Amikacin (Oral Inhalation)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Inhalation, as sulfate:

Arikayce: 590 mg/8.4 mL (8.4 mL)

Pharmacology

Mechanism of Action

Inhibits protein synthesis in susceptible bacteria by binding to 30S ribosomal subunits

Pharmacokinetics/Pharmacodynamics

Absorption

Variable

Excretion

Urine (7.42% as unchanged drug)

Half-Life Elimination

~5.9 to 19.5 hours

Protein Binding

≤10%

Use: Labeled Indications

Mycobacterium avium complex: Treatment of Mycobacterium avium complex (MAC) lung disease in adults who have limited or no alternative treatment options, 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.

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

Contraindications

Hypersensitivity to aminoglycosides

Dosage and Administration

Dosing: Adult

Mycobacterium avium complex: Inhalation: One vial (590 mg) once daily

Dosing: Geriatric

Refer to adult dosing.

Administration

Inhalation: To be inhaled using the Lamira Nebulizer System over 14 to 20 minutes. Vial should be at room temperature prior to use (if refrigerated, remove at least 45 minutes before use). Shake vial for at least 10 to 15 seconds (until contents appear uniform and well mixed) prior to opening. Refer to the manufacturer's labeling for detailed administration instructions using the nebulizer system. Patients instructed to also use a bronchodilator should administer the bronchodilator prior to using the nebulizer.

Storage

Store vials at 2°C to 8°C (36°F to 46°F); do not freeze. May be stored at room temperature (≤25°C [77°F]) for up to 4 weeks.

Drug Interactions

Loop Diuretics: May enhance the nephrotoxic effect of Amikacin (Oral Inhalation). Loop Diuretics may enhance the ototoxic effect of Amikacin (Oral Inhalation). Monitor therapy

Mannitol (Systemic): Amikacin (Oral Inhalation) may enhance the nephrotoxic effect of Mannitol (Systemic). Avoid combination

Adverse Reactions

>10%:

Central nervous system: Voice disorder (47%), fatigue (≤16%), headache (10%)

Gastrointestinal: Diarrhea (13%), nausea (12%)

Neuromuscular & skeletal: Musculoskeletal pain (17%), asthenia (≤16%)

Otic: Ototoxicity (17%)

Respiratory: Cough (39%), bronchospasm (29%), hemoptysis (18%), upper airway symptoms (17%), exacerbation of pulmonary symptoms (15%), pneumonia (10%)

1% to 10%:

Cardiovascular: Chest discomfort (5%)

Central nervous system: Dizziness (6%), anxiety (5%), equilibrium disturbance (1%)

Dermatologic: Skin rash (6%)

Endocrine & metabolic: Weight loss (6%)

Gastrointestinal: Vomiting (7%), oral candidiasis (4%), dysgeusia (3%), xerostomia (2%)

Neuromuscular & skeletal: Neuromuscular symptoms (2%)

Otic: Tinnitus (8%)

Respiratory: Change in bronchial secretions (5%), bronchitis (4%), hypersensitivity pneumonitis (3% to 4%), epistaxis (3%), respiratory failure (3%), pneumothorax (2%)

Miscellaneous: Fever (7%), decreased exercise tolerance (1%)

Frequency not defined: Genitourinary: Nephrotoxicity

Warnings/Precautions

Concerns related to adverse effects:

• Bronchospasm: Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, exertional dyspnea, prolonged expiration, throat tightness, wheezing) has been reported; manage as medically appropriate.
• Hemoptysis: Hemoptysis has been reported; manage as medically appropriate.
• Hypersensitivity pneumonitis: Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction) has been reported; manage as medically appropriate.
• Nephrotoxicity: Nephrotoxicity has been reported with aminoglycosides; use with caution in patients with known or suspected renal dysfunction.
• Ototoxicity: Ototoxicity (including deafness, dizziness, presyncope, tinnitus, vertigo) has been reported. Use with caution in patients with known or suspected auditory or vestibular dysfunction; if ototoxicity occurs, manage as medically appropriate.

Disease-related concerns:

• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.
• Pulmonary disease: Exacerbation of underlying pulmonary disease (reported as chronic obstructive pulmonary disease, infective exacerbation of chronic obstructive pulmonary disease, infective exacerbation of bronchiectasis) has been reported; manage as medically appropriate.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy

Pregnancy Considerations

Aminoglycosides may cause fetal harm if administered to a pregnant woman. Systemic absorption of amikacin following oral inhalation is expected to be low compared to intravenous administration; however, systemic exposure was associated with total irreversible bilateral congenital deafness in children whose mothers received a different aminoglycoside during pregnancy.

Refer to the Amikacin (Systemic) monograph for details.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience voice changes, sore throat, mouth irritation, muscle pain, joint pain, back pain, loss of strength and energy, diarrhea, nausea, vomiting, headache, weight loss, or increased sputum. Have patient report immediately to prescriber signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), coughing up blood, fast breathing, change in balance, dizziness, passing out, noise or ringing in the ears, hearing loss, hearing changes, difficulty speaking, or chest pain (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.