Overview:
Amikacin liposome inhalation suspension (ALIS) is widely employed for mycobacterial infections triggered by a specific category of nontuberculous mycobacteria. The United States drug regulatory body, the Food and Drug Administration (FDA), endorsed the usage of Amikacin liposome inhalation suspension for nontuberculous mycobacterial infections on 28th September 2018. FDA-authorized Amikacin through a limited population pathway was the first medication to be granted an FDA license through this pathway.
Drug Group:
Amikacin falls under the drug class of aminoglycoside antibiotics, which can kill bacteria by disrupting the vital process in the bacterial cell. These drugs are generally employed to tackle grave infections in the body and, hence, are widely recommended.
Available Doses and Dosage Forms:
Amikacin liposome inhalation suspension, as the name suggests, is marketed as a suspension (liquid) intended to be administered into the body through an inhalational route. Amikacin liposome inhalation suspension is marketed in a specific concentration of 590 milligrams (mg) of Amikacin in 8.4 milliliters (mL) of suspension.
For Patients:
What Is Nontuberculous Mycobacteria?
Nontuberculous mycobacteria are a specific category of mycobacteria, excluding Mycobacteria tuberculosis and Mycobacteria leprae, that can infect anybody with compromised immune status. These opportunistic bacteria can bring alarming health complications when exposed to a susceptible body. In contrast, a healthy immunocompetent body remains dormant without inflicting any health issues.
Individuals with severely depleted immune status or respiratory issues are prone to infection by nontuberculous mycobacteria. The infections triggered by nontuberculous mycobacteria are collectively regarded as nontuberculous mycobacterial infections. Lungs are the primary target organ of nontuberculous mycobacteria. Fever, short breath, weight loss, fatigue, night sweats, bloody sputum, cough, decreased appetite, and atypical skin rashes are the frequently elicited manifestations associated with nontuberculous mycobacterial infections.
How Does Amikacin Liposome Inhalation Suspension Work?
Amikacin liposome inhalation suspension is designed to deliver the drug molecules directly to the lungs, the primary target site for nontuberculous mycobacteria. In Amikacin liposome inhalation suspension, each Amikacin molecule is encapsulated by liposomes (lipid spheres). These liposomes operate as a carrier for the drug molecule and aid its trajectory to the target area in the lungs. Amikacin molecules will be freed and liberated from the liposome capsules upon encountering the mycobacterium. Amikacin interrupts the protein synthesis in the nontuberculous mycobacteria, eventually resulting in bacterial death. In this way, Amikacin kills the nontuberculous mycobacteria in its target location.
What Is the Dose of Amikacin Liposome Inhalation Suspension?
590 milligrams of Amikacin is the recommended daily dosage for an adult patient. 8.4 milliliters of the inhalational suspension formulation is marketed as a single inhalation dosage unit, which accounts for 590 milligrams of Amikacin. It is supposed to be taken only through oral inhalation in the form of nebulization. Look into the formulation package for the right choice of nebulizer for that particular drug brand.
How Effective Is Amikacin Liposome Inhalation Suspension?
Amikacin liposome inhalation suspension is a highly efficacious therapeutic intervention against nontuberculous mycobacteria. Inhalational suspension formulation facilitates drug delivery at the lung's target point. The Amikacin molecules are safely carried and released only at the intended site of mycobacterial colonization. This form of targeted drug delivery potentiates the efficacy of Amikacin and ensures prompt destruction of the mycobacterium. Furthermore, it also enables sufficient concentration of Amikacin to reach the intended target point with limited drug exposure into the systemic circulation. Amikacin liposome inhalation suspension formulation curbs the possibility of severe side effects that are generally precipitated following systemic (pills and injections) antibiotic therapies.
What Are the Things to Inform the Doctor Before Taking the Drug?
Before initiating any pharmacological therapy, a thorough understanding of the patient’s medical background and health status is critical.
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Patients should inform the doctor about any prior allergic encounter with Amikacin liposome inhalation suspension or other drugs of the same class. Prior hyper-reactivity with any of the components present in the Amikacin liposome inhalation suspension should also be reported to the doctor as it carries the potential risk of allergy following Amikacin liposome inhalation suspension use.
