BETHKIS tobramycin 300 mg/4mL Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Aminoglycoside Antibacterial class.
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🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- Tobramycin is an antibiotic, but the form you have determines exactly what it treats. If you're inhaling it through a nebulizer or using the TOBI Podhaler device, it's being used t...
- That on-off cycle is by design. Inhaling tobramycin for 28 days helps knock back the Pseudomonas bacteria in your lungs, and then the 28-day break gives your body a rest and helps...
- Why do I have to take the inhaled form for 28 days and then stop for 28 days?
- Absolutely not — this is really important. The TOBI Podhaler capsules must never be swallowed. The medicine only works when it's inhaled directly into your lungs using the Podhaler...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Tobramycin — tap one for details:
Tobramycin may be associated with lower levels of 8 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII O40UQP6WCF
A strong acid used in small amounts to adjust and maintain the pH balance of a medicine, helping ensure stability and proper dissolution of the active ingredients.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
4 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $27.14 | $6,079.85 / 224 ml |
| Medicare drug plans payPart D · Q2 2026 | $26.03 | $5,831.24 / 224 ml |
| Medicare Part B allowsASP · J7682 | $12.305 / J7682 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tobramycin 300 mg/4mL 00093-3750-28 | Teva | 7 pouches | — | — | Discontinued | — |
| Bethkis 300 mg/4mLthis 10122-0820-56 | Chiesi | 14 pouches | — | AN | FDA listed | — |
| Tobramycin Inhalation 300 mg/4mL 66993-0195-94 | Prasco, | 14 pouches | — | AN | FDA listed | — |
| Tobramycin 300 mg/4mL 70756-0617-56 | Lifestar | 14 pouches | — | AN | FDA listed | — |
| Tobramycin 300 mg/4mL 72603-0630-56 | NorthStar | 14 pouches | — | AN | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 10122-0820-28 | 7 POUCH in 1 CARTON (10122-820-28) / 4 AMPULE in 1 POUCH / 4 mL in 1 AMPULE | 2013-04-15 | Active |
| 10122-0820-56 You're viewing this | 14 POUCH in 1 CARTON (10122-820-56) / 4 AMPULE in 1 POUCH / 4 mL in 1 AMPULE | 2013-04-15 | Active |
| 10122-0820-04 | 4 AMPULE in 1 POUCH (10122-820-04) / 4 mL in 1 AMPULE | 2013-04-15 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 77% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 10122-0820-56?
What NDC number is used to bill for this package of BETHKIS tobramycin 300 mg/4mL Solution?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE BETHKIS is indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa . Safety and efficacy have not been demonstrated in patients under the age of six years, patients with FEV 1 less than 40% or greater than 80% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies ( 14 )] . BETHKIS is an inhaled aminoglycoside antibacterial indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa .
( 1 ) Safety and efficacy have not been demonstrated in patients under the age of six years, patients with a forced expiratory volume in one second (FEV 1 ) less than 40% or greater than 80% predicted, or patients colonized with Burkholderia cepacia . ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For oral inhalation only ( 2.1 ) Administer the entire contents of one ampule twice daily by oral inhalation in repeated cycles of 28 days on drug, followed by 28 days off drug. ( 2.1 )
2.1Dosage Bethkis is for oral inhalation only [see Dosage and Administration ( 2.2 )] . The recommended dosage of BETHKIS for patients six years of age and older is to administer one single-use ampule (300 mg/4 mL) twice daily by oral inhalation in repeated cycles of 28 days on drug, followed by 28 days off drug. The doses should be taken as close to 12 hours apart as possible and not less than 6 hours apart.
The 300 mg/4 mL dose of BETHKIS is the same for patients regardless of age or weight. BETHKIS has not been studied in patients less than six years old. If patients miss a dose, they should take it as soon as possible anytime up to 6 hours prior to their next scheduled dose.
If less than 6 hours remain before the next dose, wait until their next scheduled dose.
2.2Administration Instructions BETHKIS is administered by oral inhalation using a hand-held PARI LC PLUS Reusable Nebulizer with a PARI Vios Air compressor over an approximately 15 minute period and until sputtering from the output of the nebulizer has occurred for at least one minute. BETHKIS should not be diluted or mixed with dornase alfa or other medications in the nebulizer. BETHKIS is not for subcutaneous, intravenous, or intrathecal administration.
