TOBI Podhaler Tobramycin 28 mg Capsule, 56-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Aminoglycoside Antibacterial class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- That on-off cycle is how the inhaled tobramycin products are designed to work for cystic fibrosis. You use it for 28 days to reduce the Pseudomonas aeruginosa bacteria in your lung...
- I have cystic fibrosis. Why is tobramycin given in a cycle of 28 days on and 28 days off?
- No — TOBI Podhaler capsules must never be swallowed. They are specially designed to be inhaled using the Podhaler device, which delivers the medicine directly to your lungs where i...
- Can I swallow the TOBI Podhaler capsules if I have trouble using the inhaler?
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 043IPI2M0K
A phospholipid derived from natural sources, commonly used as an emulsifier and surfactant in medicines. It helps mix oil and water-based ingredients together and is often used in injectable formulations and lipid-based drug delivery systems.
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UNII M4I0D6VV5M
Calcium chloride is a salt compound that acts as a firming agent and source of calcium ions in medications. It's used in formulations to help maintain tablet structure, improve texture, or serve as a buffering agent.
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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.
3 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $51.48 | $2,882.85 / 56 capsules |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| TOBI Podhaler 28 mgthis 49502-0401-57 | Viatris | 56 capsules | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 8869794 ↗ | Method of use | U-909 | Sep 12, 2028 |
| US 10207066 ↗ | Method of use | U-909 | Nov 4, 2030 |
Is there a generic version of TOBI PODHALER 28 MG INHALE CAP?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
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💊 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 |
|---|---|---|---|
| 49502-0401-09 | 8 CAPSULE in 1 BOX, UNIT-DOSE (49502-401-09) | 2022-10-04 | Active |
| 49502-0401-24 | 224 PACKAGE in 1 BOX, UNIT-DOSE (49502-401-24) / 56 BLISTER PACK in 1 PACKAGE / 4 CAPSULE in 1 BLISTER PACK | 2021-09-01 | Active |
| 49502-0401-57 You're viewing this | 7 BLISTER PACK in 1 BOX, UNIT-DOSE (49502-401-57) / 8 CAPSULE in 1 BLISTER PACK | 2022-10-04 | Active |
This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓
Pack size FAQ
What quantity is in NDC 49502-0401-57?
What is the difference between NDC 49502-0401-57 and NDC 49502-0401-09?
What NDC number is used to bill for this package of TOBI Podhaler Tobramycin 28 mg Capsule?
🧭 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 | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE TOBI Podhaler 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 6 years, patients with forced expiratory volume in 1 second (FEV 1 ) <25% or >80% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14) ] . TOBI Podhaler is an aminoglycoside antibacterial indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa .
Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV 1 ) <25% or >80%, or patients colonized with Burkholderia cepacia ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION DO NOT SWALLOW TOBI PODHALER CAPSULES FOR USE WITH THE PODHALER DEVICE ONLY FOR ORAL INHALATION ONLY TOBI Podhaler capsules must not be swallowed as the intended effects in the lungs will not be obtained. The contents of TOBI Podhaler capsules are only for oral inhalation and should only be used with the Podhaler device. The recommended dosage of TOBI Podhaler for both adults and pediatric patients 6 years of age and older is the inhalation of the contents of four 28 mg TOBI Podhaler capsules twice-daily for 28 days using the Podhaler device.
Refer to the Instructions For Use (IFU) for full administration information. Dosage is not adjusted by weight. Each dose of four capsules should be taken as close to 12 hours apart as possible; each dose should not be taken less than 6 hours apart.
TOBI Podhaler is administered twice-daily in alternating periods of 28 days. After 28 days of therapy, patients should stop TOBI Podhaler therapy for the next 28 days, and then resume therapy for the next 28-day on and 28-day off cycle. TOBI Podhaler capsules should always be stored in the blister and each capsule should only be removed IMMEDIATELY BEFORE USE.
