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Amikacin Liposome Inhalation Suspension

TABLE OF CONTENTS

1. DESCRIPTION 8. USE IN SPECIFIC POPULATIONS
2. INDICATIONS AND USAGE 9. OVERDOSAGE
3. DOSAGE AND ADMINISTRATION 10. MECHANISM OF ACTION
4. CONTRAINDICATIONS 11. PHARMACODYNAMICS
5. WARNINGS AND PRECAUTIONS 12. PHARMACOKINETICS
6. ADVERSE REACTIONS 13. HOW SUPPLIED/STORAGE AND HANDLING
7. DRUG INTERACTIONS

 


WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS

Amikacin has been associated with an increased risk of respiratory adverse reactions including, hypersensitivity pneumonitis, hemoptysis, bronchospasm, exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4)].


 

1. DESCRIPTION

The active ingredient in amikacin liposome inhalation suspension is amikacin sulfate USP, an aminoglycoside antibacterial. Its chemical name is D-Streptamine, O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-O-[6-amino-6-deoxy-α-D-glucopyranosyl-(1→4)]-N1-(4-amino-2-hydroxy-1-oxobutyl)-2-deoxy-, (S)-, sulfate (1:2) salt. Its structural formula is:

Empirical formula: C22H43N5O13•2H2SO4 - Molecular weight: 781.76 g/mol

Amikacin liposome is a white milky suspension consisting of amikacin sulfate encapsulated in liposomes and is supplied in a unit-dose 10 mL clear glass vial containing amikacin 590 mg/8.4 mL (equivalent to amikacin sulfate 623 mg/8.4 mL) as a sterile aqueous liposomal suspension for oral inhalation. Amikacin liposome consists of amikacin sulfate encapsulated in liposomes at a targeted concentration of 70 mg amikacin/mL with the pH range of 6.1 to 7.1 and lipid to amikacin weight ratio in the range of 0.60 to 0.79. The inactive ingredients are cholesterol, dipalmitoylphosphatidylcholine (DPPC), sodium chloride, sodium hydroxide (for pH adjustment), and water for injection.

Amikacin liposome is administered only using a Lamira Nebulizer System [see Dosage and Administration (3.1)]. Like all other nebulized treatments, the amount delivered to the lungs will depend upon patient factors. Under standardized in vitro testing per USP<1601> adult breathing pattern (500 mL tidal volume, 15 breaths per minute, and inhalation: exhalation ratio of 1:1), the mean delivered dose from the mouthpiece was approximately 312 mg of amikacin sulfate (53% of label claim). The mass median aerodynamic diameter (MMAD) of the nebulized aerosol droplets is about 4.7 μm (4.1 – 5.3 μm) as determined using the Next Generation Impactor (NGI) method. A percentage of the amikacin in the liposome is released by the nebulization process, thus nebulized amikacin liposome delivers a combination of free and liposomal amikacin.

2. INDICATIONS AND USAGE

LIMITED POPULATION: Amikacin liposome is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for amikacin liposome are currently available, reserve amikacin liposome for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.

This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established [see Clinical Studies]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Limitation of Use:

Amikacin liposome has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of amikacin liposome is not recommended for patients with non-refractory MAC lung disease.

3. DOSAGE AND ADMINISTRATION

3.1 Important Administration Instructions

Amikacin liposome is for oral inhalation use only. Administer by nebulization only with the LamiraTM Nebulizer System. Refer to the Instructions for Use for full administration information on use of amikacin liposome with the Lamira Nebulizer System.

Instruct patients using a bronchodilator (‘reliever’) to first use the bronchodilator following the bronchodilator leaflet for use information before using amikacin liposome.

Pre-treatment with short-acting selective beta-2 agonists should be considered for patients with known hyperreactive airway disease, chronic obstructive pulmonary disease, asthma, or bronchospasm [see Warnings and Precautions (5.3)].

3.2 Recommended Dosage

The recommended dosage of amikacin liposome in adults is once daily inhalation of the contents of one 590 mg/8.4 mL amikacin liposome vial (590 mg of amikacin) using the Lamira Nebulizer System.