Further patient instructions on how to administer BETHKIS are provided in the Patient’s Instructions for Use [see Patient Counseling Information ( 17 )]. BETHKIS should not be used if it is cloudy, if there are particles in the solution, or if it has been stored at room temperature for more than 28 days.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS BETHKIS is supplied as a sterile, clear, colorless to pale yellow, non-pyrogenic, aqueous inhalational solution for nebulization in single-use 4 mL ampule containing 300 mg of tobramycin. Inhalation solution: 300 mg tobramycin per 4-mL solution in a single-use ampoule. ( 16 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS BETHKIS is contraindicated in patients with a known hypersensitivity to any aminoglycoside. BETHKIS is contraindicated in patients with a known hypersensitivity to any aminoglycoside. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Caution should be exercised when prescribing BETHKIS to patients with known or suspected auditory, vestibular, renal, or neuromuscular dysfunction. ( 5.1 , 5.2 , 5.3 and 5.5 ) Aminoglycoside may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function. ( 5.3 ) Bronchospasm can occur with inhalation of BETHKIS.
( 5.4 ) Audiograms, serum concentration, and renal function should be monitored as appropriate. ( 5.2 and 5.5 ) Fetal harm can occur when aminoglycosides are administered to a pregnant woman. Apprise women of the potential hazard to the fetus.
( 5.6 )
5.1Ototoxicity Ototoxicity with use of BETHKIS Caution should be exercised when prescribing BETHKIS to patients with known or suspected auditory or vestibular dysfunction. Findings related to ototoxicity as measured by audiometric evaluations and auditory adverse event reports were similar between BETHKIS and placebo in controlled clinical trials. Hearing loss was reported in two (1.1%) BETHKIS-treated patients and in one (0.9%) placebo-treated patient during clinical studies.
Additionally, dizziness and vertigo, both of which may be manifestations of vestibular forms of ototoxicity, were observed in similar numbers of BETHKIS- and placebo-treated patients. Dizziness occurred in two (1.1%) BETHKIS-treated patients and one (0.9%) placebo-treated patient and vertigo occurred in two (1.1%) BETHKIS-treated patients versus no placebo patients in clinical studies. None of the BETHKIS patients discontinued their therapy due to hearing loss, dizziness or vertigo.
Tinnitus may be a sentinel symptom of ototoxicity. No reports of tinnitus occurred in patients during clinical studies with BETHKIS, but because it has been observed with inhaled tobramycin solutions [see Adverse Reactions ( 6.2 )] , onset of this symptom warrants caution. Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides.
Vestibular toxicity may be manifested by vertigo, ataxia or dizziness. Patients with known or suspected auditory or vestibular dysfunction should be closely monitored when taking BETHKIS. Monitoring may include obtaining audiometric evaluations and serum tobramycin levels.
If ototoxicity is noted, the patient should be managed as medically appropriate, including potentially discontinuing BETHKIS. Risk of Ototoxicity Due to Mitochondrial DNA Variants Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1) , particularly the m.1555A>G variant. Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range.
Mitochondrial DNA variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as the severity of ototoxicity is unknown. In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies.
5.2Nephrotoxicity Caution should be exercised when prescribing BETHKIS to patients with known or suspected renal dysfunction. Nephrotoxicity was not seen during BETHKIS clinical studies but has been associated with aminoglycosides as a class. Patients with known or suspected renal dysfunction or taking concomitant nephrotoxic drugs along with BETHKIS should have serum concentrations of tobramycin and laboratory measurements of renal function obtained at the discretion of the treating physician.
If nephrotoxicity develops, the patient should be managed as medically appropriate, including potentially discontinuing BETHKIS until serum concentrations fall below 2 mcg/mL. Twenty-six (14%) BETHKIS patien…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Common adverse reactions (more than 5%) occurring more frequently in BETHKIS patients are forced expiratory volume decreased, rales, red blood cell sedimentation rate increased, and dysphonia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi USA, Inc. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of drugs cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to BETHKIS in two placebo-controlled studies in 305 cystic fibrosis patients. Patients receiving BETHKIS ranged in age from 6 to 31 years.
