HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
ARIKAYCE safely and effectively. See full prescribing information for
ARIKAYCE.
---------------------DOSAGE FORMS AND STRENGTHS---------------------
ARIKAYCE is supplied as a sterile, aqueous, liposome suspension for oral
inhalation in a unit-dose glass vial containing amikacin 590 mg/8.4 mL. (3)
-------------------------------CONTRAINDICATIONS-----------------------------
ARIKAYCE is contraindicated in patients with a known hypersensitivity to
any aminoglycoside. (4)
ARIKAYCE (amikacin liposome inhalation suspension), for oral
inhalation use
Initial U.S. Approval: 2018
LIMITED POPULATION
------------------------WARNINGS AND PRECAUTIONS----------------------
• Hypersensitivity Pneumonitis: Reported with ARIKAYCE treatment; if
hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage
patients as medically appropriate. (5.1)
• Hemoptysis: Higher frequency of hemoptysis has been reported with
ARIKAYCE treatment. If hemoptysis occurs, manage the patients as
medically appropriate. (5.2)
• Bronchospasm: Higher frequency of bronchospasm has been reported with
ARIKAYCE treatment. Treat patients as medically appropriate if this
occurs during treatment with ARIKAYCE. (5.3)
• Exacerbations of Underlying Pulmonary Disease: Higher frequency of
exacerbations of underlying pulmonary disease has been reported with
ARIKAYCE treatment. Treat patients as medically appropriate if this
occurs during treatment with ARIKAYCE. (5.4)
• Ototoxicity: Higher frequency of ototoxicity has been reported with
ARIKAYCE treatment. Closely monitor patients with known or suspected
auditory or vestibular dysfunction. If patients develop tinnitus this may be
an early symptom of ototoxicity. (5.5)
• Nephrotoxicity: Aminoglycosides can cause nephrotoxicity. Close
monitoring of patients with known or suspected renal dysfunction may be
needed when prescribing ARIKAYCE. (5.6)
• Neuromuscular Blockade: Aminoglycosides may aggravate muscle
weakness because of a potential curare-like effect on neuromuscular
function. If neuromuscular blockade occurs, it may be reversed by the
administration of calcium salts but mechanical assistance may be necessary
.(5.7)
• Embryo-Fetal Toxicity: Aminoglycosides can cause total, irreversible,
bilateral congenital deafness in pediatric patients exposed in utero. (5.8,
8.1)
WARNING: RISK OF INCREASED RESPIRATORY ADVERSE
REACTIONS
See full prescribing information for complete boxed warning.
ARIKAYCE has been associated with a risk of increased respiratory
adverse reactions, including, hypersensitivity pneumonitis,
hemoptysis, bronchospasm, and exacerbation of underlying
pulmonary disease that have led to hospitalizations in some cases.
(5.1, 5.2, 5.3, 5.4)
-----------------------------INDICATIONS AND USAGE-------------------------
LIMITED POPULATION: ARIKAYCE is an aminoglycoside antibacterial
indicated in adults who have limited or no alternative treatment options, for
the treatment ofMycobacterium aviumcomplex (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 ARIKAYCE are currently available, reserve
ARIKAYCE 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. (1)
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. (1)
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.
-------------------------------ADVERSE REACTIONS-----------------------------
Most common adverse reactions (incidence ≥10% and higher than control) in
the patients with refractory MAC lung disease were: dysphonia, cough,
bronchospasm, hemoptysis, ototoxicity, upper airway irritation,
musculoskeletal pain, fatigue/asthenia and exacerbation of underlying
pulmonary disease, diarrhea, and nausea. (6.1).
------------------------DOSAGE AND ADMINISTRATION---------------------
• For oral inhalation use only. (2.1)
• Use ARIKAYCE vials only with the Lamira Nebulizer System. (2.1)
• The recommended dosage in adults is once daily oral inhalation of the
contents of one 590 mg/8.4 mL ARIKAYCE vial. (2.2)
• Pre-treatment with inhaled bronchodilator should be considered in patients
with a history of hyperreactive airway disease. (2.2)
To report SUSPECTED ADVERSE REACTIONS, contact Insmed
Incorporated at 1-844-4-INSMED or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and Medication
Guide.
Revised: 9/2018
FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions
2.2 Recommended Dosage
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
8.5 Geriatric Use
8.6 Hepatic Impairment
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Pneumonitis
5.2 Hemoptysis
8.7 Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
5.3 Bronchospasm
5.4 Exacerbation of Underlying Pulmonary Disease
5.5 Ototoxicity
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
5.6 Nephrotoxicity
12.3 Pharmacokinetics
5.7 Neuromuscular Disorders
12.4 Microbiology
5.8
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
7 DRUG INTERACTIONS
7.1 Drugs with Neurotoxic, Nephrotoxic, or Ototoxic Potential
7.2 Ethacrynic Acid, Furosemide, Urea, or Mannitol
Embryofetal Toxicity
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
13.2 Animal Toxicology and/or Pharmacology
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are not
listed.
Reference ID: 4327567
FULL PRESCRIBING INFORMATION
WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS
ARIKAYCE 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
INDICATIONS AND USAGE
LIMITED POPULATION: ARIKAYCE is indicated in adults, who have limited or no alternative
treatment options, for the treatment ofMycobacterium aviumcomplex (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 ARIKAYCE are currently available, reserve ARIKAYCE 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 (14)]. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory trials.
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
DOSAGE AND ADMINISTRATION
Important Administration Instructions
2.1
ARIKAYCE is for oral inhalation use only. Administer by nebulization only with the Lamira
TM
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.
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.
3
DOSAGE FORMS AND STRENGTHS
ARIKAYCE is supplied as a sterile, white, milky, aqueous, liposome suspension for oral inhalation in a
unit-dose glass vial containing amikacin 590 mg/8.4 mL (equivalent to amikacin sulfate 623 mg/8.4 mL).
Page 2 of 12
Reference ID: 4327567
4
CONTRAINDICATIONS
ARIKAYCE is contraindicated in patients with a known hypersensitivity to any aminoglycoside.
5
WARNINGS AND PRECAUTIONS
Hypersensitivity Pneumonitis
5.1
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 (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 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 has 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 (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
ARIKAYCE, treat the patients as medically appropriate.
5.5
Ototoxicity
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 plus a background regimen (17 %) compared to patients treated with background
regimen alone (9.8 %). This was primarily driven by tinnitus (7.6% in ARIKAYCE plus background
regimen vs. 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE 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
ARIKAYCE. If ototoxicity occurs, manage the patient as medically appropriate, including potentially
discontinuing ARIKAYCE.
5.6
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.
5.7
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.
Page 3 of 12
Reference ID: 4327567
5.8
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 exposedin 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
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 ARIKAYCE at the dose of 590 mg/day (median duration of exposure to ARIKAYCE was 169
days).
Trial 1 (NCT#02344004) was an open-label, randomized (2:1), multi-center Phase 3 trial in patients with
refractoryMycobacterium aviumcomplex (MAC) lung disease . Patients were randomized to either 8
months of ARIKAYCE 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 ARIKAYCE 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 andMycobacterium
abscessus. Patients were randomized to either ARIKAYCE 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 ARIKAYCE.
Adverse Reactions Leading to Treatment Discontinuation
In the three NTM studies, there was a higher incidence of premature discontinuation of ARIKAYCE. In
Trial 1, 33.5% discontinued ARIKAYCE 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 ARIKAYCE discontinued prematurely with 14.9%
discontinuing due to adverse reactions. In Trial 3, all 9 (20.5%) premature discontinuations occurred in the
ARIKAYCE 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 ARIKAYCE-treated arm as compared to the respective control arm. In Trial 1, 20.2% of
patients treated with ARIKAYCE plus background regimen reported SAR as compared to 16.1% of
Page 4 of 12
Reference ID: 4327567
patients treated with background regimen alone. In addition, in Trial 1 [2 to 1 randomization, ARIKAYCE
plus background regimen versus background regimen alone], there were 82 hospitalizations in 41 patients
(18.4%) treated with ARIKAYCE 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 ARIKAYCE 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 ARIKAYCE 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 ARIKAYCE plus background regimen group and greater than the background
regimen alone group, are shown.