Administer amikacin liposome with the Lamira Nebulizer System only. Amikacin liposome should be at room temperature before use. Prior to opening, shake the amikacin liposome vial well for at least 10 to 15 seconds until the contents appear uniform and well mixed. The amikacin liposome vial is opened by flipping up the plastic top of the vial then pulling downward to loosen the metal ring. The metal ring and the rubber stopper should be removed carefully. The contents of the amikacin liposome vial can then be poured into the medication reservoir of the nebulizer handset.

If a daily dose of amikacin liposome is missed, administer the next dose the next day. Do NOT double the dose to make up for the missed dose.

4. CONTRAINDICATIONS

Amikacin liposome is contraindicated in patients with a known hypersensitivity to any aminoglycoside.

5. WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis has been reported with the use of amikacin liposome in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to amikacin liposome) was reported at a higher frequency in patients treated with amikacin liposome plus a background regimen (3.1 %) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with amikacin liposome and received treatment with corticosteroids [see Adverse Reactions (6.1)]. If hypersensitivity pneumonitis occurs, discontinue amikacin liposome and manage the patient as medically appropriate.

5.2 Hemoptysis

Hemoptysis has been reported with the use of amikacin liposome in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with amikacin liposome plus a background regimen (17.9 %) compared to patients treated with a background regimen alone (12.5 %) [see Adverse Reactions (6.1)]. If hemoptysis occurs, manage the patients as medically appropriate.

5.3 Bronchospasm

Bronchospasm has been reported with the use of amikacin liposome 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 amikacin liposome plus a background regimen (28.7 %) compared to patients treated with a background regimen alone (10.7 %) [see Adverse Reactions (6.1)]. If bronchospasm occurs during the use of amikacin liposome treat the patients as medically appropriate.

5.4 Exacerbation of Underlying Pulmonary Disease

Exacerbations of underlying pulmonary disease has been reported with the use of amikacin liposome in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease, infective exacerbation of chronic obstructive pulmonary disease, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with amikacin liposome plus a background regimen (14.8 %) compared to patients treated with background regimen alone (9.8 %) [see Adverse Reactions (6.1)]. If exacerbations of underlying pulmonary disease occurs during the use of amikacin liposome, treat the patients as medically appropriate.

5.5 Ototoxicity

Ototoxicity has been reported with the use of amikacin liposome in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with amikacin liposome plus a background regimen (17 %) compared to patients treated with background regimen alone (9.8 %). This was primarily driven by tinnitus (7.6% in amikacin liposome plus background regimen vs. 0.9% in the background regimen alone arm) and dizziness (6.3% in amikacin liposome plus background regimen vs. 2.7% in the background regimen alone arm). [see Adverse Reactions (6.1)].

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

5.6 Nephrotoxicity

Nephrotoxicity was observed during the clinical trials of amikacin liposome in patients with MAC lung disease but not at a higher frequency than the background regimen alone [see Adverse Reactions (6.1)]. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing amikacin liposome.

5.7 Neuromuscular Blockade

Patients with neuromuscular disorders were not enrolled in amikacin liposome 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.

5.8 Embryo-Fetal Toxicity

Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including amikacin liposome, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use amikacin liposome during pregnancy, or become pregnant while taking amikacin liposome should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].

6. ADVERSE REACTIONS

The following clinically significant adverse reactions are described in greater detail in other sections of labeling:

• Hypersensitivity pneumonitis [see Boxed Warning and Warnings and Precautions (5.1)]

• Hemoptysis [see Boxed Warning and Warnings and Precautions (5.2)]

• Bronchospasm [see Boxed Warning and Warnings and Precautions (5.3))]

• Exacerbation of Underlying Pulmonary Disease [see Boxed Warning and Warnings and Precautions (5.4)]

• Ototoxicity [see Warnings and Precautions (5.5)]

• Nephrotoxicity [see Warnings and Precautions (5.6)]

• Neuromuscular Blockade [see Warnings and Precautions (5.7)]

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.

Overview of Clinical Trials for Safety Evaluation

Within the refractory NTM clinical program, 388 patients that participated in three clinical trials were treated with amikacin liposome at the dose of 590 mg/day (median duration of exposure to amikacin liposome was 169 days).

Trial 1 (NCT#02344004) was an open-label, randomized (2:1), multi-center Phase 3 trial in patients with refractory Mycobacterium avium complex (MAC) lung disease . Patients were randomized to either 8 months of amikacin liposome plus a background regimen (n=223) or background regimen alone (n=112).