In Study 1, an eight week study, 29 patients received BETHKIS versus 30 patients who received placebo for a total of four weeks on drug and four weeks off drug. All patients were ≤ 30 years of age (mean age 12.6 years) and 46% were females. 52.5% of patients were 6 to 12 years of age while 30.5% of patients were 13-17 years old.
Only 16.5% of patients were adults (> 17 years old). Eighty percent (80%) of patients were chronically colonized with Pseudomonas aeruginosa while 20.3% of patients were initially or intermittently colonized with Pseudomonas aeruginosa during the study. More patients in the placebo group discontinued/dropped out of Study 1 than in the BETHKIS group (23% [7/30] vs 3.4% [1/29], respectively).
Five patients in the placebo group compared to none in the BETHKIS group discontinued/dropped out because of treatment-emergent adverse events (TEAEs) such as pulmonary exacerbations and respiratory disorders. In Study 2, a 24 week study, 161 patients received BETHKIS versus 85 patients who received placebo in alternating four week on-off cycles for three cycles. All patients were ≤ 46 years of age (mean age 14.8 years) and 45% were females.
41% of patients were 6-12 years old while 29% of patients were 13-17 years old. Only 30% were adults (>17 years). Eighty-seven percent (87%) of patients were chronically colonized with P. aeruginosa .
Only 13% were either initially or intermittently colonized with P. aeruginosa during the study. More patients in the placebo group discontinued/dropped out of Study 2 than in the BETHKIS group (9.4% [8/85] vs 4.3% [7/161], respectively). Of these, 3 patients in the BETHKIS group (1.9%) compared to 2 patients in the placebo group (2.4%) withdrew due to a TEAE.
The most common TEAEs causing patients to discontinue from the study drug are respiratory, thoracic, and mediastinal disorders. The most common adverse experiences reported were respiratory disorders, consistent with the underlying disease in the patient population being evaluated and these were similarly distributed between both BETHKIS- and placebo-treated patients. The following adverse reactions were reported in at least 5% of Bethkis-treated patients and at rates ≥ 2% more common compared to the placebo-treated patients: decreased forced expiratory volume, rales, red blood cell sedimentation rate increased, and dysphonia (Table 1).
Table 1: Patients with Selected Treatment-Emergent Adverse Reactions Occurring in ≥ 2% of BETHKIS Patients Adverse Reactions BETHKIS N=190 (%) Placebo N=115 (%) Forced expiratory volume decreased 59 (31%) 33 (29%) Rales 36 (19%) 18 (16%) Red blood cell sedimentation rate increased 16 (8%) 6 (5%) Dysphonia 11 (6%) 2 (2%) Wheezing 10 (5%) 4 (4%) Epistaxis 6 (3%) 0 Pharyngolaryngeal pain 5 (3%) 2 (2%) Bronchitis 5 (3%) 1 (1%) Tonsillitis 4 (2%) 0 Diarrhea 3 (2%) 1 (1%) Eosinophilia 3 (2%) 0 Immunoglobulins increased 3 (2%) 0
6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of tobramycin inhalation solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably esti…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Concurrent and/or sequential use of BETHKIS with other drugs with neurotoxic, nephrotoxic or ototoxic potential should be avoided. ( 7.1 ) BETHKIS should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. ( 7.2 )
7.1Drugs with Neurotoxic, Nephrotoxic, or Ototoxic Potential Concurrent and/or sequential use of BETHKIS with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided.
7.2Diuretics Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. Therefore, BETHKIS should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. The interaction between inhaled mannitol and BETHKIS has not been evaluated.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Aminoglycosides can cause fetal harm when administered to a pregnant woman. ( 8.1 ) Nursing mothers: discontinue drug or nursing, taking into consideration the importance of the drug to a mother. ( 8.2 ) __________________________________________________________________
8.1Pregnancy Risk Summary Aminoglycosides can cause fetal harm. Published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [Warnings and Precautions ( 5.6 )] . Although there are no available data on use of BETHKIS in pregnant women to be able to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology ( 12.3 )] .
