Tobi Podhaler

Description

TOBI Podhaler consists of a dry powder formulation of tobramycin for oral inhalation only with the Podhaler device. Each clear, colorless hypromellose capsule contains a spray dried powder of 28 mg of tobramycin as the active ingredient, along with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid for pH adjustment. The active component, tobramycin, is an aminoglycoside antibiotic with a chemical name of O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)-2-deoxy-L-streptamine. Tobramycin has a molecular weight of 467.52 and an empirical formula of C18H37N5O9. It appears as a white to almost white powder, visually free from any foreign contaminants. Tobramycin is freely soluble in water, very slightly soluble in ethanol, and practically insoluble in chloroform and ether.

Uses and Indications

TOBI Podhaler is an aminoglycoside antibacterial indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa.

Limitations of Use: There are no teratogenic or nonteratogenic effects associated with TOBI Podhaler.

Dosage and Administration

The TOBI Podhaler is intended for oral inhalation only and must be used exclusively with the Podhaler device. Healthcare professionals should instruct patients not to swallow the TOBI Podhaler capsules.

The recommended dosage for TOBI Podhaler is the inhalation of four 28 mg capsules, administered twice daily. This regimen should be followed for a duration of 28 days. It is essential to ensure that the capsules are properly placed in the Podhaler device prior to inhalation to achieve the intended therapeutic effect.

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

Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected auditory, vestibular, renal, or neuromuscular dysfunction. The use of this medication in such populations may exacerbate existing conditions or lead to additional complications.

Ototoxicity has been reported in clinical trials, with patients experiencing complaints of hearing loss or tinnitus. Healthcare professionals should remain vigilant for these symptoms and consider appropriate monitoring strategies.

Aminoglycosides, including TOBI Podhaler, may aggravate muscle weakness due to a potential curare-like effect on neuromuscular function. This risk necessitates careful assessment of patients with pre-existing neuromuscular disorders.

Bronchospasm is a potential adverse effect associated with the inhalation of TOBI Podhaler. Clinicians should be prepared to manage this reaction and monitor patients accordingly.

To ensure safe use of TOBI Podhaler, it is recommended that audiograms, serum concentrations, and renal function be monitored as appropriate. These parameters will aid in the early detection of adverse effects and facilitate timely intervention.

Additionally, it is important to inform women of childbearing potential about the risks of embryo-fetal toxicity associated with aminoglycosides. This class of medications can cause fetal harm, and patients should be apprised of the potential hazards to the fetus prior to initiation of therapy.

Side Effects

Patients receiving TOBI Podhaler may experience a range of adverse reactions. Common adverse reactions observed include cough, lung disorder, productive cough, dyspnea, pyrexia, oropharyngeal pain, dysphonia, hemoptysis, and headache.

Serious adverse reactions warranting caution include ototoxicity, which has been reported in clinical trials as complaints of hearing loss or tinnitus. Additionally, bronchospasm may occur following inhalation of TOBI Podhaler. It is important to note that aminoglycosides, including TOBI, may exacerbate muscle weakness due to a potential curare-like effect on neuromuscular function.

Patients with known or suspected auditory, vestibular, renal, or neuromuscular dysfunction should be prescribed TOBI Podhaler with caution. Furthermore, there is a risk of embryo-fetal toxicity associated with aminoglycosides, necessitating that women of childbearing potential be informed of the potential hazards to the fetus.

Hypersensitivity reactions to any aminoglycoside have also been reported. In clinical observations, dysgeusia (taste disturbance) was noted to occur more frequently in younger patients aged six to 19 years compared to those aged 20 years and older, with incidences of 7.4% and 2.7%, respectively.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

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

Pediatric Use

Pediatric patients aged 6 years and older were included in the Phase 3 studies with TOBI Podhaler, with a total of 206 patients under 20 years of age receiving the treatment. No dosage adjustments are necessary based on age. The overall pattern of adverse events observed in pediatric patients was consistent with that seen in adults. However, dysgeusia (taste disturbance) was reported more frequently in younger patients aged 6 to 19 years, occurring in 7.4% of this group compared to 2.7% in patients aged 20 years and older. Safety and effectiveness in pediatric patients below the age of 6 years have not been established.