Trial 2 was a single-arm extension of Trial 1 for refractory MAC lung disease patients that failed to achieve negative sputum cultures after 6 months of treatment or had a relapse or recurrence by Month 6 from either study arm of Trial 1. A total of 133 patients (n=74 from the prior background regimen alone arm of Trial 1, and n=59 from the prior amikacin liposome plus background regimen arm in Trial 1) participated in the trial.

Trial 3 (NCT#01315236) was a double-blind, randomized, placebo-controlled Phase 2 study in patients with refractory nontuberculous mycobacterial (NTM) lung disease caused by MAC and Mycobacterium abscessus. Patients were randomized to either amikacin liposome plus background regimen or an inhaled diluted empty liposome placebo plus background regimen for 84 days.

Across all clinical trials of patients with and without refractory NTM lung infection, 802 patients were exposed to multiple doses of amikacin liposome.

Adverse Reactions Leading to Treatment Discontinuation

In the three NTM studies, there was a higher incidence of premature discontinuation of amikacin liposome. In Trial 1, 33.5% discontinued amikacin liposome prematurely; most were due to adverse reactions (17.4%) and withdrawal by subject (9.4%).In the comparator arm 8% of subjects discontinued theirbackground regimen, with 0.9% due to adverse reactions and 5.4% due to withdrawal by subject. In Trial 2 (the single-arm extension of Trial 1), 20.3% of patients starting on amikacin liposome discontinued prematurely with 14.9% discontinuing due to adverse reactions. In Trial 3, all 9 (20.5%) premature discontinuations occurred in the amikacin liposome plus background regimen -treated patients and there were no premature discontinuations in the placebo plus background regimen arm.

Serious Adverse Reactions in Trials 1 and 3

In the two randomized trials (Trial 1 and Trial 3), there were more serious adverse reactions (SARs) reported in the amikacin liposome-treated arm as compared to the respective control arm. In Trial 1, 20.2% of patients treated with amikacin liposome plus background regimen reported SAR as compared to 16.1% of patients treated with background regimen alone. In addition, in Trial 1 [2 to 1 randomization, amikacin liposome plus background regimen versus background regimen alone], there were 82 hospitalizations in 41 patients (18.4%) treated with amikacin liposome plus background regimen compared to 23 hospitalizations in 15 patients (13.4%) treated with background regimen alone. The most common SARs and reasons for hospitalization in the amikacin liposome plus background regimen arm were related to exacerbation of underlying pulmonary disease and lower respiratory tract infections, such as pneumonia.

In Trial 3, 18.2% of patients treated with amikacin liposome plus background regimen reported SARs compared to 8.9% of patients treated with background regimen plus inhaled placebo.

Common Adverse Reactions

The incidence of adverse reactions in Trial 1 are displayed in Table 1. Only those adverse reactions with a rate of at least 5% in the amikacin liposome plus background regimen group and greater than the background regimen alone group, are shown.

Table 1: Adverse Reactions in ≥ 5% of Amikacin Liposome-treated MAC Patients and More Frequent than Background Regimen Alone in Trial 1

a Includes aphonia and dysphonia

b Includes cough, productive cough and upper airway cough syndrome

c Includes asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing

d Includes deafness, deafness neurosensory, deafness unilateral, dizziness, hypoacusis, presyncope, tinnitus, vertigo

e Includes oropharyngeal pain, oropharyngeal discomfort, throat irritation, pharyngeal erythema, upper airway inflammation, pharyngeal edema, vocal cord inflammation, laryngeal pain, laryngeal erythema, laryngitis

f Includes back pain, arthralgia, myalgia, pain/body aches, muscle spasm and musculoskeletal

g Includes COPD, infective exacerbation of COPD, infective exacerbation of bronchiectasis

h Includes 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

i Includes vomiting and post-tussive vomiting

j Includes rash, rash maculo-papular, drug eruption and urticaria

k Includes increased sputum, sputum purulent and sputum discolored

Selected adverse drug reactions that occurred in <5% of patients and at higher frequency in amikacin liposome-treated patients in Trial 1 are presented in Table 2.