There are risks to the mother associated with cystic fibrosis in pregnancy (see Clinical Considerations) . In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis there were no adverse developmental outcomes; however, ototoxicity was not evaluated in the offspring from these studies (see Data ) . Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, 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 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Cystic fibrosis may increase the risk for preterm delivery. Data Animal Data No reproduction toxicology studies have been conducted with inhaled tobramycin. However, subcutaneous administration of tobramycin at doses of up to 100 (rat) or 20 (rabbit) mg/kg/day during organogenesis was not associated with adverse developmental outcomes.
Subcutaneous doses of tobramycin ≥ 40mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during nonclinical reproductive toxicity studies with tobramycin.
8.2Lactation Risk Summary There are no data on the presence of tobramycin in either human or animal milk, the effects on the breastfed infant, or the effects on milk production following oral inhalation of BETHKIS. 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 [see Clinical Pharmacology ( 12.3 )] .
Tobramycin may cause alteration in the intestinal flora of the breastfeeding infant (see Clinical Considerations) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BETHKIS and any potential adverse effects on the breastfed child from BETHKIS or from the underlying maternal condition. Clinical Considerations Tobramycin may cause intestinal flora alteration.
Advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash).
8.4Pediatric Use The safety and efficacy of BETHKIS have not been studied in pediatric cystic fibrosis patients under six years of age.
8.5Geriatric Use Clinical studies of BETHKIS did not include patients aged 65 years and over. Tobramycin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function [see Warnings and Precautions ( 5.2 , 5.5 )] .
8.6 Renal Impairment Tob…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Aminoglycosides can cause fetal harm. Published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [Warnings and Precautions ( 5.6 )] . Although there are no available data on use of BETHKIS in pregnant women to be able to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology ( 12.3 )] .
There are risks to the mother associated with cystic fibrosis in pregnancy (see Clinical Considerations) . In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis there were no adverse developmental outcomes; however, ototoxicity was not evaluated in the offspring from these studies (see Data ) . Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, 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 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Cystic fibrosis may increase the risk for preterm delivery. Data Animal Data No reproduction toxicology studies have been conducted with inhaled tobramycin. However, subcutaneous administration of tobramycin at doses of up to 100 (rat) or 20 (rabbit) mg/kg/day during organogenesis was not associated with adverse developmental outcomes.
Subcutaneous doses of tobramycin ≥ 40mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during nonclinical reproductive toxicity studies with tobramycin.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and efficacy of BETHKIS have not been studied in pediatric cystic fibrosis patients under six years of age.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of BETHKIS did not include patients aged 65 years and over. Tobramycin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function [see Warnings and Precautions ( 5.2 , 5.5 )] .
🆘 Overdosage ▾
10 OVERDOSAGE No overdoses have been reported with BETHKIS in clinical trials. Signs and symptoms of acute toxicity from overdosage of intravenous tobramycin might include dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, neuromuscular blockade, and renal impairment. Administration by inhalation results in low systemic bioavailability of tobramycin.
Tobramycin is not significantly absorbed following oral administration. Tobramycin serum concentrations may be helpful in monitoring overdosage. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment.
In the case of any overdosage, the possibility of drug interactions with alterations in drug disposition should be considered.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action BETHKIS is an aminoglycoside antibacterial [see Clinical Pharmacology ( 12.4 )] .
12.3Pharmacokinetics BETHKIS contains tobramycin, a cationic polar molecule that does not readily cross epithelial membranes. 1 The bioavailability of BETHKIS may vary because of individual differences in nebulizer performance and airway pathology. 2 Sputum Concentrations Thirty minutes after inhalation of the first 300 mg dose of BETHKIS, the maximum geometric mean concentration of tobramycin was 814 mcg/g (ranging from 23 to 2843 mcg/g) in sputum.
High variability of tobramycin concentration in sputum was observed. Three hours after inhalation started, sputum tobramycin concentrations declined to approximately 15% of those observed at 30 minutes. After four weeks of therapy with BETHKIS average mean sputum tobramycin concentrations obtained 10 minutes following administration were 717 mcg/g.
Distribution Following administration of BETHKIS, tobramycin remains concentrated primarily in the airways. Binding of tobramycin to serum proteins is negligible. Elimination Tobramycin is not metabolized.
The elimination half-life of tobramycin from serum is approximately two hours after intravenous (IV) administration. The elimination half-life following the inhalation of BETHKIS is approximately 4.4 hours. Assuming tobramycin absorbed following inhalation behaves similarly to tobramycin following intravenous administration, systemically absorbed tobramycin is eliminated principally by glomerular filtration.
