Afrezza - IMCURE

What is Afrezza?

11 DESCRIPTION 11.1 AFREZZA Cartridges Human insulin is a rapid acting human insulin produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Chemically, human insulin has the empirical formula C 257 H 383 N 65 O 77 S 6 and a molecular weight of 5808. Human insulin has the following primary amino acid sequence: AFREZZA (human insulin) inhalation powder is available in single-use plastic cartridges filled with a white powder containing insulin (human), which is administered via oral inhalation using the AFREZZA Inhaler only. 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. Primary Amino Acid Sequence 11.2 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.

Uses of Afrezza

Established uses

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 )].

How Afrezza works

In more detail: 12.1 Mechanism of Action Insulin lowers blood glucose levels in adult patients with diabetes mellitus by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in adipocytes, inhibits proteolysis, and enhances protein synthesis.

How to take Afrezza

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 sel

Dosage

Follow the dose prescribed by your doctor or pharmacist. The ranges below are general information, not a personal prescription.

Adults: 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 sel

Side effects of Afrezza

Common

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 o

Warnings and who should not take it

Who should NOT take Afrezza?

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 )

Overdose

10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.3 , 5.8 )] . Mild episodes of hypoglycemia due to insulin overdose can usually be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise, may be needed. Severe episodes of hypoglycemia (due to insulin overdose) with coma, seizure, or neurologic impairment may be treated with intramuscular or 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 should be corrected appropriately. In the event of an overdose of AFREZZA, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

Safety at a glance

PregnancyCaution

8.1 Pregnancy Risk Summary Limited available data with AFREZZA use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes. Available information from published studies with human insulin use during pregnancy has not reported a clear association with human insulin and adverse developmental outcomes ( see Data ). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations ). In animal reproduction studies, there were no adverse developmental outcomes with subcutaneous administration of carrier particles (vehicle without insulin) to pregnant rats during organogenesis at doses 21 times the human daily dose of 99 mg AFREZZA, based on AUC (see Data ) . The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,

Children and elderly

Children

8.4 Pediatric Use The safety and effectiveness of AFREZZA to improve glycemic control have been established in pediatric patients 6 years of age and older with diabetes mellitus. Use of AFREZZA for this indication is supported by evidence from an adequate and well controlled trial in pediatric patients aged 6 years and older with type 1 or type 2 diabetes mellitus and from trials in adults with type 1 or type 2 diabetes mellitus [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.2 , 14.3 , 14.4 )] . The overall safety profile in pediatric patients was similar to adults [see Adverse Reactions ( 6.1 )] . The safety and effectiveness of AFREZZA have not been established in pediatric patients less than 6 years of age.

Elderly

8.5 Geriatric Use In the AFREZZA clinical studies , 671 (12%) patients were 65 years of age or older, of which 42 (0.8%) were 75 years of age or older. In these studies, 381 (13%) of AFREZZA-treated patients were 65 years of age or older, of which 20 (0.7%) were 75 years of age or older. No overall differences in effectiveness of AFREZZA have been observed between patients 65 years of age and older and younger adult patients [see Clinical Studies ( 14 )] . Clinical studies of AFREZZA did not include sufficient numbers of patients 65 years of age and older to determine whether there were differences in safety between these patients and younger adult patients. Pharmacokinetic and pharmacodynamic studies to assess the effect of age on pharmacokinetics or pharmacodynamics on insulin human, respectively, have not been conducted.

Interactions

Medicine and medicine

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 )] 7 DRUG INTERACTIONS Table 6 presents clinically significant drug interactions with AFREZZA.
Table 6.
Clinically Significant Drug Interactions with AFREZZA Antidiabetic agents, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blocking Agents, Disopyramide, Fibrates, Fluoxetine, Monoamine Oxidase Inhibitors, Pentoxifylline, Pramlintide, Salicylates, Somatostatin Analogs (e.g., octreotide), and Sulfonamide Antibiotics Prevention or Management Monitor blood glucose more frequently and modify AFREZZA dosage, as clinically indicated, when used concomitantly with these drugs.
Mechanism and Clinical Effect(s) Concomitant use of these drugs with AFREZZA may increase the risk of hypoglycemia.
Atypical Antipsychotics (e.g., olanzapine and clozapine), Corticosteroids, Danazol, Diuretics, Estrogens, Glucagon, Isoniazid, Niacin, Oral Contrac

Frequently asked questions

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 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 )]..

How should I take Afrezza?

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 sel

What are the common side effects?

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 o.

Who should not take Afrezza?

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 ).

Can I take Afrezza during pregnancy?

8.1 Pregnancy Risk Summary Limited available data with AFREZZA use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes. Available information from published studies with human insulin use during pregnancy has not reported a clear association with human insulin and adverse developmental outcomes ( see Data ). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy ( see Clinical Considerations ). In animal reproduction studies, there were no adverse developmental outcomes with subcutaneous administration of carrier particles (vehicle without insulin) to pregnant rats during organogenesis at doses 21 times the human daily dose of 99 mg AFREZZA, based on AUC (see Data ) . The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,

Can children take Afrezza?

8.4 Pediatric Use The safety and effectiveness of AFREZZA to improve glycemic control have been established in pediatric patients 6 years of age and older with diabetes mellitus. Use of AFREZZA for this indication is supported by evidence from an adequate and well controlled trial in pediatric patients aged 6 years and older with type 1 or type 2 diabetes mellitus and from trials in adults with type 1 or type 2 diabetes mellitus [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.2 , 14.3 , 14.4 )] . The overall safety profile in pediatric patients was similar to adults [see Adverse Reactions ( 6.1 )] . The safety and effectiveness of AFREZZA have not been established in pediatric patients less than 6 years of age.

Does Afrezza interact with other medicines?

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 )] 7 DRUG INTERACTIONS Table 6 presents clinically significant drug interactions with AFREZZA.; Table 6.; Clinically Significant Drug Interactions with AFREZZA Antidiabetic agents, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blocking Agents, Disopyramide, Fibrates, Fluoxetine, Monoamine Oxidase Inhibitors, Pentoxifylline, Pramlintide, Salicylates, Somatostatin Analogs (e.g., octreotide), and Sulfonamide Antibiotics Prevention or Management Monitor blood glucose more frequently and modify AFREZZA dosage, as clinically indicated, when used concomitantly with these drugs.; Mechanism and Clinical Effect(s) Concomitant use of these drugs with AFREZZA may increase the risk of hypoglycemia.; Atypical Antipsychotics (e.g., olanzapine and clozapine), Corticosteroids, Danazol, Diuretics, Estrogens, Glucagon, Isoniazid, Niacin, Oral Contrac.