Table 1: Adverse Reactions in ≥ 5% of ARIKAYCE-treated MAC Patients and More Frequent
than Background Regimen Alone in Trial 1
Adverse Reaction
ARIKAYCE plus
Background
Regimen
(n=223)
n (%)
Background
Regimen Alone
(n=112)
n (%)
Dysphonia
a
105 (47)
87 (39)
64 (29)
40 (18)
38 (17)
37 (17)
37 (17)
36 (16)
33 (15)
28 (13)
26 (12)
22 (10)
22 (10)
16 (7)
1 (1)
19 (17)
12 (11)
14 (13)
11 (10)
2 (2)
Cough
b
Bronchospasm
Hemoptysis
c
Ototoxicity
d
Upper airway irritation
Musculoskeletal pain
Fatigue and asthenia
e
f
9 (8)
11 (10)
11 (10)
5 (5)
4 (4)
9 (8)
Exacerbation of underlying pulmonary disease
g
Diarrhea
Nausea
Pneumonia
Headache
Pyrexia
h
5 (5)
5 (5)
Vomiting
i
15 (7)
4 (4)
Rash
j
14 (6)
2 (2)
Weight decreased
14 (6)
1 (1)
Change in sputum
Chest discomfort
k
12 (5)
12 (5)
1 (1)
3 (3)
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
Includes deafness, deafness neurosensory, deafness unilateral, dizziness, hypoacusis, presyncope, tinnitus, vertigo
Includes oropharyngeal pain, oropharyngeal discomfort, throat irritation, pharyngeal erythema, upper airway inflammation,
pharyngeal edema, vocal cord inflammation, laryngeal pain, laryngeal erythema, laryngitis
Includes back pain, arthralgia, myalgia, pain/body aches, muscle spasm and musculoskeletal
exacerbation of COPD, infective exacerbation of bronchiectasis
Includes atypical pneumonia, empyema, infection pleural effusion, lower respiratory tract infection, lung infection, lung
d
e
f
g
Includes COPD, infective
h
infection pseudomonas, pneumonia, pneumonia aspiration, pneumonia pseudomonas, pseudomonas infection and respiratory
tract infection
i
Includes vomiting and post-tussive vomiting
Includes rash, rash maculo-papular, drug eruption and urticaria
Includes increased sputum, sputum purulent and sputum discolored
j
k
Selected adverse drug reactions that occurred in <5% of patients and at higher frequency in ARIKAYCE-
treated patients in Trial 1 are presented in Table 2.
Page 5 of 12
from clipboard
Table 2: Selected Adverse Reactions in < 5% of ARIKAYCE-treated MAC Patients and More
Frequent than Background Regimen Alone in Trial 1
ARIKAYCE plus
Background Regimen
N=223
10 (4.5)
9 (4)
Background
Regimen Alone
N=112
0 (0)
2 (1.8)
3 (2.7)
0 (0)
Anxiety
Oral fungal infection
a
Bronchitis
8 (3.6)
8 (3.6)
Hypersensitivity pneumonitis
b
Dysgeusia
7 (3.1)
0 (0)
Respiratory failure
Epistaxis
c
6 (2.7)
6 (2.7)
5 (2.2)
5 (2.2)
1 (0.9)
1 (0.9)
0 (0)
Neuromuscular disorder
Dry mouth
d
0 (0)
Pneumothorax
e
5 (2.2)
3 (1.3)
3 (1.3)
1 (0.9)
0 (0)
0 (0)
Exercise tolerance decreased
Balance disorder
a
Includes oral candidiasis and oral fungal infection
b
Includes allergic alveolitis, interstitial lung disease, and pneumonitis
Includes acuter respiratory failure and respiratory failure
c
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 INTERACTONS
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
USE IN SPECIFIC POPULATIONS
Pregnancy
8.1
Risk Summary
There are no data on ARIKAYCE 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 (12.3)],systemic exposure to
aminoglycoside antibacterial drugs, including ARIKAYCE, 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.
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Data
Animal Data
No animal reproductive toxicology studies have been conducted with ARIKAYCE 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 ARIKAYCE in human milk, the effects on the breastfed
infant, or the effects on milk production after administration of ARIKAYCE by inhalation. Although
limited published data on other routes of administration of amikacin indicate that amikacin is present in
human milk, systemic absorption of ARIKAYCE following inhaled administration is expected to be low
[see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be
considered along with the mother’s clinical need for ARIKAYCE and any potential adverse effects on the
breastfed child from ARIKAYCE or from the underlying maternal condition.
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, 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
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 (5.6), Use in Specific Populations (8.5)].
10
OVERDOSAGE
Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute
toxicity should be treated with immediate withdrawal of ARIKAYCE, 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.
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Reference ID: 4327567
11 DESCRIPTION
The active ingredient in ARIKAYCE (amikacin liposome inhalation suspension) is amikacin sulfate USP,
an aminoglycoside antibacterial. Its chemical name is D-Streptamine,O-3-amino-3-deoxy-α-D
1
glucopyranosyl-(1→6)-O-[6-amino-6-deoxy-α-D-glucopyranosyl-(1→4)]-N -(4-amino-2-hydroxy-1
oxobutyl)-2-deoxy-, (S)-, sulfate (1:2) salt with a chemical formula of C22H43N5O13•2H2SO4 with a
molecular weight of 781.76. Its structural formula is:
from clipboard
ARIKAYCE 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. ARIKAYCE 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.
ARIKAYCE is administered only using a Lamira Nebulizer System[see Dosage and Administration (2.1)].
Like all other nebulized treatments, the amount delivered to the lungs will depend upon patient factors.
Under standardizedin vitrotesting 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 ARIKAYCE delivers a combination of free and liposomal amikacin.
12
CLINICAL PHARMACOLOGY
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
Sputum Concentrations
Following once daily inhalation of 590 mg ARIKAYCE inMycobacterium aviumcomplex (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 ARIKAYCE 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
Page 8 of 12
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 ARIKAYCE 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 ARIKAYCE 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 ARIKAYCE administration is eliminated principally via
glomerular filtration. On average, 7.42% (ranging from 0.72 to 22.60%; n=14) of the total ARIKAYCE
dose was excreted in urine as unchanged drug compared to 94% following intravenous administration of
amikacin sulfate for injection. Unabsorbed amikacin, following ARIKAYCE inhalation, is probably
eliminated primarily by cellular turnover and expectoration.
Drug Interaction Studies
No clinical drug interaction studies have been conducted with ARIKAYCE[see Drug Interactions (7)].
12.4 Microbiology
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 ARIKAYCE[see Clinical Studies (14)].
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.
13.
NONCLINICAL TOXICOLOGY
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 ofin vitroandin vivogenotoxicity
studies with a liposome-encapsulated amikacin formulation similar to ARIKAYCE (in vitromicrobial
Page 9 of 12
Reference ID: 4327567
mutagenesis test,in vitromouse lymphoma mutation assay,in vitrochromosomal aberration study, and an
in vivomicronucleus 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.
14.
CLINICAL STUDIES
Trial 1 (NCT# 02344004) was an open-label, randomized (2:1), multi-center trial in patients with refractory
Mycobacterium aviumcomplex (MAC) lung disease as confirmed by at least 2 sputum culture results.
Patients were considered to have refractory MAC lung disease if they did not achieve negative sputum
cultures after a minimum duration of 6 consecutive months of background regimen therapy that was either
ongoing or stopped no more than 12 months before the screening visit. Patients were randomized to either
ARIKAYCE plus a background regimen or background regimen alone. The surrogate endpoint for
assessing efficacy was based on achieving culture conversion (3 consecutive monthly negative sputum
cultures) by Month 6. The date of conversion was defined as the date of the first of the 3 negative monthly
cultures, which had to be achieved by Month 4 in order to meet the endpoint by Month 6.
A total of 336 patients were randomized (ARIKAYCE plus background regimen, n=224; background
regimen alone, n=112) (ITT population), with a mean age of 64.7 years and there was a higher percentage
of females (69.3%) than males (30.7%) in the study. At the time of enrollment, of the 336 subjects in the
ITT population, 302 (89.9%) were either on a guideline-based regimen for MAC or off guideline-based
therapy for MAC for less than 3 months while 34 (10.1%) were off treatment for 3 to 12 months prior to
enrollment. At screening, patients were stratified by smoking status (current smoker or not) and by
whether patients were on treatment or off treatment for at least 3 months. Most patients at screening were
not current smokers (89.3%) and had underlying bronchiectasis (62.5%). At baseline, background regimens
included a macrolide (91.9%), a rifamycin (85.7%), or ethambutol (80.3%). Overall, 54.9% of subjects
were receiving a triple background regimen of a macrolide, a rifamycin and ethambutol.
The proportion of patients achieving culture conversion (3 consecutive monthly negative sputum cultures)
by Month 6 was significantly (p<0.0001) greater for ARIKAYCE plus background regimen (65/224,
29.0%) compared to background regimen alone (10/112, 8.9%). An analysis of sustained sputum culture
conversion through Month 6 (defined as consecutive negative sputum cultures with no positive culture on
solid media or no more than 2 consecutive positive cultures on liquid media following achieving initial
culture conversion) showed that 3 subjects in each treatment arm who initially achieved culture conversion
did not have sustained sputum culture conversion through Month 6. Thus, 27.7% (62/224) of ARIKAYCE
plus background regimen patients and 6.3% (7/112) of background regimen alone patients had sustained
sputum culture conversion through Month 6.
from clipboard
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Reference ID: 4327567
In Trial 1, 23/224 (10.3%) of patients had MAC isolates that developed MIC of > 64 mcg/mL while
receiving treatment with ARIKAYCE. In the background regimen alone arm, 4/112 (3.6%) of patients had
MAC isolates that developed amikacin MIC of > 64 mcg/mL.