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A detailed medical history of the patient is another important thing that the doctor must be made aware of. The medical history needs to be highly comprehensive, detailing all the previous ailments that the person suffered from, underlying medical conditions, health challenges, and surgeries undergone or plans to undertake.
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Besides the medical history, the doctor must thoroughly understand the patient’s drug history. Drug history should encompass all medicines, whether dietary supplements, over-the-counter, herbal, or alternative. Understanding the patient's drug history aids the doctors in optimal drug choice, thus minimizing the possibility of adverse drug-drug associations.
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The doctors should be made aware of the pregnancy and lactating status of the patient. Certain drugs can bring complications in pregnant women, bringing harm to the baby in the womb (fetus). Similarly, when a nursing woman undergoes any drug therapy, there are chances for the medicine to gain access to the baby’s body through breastmilk, which can result in adverse effects on the baby’s body.
How Is Amikacin Liposome Inhalation Suspension Administered?
Amikacin liposome inhalation suspension should only be administered through the oral inhalation route. Nebulizer converts the suspension formulation into fumes to enter the breathing tract. Amikacin liposome inhalation suspension is marketed under different brand names; each brand advises its own choice of nebulizer that should be used. Ensure that the medicine formulation is brought to room temperature before administration. Before dispensing the inhalation suspension formulation into the nebulizer unit, agitate the suspension by gentle shaking motion for 15 to 20 seconds, which ensures homogeneity in the suspension. Overturning the drug vials' plastic knob opens the medicine. Following this, the stopper can be easily taken out, and the medicine can be expressed into the medication reservoir.
What Are the Side Effects of Amikacin Liposome Inhalation Suspension?
Like any other medication, Amikacin liposome inhalation suspension does precipitate certain side effects during therapy. Some of the frequently reported side effects concerning Amikacin liposome inhalation suspension include the following:
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Sore throat, cough, chest discomfort, troubled breathing, hemoptysis (coughing up blood), noisy breathing (wheezing), and voice change are some routinely reported side effects.
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Fever, ear discomfort, compromised hearing, and challenges in body balance also often accompany Amikacin liposome inhalation therapy.
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Patients with preexisting lung conditions elicited an abrupt exacerbation following therapy with Amikacin liposome inhalation suspension.
In cases of severe breathing issues or an allergic response, immediate medical care should be sought.
Dietary Considerations:
No dietary considerations must be followed during therapy using Amikacin liposome inhalation suspension. However, each patient’s health status may differ, and the doctor may sometimes advise certain dietary regulations that must be followed.
Missed Dose:
In case the person misses the daily inhalational dose, it is better advised to proceed with the subsequent day dosing. No dose or dosing frequency alteration should be made without the doctor’s advice.
Overdose:
No overdose-specific health hazard has been reported to date. Following acute toxicity, supportive measures should be employed to extract the excess Amikacin concentration from the body. The poison control center needs to be immediately contacted following an event of symptomatic overdose.
Storage:
Amikacin liposome inhalation suspension is marketed in glass vials, and the formulation should be stored until administration. Two to eight degrees Celsius (36 to 46 degrees Fahrenheit) is the preferred storage temperature for the inhalation suspension; therefore, it should be refrigerated to preserve the therapeutic efficacy of the formulation. The Amikacin liposome inhalation suspension remains safe for four weeks, even at room temperature. However, inhalation formulations kept under room temperature for over four weeks are not recommended.
For Doctors:
Indications:
Amikacin liposome inhalation suspension is indicated for a specific category of patients with nontuberculous mycobacterial infections, particularly of Mycobacterium avium complex (MAC), who exhibit resistance to other treatment choices. It is indicated for tackling refractory lung conditions triggered by Mycobacterium avium complex for a limited adult population who fail to achieve desired treatment outcomes with other standard antibiotic regimens for at least six months.
