Tobi

Description

TOBI® is a sterile solution of tobramycin for inhalation, presented as a clear, slightly yellow, non-pyrogenic aqueous solution. The formulation is specifically adjusted for pH and salinity to facilitate administration via a compressed air-driven reusable nebulizer. The chemical formula of tobramycin is C18H37N5O9, with a molecular weight of 467.52 g/mol.

Each single-dose 5 mL ampoule contains 300 mg of tobramycin and 11.25 mg of sodium chloride, dissolved in sterile water for injection. The pH of the solution is adjusted to 6.0 using sulfuric acid and sodium hydroxide, while nitrogen is employed for sparging. All components of the formulation comply with USP standards, and the product is free from preservatives.

Uses and Indications

This drug is indicated for the management of cystic fibrosis in adults and pediatric patients aged 6 years and older who are infected with Pseudomonas aeruginosa.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

The medication is intended for oral inhalation only. The recommended dosage for adults and pediatric patients aged 6 years and older is one single-dose ampoule (300 mg) administered twice daily via oral inhalation. This regimen should be followed in alternating cycles of 28 days on the medication, followed by 28 days off.

Dosage adjustments based on body weight are not necessary. It is advised that doses be taken as close to 12 hours apart as possible, with a minimum interval of 6 hours between doses. Each 300 mg dose should be administered using a hand-held PARI LC PLUS Reusable Nebulizer in conjunction with a DeVilbiss Pulmo-Aide compressor to ensure proper delivery of the medication.

Contraindications

Use of this product is contraindicated in patients with a known hypersensitivity to any aminoglycoside. This contraindication is based on the potential for severe allergic reactions in individuals with a history of such hypersensitivity.

Warnings and Precautions

Bronchospasm may occur following the inhalation of TOBI. In such instances, it is imperative to treat the bronchospasm as medically appropriate to ensure patient safety and comfort.

Ototoxicity has been reported in patients receiving TOBI, with symptoms including tinnitus and hearing loss. Should these symptoms arise, it is essential to manage them appropriately, which may include the consideration of discontinuing TOBI.

Nephrotoxicity is a known risk associated with aminoglycosides, including TOBI. If signs of nephrotoxicity develop, healthcare professionals should manage the patient accordingly, which may involve discontinuation of the medication.

Patients with pre-existing neuromuscular disorders may experience exacerbated muscle weakness due to the potential curare-like effects of aminoglycosides on neuromuscular function. In cases of neuromuscular blockade, administration of calcium salts may reverse the effects; however, mechanical assistance may be required.

Aminoglycosides, including TOBI, have been associated with embryo-fetal toxicity, indicating a risk of fetal harm. It is crucial for healthcare providers to counsel patients regarding this risk, particularly in pregnant individuals.

Healthcare professionals are advised to monitor patients closely for the aforementioned adverse effects and to take appropriate action, including discontinuation of TOBI, if necessary.

Side Effects

Patients receiving TOBI may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Most commonly reported adverse reactions include increased cough, pharyngitis, increased sputum production, dyspnea, hemoptysis, decreased lung function, voice alteration, taste perversion, and rash. These reactions were observed in clinical trials and may vary in severity among individuals.

Serious adverse reactions warranting caution include bronchospasm, which can occur with the inhalation of TOBI. If bronchospasm occurs, it should be treated as medically appropriate. Ototoxicity has also been reported, with patients experiencing tinnitus and hearing loss; management may require discontinuation of TOBI. Nephrotoxicity is a concern associated with aminoglycosides, including TOBI. If nephrotoxicity develops, appropriate management should be undertaken, which may include discontinuation of the medication. Additionally, patients with neuromuscular disorders may experience exacerbated muscle weakness due to a potential curare-like effect on neuromuscular function. In cases of neuromuscular blockade, administration of calcium salts may reverse the effects, although mechanical assistance may be necessary.