Additional endpoints to assess the clinical benefit of ARIKAYCE, for example, change from baseline in
six-minute walk test distance and the Saint George’s Respiratory Questionnaire, did not demonstrate
clinical benefit by Month 6.
16
HOW SUPPLIED/STORAGE AND HANDLING
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.
17
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Patient Instructions
for Use).
Important Instructions for Administration of ARIKAYCE
Instruct patients to read theInstructions for Usebefore starting ARIKAYCE. Instruct patients to only use
the Lamira
TM
Nebulizer System to administer ARIKAYCE. Advise the patient or caregiver not 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.
Page 11 of 12
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 (6.2)].
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 (6.2)].
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)].
Embryofetal 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 Population (8.1)].
Manufactured for:
Insmed
, Bridgewater, NJ 08807
Insmed
and, ARIKAYCE are trademarks of Insmed Incorporated. Lamira is a trademark of PARI
TM
Pharma GmbH.
© Insmed Incorporated. All rights reserved. 2010 7,718,189; 2012 8,226,975; 2014 8,632,804, 8,642,075,
8,679,532 and 8,802,137; 2017 9,566,234 and 9,827,317 and 2018 9,895,385
Page 12 of 12
Reference ID: 4327567
MEDICATION GUIDE
ARIKAYCE (ar' i kase) LIMITED POPULATION
(amikacin liposome inhalation suspension)
for oral inhalation use
Important: For oral inhalation only.
What is the most important information I should know about ARIKAYCE?
ARIKAYCE can cause serious side effects, including:
• allergic inflammation of the lungs: These respiratory problems may be symptoms of allergic inflammation
of the lungs and often come with:
o fever
o wheezing
o coughing
o fast breathing
o shortness of breath
• coughing up of blood (hemoptysis): Coughing up blood is a serious and common side effect of
ARIKAYCE.
• severe breathing problems: Severe breathing problems can be symptoms of bronchospasm.
Bronchospasm is a serious and common side effect of ARIKAYCE. Bronchospasm symptoms include:
o shortness of breath o difficult or labored breathing
o wheezing
o coughing or chest tightness
• worsening of chronic obstructive pulmonary disease (COPD): This is a serious and common side effect
of ARIKAYCE.
While using ARIKAYCE these side effects may become serious enough that treatment in a hospital is
needed.
Call your healthcare provider or get medical help right away if you have any of these serious side effects while
taking ARIKAYCE. Your healthcare provider may ask you to stop using ARIKAYCE for a short period of time or
completely stop using ARIKAYCE.
What is ARIKAYCE?
ARIKAYCE is a prescription medicine used to treat adults with refractory (difficult to treat)Mycobacterium avium
complex (MAC) lung disease as part of a combination antibacterial drug treatment plan (regimen).
It is not known if ARIKAYCE is safe and effective in children younger than 18 years of age.
This product was approved by FDA using the Limited Population pathway. This means FDA has approved this drug
for a limited and specific patient population, and studies on the drug may have only answered focused questions
about its safety and effectiveness.
Do not use ARIKAYCE if you:
• are allergic to any aminoglycoside, or any of the ingredients in ARIKAYCE. See “What are the ingredients in
ARIKAYCE?” at the end of this leaflet for a complete list of ingredients in ARIKAYCE.
Before using ARIKAYCE, tell your healthcare provider about all of your medical conditions, including if you:
• have asthma, chronic obstructive pulmonary disease (COPD), shortness of breath or wheezing (bronchospasm).
• have been told you have poor lung function.
• have hearing problems such as ringing in your ears or hearing loss.
• have dizziness or sense of the room spinning.
• have kidney problems.
• have neuromuscular disease such as myasthenia gravis.
• are pregnant or plan to become pregnant. It is not known if ARIKAYCE can harm your unborn baby. ARIKAYCE is
in a class of medicines that may be connected with complete deafness in babies at birth. The deafness affects both
ears and cannot be changed.
• are breastfeeding or plan to breastfeed. It is not known if the medicine in ARIKAYCE passes into your breast milk
and if it can harm your baby. Talk to your healthcare provider about the best way to feed your baby during treatment
with ARIKAYCE.
Tell your healthcare provider about all the medicines you take, including prescription medicines and over
the-counter medicines, vitamins, and herbal supplements.
Reference ID: 4327567
How should I use ARIKAYCE?
• Read the step-by-step instructions for using ARIKAYCE at the end of the Medication Guide and the full
Instructions for Use provided in your kit . The manufacturer’s Instructions for Use provides complete
information about how to put together (assemble), prepare, use, clean, and disinfect your Lamira Nebulizer
System.
• Do not use ARIKAYCE unless you understand the directions provided. If you have questions talk to your
health care provider or call Arikares Support at 1-833-ARIKARE (1-833-274-5273).
• Use ARIKAYCE exactly as your healthcare provider tells you to use it. Do not use ARIKAYCE more
often than prescribed for you.
• Only use ARIKAYCE with the Lamira Nebulizer System.
• Inhale each daily dose of ARIKAYCE 1 time each day through the Lamira Nebulizer Handset. Do not use more
than 1 vial of ARIKAYCE in a day.
• Do not use ARIKAYCE after the expiration date on the vial. If you forget to take your daily dose of ARIKAYCE,
take your next dose at your usual time the next day.
• Do not double the dose to make up for the missed dose.
• Do not stop using ARIKAYCE or other medicines to treat your MAC lung disease unless told to do so by your
healthcare provider.
• If you use too much ARIKAYCE, call your healthcare provider or go to the nearest emergency room right away.
What are the possible side effects of ARIKAYCE?
ARIKAYCE may cause serious side effects, including:
• See “What is the most important information I should know about ARIKAYCE?”
• hearing loss or ringing in the ears (ototoxicity). Ototoxicity is a serious and common side effect of
ARIKAYCE. Tell your healthcare provider right away if you have hearing loss or you hear noises in your ears
such as ringing or hissing. Tell your healthcare provider if you start having problems with balance or dizziness
(vertigo).
• worsening kidney problems (nephrotoxicity). ARIKAYCE is in a class of medicines which may cause
worsening kidney problems. Your healthcare provider may do a blood test to check how well your kidneys are
working during your treatment with ARIKAYCE.
• worsening muscle weakness (neuromuscular blockade). ARIKAYCE is in a class of medicines which can
cause muscle weakness to get worse in people who already have problems with muscle weakness
(myasthenia gravis).
The most common side effects of ARIKAYCE include:
• changes in your voice and
hoarseness (dysphonia)
• tiredness (fatigue)
• sore throat
• diarrhea
• fever
• muscle pain
• nausea
• vomiting
• headache
• rash
• decreased weight
• chest discomfort
• increased sputum
• cough during or after a dose of
ARIKAYCE, especially in the first
month after starting treatment.
These are not all of the possible side effects of ARIKAYCE.
Call your doctor or pharmacist for medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088
How should I store ARIKAYCE?
• Store ARIKAYCE vials refrigerated between 36°F to 46°F (2°C to 8°C) until the expiration date on the vial. Do not
freeze.
• After ARIKAYCE has been stored in the refrigerator, any unused medicine must be thrown away (disposed of)
after the expiration date on the vial.
• Store ARIKAYCE vials at room temperature between 68°Fto 77°F (20°C to 25°C) for up to 4 weeks
• After ARIKAYCE has been stored at room temperature any unused medicine must be thrown away
Reference ID: 4327567
(disposed of) at the end of 4 weeks.
• Use an opened ARIKAYCE vial right away.
• Throw away the ARIKAYCE vial right away after use.
Keep ARIKAYCE and all medicines out of the reach of children.
General information about safe and effective use of ARIKAYCE
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use
ARIKAYCE for a condition for which it was not prescribed. Do not give ARIKAYCE to other people even if they have
the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for
information about ARIKAYCE that is written for health professionals.
What are the ingredients in ARIKAYCE?
Active ingredient: amikacin sulfate
Inactive ingredients: Dipalmitoylphosphatidylcholine (DPPC), cholesterol, sodium chloride, sodium hydroxide (for
pH adjustment), and water for injection
Manufactured by: Insmed Incorporated, 10 Finderne Ave, Bldg. 10, Bridgewater, NJ 08807-3365
Insmed Incorporated, All rights reserved.
For more information, call Insmed Arikares Support at: 1- 833-ARIKARE (1-833-274-2573)
This Medication Guide has been approved by the U.S. Food and Drug Administration
Issued: 09/2018
Reference ID: 4327567
Instructions for Use
LIMITED POPULATION
ARIKAYCE
®
(amikacin liposome inhalation suspension)
For oral inhalation use
Lamira
TM
Nebulizer System
Before using your Lamira Nebulizer System, be sure you read and understand the detailed
information in the full Instructions for Use that comes with the Lamira Nebulizer System. This will
provide more complete information about how to put together (assemble), prepare, use, clean,
and disinfect your Lamira Nebulizer System. If you do not understand any part of the instructions,
contact Arikares Support at 1-833-ARIKARE (1-833-274-5273) before using the Lamira
Nebulizer System.