Geriatric Use

Clinical studies of TOBI Podhaler did not include a sufficient number of subjects aged 65 years and older to determine whether these elderly patients respond differently from younger subjects.

Tobramycin is substantially excreted by the kidneys, and the risk of adverse reactions to this medication 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 may help mitigate potential risks associated with the use of tobramycin in elderly patients.

Pregnancy

Aminoglycosides, including tobramycin, have been associated with potential fetal harm. Specifically, the use of streptomycin during pregnancy has been linked to total, irreversible, bilateral congenital deafness. While there are no available data on the use of TOBI Podhaler 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 women should be informed of the potential risks to the fetus associated with aminoglycoside use. The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2% to 4% and 15% to 20%, respectively. However, the specific background risk for the indicated populations remains unknown.

Additionally, cystic fibrosis in pregnant patients may pose risks, including an increased likelihood of preterm delivery. 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 advised when considering the use of tobramycin in pregnant women, and the potential risks should be carefully weighed against the benefits.

Lactation

There are no data on the presence of tobramycin following administration of TOBI Podhaler in either human or animal milk, nor on the effects on the breastfed infant or 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. The developmental and health benefits of breastfeeding should be considered alongside the mother's clinical need for TOBI Podhaler and any potential adverse effects on the breastfed infant from TOBI Podhaler or from the underlying maternal condition.

Lactating mothers are advised to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash).

Renal Impairment

Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected renal dysfunction. It is important to monitor audiograms, serum concentrations, and renal function as appropriate to ensure patient safety and therapeutic efficacy.

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

In the event of overdosage with TOBI Podhaler, it is important to note that the maximum tolerated daily dose has not been established. However, accidental oral ingestion of TOBI Podhaler capsules is unlikely to result in systemic toxicity due to the poor absorption of tobramycin.

Monitoring of tobramycin serum concentrations may be beneficial in assessing the extent of overdosage. Should acute toxicity occur, immediate withdrawal of TOBI Podhaler is recommended, and baseline tests of renal function should be conducted to evaluate any potential impact on kidney health.

In cases of significant overdosage, hemodialysis may be considered as a method to facilitate the removal of tobramycin from the body. It is crucial for healthcare professionals to contact the Regional Poison Control Center for guidance on effective treatment strategies in all instances of suspected overdosage.

Additionally, it is essential to consider the possibility of drug interactions that may alter drug disposition, which could further complicate the management of overdosage.

Nonclinical Toxicology

Carcinogenicity studies were not conducted with TOBI Podhaler. However, a 2-year rat inhalation toxicology study was completed to assess the carcinogenic potential of TOBI (tobramycin inhalation solution, USP). In this study, rats were exposed to TOBI for up to 1.5 hours per day over a period of 95 weeks. Serum levels of tobramycin reached up to 35 mcg/mL in rats, which is significantly higher than the maximum level of 1.99 ± 0.59 mcg/mL observed in cystic fibrosis patients during TOBI Podhaler clinical trials. Importantly, there was no drug-related increase in the incidence of any type of tumor.

Tobramycin has also been evaluated for genotoxicity through a series of in vitro and in vivo tests. The Ames bacterial reversion test, which utilized five tester strains, did not demonstrate a significant increase in revertants, regardless of metabolic activation. Additionally, 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.

Furthermore, subcutaneous administration of tobramycin at doses of up to 100 mg/kg did not affect mating behavior or cause impairment of fertility in either male or female rats.

Postmarketing Experience

Postmarketing experience with TOBI Podhaler has revealed several important observations. Decreased susceptibility of Pseudomonas aeruginosa to tobramycin has been reported, although the relationship between in vitro susceptibility test results and clinical outcomes remains unclear. Monitoring for decreased susceptibility during treatment is recommended, and consideration of alternative therapies should be made in cases of clinical worsening.