Dose:
The preferred daily dose is 590 mg of Amikacin liposome inhalation suspension. 8.4 milliliter (ml) of the inhalation formulation can deliver 590 milligrams of Amikacin. It is advised as a single dose, where 8.4 ml of the suspension formulation is dispensed into the nebulizer for inhalational administration.
Dosing Considerations:
For patients undergoing bronchodilator therapy, inhalational administration of the Amikacin liposome formulation should be given only after bronchodilator administration. In case of confusion, the time lapse between the two drug administrations should be clarified with the doctor.
Individuals with lung diseases like asthma and hyperreactive airway disease are more likely to precipitate complications during inhalational therapy. Therefore, such patients are prophylactically given selective beta-2 agonists (short-acting) to curb unintended respiratory complications.
What Are the Pharmacological Aspects of Amikacin Liposome Inhalation Suspension?
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Mechanism of Action: Amikacin liposome inhalation suspension works to tackle various lung conditions triggered by nontuberculous mycobacterium. Amikacin liposome inhalation suspension bears the added benefit of Amikacin and liposome. Amikacin, an aminoglycoside, disrupts the vital process in the bacterial cell, eventually bringing about bacterial death. The liposomal component in the inhalation formulation contributes to promptly delivering the Amikacin drug molecule to the target point. Liposome encapsulates the Amikacin and functions as a carrier. Liposomal encapsulation facilitates the targeted delivery. Thus, the Amikacin molecules gain access to the alveolar macrophage with the enhanced penetrative ability offered by the liposomal encapsulation. This allows the Amikacin to attain appreciable concentration at the target point with minimal possibility for systemic exposure.
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Pharmacodynamics: Amikacin liposome inhalation formulation exhibits an enhanced effectivity with minimal adverse effects. Amikacin liposomal combination can remarkably pierce the macrophages in the lungs infected with the nontuberculous mycobacterium. In addition, it also exhibits enhanced retention of the Amikacin molecule in the targeted site, thus protracting the antibacterial properties for a significant duration.
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Pharmacokinetics: Following inhalational therapy of Amikacin liposome inhalation suspension, the Amikacin liposome complex gains access to the lung tissues, where the liposomal component expels the Amikacin molecules gradually. The drug distribution is primarily restricted within the lung tissue, aided by the liposomal component. These drug molecules immediately act upon the alveolar macrophage infected with nontuberculous mycobacterium. Amikacin exhibits limited metabolism in the body; a major proportion of the drug molecule remains in the lung, contributing to extended bactericidal properties. However, some Amikacin molecules that gain access into the circulation get eliminated through the urinary route following renal metabolism.
Toxicity:
Administration of more than the intended dosage of the inhalation suspension can bring toxicity issues. Only limited information is available concerning the toxicity profile of Amikacin liposome inhalation suspension. Immediate medical attention needs to be sought in the event of overdosage.
Clinical studies in humans have not demonstrated the carcinogenicity, genotoxicity, and mutagenicity aspects of Amikacin liposome inhalation suspension. However, in vivo and in vitro studies could not expose any remarkable genotoxicity issues concerning Amikacin liposome inhalation therapy. Animal studies have reported instances of carcinogenic changes. The inhalational therapy’s impact on fertility is unknown and needs to be exposed more to establish a conclusion.
Clinical Studies:
Randomized clinical studies have been conducted to demonstrate the potency and safety profile concerning Amikacin liposome inhalation suspension. Patients detected with the refractory form of lung diseases triggered by Mycobacterium avium complex were chosen as subjects. Smoking and treatment status were employed to stratify the subject group further. The study reports suggested that patients trialed with Amikacin liposome inhalational therapy flagged appreciably faster negative sputum culture conversion than those administered the conventional therapy regimen.
What Are the Contraindications of Amikacin Liposome Inhalation Suspension?
Amikacin liposome inhalation suspension is not supposed to be advised for patients who have had prior hypersensitivity responses towards Amikacin or other medications of the same or related drug class.