Gather your ARIKAYCE medicine. The ARIKAYCE 28-day kit contains:
•
•
•
•
•
•
1 ARIKAYCE Quick Start Guide
1 Instructions for Use insert
1 Full Prescribing Information insert
1 Lamira Nebulizer Handset
4 Lamira Aerosol Heads (1 in each weekly box)
28 vials (1 vial each day) of ARIKAYCE (7 in each weekly box)
Check to make sure you have all the necessary parts for your Lamira Nebulizer System:
a.
b.
c.
d.
e.
Carrying Case
Connection Cord
Controller
A/C Power Supply
“AA” Batteries
Spare Lamira Nebulizer
Handset:
f.
g.
h.
i.
Medication Cap and Seal
Medication Reservoir
Blue Valve
Aerosol Chamber
Mouthpiece
j.
k.
Spare Aerosol Head
You will also need the following supplies that do not come in your ARIKAYCE 28-day kit
that will help you care for your Lamira Nebulizer System:
Page 1 of 8
Reference ID: 4327567
•
•
Clear liquid soap for cleaning the Handset and Aerosol Head
Distilled water for disinfecting the Handset and Aerosol Head
Choose your power supply and get it ready.
a. 4 “AA” batteries
or
b. A/C Power Supply
• Plug the A/C Power Supply into
the Controller.
• Plug the A/C Power Supply into
the wall outlet.
Do not insert the A/C Power into the
front of the Controller.
Cleaning and Disinfecting
Clean and disinfect your Handset and Aerosol Head before you use it for the first time, and
immediately after each use.
When you receive your Handset and Aerosol Head, they will not be sterile. Cleaning and
disinfecting your Handset and Aerosol Head is important to reduce the risk of infection, illness,
and contamination.
1. Cleaning the Handset and Aerosol Head Reminder: Clean the Handset and Aerosol Head
before first use and immediately after each use.
•
•
Take apart (disassemble) the
Handset for cleaning
Gently wipe away any drops
of medicine from the
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Medication Reservoir (a),
Aerosol Chamber (b), and
Mouthpiece (c) before rinsing,
to reduce antibiotics added to
water systems.
Use only plain, dry paper
towels or wipes. Do not use
towels or wipes that have any
chemicals added to them such
as alcohol, lotion, or baby
wipes.
Be careful not to harm the
parts. Do not wipe Aerosol
Head.
Throw away paper towels by
disposing in trash with solid
waste.
•
Rinse each of the parts under
warm running tap water for 10
seconds. Rinse the Aerosol
Head for 10 seconds on each
side.
•
Clean all Handset parts by
adding a few drops of clear
liquid dish soap and warm tap
water to a clean tub or bowl.
Cover the Handset parts in the
warm soapy water and soak for
5 minutes, shaking them
periodically. Then rinse them
thoroughly under warm running
tap water.
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2. Disinfecting the Handset and Aerosol Head Before First Use
Reminder: Disinfect the Handset and Aerosol Head before first use.
•
•
Be sure your Handset and
Aerosol Head are clean before
you disinfect.
Boil the Handset parts,
including the Aerosol Head, in a
clean pot of distilled water for a
full 5 minutes.
•
Air dry on a lint-free towel.
When fully dry, wrap up the
parts in a lint-free towel for
storage. You can put them
together again just before
taking your next treatment.
Assembling Your Handset
Step 1: Wash your hands with soap
and water, and dry them well.
Step 2: Insert the Blue Valve.
Open the Handset by gently pulling up
on the tab of the Medication Reservoir.
Insert the Blue Valve so that it rests on
top of the Aerosol Chamber with the 2
valve flaps facing down.
Step 3: Insert the Aerosol Head.
Grasp the Aerosol Head by the 2
flexible plastic tabs on each side. Be
sure the text “For amikacin liposome
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Reference ID: 4327567
inhalation suspension” is facing toward
you and is at the top of the Aerosol
Head.
Squeeze the 2 flexible plastic tabs
together while inserting the Aerosol
Head into the Medication Reservoir.
Close the Handset when you are done.
Do not touch the silver part of the
Aerosol Head at any time.
After the Aerosol Head has been
used 7 times, throw away (dispose
of) and replace with a new one
during the cleaning process.
Step 4: Attach the Mouthpiece to
your Handset with the Blue Flap
facing up.
Step 5: Finally, attach the Handset to
the Controller.
a. Attach the Connection Cord
to the Handset.
a1. Line up the bottom of the
Connector with the bottom
of the Handset.
a2. Push upward against the
Handset until you hear the
pieces snap together.
b. Connect the Connection
Cord to the Controller.
Taking ARIKAYCE
Your ARIKAYCE should be at room temperature before use to make sure that your Lamira
Nebulizer System operates properly. Do not use other medicines in your Handset.
Bring ARIKAYCE to room temperature by removing it from the refrigerator at least 45 minutes
before use. Do not use if your ARIKAYCE has been frozen.∫
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Step 1: Get your ARIKAYCE ready.
•
•
Place the Handset on a clean,
flat, stable surface.
Shake the ARIKAYCE vial well
for at least 10 to 15 seconds,
until the medicine looks the
same throughout and well
mixed.
How to open the ARIKAYCE vial
•
Lift the orange cap from the
vial.
•
Grip the metal ring on top of
the vial and pull it down gently
until 1 side breaks away from
the vial.
•
•
Pull the metal band from
around the vial top in a circular
motion until it comes off
completely.
Carefully remove the rubber
stopper.
a. Open the vial and pour the
ARIKAYCE into the Medication
Reservoir.
b. Attach the Medication Cap.
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Reference ID: 4327567
Step 2: Sit in a relaxed, upright
position.
•
Press and hold down on the
On/Off button for a few
seconds to turn the Lamira on.
•
Mist will begin to flow.
Step 3: Insert the Mouthpiece and
take slow, deep breaths.
•
Then, breathe normally in and
out through the Mouthpiece
until your treatment is
complete.
•
Treatment should take about
14 minutes but could take up to
20 minutes.
Be sure to hold the Handset level
throughout the treatment.
Step 4: Check that your treatment
has ended.
•
•
The Lamira will beep 2 times.
The LED light will flash red 2
times.
•
•
•
A Checkmark will briefly
appear on the screen.
The Controller will
automatically shut off.
Remove the Medication Cap
and check the Medication
Reservoir to make sure that
no more than a few drops of
ARIKAYCE remains. If
ARIKAYCE remains, replace
the Medication Cap, press
the On/Off button, and
complete your dose.
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Reference ID: 4327567
For any issues you may have with your Lamira Nebulizer System, see Section K –
Troubleshooting of the full Instructions for Use that comes with your medicine.
Cleaning your Lamira Handset and Aerosol Head After Use
•
Rinse, clean, and disinfect handset right away after each use to reduce infection, illness,
and contamination.
•
•
Disinfect the Handset and Aerosol Head every day.
See “Cleaning and Disinfecting” at the beginning of the Instructions for Use on how to
properly clean and disinfect your handset and aerosol head.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Issued: 09/2018
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Reference ID: 4327567
Reference ID: 4327567
A Table of Contents And Introduction
Introduction
Table of Contents
The Lamira Nebulizer System (Lamira) is a battery operated
™
A. Introduction
1
2
electronic nebulizer, which vibrates and forces liquid ARIKAYCE
through thousands of small holes to form an aerosol mist for
inhalation.
B. Safety Precautions
C. Getting Started
3
These Instructions for Use contain information and safety
precautions for the Lamira nebulizer that is made just for the
®
medicine ARIKAYCE (amikacin liposome inhalation
suspension). Do not use any other medicine in the Lamira
nebulizer.
D. Using Batteries or the A/C Power Supply
E. Maintaining Your Lamira
F. Cleaning Your Lamira
G. Disinfecting Your Lamira
H. Assembling your Lamira Handset
I. Taking ARIKAYCE
4
5
6
9
10
13
16
17
19
Warning
Before using your Lamira nebulizer, read and understand all the
Instructions for Use and save them for future reference. If you do
not understand any part of these directions, contact the Arikares
Support Program at 1-833-ARIKARE (1-833-274-5273) before
using the Lamira nebulizer.
J. Frequently Asked Questions
K. Troubleshooting
L. Specifications
To reduce the risk of infection, illness, or injury from
contamination or improper use, it is important to complete
the following 2 steps:
1) Rinse and clean the Handset including the Aerosol
Head before first use and right after each use. (see
Section F) Do not wash the Controller, Connection Cord, or
A/C Power Supply. Use clear liquid soap made for washing
dishes to clean the Handset including the Aerosol Head. Do
not use liquid dish soaps that are white or antibacterial liquid
dish soaps because these may contain additives harmful to
the Aerosol Head.