For patients taking several different inhaled medications and/or performing chest physiotherapy, the order of therapies should follow the physician’s recommendation. It is recommended that TOBI Podhaler is taken last. • DO NOT swallow TOBI Podhaler capsules ( 2 ) • For use with the Podhaler device only ( 2 ) • For oral inhalation only ( 2 ) • The recommended dosage is the inhalation of four 28 mg capsules twice-daily for 28 days ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Inhalation powder: 28 mg: clear, colorless hypromellose capsule with “MYL TPH” in blue radial imprint on one part of the capsule and the Mylan logo in blue radial imprint on the other part of the capsule. Inhalation powder: 28 mg in a capsule ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS TOBI Podhaler is contraindicated in patients with a known hypersensitivity to any aminoglycoside. Known hypersensitivity to any aminoglycoside ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected auditory, vestibular, renal, or neuromuscular dysfunction ( 5.2 , 5.3 , 5.4 ) • Ototoxicity, as measured by complaints of hearing loss or tinnitus, was reported in clinical trials ( 5.2 ) • Aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function ( 5.6 ) • Bronchospasm can occur with inhalation of TOBI Podhaler ( 5.1 ) • Audiograms, serum concentrations, and renal function should be monitored as appropriate ( 5.3 , 5.5 , 5.6 ) • Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm Apprise women of the potential hazard to the fetus ( 5.6 , 8.1 )
5.1Bronchospasm Bronchospasm has been reported with inhalation of TOBI Podhaler [see Adverse Reactions (6.1) ] . Bronchospasm should be treated as medically appropriate.
5.2Ototoxicity Ototoxicity with use of TOBI Podhaler Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected auditory or vestibular dysfunction. Ototoxicity, as measured by complaints of hearing loss or tinnitus, was reported by patients in the TOBI Podhaler clinical studies [see Adverse Reactions (6.1) ] . Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution.
Ototoxicity, manifested as both auditory (hearing loss) and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness. 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.
5.3Nephrotoxicity Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected renal dysfunction. Nephrotoxicity was not observed during TOBI Podhaler clinical studies but has been associated with aminoglycosides as a class.
5.4Neuromuscular Disorders Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected neuromuscular dysfunction. TOBI Podhaler should be used cautiously in patients with neuromuscular disorders, such as myasthenia gravis or Parkinson’s disease, since aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.
5.5Embryo-Fetal Toxicity Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. However, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3) ] .
Patients who use TOBI Podhaler during pregnancy, or become pregnant while taking TOBI Podhaler should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1) ] .
5.6Concomitant Use of Systemic Aminoglycosides Patients receiving concomitant TOBI and parenteral aminoglycoside therapy should be monitored as clinically appropriate for toxicities associated with aminoglycosides as a class. Serum tobramy…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most common adverse reactions (≥10 % of TOBI Podhaler and TOBI patients in primary safety population) are cough, lung disorder, productive cough, dyspnea, pyrexia, oropharyngeal pain, dysphonia, hemoptysis, and headache ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) 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 the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. TOBI Podhaler has been evaluated for safety in 425 cystic fibrosis patients exposed to at least one dose of TOBI Podhaler, including 273 patients who were exposed across three cycles (6 months) of treatment. Each cycle consisted of 28 days on-treatment (with 112 mg administered twice-daily) and 28 days off-treatment.
Patients with serum creatinine ≥2 mg/dL and blood urea nitrogen (BUN) ≥40 mg/dL were excluded from clinical studies. There were 218 males and 207 females in this population, and reflecting the cystic fibrosis population in the U.S., the vast majority of patients were Caucasian. There were 221 patients ≥20 years old, 121 patients ≥13 to <20 years old, and 83 patients ≥6 to <13 years old.