Table 2: Selected Adverse Reactions in < 5% of Amikacin Liposome-treated MAC Patients and More Frequent than Background Regimen Alone in Trial 1

a Includes oral candidiasis and oral fungal infection

b Includes allergic alveolitis, interstitial lung disease, and pneumonitis

c Includes acuter respiratory failure and respiratory failure

d Includes muscle weakness, neuropathy peripheral, and balance disorder

e Includes pneumonthorax, pneumothorax spontaneous and pneumomediastinum

Refer to Table 1 and Table 2 for the incidence rate of hypersensitivity pneumonitis, bronchospasm, cough, dysphonia, exacerbation of underlying disease, hemoptysis, ototoxicity, upper airway irritation, and neuromuscular disorders [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4, 5.6)]

7. DRUG INTERACTIONS

7.1 Drugs with Neurotoxic, Nephrotoxic, or Ototoxic Potential

Avoid concomitant use of amikacin liposome with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity.

7.2 Ethacrynic Acid, Furosemide, Urea, or Mannitol

Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of amikacin liposome with ethacrynic acid, furosemide, urea, or intravenous mannitol.

8. USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no data on amikacin liposome use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Although systemic absorption of amikacin following oral inhalation is expected to be low [see Clinical Pharmacology], systemic exposure to aminoglycoside antibacterial drugs, including amikacin liposome, may be associated with total, irreversible, bilateral congenital deafness when administered to pregnant women [see Warning and Precautions (5.8)]. Advise pregnant women of the potential risk to a fetus.

Animal reproductive toxicology studies have not been conducted with inhaled amikacin. Subcutaneous administration of amikacin to pregnant rats (up to 100 mg/kg/day) and mice (up to 400 mg/kg/day) during organogenesis was not associated with fetal malformations. Ototoxicity was not adequately evaluated in offspring in animal studies.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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%, respectively.

Data

Animal Data

No animal reproductive toxicology studies have been conducted with amikacin liposome or non-liposomal amikacin administered by inhalation.

Amikacin was subcutaneously administered to pregnant rats (Gestation Days 8-14) and mice (Gestation Days 7-13) at doses of 25, 100, or 400 mg/kg to assess developmental toxicity. These doses did not cause fetal visceral or skeletal malformations in mice. The high dose was excessively maternally toxic in rats (nephrotoxicity and mortality were observed), precluding the evaluation of offspring at this dose. Fetal malformations were not observed at the low or mid dose in rats. Postnatal development of the rats and mice exposed to these doses of amikacin in utero did not differ significantly from control.

Ototoxicity was not adequately evaluated in offspring in animal developmental toxicology studies.

8.2 Lactation

Risk Summary

There is no information regarding the presence of amikacin liposome in human milk, the effects on the breastfed infant, or the effects on milk production after administration of amikacin liposome by inhalation. Although limited published data on other routes of administration of amikacin indicate that amikacin is present in human milk, systemic absorption of amikacin liposome following inhaled administration is expected to be low [see Clinical Pharmacology]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for amikacin liposome and any potential adverse effects on the breastfed child from amikacin liposome or from the underlying maternal condition.

8.4 Pediatric Use

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

8.5 Geriatric Use

In the NTM clinical trials, of the total number of patients receiving amikacin liposome, 196 (50.5%) were ≥ 65 years and 55 (14.2%) were ≥ 75 years. No overall differences in safety and effectiveness were observed between elderly subjects and younger subjects. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function [see Warnings and Precautions (5.6)].

8.6 Hepatic Impairment

Amikacin liposome has not been studied in patients with hepatic impairment. No dose adjustments based on hepatic impairment are required since amikacin is not hepatically metabolized [see Clinical Pharmacology].

8.7 Renal Impairment

Amikacin liposome has not been studied in patients with renal impairment. Given the low systemic exposure to amikacin following administration of amikacin liposome, 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 [see Warnings and Precautions (5.6), Use in Specific Populations (8.5)].

9. OVERDOSAGE

Adverse reactions specifically associated with overdose of amikacin liposome have not been identified. Acute toxicity should be treated with immediate withdrawal of amikacin liposome, and baseline tests of renal function should be undertaken.

Hemodialysis may be helpful in removing amikacin from the body.

In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. In the case of any overdosage, the possibility of drug interactions with alterations in drug disposition should be considered.

10. MECHANISM OF ACTION

Amikacin liposome is an antibacterial drug.

