Kitabis Pak

Description

KITABIS PAK contains tobramycin inhalation solution, USP, and the PARI LC PLUS Reusable Nebulizer (PARI LC PLUS). The tobramycin inhalation solution is a sterile, clear, slightly yellow, non-pyrogenic aqueous solution, with pH and salinity specifically adjusted for administration via the PARI LC PLUS Reusable Nebulizer. The chemical formula for tobramycin is C18H37N5O9, with a molecular weight of 467.52. The structure of tobramycin is described as O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-2,6-diamino-2,3,6-trideoxy-a-D-ribo-hexopyranosyl-(1→6)-2-deoxy-L-streptamine.

Each single-use 5 mL ampule contains 300 mg of tobramycin and 11.25 mg of sodium chloride in sterile water for injection. The pH is adjusted to 6.0 using sulfuric acid and sodium hydroxide, and nitrogen is utilized for sparging. The formulation is preservative-free and has an osmolality ranging from 135 to 200 mOsmol/kg.

The PARI LC PLUS Reusable Nebulizer demonstrates specific performance characteristics when used with the tobramycin inhalation solution, as measured using a Next Generation Impactor (NGI) at a continuous flow rate of 15 L/min under standard conditions (50% RH, 23°C). These characteristics include a delivered dose of 174 mg, a fine particle dose of 97 mg (particles < 5μm), a nebulization time of 13 minutes, a mass median aerodynamic diameter of 4.3 μm, and a geometric standard deviation of 2.2 μm.

Uses and Indications

KITABIS PAK contains tobramycin, an aminoglycoside antibacterial drug 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

Tobramycin inhalation solution is to be administered as one single-use ampule (300 mg/5 mL) via oral inhalation, twice daily. The dosing regimen consists of alternating periods of 28 days on the medication followed by 28 days off.

Dosing is not adjusted based on patient weight. It is recommended that doses be taken as close to 12 hours apart as possible, but not less than 6 hours apart. Each 300 mg dose should be administered using the PARI LC PLUS Reusable Nebulizer in conjunction with the 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 tobramycin inhalation solution. In the event of bronchospasm, it is essential to treat the condition as medically appropriate.

Ototoxicity is a significant concern associated with the use of tobramycin inhalation solution, with reports of tinnitus and hearing loss in patients. Should these symptoms arise, it is crucial to manage them appropriately, which may include the discontinuation of tobramycin inhalation solution.

Nephrotoxicity is another potential risk linked to aminoglycosides, including tobramycin. If signs of nephrotoxicity develop, healthcare professionals should manage the patient accordingly, which may involve discontinuing the use of tobramycin inhalation solution.

Patients with neuromuscular disorders should be monitored closely, as aminoglycosides can exacerbate muscle weakness due to a possible curare-like effect on neuromuscular function. In cases of neuromuscular blockade, administration of calcium salts may reverse the effects; however, mechanical assistance may be required.

It is important to note that aminoglycosides, including tobramycin, have the potential to cause fetal harm, indicating a risk of embryo-fetal toxicity. Healthcare providers should exercise caution when prescribing to pregnant individuals.

Side Effects

Patients receiving tobramycin inhalation solution may experience a range of adverse reactions. Common adverse reactions, occurring in more than 5% of patients, include increased cough, pharyngitis, increased sputum production, dyspnea, hemoptysis, decreased lung function, voice alteration, taste perversion, and rash.

Serious adverse reactions have also been reported. Bronchospasm may occur with the inhalation of tobramycin inhalation solution and should be treated as medically appropriate if it arises. Ototoxicity, characterized by tinnitus and hearing loss, has been noted in patients receiving this treatment; management may require discontinuation of the medication. Nephrotoxicity, a known risk associated with aminoglycosides, necessitates appropriate management if it develops, which may include discontinuation of tobramycin inhalation solution. 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 required.

It is important to note that tobramycin inhalation solution carries a risk of embryo-fetal toxicity, which can result in fetal harm. Patients with known hypersensitivity to any aminoglycoside should not use this medication. Signs and symptoms of acute toxicity from overdosage of intravenous tobramycin may include dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, and neuromuscular blockade. While administration by inhalation results in low systemic bioavailability, monitoring tobramycin serum concentrations may be beneficial in cases of suspected overdosage.

Drug Interactions

Concurrent and/or sequential use of this drug with other agents that possess neurotoxic, nephrotoxic, or ototoxic potential should be avoided to minimize the risk of adverse effects.

In particular, concomitant administration with ethacrynic acid, furosemide, urea, or intravenous mannitol is not recommended. The combination of these agents may enhance the toxicity of aminoglycosides, necessitating careful consideration of alternative therapies or close monitoring of renal function and auditory status if such combinations are deemed necessary.

Packaging & NDC

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

Pediatric Use

The safety and efficacy of tobramycin inhalation solution have not been established in pediatric patients under 6 years of age. Therefore, caution is advised when considering its use in this population.