There were 239 patients with screening FEV 1 % predicted ≥50%, 156 patients with screening FEV 1 % predicted <50%, and 30 patients with missing FEV 1 % predicted. The primary safety population reflects patients from Study 1, an open-label study comparing TOBI Podhaler with TOBI (tobramycin inhalation solution, USP) over three cycles of 4 weeks on treatment followed by 4 weeks off treatment. Randomization, in a planned 3:2 ratio, resulted in 308 patients treated with TOBI Podhaler and 209 patients treated with TOBI.
For both the TOBI Podhaler and TOBI groups, mean exposure to medication for each cycle was 28 to 29 days. The mean age for both arms was between 25 and 26 years old. The mean baseline FEV 1 % predicted for both arms was 53%.
Table 1 displays adverse drug reactions reported by at least 2% of TOBI Podhaler patients in Study 1, inclusive of all cycles (on and off treatment). Adverse drug reactions are listed according to MedDRA system organ class and sorted within system organ class group in descending order of frequency. Table 1: Adverse Reactions Reported in Study 1 (Occurring in ≥2% of TOBI Podhaler Patients) Primary System Organ Class Preferred Term TOBI Podhaler N=308 % TOBI N=209 % Respiratory, thoracic, and mediastinal disorders Cough 48.4
31.1Lung disorder This includes adverse events of pulmonary or cystic fibrosis exacerbations 33.8
30.1Productive cough 18.2
19.6Dyspnea 15.6
12.4Oropharyngeal pain 14.0
10.5Dysphonia 13.6
3.8Hemoptysis 13.0
12.4Nasal congestion 8.1
7.2Rales 7.1
6.2Wheezing 6.8
6.2Chest discomfort 6.5
2.9Throat irritation 4.5
1.9Gastrointestinal disorders Nausea 7.5
9.6Vomiting 6.2
5.7Diarrhea 4.2
1.9Dysgeusia 3.9
0.5Infections and infestations Upper respiratory tract infection 6.8
8.6Investigations Pulmonary function test decreased 6.8
8.1Forced expiratory volume decreased 3.9
1.0Blood glucose increased 2.9
0.5Vascular disorders Epistaxis 2.6
1.9Nervous system disorders Headache 11.4
12.0General disorders and administration site conditions Pyrexia 15.6
12.4Musculoskeletal and connective tissue disorders Musculoskeletal chest pain 4.5
4.8Skin and subcutaneous tissue disorders Rash 2.3
2.4Adverse drug reactions that occurred in <2% of patients treated with TOBI Podhaler in Study 1 were: bronchospasm (TOBI Podhaler 1.6%, TOBI 0.5%); deafness including deafness unilateral (reported as mild to moderate hearing loss or increased hearing loss) (TOBI Podhaler 1.0%, TOBI 0.5%); and tinnitus (TOBI Podhaler 1.9%, TOBI 2.4%). Discontinuations in Study 1 were higher in the TOBI Podhaler arm compared to TOBI (27%…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No clinical drug interaction studies have been performed with TOBI Podhaler. In clinical studies, patients receiving TOBI Podhaler continued to take dornase alfa, bronchodilators, inhaled corticosteroids, and macrolides. No clinical signs of drug interactions with these medicines were identified.
Concurrent and/or sequential use of TOBI Podhaler with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided. Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. TOBI Podhaler should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol.
The interaction between inhaled mannitol and TOBI Podhaler has not been evaluated. Concurrent and/or sequential use of TOBI Podhaler with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided ( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
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 (5.5) ] . Although there are no available data on TOBI Podhaler use in pregnant women 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 TOBI Podhaler. 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.
Doses of tobramycin ≥40 mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during non-clinical reproductive toxicity studies with tobramycin.
8.2Lactation Risk Summary There are no data on the presence of tobramycin following administration of TOBI Podhaler in either human or animal milk, the effects on the breastfed infant, or the effects 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 [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 TOBI Podhaler and any potential adverse effects on the breastfed infant from TOBI Podhaler 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 Patients 6 years and older were included in the Phase 3 studies with TOBI Podhaler; 206 patients below 20 years of age received TOBI Podhaler. No dosage adjustments are needed based on age. The overall pattern of adverse events in pediatric patients was similar to the adults.