Unabsorbed tobramycin following inhalation is likely eliminated in expectorated sputum.
12.4Microbiology Mechanism of Action Tobramycin, an aminoglycoside antibacterial, acts primarily by disrupting protein synthesis in the bacterial cell which eventually leads to death of the cell. Tobramycin has activity against a wide range of gram-negative bacteria including P. aeruginosa . It is bactericidal at or above the minimal inhibitory concentration (MIC) needed to inhibit growth of bacteria.
Mechanism of Resistance The predominant mechanism of resistance to tobramycin in P. aeruginosa isolated from CF patients is impermeability and to a lesser extent enzymatic modification and other mechanisms which cumulatively lead to decreased susceptibility of P. aeruginosa to tobramycin. Cross Resistance Cross resistance between aminoglycosides exists but the cross resistance is variable. Development of Resistance Treatment for six months with BETHKIS in one clinical trial did not affect the susceptibility of the majority of P. aeruginosa isolates tested; however, increases in minimal inhibitory concentrations (MIC) were noted in some patients.
The clinical significance of this information has not been clearly established in the treatment of cystic fibrosis patients. Susceptibility Testing The clinical microbiology laboratory should provide cumulative results of the in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physicians as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Susceptibility Testing Techniques Dilution Techniques Quantitative methods can be used to determine the minimum inhibitory concentration (MIC) of tobramycin that will inhibit the growth of the bacteria being tested. The MIC provides an estimate of the susceptibility of bacteria to tobramycin. The MIC should be determined using a standardized procedure.
3, 5 Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of tobramycin powder. Diffusion Techniques Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedu…
🧬 Mechanism of Action ▾
12.1Mechanism of Action BETHKIS is an aminoglycoside antibacterial [see Clinical Pharmacology ( 12.4 )] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied BETHKIS 300 mg/4 mL is supplied as a sterile, clear, colorless to pale yellow, non-pyrogenic, aqueous solution and is available as follows: NDC 10122-820-56: 4 mL single-use ampule (carton of 14 foil pouches each containing four ampules) NDC 10122-820-28: 4 mL single-use ampule (carton of 7 foil pouches each containing four ampules)
16.2Storage and Handling BETHKIS should be stored under refrigeration at 2°C ‑ 8°C (36°F ‑ 46°F). Upon removal from the refrigerator, or if refrigeration is unavailable, BETHKIS pouches (opened or unopened) may be stored at room temperature [up to 25°C (77°F)] for up to 28 days. BETHKIS should not be used beyond the expiration date stamped on the ampule when stored under refrigeration 2°C ‑ 8°C (36°F ‑ 46°F) or beyond 28 days when stored at room temperature [up to 25°C (77°F)].
BETHKIS ampules should not be exposed to intense light. BETHKIS is light sensitive; unopened ampules should be returned to the foil pouch. The solution in the ampule is colorless to pale yellow, but may darken with age if not stored in the refrigerator; however, the color change does not indicate any change in the quality of the product as long as it is stored within the recommended storage conditions.
16.1How Supplied BETHKIS 300 mg/4 mL is supplied as a sterile, clear, colorless to pale yellow, non-pyrogenic, aqueous solution and is available as follows: NDC 10122-820-56: 4 mL single-use ampule (carton of 14 foil pouches each containing four ampules) NDC 10122-820-28: 4 mL single-use ampule (carton of 7 foil pouches each containing four ampules)
📦 Storage and Handling ▾
16.2Storage and Handling BETHKIS should be stored under refrigeration at 2°C ‑ 8°C (36°F ‑ 46°F). Upon removal from the refrigerator, or if refrigeration is unavailable, BETHKIS pouches (opened or unopened) may be stored at room temperature [up to 25°C (77°F)] for up to 28 days. BETHKIS should not be used beyond the expiration date stamped on the ampule when stored under refrigeration 2°C ‑ 8°C (36°F ‑ 46°F) or beyond 28 days when stored at room temperature [up to 25°C (77°F)].
