ARIKAYCE safety profile

Clinical trial safety experience

Most patients reported at least 1 treatment-emergent adverse event (TEAE)* (98.2% in ARIKAYCE + background regimen arm vs 91.1% in background regimen alone arm).1,2

In the CONVERT trial, 20.2% of patients treated with ARIKAYCE + background regimen reported serious TEAEs vs 16.1% of patients treated with the background regimen alone.3

Most TEAEs occurring in the CONVERT trial were respiratory in nature.1,3

*Adverse events that occurred on or after date of first visit and within 28 days after the last study drug (ARIKAYCE) dose were considered TEAEs.2

Serious TEAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.2

Adverse reactions in ≥5% of ARIKAYCE-treated MAC patients
and more frequent than background regimen alone in the CONVERT trial3‡

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Adverse Reaction Chart

aIncludes aphonia and dysphonia.

bIncludes cough, productive cough, and upper airway cough syndrome.

cIncludes asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, and wheezing.

dIncludes deafness, deafness neurosensory, deafness unilateral, dizziness, hypoacusis, presyncope, tinnitus, and vertigo.

eIncludes oropharyngeal pain, oropharyngeal discomfort, throat irritation, pharyngeal erythema, upper airway inflammation, pharyngeal edema, vocal cord inflammation, laryngeal pain, laryngeal erythema, and laryngitis.

fIncludes back pain, arthralgia, myalgia, pain/body aches, muscle spasm, and musculoskeletal.

gIncludes COPD, infective exacerbation of COPD, and infective exacerbation of bronchiectasis.

hIncludes atypical pneumonia, empyema, infection pleural effusion, lower respiratory tract infection, lung infection, lung infection pseudomonas, pneumonia, pneumonia aspiration, pneumonia pseudomonas, pseudomonas infection, and respiratory tract infection.

iIncludes vomiting and post-tussive vomiting.

jIncludes rash, rash maculo-papular, drug eruption, and urticaria.

kIncludes increased sputum, sputum purulent, and sputum discolored.

Selected adverse reactions in <5% of ARIKAYCE-treated MAC patients and more
frequent than background regimen alone in the CONVERT trial3

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Selected Adverse Reaction Chart

aIncludes oral candidiasis and oral fungal infection.

bIncludes allergic alveolitis, interstitial lung disease, and pneumonitis.

cIncludes acute respiratory failure and respiratory failure.

dIncludes muscle weakness, neuropathy peripheral, and balance disorder.

eIncludes pneumothorax, pneumothorax spontaneous, and pneumomediastinum.

Hospitalization rates

In the CONVERT trial, there were 82 hospitalizations in 41 patients (18.4%) treated with ARIKAYCE + background regimen compared to 23 hospitalizations in 15 patients (13.4%) treated with background regimen alone. The most common serious adverse reactions and reasons for hospitalization in the ARIKAYCE + background regimen arm were related to exacerbation of underlying pulmonary disease and lower respiratory tract infections, such as pneumonia.3

Discontinuation rates

In the CONVERT trial, there was a higher incidence of premature discontinuation of ARIKAYCE. 33.5% discontinued ARIKAYCE prematurely; most were due to adverse reactions (17.4%) and withdrawal by patient (9.4%). In the comparator arm, 8% of patients discontinued their background regimen, 0.9% due to adverse reactions and 5.4% due to withdrawal by patient.3

Important safety considerations

Hypersensitivity Pneumonitis has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE + background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate.3

Hemoptysis has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE + background regimen (17.9%) compared to patients treated with a background regimen alone (12.5%). If hemoptysis occurs, manage patients as medically appropriate.3

Bronchospasm has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE + background regimen (28.7%) compared to patients treated with a background regimen alone (10.7%). If bronchospasm occurs during the use of ARIKAYCE, treat the patients as medically appropriate.3

Exacerbations of underlying pulmonary disease has been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as COPD, infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE + background regimen (14.8%) compared to patients treated with background regimen alone (9.8%). If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat the patients as medically appropriate.3

Ototoxicity has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE + background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (7.6% in ARIKAYCE + background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE + background regimen vs 2.7% in the background regimen alone arm).3

Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage the patient as medically appropriate, including potentially discontinuing ARIKAYCE.3

Nephrotoxicity was observed during the clinical trials of ARIKAYCE in patients with Mycobacterium avium complex (MAC) lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of the patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE.3

Neuromuscular Blockade: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Patients with known or suspected neuromuscular disorders, such as myasthenia gravis, should be closely monitored since aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions.3

Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use ARIKAYCE during pregnancy or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus.3

Contraindications: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside.3

Additional safety considerations

Dysphonia

In the CONVERT trial, dysphonia was the most commonly reported adverse reaction in the ARIKAYCE + background regimen arm (47% ARIKAYCE + background regimen vs 1% background regimen alone). Dysphonia was managed in the CONVERT trial with temporary interruption of ARIKAYCE. In the CONVERT trial, the discontinuation rate due to dysphonia was 2.2%.1-3

Cough

Cough is a common symptom of MAC lung disease. In the CONVERT trial, cough was a frequently reported adverse reaction and was more common in the ARIKAYCE + background regimen arm (39% ARIKAYCE + background regimen vs 17% background regimen alone). There was a higher rate of cough adverse event (AE) reporting particularly in the first month of active treatment with ARIKAYCE. In the CONVERT trial, the discontinuation rate due to cough was 0.9%.1-3

Of the patients who experienced cough, most events were episodic and occurred either during or after ARIKAYCE administration. The majority of episodes of cough lasted less than 1 minute with most episodes lasting less than 10 minutes.2

Pediatric use

Safety and effectiveness of ARIKAYCE in pediatric patients below 18 years of age have not been established.3

Geriatric use

In the MAC clinical trials, of the total number of patients receiving ARIKAYCE, 196 (50.5%) were ≥65 years and 55 (14.2%) were ≥75 years. No overall differences in safety and effectiveness were observed between elderly patients and younger patients. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.3

Hepatic impairment

ARIKAYCE has not been studied in patients with hepatic impairment. No dose adjustments based on hepatic impairment are required since amikacin is not hepatically metabolized.3

Renal impairment

ARIKAYCE has not been studied in patients with renal impairment. Given the low systemic exposure to amikacin following administration of ARIKAYCE, clinically relevant accumulation of amikacin is unlikely to occur in patients with renal impairment. However, renal function should be monitored in patients with known or suspected renal impairment, including elderly patients with potential age-related decreases in renal function.3

The CONVERT trial is referred to as "Trial 1" in the ARIKAYCE full Prescribing Information.