Dysgeusia (taste disturbance) was more commonly reported in younger patients six to 19 years of age than in patients 20 years and older, 7.4% versus 2.7%, respectively. Safety and effectiveness in pediatric patients below the age of 6 years have not been established.
8.5Geriatric Use Clinical studies of TOBI Podhaler did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Tobramycin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug m…
🤰 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 (5.5) ] . Although there are no available data on TOBI Podhaler use in pregnant women 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 TOBI Podhaler. 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.
Doses of tobramycin ≥40 mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during non-clinical reproductive toxicity studies with tobramycin.
🧒 Pediatric Use ▾
8.4Pediatric Use Patients 6 years and older were included in the Phase 3 studies with TOBI Podhaler; 206 patients below 20 years of age received TOBI Podhaler. No dosage adjustments are needed based on age. The overall pattern of adverse events in pediatric patients was similar to the adults.
Dysgeusia (taste disturbance) was more commonly reported in younger patients six to 19 years of age than in patients 20 years and older, 7.4% versus 2.7%, respectively. Safety and effectiveness in pediatric patients below the age of 6 years have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of TOBI Podhaler did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. 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 The maximum tolerated daily dose of TOBI Podhaler has not been established. In the event of accidental oral ingestion of TOBI Podhaler capsules, systemic toxicity is unlikely as tobramycin is poorly absorbed. Tobramycin serum concentrations may be helpful in monitoring overdosage.
Acute toxicity should be treated with immediate withdrawal of TOBI Podhaler, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing tobramycin from the body. 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 Tobramycin is an aminoglycoside antibacterial [see Clinical Pharmacology (12.4) ] .
12.3Pharmacokinetics Absorption TOBI Podhaler contains tobramycin, a cationic polar molecule that does not readily cross epithelial membranes. TOBI Podhaler is specifically formulated for administration by oral inhalation. The systemic exposure to tobramycin after inhalation of TOBI Podhaler is expected to result from pulmonary absorption of the dose fraction delivered to the lungs as tobramycin and is not absorbed to any appreciable extent when administered via the oral route.
Serum Concentrations After inhalation of a 112 mg single dose (4 times 28 mg capsules) of TOBI Podhaler in cystic fibrosis patients, the maximum serum concentration (C max ) of tobramycin was 1.02 ± 0.53 mcg/mL (mean ± SD) and the median time to reach the peak concentration (T max ) was 1 hour. In comparison, after inhalation of a single 300 mg dose of TOBI, C max was 1.04 ± 0.58 mcg/mL and median T max was 1 hour. The extent of systemic exposure (AUC 0-12 ) was also similar: 4.6 ± 2.0 mcg∙h/mL following the 112 mg TOBI Podhaler dose and 4.8 ± 2.5 mcg∙h/mL following the 300 mg TOBI dose.
At the end of a 4-week dosing cycle of TOBI Podhaler (112 mg twice-daily), the maximum serum concentration of tobramycin 1 hour after dosing ranged from 1.48 ± 0.69 mcg/mL to 1.99 ± 0.59 mcg/mL (mean ± SD). Sputum Concentrations After inhalation of a 112 mg single dose (4 times 28 mg capsules) of TOBI Podhaler in cystic fibrosis patients, sputum C max of tobramycin was 1048 ± 1080 mcg/g (mean ± SD). In comparison, after inhalation of a single 300 mg dose of TOBI, sputum C max was 737 ± 1028 mcg/g.
The variability in pharmacokinetic parameters was higher in sputum as compared to serum. Distribution A population pharmacokinetic analysis for TOBI Podhaler in cystic fibrosis patients estimated the apparent volume of distribution of tobramycin in the central compartment to be
85.1L for a typical cystic fibrosis (CF) patient. Binding of tobramycin to serum proteins is negligible. Metabolism Tobramycin is not metabolized and is primarily excreted unchanged in the urine.