Warnings and Precautions:
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Worsening Lung Disease: Amikacin liposome inhalation therapy in the presence of pre-existing lung conditions can bring about abrupt worsening of the lung condition. Therefore, while advising Amikacin liposome inhalational treatment for an individual with preexisting pulmonary issues, periodic monitoring is warranted to check for exacerbation. Underlying conditions like bronchiectasis, chronic obstructive pulmonary disease, and bronchospasm are some of the lung conditions that were reported to flag exacerbation following Amikacin liposome inhalational therapy.
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Hemoptysis: There are reports of hemoptysis in patients undergoing therapy using Amikacin liposome inhalation suspension. Therefore, the patient should be informed about this beforehand. In the event of hemoptysis, immediate therapeutic intervention needs to be sought.
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Hypersensitivity Pneumonitis: Certain studies reported hypersensitivity pneumonitis in patients who underwent inhalational therapy using Amikacin liposome inhalation suspension. As soon as hypersensitivity pneumonitis is identified, the patient should be immediately withdrawn from Amikacin liposome inhalational therapy.
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Ototoxicity Issues: Amikacin liposome inhalational therapy is known to trigger severe ear problems. Tinnitus, presyncope, vertigo, deafness, and dizziness are some of the frequently reported ear issues during Amikacin liposome inhalational therapy. Ototoxicity issues are more palpable in individuals with an underlying predisposition for ear issues, which requires thorough auditory assessment.
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Bronchospasm: At times, Amikacin liposome inhalational therapy may also precipitate bronchospasm, wheezing, bronchial hyperreactivity, and dyspnea. During the therapy course, appropriate medical intervention should be advised for those detected with bronchospasms.
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Fetal Harm: Amikacin, being an aminoglycoside, holds the potential for fetal harm when administered to a pregnant woman. Hence, the patient should be cautioned about Amikacin’s ability for fetal harm. Appropriate birth control measures should be advised to check unintended pregnancy during the therapy.
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Check Neurotransmitter: Therapy using Amikacin liposome inhalation suspension in patients with existing neuromuscular illnesses can check neurotransmitter discharge, which enhances muscular weakening.
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Nephrotoxicity: Caution should be employed while advising Amikacin liposome inhalation therapy to patients with compromised kidney functioning.
What Are the Drug Interactions of Amikacin Liposome Inhalation Suspension?
Certain drugs are reported to interact with Amikacin liposome inhalation suspension. Simultaneous intake of such drugs brings about undesired impacts on the body. Simultaneous administration of Amikacin liposome inhalation suspension with Furosemide or Ethacrylic acid can result in an appreciable hike in the Amikacin concentration, potentially enhancing the risk for toxicity. Drugs that are known to precipitate ototoxicity, neurotoxicity, and nephrotoxicity should never be coupled with Amikacin liposome inhalation therapy, as this combination is capable of further worsening these toxicity issues.
Specific Considerations:
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Amikacin Liposome Inhalation Suspension During Pregnancy: Amikacin liposome inhalation suspension is generally not advised for pregnant women. Amikacin’s systemic exposure can bring in serious fetal harm. Though it is an inhalational therapy, there are chances for minor systemic exposure. Therefore, the possibility for fetal harm does stand evident with Amikacin liposome inhalation therapy.
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Amikacin Liposome Inhalation Suspension During Lactation: No conclusive evidence demonstrates Amikacin’s presence in the breast milk following maternal exposure to inhalational therapy using Amikacin liposome inhalation suspension. However, systemically administered Amikacin is detected in the mother’s breast milk following maternal therapy. Therefore, before advising the medicine, a thorough assessment of the potential risk and maternal need for inhalational therapy is warranted.
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Amikacin Liposome Inhalation Suspension in the Pediatric Population: Amikacin liposome inhalation suspension has limited application and is not advisable for the pediatric population. Only the adult population over 18 years is considered for inhalational therapy.
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Amikacin Liposome Inhalation Suspension in the Geriatric Population: The therapeutic efficacy of Amikacin liposome inhalation therapy in the geriatric population was more or less comparable with that of the adult population. However, the functional status of the kidney and liver needs to be periodically assessed in geriatric patients as they are more susceptible to kidney and liver dysfunctions.
