The Food and Drug Administration (FDA) has for the second time approved an inhaled form of insulin to treat diabetes. Afrezza (insulin human), manufactured by MannKind Corporation, is a fast-acting inhaled insulin that can be used to treat type 1 or type 2 diabetes. When Afrezza is used to treat type 1 diabetes, it must be used in conjunction with a long-acting insulin; in preapproval studies of Afrezza in patients with type 2 diabetes, it was used in addition to oral antidiabetic therapy, such as metformin alone or two or more drugs in combination. Afrezza cannot be used in the treatment of diabetic ketoacidosis.
In 2006 the FDA approved the first inhaled insulin, Pfizer's Exubera, but Pfizer voluntarily pulled the drug from the market in 2007 because of poor sales. Exubera's poor market performance has been attributed to several factors: a cost higher than that of injected insulin; its large, unwieldy inhaler (about the size of a tennis ball can); and difficulties in determining the proper dose, which varied from 1 to 6 mg based on the patient's weight. MannKind Corporation addressed these concerns in designing Afrezza: the inhaler is now the size of a whistle, and the drug is dosed in amounts resembling doses of other insulins (an easy-to-use conversion guide is also part of the prescribing information). Afrezza's more-rapid onset of action gives it another advantage over Exubera. The exact cost of Afrezza hadn't been revealed at the time of this writing. On June 27, the date the drug was approved by the FDA, MannKind Corporation was in negotiations with major pharmaceutical companies to find a partner that can provide a sales force; the company announced in August that it had signed an exclusive worldwide licensing agreement with Sanofi to develop and commercialize Afrezza.
Afrezza has been found to increase the risk of acute bronchospasm in patients with asthma and chronic obstructive pulmonary disease (COPD); the labeling carries a boxed warning to that effect. Asthma and COPD and other chronic lung diseases are therefore contraindications to the use of Afrezza. Before starting Afrezza patients should be carefully assessed for lung disease (assessment should include a detailed medical history, physical examination, and spirometric evaluation). Afrezza produces a decline in lung function, as measured by forced expiratory volume in one second (FEV1), although lung function stabilizes and doesn't continue to decline with long-term use. Despite that stabilization, the FDA recommends that the FEV1 be assessed at baseline, after six months of therapy, and then annually, even if the patient is without pulmonary symptoms.
Patients who smoke or who recently stopped smoking (within the previous six months) should not use Afrezza because its safety and efficacy in this population haven't been confirmed. Two patients in clinical trials (covering a total of 2,750 patient-years of exposure) were diagnosed with lung cancer, and both had a history of heavy tobacco use. Two additional cases of lung cancer in nonsmokers were diagnosed after the clinical trials were completed. MannKind Corporation has been asked to complete a postmarketing trial to gather more information on a possible risk of lung cancer associated with use of the drug.
Afrezza use may increase patients' risk of diabetic ketoacidosis. Other adverse effects are similar to those experienced with other fast-acting insulins: hypoglycemia, hypersensitivity reactions, and hypokalemia. Common adverse effects unique to Afrezza include cough and productive cough, throat pain or irritation, headache, diarrhea, fatigue, and nausea.
Afrezza is administered at the beginning of a meal. Inhalation cartridges are single use and carry either four or eight units. The Afrezza inhaler is activated by the patient's breathing. When the patient inhales through the device, the powder is aerosolized and delivered to the lungs. The insulin molecules are attached to carrier particles, which aren't metabolized but are eliminated unchanged in the urine after absorption of the drug in the lung. The maximum serum insulin concentration from Afrezza eight units was reached 12 to 15 minutes after inhalation. In clinical trials patients with type 1 diabetes who received Afrezza had a mean reduction in glycated hemoglobin (HbA1c) that met the prespecified noninferiority margin of 0.4%. Afrezza, however, provided statistically significantly less HbA1c reduction than insulin aspart. Clinical trials of patients with type 2 diabetes found that therapy with Afrezza plus oral antidiabetic medication created a mean reduction in HbA1c that was significantly greater than therapy with oral antidiabetic therapy plus a placebo.
Nurses should teach patients prescribed Afrezza how to use the inhaler and the cartridges. The single-use cartridges are either blue, containing four units of Afrezza insulin, or green, containing eight units. If stored in the refrigerator, the cartridges are placed into the inhaler after being brought to room temperature for 10 minutes, although unopened blister strips can be kept at room temperature for 10 days. The inhaler can be used for as long as 15 days and must then be replaced. Additional specific instructions regarding the administration technique are included in the drug labeling and the patient medication guide. The nurse should review these with the patient prior to the first use of the drug.
Before the beginning of Afrezza therapy nurses should confirm that patients do not have any chronic lung diseases, do not smoke, or did not stop smoking within the previous six months. Nurses should tell patients that a decline in lung function with Afrezza therapy is possible and that they should report any changes. Pulmonary function should be monitored using spirometry prior to the start of therapy and then at the recommended intervals, even in asymptomatic patients. Patients should understand the importance of reading the medication guide every time they have a prescription filled because it will contain the most current information regarding adverse effects. Nurses should emphasize that Afrezza doesn't eliminate one's need to follow prescribed recommendations regarding diet and physical activity.
To read the FDA news release regarding the approval of Afrezza, go to http://1.usa.gov/1zzPb8I. Complete prescribing information can be found at http://1.usa.gov/1xFTrRi.