It is important to note that aminoglycosides, including TOBI, can cause embryo-fetal toxicity, posing risks of fetal harm.

In cases of acute toxicity from intravenous tobramycin overdosage, symptoms may include dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, neuromuscular blockade, and renal impairment. Immediate withdrawal of TOBI is recommended, along with baseline tests of renal function. Physicians should contact the Regional Poison Control Center for guidance on effective treatment in suspected overdosage cases. Hemodialysis may be beneficial in removing tobramycin from the body.

Drug Interactions

Concurrent and/or sequential use of TOBI with other agents that possess neurotoxic, nephrotoxic, or ototoxic potential is contraindicated. This precaution is essential to mitigate the risk of compounded toxic effects.

In addition, the concomitant administration of TOBI with ethacrynic acid, furosemide, urea, or intravenous mannitol is not recommended. The combination of these medications may enhance the toxicity associated with aminoglycosides, necessitating careful consideration of alternative therapeutic options. Monitoring for signs of toxicity is advised if such combinations are deemed necessary.

Packaging & NDC

The table below lists all NDC Code configurations of Tobi (tobramycin), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and efficacy of TOBI have not been established in pediatric patients under 6 years of age. Consequently, the use of TOBI is not indicated in children younger than 6 years.

Geriatric Use

Clinical studies of TOBI did not include elderly patients aged 65 years and over. Therefore, the safety and efficacy of this medication in this age group have not been established.

Tobramycin is primarily excreted by the kidneys, and the risk of adverse reactions may be heightened in patients with impaired renal function. Given that geriatric patients are more likely to experience decreased renal function, it is advisable to monitor renal function closely in this population. This monitoring can help mitigate potential risks associated with the use of tobramycin in elderly patients.

Pregnancy

Aminoglycosides, including tobramycin, have the potential to cause fetal harm. Published literature indicates that the use of streptomycin, an aminoglycoside, during pregnancy can result in total, irreversible, bilateral congenital deafness. While there are no available data on the use of TOBI (tobramycin inhalation solution) in pregnant women to assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, it is important to note that systemic absorption of tobramycin following inhaled administration is expected to be minimal.

Pregnant patients with cystic fibrosis may face additional risks, including complications associated with the condition itself, which can increase the likelihood of preterm delivery. The estimated background risk of major birth defects and miscarriage for the general population is not well defined for the indicated populations. However, in the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2% to 4% and 15% to 20%, respectively.

Healthcare professionals should advise pregnant women of the potential risks to the fetus associated with aminoglycoside use. In animal reproduction studies involving subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis, no adverse developmental outcomes were observed; however, ototoxicity was not evaluated in the offspring from these studies. Therefore, caution is warranted when considering the use of tobramycin in pregnant patients.

Lactation

There are no data on the presence of TOBI in either human or animal milk, nor are there any known effects on the breastfed infant or on milk production. Limited published data on other formulations of tobramycin in lactating women indicate that tobramycin is present in human milk; however, systemic absorption of tobramycin following inhaled administration is expected to be minimal.

Tobramycin may cause alterations in the intestinal flora of the breastfeeding infant. Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for TOBI and any potential adverse effects on the breastfed infant from TOBI or from the underlying maternal condition.

Healthcare professionals should advise lactating mothers to monitor their breastfed infants for signs of loose or bloody stools and candidiasis (thrush, diaper rash).

Renal Impairment

Patients with renal impairment may experience nephrotoxicity associated with aminoglycosides as a class. In the event that nephrotoxicity develops, it is essential to manage the patient appropriately, which may include the consideration of discontinuing TOBI. Monitoring renal function is recommended to ensure patient safety and to guide any necessary dosing adjustments or treatment modifications.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Acute toxicity resulting from an overdosage of intravenous (IV) tobramycin can manifest through a variety of signs and symptoms. Healthcare professionals should be vigilant for indications such as dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, neuromuscular blockade, and renal impairment.