2) Disinfect the Handset including the Aerosol Head every
day (see Section G).
Take special note of all safety precautions marked Danger and
Warning.
Indications for use
Limited by Federal Law for use only with ARIKAYCE.
1
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Reference ID: 4327567
B
Safety Precautions
•
•
To reduce the risk of infection, illness, or injury from contamination,
clean and dry all parts of the Handset after each use. Follow the
instructions in Section E to maintain and clean the Lamira.
Cleaning the Handset properly will help prevent the Aerosol Head
from clogging. Replace the Aerosol Head with a new one after 7
uses. If the Aerosol Head becomes clogged, the aerosol mist will be
reduced, which may increase your inhalation time of therapy. If
clogging occurs, use the instructions inSection Fto clean the Aerosol
Head.
Cleaning the Handset and Aerosol Head only removes the medicine
and saliva. To reduce the risk of serious or fatal illness caused by
contamination of the Handset, you must also disinfect the Handset
and Aerosol Head after every cleaning. See Section G for
disinfection instructions.
The Lamira contains small parts that may become a choking hazard
to small children. The Lamira Connection Cord (Connection Cord)
also may become a strangulation hazard.
Do Not allow pets, for example dogs or rodents, near the cables.
Keep the Lamira out of reach of children.
Keep the Handset level when in use. Excessive tilting can cause the
Controller to shut off leaving unused ARIKAYCE in the Medication
Reservoir and resulting in incomplete dosing.
Closely supervise use when the Lamira is used near children or the
physically or mentally impaired.
Read all dangers and warnings before using.
Danger
To reduce the risk of fatal injury from electrocution:
•
Do not place or store the Lamira Nebulizer System near water or
other liquid such as bathtub or sink. Do not place or drop into water
or other liquid. Do not use while bathing.
Do not reach for the Lamira Nebulizer System if it has fallen into
water or other liquid. Unplug right away. Pick up the Lamira only
after it has been unplugged.
•
•
•
Warning
•
•
•
To reduce the risk of serious injury:
•
•
The Lamira Nebulizer Handset (Handset) is for single patient use.
Do not share your Handset with other people.
The Handset is made just for ARIKAYCE. Never use other
medicine in the Handset. Using other medicine in the Lamira
nebulizer can result in severe injury or death.
Read, understand and follow all warnings and instructions in these
Instructions for Use before using the Lamira nebulizer.
To reduce the risk of fire, burns and damage or malfunction of the
Controller:
Do not overload wall outlets or use extension cords.
Keep all electrical cords away from heated surfaces.
Do not spray liquids onto the housing of the Controller
(Controller). (See Section C: Getting Started) Liquid may cause
damage to the electrical parts and could lead to a malfunction. If
liquids enter the Controller, contact the Arikares Support
Program at 1-833-ARIKARE (1-833-274-5273).
•
•
•
•
Do not use your Lamira while driving or in any situation which takes
away your full attention.
•
•
If the Lamira has been damaged or is not operating properly, contact
the Arikares Support Program at 1-833-ARIKARE (1-833-274-5273).
Do not take the Controller apart at any time. There are no user
serviceable parts inside the Controller. Contact the Arikares Support
Program at 1-833-ARIKARE (1-833-274-5273) for all Controller
service needs.
Do not modify this equipment without authorization from the
manufacturer.
Do not use the device in areas exposed to elevated electromagnetic
or electrical radiation such as a MRI scanner or high frequency
surgical equipment.
Do not place near other medical devices during operation unless
both devices are monitored constantly to make sure both are
operating properly.
Do not use within 12 inches (30 cm) of portable wireless
communication devices such as cell phones or antenna cables or
external antennas.
ü
ü
ü
•
•
ü
ü
Do not insert any object into any opening on the Lamira.
Do not operate where oxygen is being given in a closed
environment such as an oxygen tent.
•
•
•
•
Always unplug the Lamira right after using and before cleaning.
Before use, check your Lamira for proper assembly. All parts must
be connected and firmly in place. Use of an improperly assembled
Lamira could decrease or stop the effectiveness of your treatment.
Use only adapters and accessories that are made for the Lamira.
Use of unapproved adapters or accessories can lead to improper
administration, injury, leading to damage to the Controller.
Never substitute the Handset for any other eFlow® Technology
Handset such as Altera®, eRapid® or any other eFlow®. Never use
the Lamira Aerosol Head (Aerosol Head) in any other eFlow®
Technology Handset. This Aerosol Head has unique performance
characteristics for ARIKAYCE.
Never operate the Controller if it is improperly or incompletely
assembled or damaged. See Section K: Troubleshooting for more
information about alerts that appear when the Lamira is improperly
assembled or might be damaged.
Never operate the Lamira if:
It has damaged cords or plugs,
it is not working properly,
•
•
•
•
Do not use near airplane or train control systems. Do not use aboard
aircraft.
Do not use the nebulizer near anti-theft systems and Radio
Frequency Identification (RFID) readers, which are used in a wide
variety of settings, including stores, libraries, and hospitals. Do not
power on the nebulizer when passing through security screening
or theft protection (RFID) systems at entrances or exits of stores,
libraries or hospitals. Note that some entrance and exit security
systems are not visible.
•
•
Technical electromagnetic compatibility data is available in table form
upon request from PARI Pharma GmbH or on the Internet at
https://www.pari.com/fileadmin/Electromagnetic-compatibility-4.pdf
ü
ü
ü
ü
it has been dropped or damaged,
the Controller has been exposed to liquids
2
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Reference ID: 4327567
C Getting Started
Step C1: Gather your dosing supplies:
•
•
•
Clear liquid soap for cleaning the Handset
Distilled water for disinfecting the Handset
The ARIKAYCE 28 day drug kit will contain the following:
o
o
o
o
o
o
28 vials of ARIKAYCE (1 vial to be used each day for 28 days)
4 Lamira Aerosol Heads (1 Aerosol Head to be used for 7 days and then replaced)
1 Lamira Handset (to be used for 28 days until the next ARIKAYCE drug box arrives)
1 ARIKAYCE Quick Start Guide
1 Instructions For Use Insert
1 Full Prescribing Information Insert
Step C2: Check your Lamira Nebulizer System package to make sure you have the items shown below. Note that the package
contains a Handset that should be set aside as a spare. If anything looks damaged, contact the Arikares Support Program at
1-833-ARIKARE (1-833-274-5273).
CONTROLLER
CONNECTION CORD
SPARE HANDSET
CARRYING CASE
SPARE AEROSOL HEAD
A/C POWER SUPPLY
MEDICATION CAP
BLUE VALVE
MEDICATION RESERVOIR
AEROSOL CHAMBER
“AA” BATTERIES
MOUTH PIECE
3
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Reference ID: 4327567
D
Using Batteries or the A/C Power Supply
The Lamira is made to be used with “AA” batteries or with the A/C
Power Supply.
D-1
Using Batteries: Four (4) high quality “AA” batteries should
provide 2 hours of total use.
Step D1: Open the Battery Door on the Controller by placing
your thumb on the tab of the Battery Door and firmly
pulling the tab to open the Door (D-1).
Step D2: Load the Batteries. Each Battery Chamber has a
small figure that shows the proper position of each
battery (D-2). Using the battery “tips” as guides and
starting left-to-right for each row, insert the batteries:
Tip Out, Tip In, Tip Out, Tip In.
CONTROLLER
BATTERY DOOR
D-2
Close the Battery Door. To close the Battery Door,
push it closed until you hear it “click” into place.
NOTE:
Rechargeable and Disposable Batteries have
differences in storage life and output. If you plan to
store the Controller for more than 30 days, it is
recommended to remove the batteries to reduce the
risk of battery leakage.
If you choose not to use the A/C Power Supply, you should
have an extra battery set with you at all times.
A/C Power Supply
Using the A/C power supply: The A/C Power Supply will
automatically adjust to the incoming voltage and will power the
Controller with or without installed batteries. It can be used
worldwide, but requires “Plug Converters” for use outside the
USA.
Step D3: Plug the A/C Power Supply into the Controller. To
connect the A/C Power Supply to the Controller, place
the Controller on a clean, flat, stable surface. The plug
inlet port is located on the underside of the gray
Battery Door. Push the round end of the A/C Power
Supply plug into the plug inlet port (D-3). Do not try to
insert the A/C Power Supply into the front of the
Controller.
GRAY BATTERY DOOR
PLUG INLET PORT
Step D4: Plug the A/C Power Supply into the wall outlet.
Note that the A/C Power Supply will not charge the
batteries in the Controller.