BETHKIS ampules should not be exposed to intense light. BETHKIS is light sensitive; unopened ampules should be returned to the foil pouch. The solution in the ampule is colorless to pale yellow, but may darken with age if not stored in the refrigerator; however, the color change does not indicate any change in the quality of the product as long as it is stored within the recommended storage conditions.
📋 Description ▾
11 DESCRIPTION BETHKIS is a sterile, clear, colorless to pale yellow, non-pyrogenic, aqueous solution with pH and salinity adjusted. BETHKIS is administered by a compressed air driven reusable nebulizer. The chemical formula for tobramycin is C 18 H 37 N 5 O 9 and the molecular weight is 467.52.
Tobramycin is 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. The structural formula for tobramycin is: Each single-use 4 mL ampule of BETHKIS contains one 300 mg dose of tobramycin, with sodium chloride and sulfuric acid in water for injection. Sulfuric acid and sodium hydroxide are used, as needed, to adjust the pH to 5.0.
Nitrogen is used for sparging, filling and pouching. The formulation contains no preservatives. Tobramycin structural formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Information for Patients Information on the long term efficacy and safety of BETHKIS is limited. There is no information in patients with severe cystic fibrosis (FEV 1 < 40% predicted).
Patients should be advised to complete a full 28-day course of BETHKIS, even if they are feeling better. After 28 days of therapy, patients should stop BETHKIS therapy for the next 28 days, and then resume therapy for the next 28 day on and 28 day off cycle. For patients taking several different inhaled medications and/or performing chest physiotherapy, advise the patient regarding the order they should take the therapies.
It is recommended that BETHKIS be taken last. BETHKIS is to be used with the PARI LC PLUS reusable nebulizer and the PARI VIOS air compressor. Refer to the manufacturer’s instructions for care and use of the nebulizer and compressor.
17.1Ototoxicity Inform patients that ototoxicity, as measured by complaints of hearing loss or tinnitus, was reported by patients treated with tobramycin. Physicians should consider an audiogram at baseline, particularly for patients at increased risk of auditory dysfunction. If a patient reports tinnitus or hearing loss during BETHKIS therapy, the physician should refer that patient for audiological assessment.
Patients should be reminded that vestibular toxicity may manifest as vertigo, ataxia, or dizzines.
17.2Bronchospasm Inform patients that bronchospasm can occur with inhalation of tobramycin.
17.3Risks Associated with Aminoglycosides Inform patients of adverse reactions associated with aminoglycosides such as nephrotoxicity and neuromuscular disorders.
17.4Laboratory Tests Inform patients of the need to monitor hearing, serum concentrations of tobramycin, or renal function as necessary during treatment with BETHKIS.
17.5Embryo-Fetal Toxicity Inform patients that aminoglycosides can cause fetal harm when administered to a pregnant woman. Advise them to inform their doctor if they are pregnant, become pregnant, or plan to become pregnant.
17.6Administration Patients should be informed about what to do in the event they miss a dose of BETHKIS: In case a dose of BETHKIS is missed and there are at least 6 hours until the next dose, patients should be instructed to take the prescribed dose of BETHKIS as soon as possible. Otherwise, the missed dose should not be taken and the patient should resume the usual dosing schedule. Patients should be advised to contact their healthcare provider if they have questions.
17.7Storage Instructions You should store BETHKIS ampules in a refrigerator (36-46 °F or 2-8 °C). However, when you don’t have a refrigerator available (e.g., transporting your BETHKIS), you may store the foil pouches (opened or unopened) at room temperature (up to 77 °F/25 °C) for up to 28 days. BETHKIS is light sensitive; unopened ampules should be returned to the foil pouch.
Avoid exposing BETHKIS ampules to intense light. Unrefrigerated BETHKIS, which is normally colorless to pale yellow, may darken with age; however, the color change does not indicate any change in the quality of the product. You should not use BETHKIS if it is cloudy, if there are particles in the solution, or if it has been stored at room temperature for more than 28 days.
You should not use BETHKIS beyond the expiration date stamped on the ampule. Nebulizers and Compressors: 1-800-327-8632 BETHKIS: 1-888-661-9260 U.S. Patent 6,987,094.
Manufactured for Chiesi USA, Inc. by Woodstock Sterile Solutions, Inc. Woodstock, Illinois 60098 © Chiesi USA, Inc. 2023 Printed in USA CTB-004-1022-07-SPL