Amikacin liposome inhalation suspension (Arikayce) is a newly approved aminoglycoside antibiotic for treating adults with refractory Mycobacterium avium complex (MAC). It is intended for patients who haven't achieved a negative sputum culture after a minimum of six months of multidrug treatment. The product has only been studied in this population and should not be used in other populations.
MAC is a type of nontuberculous mycobacteria that can be found in soil, food, dust, and water. Although exposure to the bacterium is common, a normal immune system will suppress its growth and prevent illness. If the immune system is very suppressed, however, as in patients with HIV or cancer, or in those who have received long-term corticosteroids or an organ or bone marrow transplant, MAC is an opportunistic infection that will persist. Symptoms of MAC are similar to those of tuberculosis and include persistent cough, fatigue, weight loss, night sweats, and occasionally shortness of breath and hemoptysis. Unlike tuberculosis, MAC is not infectious.
Amikacin liposome inhalation suspension acts on MAC by binding to specialized parts of the bacterial cell wall to disrupt it. Once it enters the cell, it inhibits protein synthesis, so that the bacteria cannot reproduce. It is the first antibiotic approved through the Limited Population Pathway for Antibacterial and Antifungal Drugs, established by Congress under the 21st Century Cures Act. The act was designed to help spur development of new drugs within a streamlined clinical development program. Because of this shortened process, the drug's label states that it is only safe and effective in those groups included in clinical trials of the drug. Because amikacin liposome inhalation suspension also received accelerated approval by the Food and Drug Administration, the drug's manufacturer is required to conduct a postmarketing study to determine the full clinical benefits and risks of the drug.
Amikacin liposome inhalation suspension was evaluated in three clinical trials: an open-label, randomized, multicenter phase 3 trial; a single-arm extension of the first trial in patients who had failed to achieve a negative sputum culture after six months of treatment or who had a relapse by month 6; and a double-blind, randomized, placebo-controlled phase 2 trial. In all, 802 patients were exposed to the drug. The primary outcome was to achieve three consecutive negative sputum cultures. Amikacin liposome inhalation suspension was given in conjunction with a mix of antibiotics; the control groups received only standard antibiotic therapy. At the end of the study, amikacin liposome inhalation suspension, when given with the regimen of antibiotics, was significantly more effective in producing three consecutive negative sputum cultures than standard antibiotic therapy.
Amikacin liposome inhalation suspension carries a black box warning that it is associated with several respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease. The most common adverse effects, occurring in 10% or more of study participants, include dysphonia, cough, bronchospasm, hemoptysis, ototoxicity, upper airway irritation, musculoskeletal pain, fatigue and weakness, exacerbation of underlying pulmonary disease, diarrhea, and nausea.
Amikacin liposome inhalation suspension is administered once daily using the Lamira Nebulizer System, which comes with the prescription. Nurses should teach patients to clean the aerosol head and handset prior to first use and after each subsequent use. Patients need to shake the vial of amikacin liposome inhalation suspension well, for at least 10 to 15 seconds, to create a thoroughly uniform appearance. The vial should be at room temperature before use, and the full vial should be administered. Specific information on how to use the Lamira Nebulizer System can be found in the drug's labeling, as well as in the patient medication guide accompanying each prescription.
Patients who also use a bronchodilator should use the bronchodilator prior to nebulizer treatment with amikacin liposome inhalation suspension. Patients with a history of hyperactive airway disease, chronic obstructive pulmonary disease, asthma, or bronchospasm should also consider pretreatment with a short-acting beta-2 agonist inhaler. For complete prescribing information, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207356s000lbl.pdf.