PLUG INSERT
D-3
4
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Reference ID: 4327567
E Maintaining Your Lamira
Warning
To reduce the risk of infection, illness, or injury from contamination or improper use, it is important to complete the following 2
steps:
1)
Rinse and clean the Handset including the Aerosol Head before first use and right after each use. (see Section F) Do not
wash the Controller, Connection Cord, or A/C Power Supply. Use clear liquid soap made for washing dishes to clean the Handset.
Do not use liquid dish soaps that are white or antibacterial liquid dish soaps because these may contain additives harmful to the
Aerosol Head.
2)
Disinfect the Handset every day (see Section G).
Caution
•
•
•
Do not put the Handset or the Aerosol Head in the microwave oven.
Do not try to clean the Handset or Aerosol Head in a dishwasher.
Do not try to clean the Handset or the Aerosol Head with brushes or abrasives.
Handset Maintenance Summary (see the next page for complete instructions)
Instruction
When
Parts cleaned
Method
How
Comments
Long
Wipe
After
each use
• Medication Reservoir and
Aerosol Chamber
Wipe with clean 1 second
Wipe to remove residual
medicine and then
disposable
per part
• Mouthpiece
paper towel.
dispose of paper towel in
trash with solid waste.
Rinse
Clean
Prior to
• Aerosol Head
Warm running
tap water.
10 seconds Rinse each side of the
Aerosol Head for 10
seconds.
first use • Medication Cap and Seal
and after • Blue Valve
each use
• Medication Reservoir and
Aerosol Chamber
• Mouthpiece
Prior to
first use • Medication Cap and Seal
and after • Blue Valve
each use
Prior to
• Aerosol Head
Soak each
piece in warm
soapy water.
5 minutes
Use 3 to 5 drops of clear
liquid dish soap in a bowl
with enough warm water
to cover all pieces.
• Medication Reservoir and
Aerosol Chamber
• Mouthpiece
While soaking
swish or shake
each piece.
Soak longer if Handset
has dried or if visibly
dirty.
Rinse
• Aerosol Head
Warm running
tap water.
Until soap is Check each part and
first use • Medication Cap and Seal
removed.
soak for another 5
minutes if any part looks
dirty.
and after • Blue Valve
each use
• Medication Reservoir and
Aerosol Chamber
• Mouthpiece
Disinfect
Prior to
• Aerosol Head
Boil in distilled 5 minutes
water.
Air-dry in a dust-free
environment.
first use • Medication Cap and Seal
and after • Blue Valve
each use
• Medication Reservoir and
Aerosol Chamber
• Mouthpiece
5
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Reference ID: 4327567
F Cleaning Your Lamira
WARNING Your Handset including the Aerosol Head is not sterile. Contamination and
moisture may cause the growth of bacteria and the Aerosol Head can be affected by ARIKAYCE left
over in it. It is important to rinse, clean, and disinfect your Handset including the Aerosol Head
before first use and right after every use. If your Handset or Aerosol Head looks dirty, soak the
parts in soapy water for longer than 5 minutes. Do not place the Handset or the Aerosol Head in a
dishwasher.
Cleaning your Handset
Step F1: Disconnect your Handset from the
Connection Cord (F-1).
F-1
Step F2: Remove the Medication Cap by turning
F-2
counterclockwise and pulling straight up (F
2).
Step F3: Remove the Mouthpiece from the Aerosol
Chamber by pulling straight off (F-3). The
Blue Flap must still be attached to the
F-3
mouthpiece as shown in the picture.
6
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F Cleaning Your Lamira (continued)
TAB
Step F4: Gently pull up on the tab to open the
Handset and remove the Blue Valve (F-4).
F-4
FLEXIBLE PLASTIC
TABS
Step F5: Being careful to touch only the plastic outer ring
of the Aerosol Head, press the 2 flexible
F-5
plastic tabs on the side of the Aerosol Head
towards each other and remove (F-5). After
the Aerosol Head has been used 7 times, throw
away (dispose of) and replace with a new one.
Do not touch the center silver part of the
Aerosol Head.
Step F6: Gently wipe away any drops of medicine
from the medication reservoir (F-6a), aerosol
chamber (F-6b) and mouthpiece (F6c) before
rinsing to reduce antibiotics added to water
systems.
F-6a
F-6b
Use only plain, dry paper towels or wipes.
Do not use towels or wipes that have any
chemicals added to them such as alcohol,
lotion, or baby wipes.
F-6c
Be careful not to harm the parts.
Do not wipe the Aerosol Head.
Throw away paper towels by disposing in
trash with solid waste.
Step F7: Rinse each of the parts under warm running
tap water for 10 seconds. Pay special attention
to rinsing the Aerosol Head and rinse each
side of the Aerosol Head for 10 seconds
(F-7). Thorough rinsing of both sides of the
Aerosol Head helps to prevent clogging and
makes sure the Aerosol Head works properly.
Never use a brush or any other object to clean
the Aerosol Head.
F-7
10 seconds
7
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Reference ID: 4327567
F Cleaning Your Lamira (continued)
Step F8: Clean all Handset parts by adding a few
drops of clear liquid dish soap and warm tap
F-8
water to a clean tub or bowl. Cover the
Handset parts in the warm soapy water and
soak for 5 minutes, shaking them periodically
(F-8).
Step F9: Rinse all parts thoroughly under warm
running tap water to remove soap (F-9).
Check each part and soak for another 5
minutes if any of the parts look dirty. After all
parts are cleaned and free from soap,
disinfect your Handset.
F-9
Step F10: Disinfect the Handset including the
Aerosol Head after cleaning. In addition to
cleaning ARIKAYCE from your Handset, you
must also disinfect your Handset to remove
bacteria and avoid infection. See Section G
for instructions on how to disinfect your
Lamira Handset.
Cleaning your Controller and Connection
Cord
Step F11: To reduce the risk of electric shock,
disconnect all connections before
cleaning. Switch off the Controller.
Remove the Connection Cord and A/C
Power Supply cord from the Controller.
Step F12: Clean the Controller housing and
Connection Cord as needed with a soft,
clean, damp cloth. Do not place the
Controller unit under water or allow liquid to
get inside the Controller. Make sure moisture
from the cloth does not enter the Controller.
Caution
Never let the Controller come in contact with
water or cleaning agents. If liquid does get into the Controller,
contact the Arikares Support Program.
8
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Reference ID: 4327567
Disinfecting Your Lamira
G
Warning
To prevent serious or fatal illness
or injury caused by contamination, disinfect your
Handset including the Aerosol Head at the end of
every day.
Step G1: Clean your Handset right after every use with
soapy water as described in Section F.
Step G2: Disinfect your Handset at the end of every
day by boiling in distilled water.
To disinfect with boiling water, boil the
Handset parts, including the Aerosol Head, in a
clean pot of distilled water for a full 5 minutes.
Step G3: Air dry on a lint-free towel (G-3). After the
parts are completely dry, wrap them in a lint-free
towel for storage. Reassemble just before taking
your next treatment. This is to make sure the
Blue Valve will not become damaged.
G-3
9
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Reference ID: 4327567
H
Assembling your Lamira Handset
Warning
Your Handset including the Aerosol Head is not sterile.
Clean and disinfect your Handset before the first time you use it
and after each use (See Sections F and G). Inspect all parts to
make sure they are cleaned and are not visibly damaged. Do not
use dirty or damaged parts.
Clean and disinfect your Handset before the first
time you use it.
Step H1: Clean and Disinfect your Handset before the
first time you use it. See Sections F and G.
Step H2: Wash your hands with soap and water and dry
them well (H-2).
H-2
Step H3: Open the Handset. The Medication Reservoir
and the Aerosol Chamber are attached using a
“hinge”. First, gently pull up on the tab of the
Medication Reservoir (H-3). This will release the
Aerosol Chamber so that you may open it.
H-3
TAB
Step H4: Insert the Blue Valve on top of the Aerosol
Chamber (H-4). Make sure the 2 valve flaps are
positioned down as shown in H-4a. Do not push
the Blue Valve inside of the Aerosol Chamber. The
Blue Valve should be placed on top of the Aerosol
Chamber.
BLUE VALVE
H-4
AEROSOL
CHAMBER
VALVE FLAP
VALVE FLAPS
H-4a
10
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Reference ID: 4327567
H Assembling your Lamira Handset - continued
Step H5: Insert the Aerosol Head
H-5a
Note: It is important that you do not touch the
silver part of the Aerosol Head at any time
during assembly. (H-5a)
H-5b
Check to make sure the Aerosol Head is labeled
“For Amikacin Liposome Inhalation Suspension”.
Do not use other eFlow Technology Aerosol
Heads in the Lamira. (H-5b).
Carefully grasp the Aerosol Head by the 2 flexible
plastic tabs on each side of the Aerosol Head.
Turn the Aerosol Head so that “For Amikacin
Liposome Inhalation Suspension” is facing toward
you and is at the top of the Aerosol Head (H-5b).