Hearing loss has been associated with the use of TOBI Podhaler, and patients are advised to inform their physician if they experience symptoms such as ringing in the ears, dizziness, or any changes in hearing. Additionally, TOBI Podhaler belongs to a class of drugs that may cause kidney damage; therefore, patients with a history of kidney problems should notify their healthcare provider.

The medication is also known to potentially harm an unborn baby, necessitating caution in pregnant patients. Cough has been reported during clinical trials, and severe breathing problems, including bronchospasm, can occur. Patients should seek immediate medical attention if they experience symptoms of bronchospasm, such as shortness of breath with wheezing, coughing, or chest tightness.

Worsening kidney problems (nephrotoxicity) may occur, particularly in individuals with known or suspected kidney issues. Furthermore, patients with pre-existing muscle weakness conditions, such as myasthenia gravis or Parkinson’s disease, may experience worsening muscle weakness.

The most common side effects associated with TOBI Podhaler include cough, shortness of breath, coughing up blood, exacerbation of lung problems or cystic fibrosis, fever, headache, sore throat, changes in voice, and productive cough (hoarseness). Patients are encouraged to inform their healthcare provider if their symptoms worsen while using TOBI Podhaler.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use. It is important for patients to consider alternative therapy if they are unable to tolerate TOBI Podhaler. Patients should be instructed to complete a full 28-day course of TOBI Podhaler, even if they begin to feel better during treatment.

After completing 28 days of therapy, patients should stop using TOBI Podhaler for the next 28 days before resuming therapy for another 28-day on and 28-day off cycle. If patients have been prescribed a 7-day pack of TOBI Podhaler either immediately before or during a 28-day treatment, they must count each day of use toward the 28-day on-treatment part of their cycle. Similarly, if a 1-day pack has been prescribed, each day of use must also be counted toward the 28-day on-treatment period. It is crucial for patients to understand that they should only take a total of 28 consecutive days of treatment during each cycle.

Patients should be adequately trained in the correct administration of TOBI Podhaler capsules using the Podhaler device. Caregivers should assist children using TOBI Podhaler, particularly those aged 10 years or younger, by preparing the dose for inhalation and supervising them until they can use the device independently.

For patients taking multiple inhaled medications or performing chest physiotherapy, healthcare providers should advise them on the appropriate order of administration, recommending that TOBI Podhaler be taken last. Patients should be informed to notify their physician if they experience shortness of breath or wheezing after using TOBI Podhaler. Additionally, they should report any ringing in the ears, dizziness, or changes in hearing, as TOBI Podhaler has been associated with hearing loss.

Patients with a history of kidney problems should inform their physician, as TOBI Podhaler belongs to a class of drugs that may cause kidney damage. Pregnant women should be advised that aminoglycosides can lead to irreversible congenital deafness when administered during pregnancy. Furthermore, breastfeeding women should monitor their infants for diarrhea and/or bloody stools.

Lastly, patients should be made aware that cough was reported during clinical trials with TOBI Podhaler. If coughing becomes bothersome or intolerable, healthcare providers may consider tobramycin inhalation solution or alternative therapeutic options.

Storage and Handling

TOBI Podhaler is supplied in a package that includes capsules specifically designed for use with the Podhaler device. The product must be stored at a temperature of 25°C (77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).

It is essential to protect the TOBI Podhaler from moisture to maintain its efficacy. Capsules should remain in their blister packaging until they are ready to be used, and each capsule must be removed immediately prior to administration. The Podhaler device provided with each weekly pack should be utilized exclusively with the TOBI Podhaler capsules; it is not compatible with any other capsules.

As a precaution, this product, along with all medications, should be kept out of the reach of children.

Additional Clinical Information

Patients should be advised of the potential risks to a fetus if they are pregnant. There is no additional information 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 Podhaler as submitted by Viatris Specialty LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)