Elimination Tobramycin is eliminated from the systemic circulation primarily by glomerular filtration of the unchanged compound. Systemically absorbed tobramycin following TOBI Podhaler administration is also expected to be eliminated principally by glomerular filtration. The apparent terminal half-life of tobramycin in serum after inhalation of a 112 mg single dose of TOBI Podhaler was approximately 3 hours in cystic fibrosis patients and consistent with the half-life of tobramycin after TOBI inhalation.
A population pharmacokinetic analysis for TOBI Podhaler in cystic fibrosis patients aged 6 to 58 years estimated the apparent serum clearance of tobramycin to be
14.5L/h. No clinically relevant covariates that were predictive of tobramycin clearance were identified from this analysis.
12.4Microbiology Mechanism of Action Tobramycin is an aminoglycoside antibacterial produced by Streptomyces tenebrarius . It acts primarily by disrupting protein synthesis leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death. Tobramycin has in vitro activity against Gram-negative bacteria including P. aeruginosa .
It is bactericidal in vitro at peak concentrations equal to or slightly greater than the minimum inhibitory concentration (MIC). Susceptibility Testing Interpretive criteria for inhaled antibacterial products are not defined. The in vitro antimicrobial susceptibility test methods used to determine the susceptibility for parenteral tobramycin therapy can be used to monitor the susceptibility of P. aeruginosa isolated from cystic fibrosis patients.
(1,2,3) The relationship between in vitro susceptibility test results and clinical outcome with TOBI Podhaler therapy is not clear. A single sputum sample from a cystic fibrosis p…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Tobramycin is an aminoglycoside antibacterial [see Clinical Pharmacology (12.4) ] .
Mechanism of Action Tobramycin is an aminoglycoside antibacterial produced by Streptomyces tenebrarius . It acts primarily by disrupting protein synthesis leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death. Tobramycin has in vitro activity against Gram-negative bacteria including P. aeruginosa .
It is bactericidal in vitro at peak concentrations equal to or slightly greater than the minimum inhibitory concentration (MIC).
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied TOBI Podhaler contains aluminum blister-packaged 28 mg TOBI Podhaler (tobramycin inhalation powder) clear, colorless hypromellose capsules with “MYL TPH” in blue radial imprint on one part of the capsule and the Mylan logo in blue radial imprint on the other part of the capsule, and Podhaler devices. Each Podhaler device consists of the inhaler body, mouthpiece, capsule chamber and blue push button. The Podhaler device is provided in a case that protects the device during shipment, storage and its one week in-use period.
Unit dose (blister pack), Box of 224 capsules contains: NDC 49502-401-24 4 weekly packs, each containing: 56 capsules (7 blister cards of 8 capsules) 1 Podhaler device 1 reserve Podhaler device Unit dose (blister pack), Box of 56 capsules (7-day pack) contains: NDC 49502-401-56 56 capsules (7 blister cards of 8 capsules) 1 Podhaler device
16.2Storage and Handling Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect TOBI Podhaler from moisture. o TOBI Podhaler capsules should be used with the Podhaler device only. The Podhaler device should not be used with any other capsules. o Capsules should always be stored in the blister and each capsule should only be removed immediately before use. o Always use the new Podhaler device provided with each weekly pack.
Keep this and all drugs out of the reach of children.
📋 Description ▾
11 DESCRIPTION TOBI Podhaler consists of a dry powder formulation of tobramycin for oral inhalation only with the Podhaler device. The inhalation powder is filled into clear, colorless hypromellose capsules. Each clear, colorless hypromellose capsule contains a spray dried powder of 28 mg of tobramycin active ingredient with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid (for pH adjustment).
The active component of TOBI Podhaler is tobramycin. Tobramycin is an aminoglycoside antibiotic. Its chemical name 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; its structural formula is: Tobramycin has a molecular weight of 467.52, and its empirical formula is C 18 H 37 N 5 O 9 .