MEDICATION RESERVOIR WITH 4 HOLES
FLEXIBLE PLASTIC
TABS
H-5c
Squeeze the two flexible plastic tabs together while
inserting the metal arms and flexible plastic tabs
into the Medication Reservoir (H-5c). You should
feel the flexible plastic tabs “grab” as you insert it.
H-6
Step H6: Close your Handset by pushing the Aerosol
Chamber together with the Medication Reservoir
until you hear a “snap” (H-6). If you do not hear a
snap, open the Handset and check that the Blue
Valve is seated properly (See Step H-4).
11
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Reference ID: 4327567
H Assembling your Lamira Handset - continued
Step H7: Attach Mouthpiece to your Handset. Make sure
the Blue Flap is facing up (H-7) and is pressed in
the slot on the Mouthpiece. Push the Mouthpiece
straight onto the Handset. Make sure the
Mouthpiece stays attached to the Handset during
treatment.
H-7
.
BLUE
FLAP
SLOT
Step H8: Attach the Connection Cord by lining up the
bottom of the Connector with the bottom of the
Handset (H-8a) and pushing the Connection Cord
upward against the rear underside of the Handset
(H-8b) until you hear the parts snap together.
H-8
H-8a
H-8b
SNAP
Step H9: Connect the Connection Cord to the Controller.
Push the round end of the Connection Cord into
the plug inlet port located under the digital display
(H-9). Place the Controller with the attached
H-9
Handset on a clean, flat, stable surface.
12
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Reference ID: 4327567
I Taking ARIKAYCE
Important information to know before you start
• If you use a bronchodilator (reliever), use the
bronchodilator first, before using ARIKAYCE. Refer to your
bronchodilator leaflet for information. The nebulizer for
ARIKAYCE should only be used for giving ARIKAYCE.
• Each vial of ARIKAYCE is for single (1 time) use only.
• Do not use ARIKAYCE with any other type of Handset or
Aerosol Head than the one provided in the carton.
• Do not put other medicines in the Lamira Nebulizer
Handset.
Your ARIKAYCE should be at room temperature before
use to make sure that your Lamira operates properly.
Bring ARIKAYCE to room temperature by removing it
from the refrigerator at least 45 minutes before use. Do
not use if your ARIKAYCE has been frozen.
• Do not drink the liquid in the vial.
• Do not use ARIKAYCE if the expiration date has passed.
Do not use other medicine in your handset.
Getting your ARIKAYCE ready before adding it to the Lamira
Nebulizer Handset.
I-1
Step I1: Shake the ARIKAYCE vial well for at least 10 to 15
seconds, until the medicine looks the same throughout
and well mixed (I-1).
Step I2: Lift orange cap from vial and throw away (dispose of)
the orange cap (I-2).
Step I3: Grip metal ring on top of the vial. Pull it down gently
(I-3) until 1 side breaks away from the vial (I-3a).
I-3a
I-3
I-2
Step I4: Pull the metal band from around the vial top in a
circular motion until it comes off completely from the
vial (I-4). Throw away (dispose of) the metal band after
it is removed.
Step I5: Carefully remove the rubber stopper by pulling it
upward (I-5).
I-5
I-4
Step I6: Make sure your Handset is placed on a clean, flat, stable
surface. Pour 1 vial of ARIKAYCE into the Medication
Reservoir (I-6). Do not use more than 1 vial for each
treatment.
I-6
MEDICATION RESERVOIR
13
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Reference ID: 4327567
I Taking ARIKAYCE (continued)
Step I7: Attach the Medication Cap by lining up the Tabs on
the Medication Cap with the Tab Slots on the
INNER CAP
Medication Reservoir (I-7). Turn the Medication Cap
clockwise until it stops. As the Medication Cap is
I-7
turned, the inner cap of the Medication Cap should rise.
TAB
TAB SLOT
Step I8: To begin your treatment, sit in a relaxed, upright
position. Press and hold the On/Off (2 to 3 seconds)
(I-8) until the start screen appears on the LCD display
(I-8a). You will also hear 1 “beep” and the status light
will turn green. The Lamira is now On.
ON/OFF BUTTON
I-8
STATUS LIGHT
LCD DISPLAY
After treatment begins, the treatment screen (I-8b) will
replace the start screen (I-8a) and aerosol mist will
begin to flow.
I-8a
I-8b
START SCREEN
TREATMENT
I-9
Step I9: Insert the Mouthpiece by placing it on top of your
bottom lip and tongue. Close your lips around the
Mouthpiece (I-9). Take slow, deep breaths then breathe
normally in and out through the Mouthpiece until your
treatment is complete. Your treatment should take
about 14 minutes, but could take up to 20 minutes.
14
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Reference ID: 4327567
I Taking ARIKAYCE (continued)
Hold the Handset level throughout your treatment.
If the Handset is held at an angle over 45 degrees (I
9a), it will sound 2 beeps (and 2 green lights) and shut
off after 30 seconds. If this occurs, hold the Handset
level and press the On/Off Button to start your
treatment again.
I-9a
Note: The Lamira can be stopped at any time during
operation by pressing the On/Off button for 3 seconds.
The screen will go from On (I-9b) to Pause (I-9c), a 5
beep alarm tone will sound, and the status light on the
Controller will flash Red-Green. To resume your
treatment, press the Controller On/Off button for 1 full
second. The Controller will run for up to 20 minutes. If
your treatment is not complete after 20 minutes, press
the On/Off button to continue treatment.
I-9c
I-9b
ON – with mist
PAUSE – no mist
Important Information:
The amount of time to nebulize your ARIKAYCE may change
from dose to dose and may become longer unless the
cleaning and maintenance instructions are followed (See
Maintaining Your Lamira).
I-10a
Step I10: At the end of your treatment, the following will
happen:
•
•
•
The Lamira will beep 2 times.
The LED will flash red 2 times.
The Dose Complete Checkmark will appear briefly
on the screen (I-10a).
•
The Controller will automatically shut off.
I-10b
I-10c
Always check the Medication Reservoir by removing
the Medication Cap (I-10b) to make sure you have
completed your dose. If more than a few drops of
ARIKAYCE remains, replace the Medication Cap
(I-10c) and press On/Off start button and complete
your dose.
Change your Aerosol Head after 7 uses. After the
Aerosol Head has been used 7 times, replace it with a
new Aerosol Head during the cleaning process. Follow
the instructions in Steps F6 through F9 and replace the
Aerosol Head with a new one.
Important: Clean and disinfect your Handset after
each use. See sections F and G for instructions.
Change your Aerosol Head after 7 uses.
15
Questions about Lamira? Contact the Arikares Support Program at 1-833-ARIKARE (1-833-274-5273)
Reference ID: 4327567
J
Frequently Asked Questions
QUESTION 1: How long should my ARIKAYCE treatment
take?
QUESTION 6: What if liquid is leaking from my Handset
during my treatment?
Answer: With normal operation and proper cleaning, your
Handset should deliver 1 vial of ARIKAYCE in about 14
minutes but could take up to 20 minutes. Your Lamira
should automatically shut off shortly after your treatment is
complete or after 20 minutes. If the Lamira turns off after
20 minutes, check the Medication Reservoir. If it is empty,
you have received your full dose.
Answer: To prevent leaks, be sure (1) the Blue Valve is
properly attached to the Aerosol Chamber, (2) the Aerosol
Head is inserted correctly, (3) the Medication Cap is
screwed on fully, and (4) the Medication Reservoir and
Aerosol Chamber are closed properly and snapped
together.
Answer: It is normal to have some liquid collect in the
Aerosol Chamber. Try to hold the Handset so that liquid
does not pour out of the Mouthpiece.
QUESTION 2: How much ARIKAYCE should be left in
the Medication Reservoir at the end of my
treatment?
Answer: Only a drop of ARIKAYCE should remain in the
Medication Reservoir. If more than a drop remains, start
the Controller and complete your dose. Then clean the
Aerosol Head (Section F). If after proper cleaning, more
than a drop remains in the Medication Reservoir, contact
the Arikares Support Program at 1-833-ARIKARE (1-833
274-5273).
QUESTION 7: What if my Controller shuts off before my
treatment begins, or does not restart?
Answer: Low voltage. Replace the batteries or use
the AC adapter. Press the On/Off button to continue
your treatment.
Answer: Your Handset was tilted above 45°. Hold
your Handset level and press the On/Off button to
continue your treatment.
Answer: ARIKAYCE is cold. Allow the ARIKAYCE to
warm to room temperature and then press the On/Off
button to continue your treatment.
QUESTION 3: When I turn on my Nebulizer, nothing
happens. There does not seem to be any power.
Answer: If you are using batteries, use the figures in each
Battery Compartment to check that the batteries are
inserted correctly. If the batteries are positioned properly,
check to see if the light is blinking on the Controller
signaling low battery power. If it is, replace the batteries or
use the A/C Power Supply.
QUESTION 8: What if my Controller does not shut off at
the end of my treatment?
Answer: Your Controller may take up to 60 seconds to
shut off after you complete your dose. If you wish to stop
your Controller earlier, press the On/Off button.