It is important to note that the administration of tobramycin via inhalation leads to low systemic bioavailability, while oral administration does not result in significant absorption of the drug. Therefore, monitoring tobramycin serum concentrations may provide valuable information in assessing the extent of overdosage.

In the event of suspected overdosage, immediate withdrawal of TOBI is essential. Baseline tests of renal function should be conducted to evaluate any potential impairment. Additionally, healthcare providers are advised to contact the Regional Poison Control Center for guidance on effective treatment strategies.

Consideration should also be given to the possibility of drug interactions that may alter drug disposition in cases of overdosage. In certain situations, hemodialysis may be beneficial in facilitating the removal of tobramycin from the body, thereby mitigating the effects of toxicity.

Nonclinical Toxicology

A two-year inhalation toxicology study in rats was conducted to evaluate the carcinogenic potential of TOBI. During this study, rats were exposed to TOBI for up to 1.5 hours per day over a period of 95 weeks, utilizing the clinical formulation of the drug. Serum levels of tobramycin reached up to 35 mcg/mL in the rats, which is significantly higher than the average levels of 1 mcg/mL observed in cystic fibrosis patients during clinical trials. The results indicated no drug-related increase in the incidence of any tumor type.

Tobramycin has also undergone a comprehensive assessment for genotoxicity through a series of in vitro and in vivo tests. The Ames bacterial reversion test, which involved five tester strains, did not demonstrate a significant increase in revertants, both with and without metabolic activation across all strains tested. Furthermore, tobramycin was found to be negative in the mouse lymphoma forward mutation assay, did not induce chromosomal aberrations in Chinese hamster ovary cells, and yielded negative results in the mouse micronucleus test.

In terms of reproductive toxicity, subcutaneous administration of tobramycin at doses of up to 100 mg/kg did not adversely affect mating behavior or result in impairment of fertility in either male or female rats.

Postmarketing Experience

Postmarketing experience with tobramycin inhalation solution includes reports of hearing loss associated with its use. Additionally, cases of airway narrowing have been documented. It is important to note that tobramycin inhalation solution belongs to a class of drugs known to potentially cause kidney damage. Furthermore, there are reports indicating that aminoglycosides, the class to which tobramycin belongs, may lead to irreversible congenital deafness when administered to pregnant women.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use, to ensure they understand the proper use and potential risks associated with tobramycin inhalation solution.

Patients must be informed to report any instances of shortness of breath or wheezing following the administration of tobramycin inhalation solution, as this medication can lead to airway narrowing.

It is important for patients to notify their physician if they experience ringing in the ears, dizziness, or any changes in hearing, as tobramycin inhalation solution has been linked to hearing loss.

Patients should also be encouraged to disclose any history of kidney problems to their physician, given that tobramycin inhalation solution belongs to a class of drugs known to potentially cause kidney damage.

Pregnant women should be specifically advised that aminoglycosides, including tobramycin, can result in irreversible congenital deafness if administered during pregnancy.

Storage and Handling

TOBI is supplied in ampoules and should be stored under refrigeration at a temperature range of 2ºC to 8ºC (36ºF to 46ºF). When removed from refrigeration or if refrigeration is unavailable, TOBI pouches, whether opened or unopened, may be stored at room temperature, not exceeding 25ºC (77ºF), for a maximum of 28 days.

It is imperative that TOBI is not used beyond the expiration date indicated on the ampoule when stored under refrigeration. Similarly, if stored at room temperature, TOBI should not be used after 28 days. Care should be taken to protect the ampoules from intense light exposure.

The solution within the ampoule is slightly yellow; however, it may darken with age if not stored in the refrigerator. This color change does not signify a decline in product quality, provided that the recommended storage conditions are adhered to.

Additional Clinical Information

Patients should be advised of the potential risk to a fetus for pregnant women. No further information is available regarding laboratory tests, abuse potential, route, method, and frequency of administration, or postmarketing experience.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Tobi as submitted by Viatris Specialty LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)