Geriatric Use

Clinical studies of tobramycin inhalation solution 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 substantially excreted by the kidneys, and the risk of adverse reactions may be heightened in patients with impaired renal function. Given that elderly patients are more likely to experience decreased renal function, it is advisable to monitor renal function closely in this population. Dose adjustments may be necessary based on renal status to mitigate the risk of potential adverse effects.

Pregnancy

Aminoglycosides, including tobramycin, have the potential to cause fetal harm. Published literature indicates that the use of streptomycin, an aminoglycoside, during pregnancy can lead to total, irreversible, bilateral congenital deafness. While there are no available data on the use of KITABIS PAK in pregnant women to assess the drug-associated 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 with cystic fibrosis may face additional risks, including complications associated with the condition itself, which can increase the 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, healthcare professionals should advise pregnant women of the potential risks to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown. It is essential to recognize that all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. 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.

Lactation

There are no data on the presence of tobramycin inhalation solution 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. Therefore, the developmental and health benefits of breastfeeding should be considered alongside the mother's clinical need for KITABIS PAK and any potential adverse effects on the breastfed infant from KITABIS PAK 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

Patients with renal impairment may experience nephrotoxicity associated with aminoglycosides, including tobramycin inhalation solution. In cases where nephrotoxicity develops, it is essential to manage the patient appropriately, which may include the discontinuation of the medication. Monitoring renal function is recommended to ensure patient safety and to make necessary dosing adjustments based on the patient's renal status.

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 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 tobramycin may manifest through a range of signs and symptoms. Healthcare professionals should be vigilant for indications such as dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, and neuromuscular blockade. These symptoms necessitate immediate medical attention and intervention.

It is important to note that the administration of tobramycin via inhalation leads to low systemic bioavailability, which may influence the clinical presentation of overdosage. Additionally, tobramycin is not significantly absorbed when administered orally, further emphasizing the importance of the route of administration in assessing potential toxicity.

Monitoring tobramycin serum concentrations can be a valuable tool in the evaluation of overdosage. Regular assessment of serum levels may assist healthcare professionals in determining the extent of toxicity and guiding appropriate management strategies. In cases of suspected overdosage, prompt recognition and intervention are critical to mitigate potential adverse effects.

Nonclinical Toxicology

A two-year inhalation toxicology study in rats was conducted to evaluate the carcinogenic potential of tobramycin inhalation solution. In this study, rats were exposed to the clinical formulation of tobramycin 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 the rats, which is significantly higher than the average serum levels of 1 mcg/mL observed in cystic fibrosis patients during clinical trials. The results indicated no drug-related increase in the incidence of tumors of any 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 utilized five tester strains, did not demonstrate a significant increase in revertants, both with and without metabolic activation across all strains. 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 has identified reports of several adverse reactions associated with the use of the product. Notable among these are hearing loss, tinnitus, and dizziness. Additionally, there have been reports of renal impairment and acute kidney injury. Cases of respiratory distress and bronchospasm have also been documented in association with the use of tobramycin inhalation solution. These events were reported voluntarily or through surveillance programs and do not imply a causal relationship.

Patient Counseling

Healthcare providers should advise patients to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use, prior to starting treatment with KITABIS PAK. It is essential for patients to familiarize themselves with the Instructions for Use before initiating therapy.

Patients should be instructed to use the tobramycin inhalation solution contained in KITABIS PAK exclusively with the PARI LC PLUS Reusable Nebulizer that is included in the kit. This ensures proper administration and maximizes the effectiveness of the treatment.

Healthcare providers must emphasize the importance of reporting any instances of shortness of breath or wheezing following the administration of tobramycin inhalation solution. Such symptoms may indicate an adverse reaction that requires medical attention.

Additionally, patients should be informed to notify their physician if they experience ringing in the ears, dizziness, or any changes in hearing, as these symptoms may be associated with hearing loss linked to the use of tobramycin inhalation solution.

It is also crucial for patients with a history of kidney problems to inform their healthcare provider, as tobramycin inhalation solution belongs to a class of drugs known to potentially cause kidney damage.

Finally, healthcare providers should counsel pregnant women that aminoglycosides, including tobramycin, can lead to irreversible congenital deafness if administered during pregnancy. This information is vital for informed decision-making regarding the use of this medication.

Storage and Handling

Tobramycin inhalation solution is supplied in ampules and should be stored under refrigeration at a temperature range of 2-8°C (36-46°F). If removed from refrigeration or if refrigeration is unavailable, the solution pouches, whether opened or unopened, may be stored at room temperature (up to 25°C/77°F) for a maximum of 28 days.

It is imperative that tobramycin inhalation solution is not used beyond the expiration date indicated on the ampule when stored under refrigeration or beyond 28 days when kept at room temperature. Additionally, the ampules should be protected from intense light exposure.

The solution within the ampule is typically 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 solution has been stored according to the recommended conditions.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Kitabis Pak as submitted by Pari Respiratory Equipment, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)