incidence of severe and non-severe hypoglycemia in AFREZZA-treated patients versus placebo-treated patients with type 2 diabetes mellitus is shown in Table 4 . 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 4. Incidence of Severe and Non-Severe Hypoglycemia in a Placebo-Controlled Study of Adult Patients with Type 2 Diabetes Mellitus Hypoglycemia Severity AFREZZA (N=177) Placebo (N=176) Severe Hypoglycemia 5% 2% Non-Severe Hypoglycemia 67% 30% Other Adverse Reactions in Adults with Type 1 or Type 2 Diabetes MellitusOther Adverse Reactions in Adults with Type 1 or Type 2 Diabetes Mellitus Cough Approximately 27% of adults treated with AFREZZA reported cough, compared to approximately 5% of patients treated with comparator. In clinical trials, cough was the most common reason for discontinuation of AFREZZA therapy (3% of adult AFREZZA-treated patients). Pulmonary Function Decline In clinical trials lasting up to 2 years, excluding patients with chronic lung disease, adults treated with AFREZZA had a 40 mL (95% CI: -80, -1) greater decline from baseline in forced expiratory volume in one second (FEV 1 ) 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 1 ). A decline in FEV 1 of ≥ 15% occurred in 6% of AFREZZA-treated patients compared to 3% of comparator-treated patients [see Warnings and Precautions ( 5.4 )]. Figure 1. Mean (+/-SE) Change in FEV 1 (Liters) from Baseline for Adult Patients with Type 1 and Type 2 Diabetes Mellitus Figure 1 Weight Gain Weight gain has occurred 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 adult patients with type 2 diabetes mellitus [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. Adverse Reactions in the Clinical Trial in Pediatric Patients Aged 6 Years and Older with Type 1 or Type 2 Diabetes Mellitus A 26-week open-label, randomized clinical trial evaluated the safety of AFREZZA versus rapid-acting insulin analog (RAA), both in combination with basal insulin, in 230 pediatric patients with type 1 or type 2 diabetes mellitus [see Clinical Studies ( 14.4 )]. The trial was followed by a 26-week safety extension. The mean age of patients was 12.6 years (range: 4 to 17 in the RAA arm, 6 to 17 in the AFREZZA arm). The majority (97.8%) had type 1 diabetes mellitus; a small subset (2.2%) had type 2 diabetes mellitus [see Clinical Studies ( 14.4 )] . The trial population had the following characteristics: 38% were female, 77% were White, 10% were Black or African American, 3% were Asian, 6% multiracial, and 20% were Hispanic or Latino ethnicity. Table 5 shows the frequency of common adverse reactions, excluding hypoglycemia, associated with the use of AFREZZA during the pediatric clinical trial. Data observed for 52 weeks was consistent with the 26-week safety profile. These adverse reactions occurred more commonly on AFREZZA than the comparator and occurred in at least 5% of patients treated with AFREZZA. The overall safety profile was similar to that of adults. In this trial, the change in percent predicted FEV1 from baseline to Week 26 was similar in both groups. Table 5. Common Adverse Reactions That Occurred in ≥ 5% of Pediatric Patients Aged 6 Years and Older With Type 1 and Type 2 Diabetes Mellitus (excluding Hypoglycemia) Treated with AFREZZA and More Commonly on AFREZZA Than on RAA Adverse Reaction a AFREZZA (n=117) % RAA (n=113) % Cough 21 3 Upper respiratory tract infection 18 14 Oropharyngeal pain 11 4 Headache 8 5 Vomiting 5 3 a This study was not designed to evaluate meaningful comparisons of adverse reaction incidence between AFREZZA and RAA. Hypoglycemia In the pediatric clinical trial [see Clinical Studies ( 14.4 )] , events of severe hypoglycemia (level 3) were defined as an episode associated with severe cognitive impairment requiring external assistance for recovery. Level 3 hypoglycemia was reported in 2 (1.7%) AFREZZA-treated pediatric patients versus 1 (0.9%) RAA-treated patient during the randomized treatment period. 6.2 Postmarketing Experience The following adverse reaction has been identified during post approval use of AFREZZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Respiratory : bronchospasm.

FDA lists 5 drug label records with INSULIN HUMAN as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

What is AFREZZA used for?
1 INDICATIONS AND USAGE AFREZZA ® is indicated to improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus. AFREZZA ® is a rapid acting inhaled human insulin indicated to improve glycemic control in adult and pediatric patients 6 years of age and older with diabetes mellitus. ( 1 ) Limitations of Use : Not recommended for the treatment of diabetic …

Who makes AFREZZA?
Mannkind Corporation is the labeler of record for AFREZZA. 5 FDA label records share the active ingredient INSULIN HUMAN, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does AFREZZA come in?
administered by respiratory (inhalation). Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is AFREZZA prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing INSULIN HUMAN?
Yes. 5 FDA drug label records list INSULIN HUMAN as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has AFREZZA been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.