Answer: If you are using the A/C Power Supply, check
the connection to be sure it is firmly connected to the
Power Supply Port located underneath the Battery
Compartment.
Answer: Disconnect the A/C Power Supply from the
Controller and remove the batteries. Then, reinsert the
Batteries following the procedure in Section D.
Be sure that the A/C Power Supply is plugged into a
working wall outlet.
Answer: If this situation continues 3 or 4 times, contact
the Arikares Support Program at 1-833-ARIKARE (1
833-274-5273).
QUESTION 4: Sometimes I have trouble removing the
Medication Cap at the end of my therapy session.
Answer: A vacuum has formed in the Medication
Reservoir. Remove the Connection Cord, open the
Handset and carefully remove the Aerosol Head. The
Medication Cap will then be easier to remove.
QUESTION 9: How long will a new set of batteries last?
Answer: A new set of batteries should provide 2 hours
of total use.
Answer: Consider using rechargeable batteries.
QUESTION 5: What if no mist is coming out of your
Handset?
QUESTION 10: What if something arrives damaged?
Answer: Contact the Arikares Support Program at 1-833
Answer: First, check that the Controller has power.
Secondly, make sure the Connection Cord is correctly
attached. Thirdly, check to be sure that your Handset
has been assembled properly (Section H). Lastly, check
to be sure that the ARIKAYCE is in the Medication
Reservoir. If the Controller or your Handset still do not
function properly, contact the Arikares Support Program
at 1-833-ARIKARE (1-833-274-5273).
ARIKARE (1-833-274-5273).
16
Questions about Lamira? Contact the Arikares Support Program at 1-833-ARIKARE (1-833-274-5273)
Reference ID: 4327567
Troubleshooting
K
Fault and Condition
Possible Cause and Solution
1
Controller running on AC Power.
Steady
2
3
4
Steady
Controller running on battery power.
Flashing
Flashing
Empty battery, replace batteries or switch to A/C power.
Low battery, replace batteries or switch to A/C power.
The LED changed from green to red and the battery
symbol is blinking during treatment
5
6
Bad or missing Connection Cord. Check Connection Cord between
Handset and Controller. Bad or missing Aerosol Head. Correct then
restart Controller.
Flashing
Lamira turns on but LED flashes green-red and LCD
display flashes this symbol
Flashing
No ARIKAYCE detected. Add ARIKAYCE. If you have already added
ARIKAYCE, gently tap the Handset, hold the Handset level and restart
the Controller.
Lamira beeps 1x, then beeps highlow with the LED
flashing and the LCD display flashing this symbol
7
8
Flashing
Have reached 20 minute maximum time and will shut down. If
ARIKAYCE remains, restart the Controller. After treatment is
complete, clean and disinfect the Handset including the Aerosol Head.
Lamira beeps low-high 3 times, the LED flashed green-
red, the LCD displays this symbol, and then turns off
Steady
Misting and working properly.
Lamira beeps 1 time and LCD shows this symbol
9
Steady
Controller has paused. To resume press On/Off button.
Press button to start treatment.
10
Flashing
11
Brief
Functioning properly, the Controller has started properly.
17
Questions about Lamira? Contact the Arikares Support Program at 1-833-ARIKARE (1-833-274-5273)
Reference ID: 4327567
K
Troubleshooting (continued)
Fault and Condition
Possible Cause and Solution
12
Brief
No ARIKAYCE remaining, your treatment is done.
If ARIKAYCE is remaining, your Handset might be tilted. Keep
Handset level, gently tap Handset and restart Controller.
The Lamira beeps 2 times, displays this checkmark
symbol then turns off.
13
14
The Lamira cannot be activated and no green LED, no
screen, and no beep.
Bad, missing or misloaded batteries.
Bad or missing A/C Power Supply.
The Lamira beeps 1 time and begins to produce a mist,
Bad batteries or bad A/C Power Supply. Replace batteries or A/C
then stops and shuts off with no beep, no LED, and with Power Supply and restart Controller.
ARIKAYCE still present.
15
The Lamira stops before ARIKAYCE is completely used Lost power. Replace batteries or use A/C Power Supply.
up.
Tilted Handset. Keep Handset level, gently tap Handset and restart
Controller.
16
17
The Lamira does not stop automatically after all
ARIKAYCE is consumed
Clean and disinfect the Aerosol Head. If condition continues, contact
the Arikares Support Program at 1-833-ARIKARE (1-833-274-5273).
Longer than normal nebulization time.
Aerosol Head is dirty. Clean and disinfect the Aerosol Head. Replace
the Aerosol Head with a new one from your kit after 7 uses.
18
Handset leaks.
Make sure Blue Valve is placed correctly in the Handset and the 2
flaps point into the Handset Chamber (see Section H).
Make sure Aerosol Head is correctly placed in the Handset.
It is normal to have some liquid collect in the Aerosol Chamber and
Mouthpiece. The amount depends on the volume of the ARIKAYCE
and on your breathing pattern.
19
The On button was accidently pressed for 10 seconds, which
activated the easycare function. The easycare is an accessory that
assists in cleaning the Aerosol Head but it is not used for your Lamira.
Press the On button briefly to turn-off the Controller and stop the
easycare function.
18
Questions about Lamira? Contact the Arikares Support Program at 1-833-ARIKARE (1-833-274-5273)
Reference ID: 4327567
Specifications
L
Mechanical
Weight: Controller and Handset................................................................................................................ approx. 8.2 oz.
Weight: Controller, Handset, and Batteries............................................................................................... approx. 11 oz.
Handset Dimensions (W x H x D)............................................................................................................. 2.0" X 2.4” X 5.5"
Controller Dimensions (H x Ø) ................................................................................................................. 1.6” X 4.6"
Minimum Fill Volume ............................................................................................................................... 0.5 mL
Maximum Fill Volume .............................................................................................................................. 8.4 mL
Electrical
Electrical Requirements .............................................................................................................. 110 V - 240 V, 50 Hz/60 Hz
Power Wattage ........................................................................................................................... 2.0 Watts under normal load
Transport and Storage
Temperature............................................................................................................................................. -13° to 158° F
Relative Humidity (non-condensing)......................................................................................................... 0% to 93%
Air Pressure.............................................................................................................................................. 9 to 15 PSI
Operational
Temperature............................................................................................................................................. 41° to 104° F
Relative Humidity (non-condensing)......................................................................................................... 15% to 93%
Air Pressure.............................................................................................................................................. 10 to 15 PSI
Device Classification According to IEC 60601-1
Type of electric shock protection (AC power adapter).............................................................................. Protection Class II
Degree of protection from electric shock of part used (nebulizer) ............................................................ Type BF
Degree of protection against water ingress per IEC 60529 IP rating (nebulizer)...................................... IP 21
Degree of protection when in the presence of flammable mixtures.......................................................... No protection
Continuous operation................................................................................................................................ Operating mode
Device Performance Characteristics
Mean
312.1
52.9
Range
a
Total Delivered Dose by Breath Simulation
Total Delivered Dose by Breath Simulation (% of label claim
by NGI
b
(mg)
273.8 – 350.4
46.4 – 59.4
4.38 – 4.52
1.59 – 1.60
316.5 – 337.6
53.8 – 57.4
c
)
MMAD
d
e
(µm)
4.45
GSD
f
1.59
327.1
55.6
Respiratory Dose by NGI (≤ 5µm, mg)
Respiratory Fraction by NGI (≤5µm, % of delivered dose)
Range - two-sided tolerance interval, proportion of total population=0.95
Breath simulation - tidal volume of 500 mL, 15 breath per minutes, and inhalation:exhalation ratio is 50:50
label claim - 590 mg
a
b
c
d
e
f
MMAD - Mass Median Aerodynamic Diameter
NGI - Next Generation Impactor
GSD - Geometric Standard Deviation
Handset materials
Polypropylene, polyamide, silicone, stainless steel, thermoplastic elastomers. Does not contain any natural rubber (latex).
Disposal
The Lamira components and batteries must be disposed of in accordance with local (state, county or municipal) regulations.
Manufactured by:
PARI Respiratory Equipment, Inc.
2412 PARI Way
Midlothian, Virginia 23112 USA
For patent information: www.PARI.com/ip
©2018 PARI Pharma GmbH. All rights reserved. The PARI logo is a registered trademark of PARI GmbH. Altera®, eRapid®, and eFlow® logo are registered trademarks of PARI
Pharma GmbH. Lamira™ is a trademark of PARI Pharma GmbH. ARIKAYCE is a registered trademark of Insmed Incorporated.. Touchspray® made under license from the Technology
Partnership.
This Instructions for Use has been approved by the U.S. Food and Drug Administration
678D0204 Draft Rev 18a 9/18
19
Questions about Lamira? Contact the Arikares Support Program at 1-833-ARIKARE (1-833-274-5273)
Reference ID: 4327567
