amikacin liposome inhalation (Rx)

>10%

Dysphonia (47%)

Cough (39%)

Bronchospasm (29%)

Hemoptysis (18%)

Ototoxicity (17%)

Upper airway irritation (17%)

Musculoskeletal pain (17%)

Fatigue and asthenia (16%)

Exacerbation of underlying pulmonary disease (15%)

Diarrhea (13%)

Nausea (12%)

1-10%

Pneumonia (10%)

Headache (10%)

Pyrexia (7%)

Vomiting (7%)

Rash (6%)

Weight decreased (6%)

Change in sputum (5%)

Chest discomfort (5%)

Anxiety (4.5%)

Oral fungal infection (4%)

Bronchitis (3.6%)

Hypersensitivity pneumonitis (3.6%)

Dysgeusia (3.1%)

Respiratory failure (2.7%)

Epistaxis (2.7%)

Neuromuscular disorder (2.2%)

Dry mouth (2.2%)

Pneumothorax (2.2%)

Exercise tolerance decreased (1.3%)

Balance disorder (1.3%)

Contraindications

Hypersensitivity to any aminoglycoside

Cautions

Hypersensitivity pneumonitis (eg, allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction) reported; if hypersensitivity pneumonitis occurs, discontinue drug and manage as medically appropriate

Hemoptysis reported; if hemoptysis occurs, manage as medically appropriate

Bronchospasm (eg, asthma, bronchial hyperreactivity, bronchospasm, dyspnea, exertional dyspnea, prolonged expiration, throat tightness, wheezing) reported; if bronchospasm occurs, treat as medically appropriate

Exacerbations of underlying pulmonary disease (eg, chronic obstructive pulmonary disease, infective exacerbation of chronic obstructive pulmonary disease, infective exacerbation of bronchiectasis) reported in clinical trials; if exacerbations of underlying pulmonary disease occur, treat as medically appropriate

Nephrotoxicity observed during clinical trials in patients with MAC lung disease; nephrotoxicity has been associated with the antimicrobials#aminoglycosides; closely monitor patients with known or suspected renal dysfunction

Patients with neuromuscular disorders were not enrolled in clinical trials; closely monitor patients with known or suspected neuromuscular disorders (eg, myasthenia gravis) since antimicrobials#aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions

Fetal harm may occur when administered to a pregnant woman (see Pregnancy)

Ototoxicity

• Ototoxicity (eg, deafness, dizziness, presyncope, tinnitus, vertigo) reported in clinical trials; closely monitor patients with known or suspected auditory or vestibular dysfunction; ototoxicity may occur in some patients even when their aminoglycoside serum levels are within recommended range
• Mitochondrial DNA variants are present in <1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as severity of ototoxicity is unknow
• In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than antimicrobials#aminoglycosides unless increased risk of permanent hearing loss is outweighed by severity of infection and lack of safe and effective alternative therapies

Drug interactions overview

• Avoid use with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity
• Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue; avoid use with ethacrynic acid, furosemide, urea, or IV mannitol

Pregnancy

There are no data on 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, systemic exposure to aminoglycoside antibacterial drugs, including inhaled amikacin, may be associated with total, irreversible, bilateral congenital deafness when administered to pregnant women

Advise pregnant women of the potential risk to a fetus

Animal data

• Animal reproductive toxicology studies have not been conducted with inhaled amikacin
• SC 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

Lactation

There is no information regarding presence of inhaled amikacin in human milk, effects on the breastfed infant, or effects on milk production

Although limited published data on other routes of administration indicate that amikacin is present in human milk, systemic absorption following inhaled administration is expected to be low

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need and any potential adverse effects on the breastfed child or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Bactericidal aminoglycoside enters bacterial cell by disrupting overall cell wall architecture

Disrupts and inhibits protein synthesis in target bacteria by binding to the 30S ribosomal subunit

Mechanism of resistance to amikacin in Mycobacteria linked to mutations in rrs gene of the 16S rRNA

Absorption

Bioavailability is expected to vary primarily from individual difference in nebulizer efficiency and airway pathology

Sputum concentrations (1-4 hr post inhalation): 1720 mcg/g (1 month), 884 mcg/g (3 months), and 1300 mcg/g (6 months)

Peak plasma concentration: 2.8 mcg/mL AUC: 23.5 mcg·hr/mL

After 48-72 hr post inhalation, amikacin sputum concentrations decreased to ~5% of those at 1-4 hr post inhalation

Distribution

Protein bound: ≤10%

Metabolism

Does not undergo appreciable metabolism

Elimination

Half-life: 5.9-19.5 hr

Excretion: Urine (7.42%, unchanged)

Systemically absorbed amikacin following administration is eliminated principally via glomerular filtration

Unabsorbed amikacin, following inhalation, is probably eliminated primarily by cellular turnover and expectoration

Oral Inhalation Preparation

Suspension should be at room temperature before use

Shake vial well for at least 10-15 seconds until contents appear uniform and well mixed

Pour suspension into medication reservoir of nebulizer handset

Oral Inhalation Administration

For oral inhalation use only

Administer by nebulization only with Lamira Nebulizer System (refer to prescribing information)

If patient also uses a bronchodilator, instruct them to first use bronchodilator (according to bronchodilator instructions) before using amikacin liposome inhalation

Consider pretreatment with short-acting selective beta-2 agonists for patients with known hyperreactive airway disease, chronic obstructive pulmonary disease, asthma, or bronchospasm

Missed dose: Administer next dose the next day; do not double dose to make up for missed dose

Storage

Refrigerate 2-8°C (36-46°F) until expiration date on vial; do not freeze

May be stored at room temperature (up to 25°C [77°F]) for up to 4 weeks

Once at room temperature, discard any unused drug at end of 4 weeks