Limitation of Use:

ARIKAYCE 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 ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.

2.1 Important Administration Instructions

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

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)].

2.2 Recommended Dosage

The recommended dosage of ARIKAYCE in adults is once daily inhalation of the contents of one 590 mg/8.4 mL ARIKAYCE vial (590 mg of amikacin) using the Lamira Nebulizer System [see Clinical Studies (14)].

Administer ARIKAYCE with the Lamira Nebulizer System only. ARIKAYCE should be at room temperature before use. Prior to opening, shake the ARIKAYCE vial well for at least 10 to 15 seconds until the contents appear uniform and well mixed. The ARIKAYCE 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 ARIKAYCE vial can then be poured into the medication reservoir of the nebulizer handset.

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

5.1 Hypersensitivity Pneumonitis

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 plus a 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 [see Adverse Reactions (6.1)].

If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage the patient as medically appropriate.

5.2 Hemoptysis

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 plus a background regimen (18.4%) compared to patients treated with a background regimen alone (13.4%) [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 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 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 ARIKAYCE, treat the patients as medically appropriate.

5.4 Exacerbation of Underlying Pulmonary Disease

Exacerbations of underlying pulmonary disease have been reported with the use of ARIKAYCE 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 ARIKAYCE plus a background regimen (15.2%) compared to patients treated with background regimen alone (9.8%) [see Adverse Reactions (6.1)]. If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat the patients as medically appropriate.

5.5 Anaphylaxis and Hypersensitivity Reactions

Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures.

5.6 Ototoxicity

5.7 Nephrotoxicity

Nephrotoxicity was observed during the clinical trials of ARIKAYCE 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 ARIKAYCE.

5.8 Neuromuscular Blockade

Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions. Closely monitor patients with known or suspected neuromuscular disorders, such as myasthenia gravis. If neuromuscular blockade occurs, it may be reversed by the administration of calcium salts but mechanical respiratory assistance may be necessary.

5.9 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 [see Use in Specific Populations (8.1)].

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.

6.2 Postmarketing Experience

The following adverse reactions have been identified from postmarketing surveillance. Because these adverse reactions are reported voluntarily from a population of unknown size, precise estimates of frequency cannot be made and a causal relationship to drug exposure cannot be established.

Immune System Disorders: hypersensitivity, anaphylaxis [see Warnings and Precautions (5.5)]

7.1 Drugs with Neurotoxic, Nephrotoxic, or Ototoxic Potential

Avoid concomitant use of ARIKAYCE 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 ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

Safety and effectiveness of ARIKAYCE 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 ARIKAYCE, 208 (51.5%) were ≥ 65 years and 59 (14.6%) 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 (5.7)].

8.6 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 [see Clinical Pharmacology (12.3)].

8.7 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 [see Warnings and Precautions (5.7), Use in Specific Populations (8.5)].

12.1 Mechanism of Action

ARIKAYCE is an antibacterial drug [see Microbiology (12.4)].

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

12.4 Microbiology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year inhalation carcinogenicity study, rats were exposed to ARIKAYCE for 15-25, 50-70, or 155-170 minutes per day for 96-104 weeks. These provided approximate inhaled doses of 5, 15, and 45 mg/kg/day. Squamous cell carcinoma was observed in the lungs of 2 of 120 rats administered the highest dose tested. Maximum serum AUC levels of amikacin in the rats at steady state were approximately 1.3, 2.8, and 7.6 mcg∙hr/mL at the low, mid, and high doses, respectively, compared with 23.5 mcg∙hr/mL (8.0 to 46.5 mcg∙hr/mL) measured in humans. The squamous cell carcinomas may be the result of a high lung burden of particulates from ARIKAYCE in the rat lung. The relevance of the lung tumor findings with regards to humans receiving ARIKAYCE is unknown.

No evidence of mutagenicity or genotoxicity was observed in a battery of in vitro and in vivo genotoxicity studies with a liposome-encapsulated amikacin formulation similar to ARIKAYCE (in vitro microbial mutagenesis test, in vitro mouse lymphoma mutation assay, in vitro chromosomal aberration study, and an in vivo micronucleus study in rats).

No fertility studies were conducted with ARIKAYCE. Intraperitoneal administration of amikacin to male and female rats at doses up to 200 mg/kg/day prior to mating through Day 7 of gestation were not associated with impairment of fertility or adverse effects on early embryonic development.

13.2 Animal Toxicology and/or Pharmacology

To provide information about chronic dosing of ARIKAYCE to another animal species, a 9-month inhalation toxicology study was conducted in dogs. Foamy alveolar macrophages associated with clearance of the inhaled product were present at dose-related incidence and severity, but they were not associated with inflammation, tissue hyperplasia, or the presence of preneoplastic or neoplastic changes. Dogs were exposed to ARIKAYCE for up to 90 minutes per day, providing inhaled amikacin doses of approximately 5, 10, and 30 mg/kg/day.

16.1 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.

16.2 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.

Important Instructions for Administration of ARIKAYCE

Instruct patients to read the Instructions for Use before starting ARIKAYCE. Instruct patients to only use the Lamira® Nebulizer System to administer ARIKAYCE. Advise the patient or caregiver not to use the Lamira Nebulizer System with any other medicine.

Hypersensitivity Pneumonitis and Bronchospasm (Difficulty Breathing)

Advise patients to inform their healthcare provider if they experience shortness of breath or wheezing after administration of ARIKAYCE. Advise patients with a history of reactive airway disease, asthma, or bronchospasm, to administer ARIKAYCE after using a short-acting bronchodilator [see Warnings and Precautions (5.1, 5.3)].

Hemoptysis or Cough

Advise patients to inform their healthcare provider if they cough up blood or experience episodic cough either during or after ARIKAYCE administration particularly in the first month after starting ARIKAYCE [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

Exacerbations of Underlying Pulmonary Disease

Advise patients to inform their healthcare provider if they experience worsening of their lung disease after starting ARIKAYCE [see Warnings and Precautions (5.4)].

Dysphonia or Difficulty Speaking

Advise patients to inform their healthcare provider if they have difficulty speaking. Difficulty speaking or loss of ability to speak has been reported with ARIKAYCE [see Adverse Reactions (6.1)].

Anaphylaxis and Hypersensitivity Reactions

Advise patients and caregivers that serious and potentially life-threatening hypersensitivity reactions, that require immediate treatment could occur. Advise the patient to discontinue ARIKAYCE and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction occur [see Warnings and Precautions (5.5)].

Ototoxicity (Ringing in the Ears)

Advise patients to inform their healthcare provider if they experience ringing in the ears, dizziness, or any changes in hearing because ARIKAYCE has been associated with hearing loss [see Warnings and Precautions (5.6)].

Advise the patient not to operate heavy machinery or do dangerous activities while inhaling ARIKAYCE through the Lamira Nebulizer System because ARIKAYCE can cause symptoms such as dizziness or respiratory symptoms.

Nephrotoxicity or Kidney Damage

Advise patients to inform their health care provider if they have kidney problems because kidney damage has been reported with aminoglycosides [see Warnings and Precautions (5.7)].

Neuromuscular Blockade

Advise patients to inform their healthcare provider of known neuromuscular disease (e.g., myasthenia gravis) [see Warnings and Precautions (5.8)].

Embryo-Fetal Toxicity

Advise pregnant women that aminoglycosides, including ARIKAYCE, may cause irreversible congenital deafness when administered during pregnancy [see Warnings and Precautions (5.9) and Use in Special Populations (8.1)].