Mechanism of Action

Amikacin is a polycationic, semisynthetic, bactericidal aminoglycoside. Amikacin enters the bacterial cell by binding to negatively charged components of the bacterial cell wall disrupting the overall architecture of the cell wall. The primary mechanism of action is the disruption and inhibition of protein synthesis in the target bacteria by binding to the 30S ribosomal subunit.

Resistance

The mechanism of resistance to amikacin in mycobacteria has been linked to mutations in the rrs gene of the 16S rRNA. In clinical trials, MAC isolates developing an amikacin MIC of > 64 mcg/mL after baseline were observed in a higher proportion of subjects treated with amikacin liposome [see Clinical Studies].

Interaction with Other Antimicrobials

There has been no in vitro signal for antagonism between amikacin and other antimicrobials against MAC based on fractional inhibitory concentration (FIC) and macrophage survival assays. In select instances, some degree of synergy between amikacin and other agents has been observed, as for example, synergy between aminoglycosides, including amikacin, and the beta-lactam class has been documented.

11. PHARMACODYNAMICS

Amikacin liposome exposure-response relationships and the time course of pharmacodynamic response are unknown.

12. PHARMACOKINETICS

Sputum Concentrations

Following once daily inhalation of 590 mg amikacin liposome in Mycobacterium avium complex (MAC) patients, sputum concentrations at 1 to 4 hours post-inhalation were 1720, 884, and 1300 mcg/g at 1, 3, and 6 months, respectively. High variability in amikacin concentrations were observed (CV% >100%). After 48 to 72 hours post-inhalation, amikacin sputum concentrations decreased to approximately 5% of those at 1 to 4 hours post-inhalation.

Serum Concentrations

Following 3 months of once daily inhalation of 590 mg amikacin liposome in MAC patients, the mean serum AUC0-24 was 23.5 mcg*hr/mL (range: 8.0 to 46.5 mcg*hr/mL; n=12) and the mean serum Cmax was 2.8 mcg/mL (range: 1.0 to 4.4 μg/mL; n=12). The maximum Cmax and AUC0-24 were below the mean Cmax of approximately 76 mcg/mL and AUC0-24 of 154 mcg*hr/mL observed for intravenous administration of amikacin sulfate for injection at the approved dosage of 15 mg/kg once daily in healthy adults.

Absorption

The bioavailability of amikacin liposome is expected to vary primarily from individual differences in nebulizer efficiency and airway pathology.

Distribution

The protein binding of amikacin in serum is ≤ 10%.

Elimination

Following inhalation of amikacin liposome in MAC patients, the apparent serum half-life of amikacin ranged from approximately 5.9 to 19.5 hrs.

Metabolism

Amikacin does not undergo appreciable metabolism.

Excretion

Systemically absorbed amikacin following amikacin liposome administration is eliminated principally via glomerular filtration. On average, 7.42% (ranging from 0.72 to 22.60%; n=14) of the total amikacin liposome dose was excreted in urine as unchanged drug compared to 94% following intravenous administration of amikacin sulfate for injection. Unabsorbed amikacin, following amikacin liposome inhalation, is probably eliminated primarily by cellular turnover and expectoration.

Drug Interaction Studies

No clinical drug interaction studies have been conducted with amikacin liposome [see Drug Interactions (7)].

13. HOW SUPPLIED/STORAGE AND HANDLING

How Supplied:

ARIKAYCE (amikacin liposome inhalation suspension), 590 mg/8.4 mL, is supplied in a sterile, unit-dose 10-mL glass vial. The product is dispensed as a 28-vial kit.

Each carton contains a 28-day supply of medication (28 vials). In addition to the ARIKAYCE vials in the carton, one Lamira Nebulizer Handset and four Lamira aerosol heads are provided.

NDC 71558-590-28

The Lamira Nebulizer System contains a controller, a spare aerosol head, a spare handset, power cord and accessories.

Storage and Handling:

Store ARIKAYCE vials refrigerated at 2°C to 8°C (36°F to 46°F) until expiration date on vial. Do not freeze. Once expired, discard any unused drug.

ARIKAYCE can be stored at room temperature up to 25°C (77°F) for up to 4 weeks. Once at room temperature, any unused drug must be discarded at the end of 4 weeks.

Rx only

Rev 09/18