Tobramycin is 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. The Podhaler device is a plastic device used to inhale the dry powder contained in the TOBI Podhaler capsule.
Under standardized in vitro testing at a fixed flow rate of 60 L/min and volume of 2 L for 2 seconds, the Podhaler device has a target delivered dose of 102 mg of tobramycin from the mouthpiece (4 capsules per dose). Peak inspiratory flow rate and inhaled volumes were explored in 96 cystic fibrosis patients aged 6 years and older. Older patients with significant disease progression and associated decreases in forced expiratory volume (FEV 1 ) and younger patients with inhaled volumes <1 L were able to generate inspiratory flow rates and volumes required to receive their medication when following the instructions for use.
However, no pediatric patients aged 6 to 10 years with FEV 1 less than 40% predicted were evaluated. 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 ). Important Administration Information Information on the long-term efficacy and safety of TOBI Podhaler is limited. There is no information in patients with limited pulmonary reserve (FEV 1 <25% predicted).
Decreased susceptibility of Pseudomonas aeruginosa to tobramycin has been seen with use of TOBI Podhaler. The relationship between in vitro susceptibility test results and clinical outcome with TOBI Podhaler therapy is not clear. Occurrence of decreased susceptibility on treatment should be monitored, and treatment with an alternative therapy should be considered if clinical worsening is observed.
TOBI Podhaler may not be tolerated by all patients. Patients should be instructed to consider alternative therapy if they are unable to tolerate TOBI Podhaler. Patients should be advised to complete a full 28-day course of TOBI Podhaler, even if they are feeling better.
After 28 days of therapy, patients should stop TOBI Podhaler therapy for the next 28 days, and then resume therapy for the next 28-day on and 28-day off cycle. Patients should be advised that if they have been prescribed a 7-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then they must count each day of use toward the 28 day on-treatment part of their cycle. Patients should only take a total of 28 consecutive days of treatment during a cycle.
Similarly, patients should be advised that if they have been prescribed a 1-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then they must count each day of use toward the 28 day on-treatment part of their cycle. Patients should only take a total of 28 consecutive days of treatment during a cycle. It is important for patients to understand how to correctly administer TOBI Podhaler capsules using the Podhaler device.
It is recommended that caregivers and patients be adequately trained in the proper use of the TOBI Podhaler prior to use. [See Instructions for Use at the end of the Patient Information leaflet.] Caregivers should provide assistance to children using TOBI Podhaler (including preparing the dose for inhalation) particularly for those aged 10 years or younger, and should continue to supervise them until they are able to use the Podhaler device properly without help. For patients taking several different inhaled medications and/or performing chest physiotherapy, advise the patient regarding the order in which they should take the therapies.
It is recommended that TOBI Podhaler be taken last. Difficulty Breathing : Advise patients to inform their physicians if they experience shortness of breath or wheezing after administration of Tobi Podhaler. Tobi Podhaler can cause a narrowing of the airway [see Warnings and Precautions (5.1) ] .
Hearing Loss : Advise patients to inform their physician if they experience ringing in the ears, dizziness, or any changes in hearing because Tobi Podhaler has been associated with hearing loss [see Warnings and Precautions (5.2) ] . Kidney Damage : Advise patients to inform their physician if they have any history of kidney problems because Tobi Podhaler is in a class of drugs that have caused kidney damage [see Warnings and Precautions (5.3) ] . Embryo-Fetal Toxicity: Advise pregnant women that aminoglycosides can cause irreversible congenital deafness when administered to a pregnant woman [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1) ] .
Lactation: Advise a woman to monitor their breastfed infants for diarrhea and/or bloody stools [see Use in Specific Populations (8.2) ] . Cough: Inform patients that cough was reported with the use of TOBI Podhaler in clinical trials. If coughing that may be experienced with TOBI Podhaler becomes bothersome or cannot be tolerated, advise patients that tobramycin inhalation solutio…