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Tobramycin Inhalation 300 mg/4mL Solution

by Prasco, LLC · 14 POUCH in 1 CARTON (66993-195-94) / 4 AMPULE in 1 POUCH / 4 mL in 1 AMPULE
NDC 66993-0195-94
🏷️ FDA NDC (as labeled) 66993-195-94 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 66993-195-94
Product NDC 66993-195
11-digit billing NDC 66993019594
NCPDP billing unit ML — per mL (volume)
RxCUI 1314763
UNII VZ8RRZ51VK
Application # NDA201820
SPL Set ID b5b51665-c427-42b9-bd6e-6e3c06f650e1
Established class (EPC) Aminoglycoside Antibacterial
Chemical class Aminoglycosides
DEA schedule Non-controlled
Marketing category NDA AUTHORIZED GENERIC
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2020-09-15
Route RESPIRATORY (INHALATION)
Dosage form SOLUTION
Substance TOBRAMYCIN
GPI-14 07000070002530
GPI class Tobramycin
GCN Seq No 064682
GCN 16122
HICL code 017765
Ingredient (HICL) Tobramycin
HIC1 code W
Therapeutic class — broad (HIC1) Anti-Infecting Agents
HIC2 code W1
Therapeutic class — intermediate (HIC2) Antibiotics
HIC3 code W1F
Therapeutic class — specific (HIC3) Aminoglycoside Antibiotics
AHFS code 08:12.02.00
AHFS class Aminoglycoside Antibiotics
FDB label name TOBRAMYCIN 300 MG/4 ML AMPULE
FDB brand name Tobramycin
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AN · RLD · RS
Why two NDCs? The FDA registers this code as 66993-195-94 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 66993-0195-94. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Aminoglycoside Antibacterial class.

Pharmacologic class Aminoglycoside Antibacterial
Drug family (ATC) Other aminoglycosides, Antibiotics
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerPrasco, LLC
Application holderCHIESI USA INC
FDA applicationNDA201820 (NDA AUTHORIZED GENERIC)
Labeler code66993
First marketedSep 2020
Product typeHuman Prescription Drug
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name TOBRAMYCIN 300 MG/4 ML AMPULE Ingredient Tobramycin
📗 Our plain-language guide HelloPharmacist
  • 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?
📖 Read our full Tobramycin guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 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.

  • 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.
  • 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.
  • 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.
  • 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.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $13.44 $3,010.76 / 224 ml
Medicare drug plans payPart D · Q2 2026 $16.66 $3,731.03 / 224 ml
Medicare Part B allowsASP · J7682 $12.305 / J7682 unit
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🧾 Billing & reimbursement

FDA NDC (as labeled)66993-195-94
11-digit billing NDC66993-0195-94
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ7682
DescriptorTOBRAMYCIN, INHALATION SOLUTION, FDA-APPROVED FINAL PRODUCT, NON-COMPOUNDED, UNIT DOSE FORM, ADMINISTERED THROUGH DME, PER 300 MILLIGRAMS
Billing units / pkg0.25 units
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Tobramycin 300 mg/4mL 00093-3750-28 Teva 7 pouches AN Discontinued
Bethkis 300 mg/4mL 10122-0820-28 Chiesi 7 pouches AN FDA listed
Tobramycin Inhalation 300 mg/4mLthis 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
About this product: this is an authorized generic — the brand-name product marketed without its brand name. Other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2020
On the market since
Sep 2020
📍
2026
Currently FDA-listed
6 years listed
🔒
·
Generic approved (availability unconfirmed)
see note
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 66993-0195-94, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
94
Units reimbursed last 4 qtrs
20.6K
Gross reimbursed last 4 qtrs
$277.2K
Avg / prescription
$2,948.99
Avg / unit
$13.4409
Latest quarter Q4 2025
14Rx
Fee-for-service vs managed care
39% FFS 61% MCO
Fee-for-service · 37 Rx Managed care · 57 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 8,288 units · 21.3 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: 2,480 units · 54.2 per 100k residents LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 9,856 units · 32.3 per 100k residents TX Florida: no data reported FL
Units reimbursed · per 100k residents
21.354.2
gray = no data reported
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Louisiana 54.2 /100k
2 Texas 32.3 /100k
3 California 21.3 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
66993-0195-94 You're viewing this 14 POUCH in 1 CARTON (66993-195-94) / 4 AMPULE in 1 POUCH / 4 mL in 1 AMPULE 2020-09-15 Active

🧭 About this NDC listing & data coverage

Finished prescription product
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 — Not published for this NDC No photo available yet for this listing.
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
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 66993-195-94, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 66993-0195-94, written without dashes as 66993019594. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 66993-0195-94, the first segment (66993) is the labeler code FDA assigned to Prasco, LLC; the middle segment (0195) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (94) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Prasco, LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Prasco, LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J7682 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage 128 words

1 INDICATIONS AND USAGE Tobramycin Inhalation Solution 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 )] . Tobramycin Inhalation Solution 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 ~1 min read

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 Tobramycin Inhalation Solution is for oral inhalation only [see Dosage and Administration ( 2.2 )] . The recommended dosage of Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution is the same for patients regardless of age or weight. Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution 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. Tobramycin Inhalation Solution should not be diluted or mixed with dornase alfa or other medications in the nebulizer. Tobramycin Inhalation Solution is not for subcutaneous, intravenous, or intrathecal administration.

Further patient instructions on how to administer Tobramycin Inhalation Solution are provided in the Patient’s Instructions for Use [see Patient Counseling Information ( 17 )]. Tobramycin Inhalation Solution 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 49 words

3 DOSAGE FORMS AND STRENGTHS Tobramycin Inhalation Solution 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 ampule. ( 16 )

Contraindications 33 words

4 CONTRAINDICATIONS Tobramycin Inhalation Solution is contraindicated in patients with a known hypersensitivity to any aminoglycoside. Tobramycin Inhalation Solution is contraindicated in patients with a known hypersensitivity to any aminoglycoside. ( 4 )

⚠️ Warnings and Cautions ~3 min read

5 WARNINGS AND PRECAUTIONS Caution should be exercised when prescribing Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution.

( 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 Tobramycin Inhalation Solution Caution should be exercised when prescribing Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution and placebo in controlled clinical trials. Hearing loss was reported in two (1.1%) Tobramycin Inhalation Solution-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 Tobramycin Inhalation Solution of ototoxicity, were observed in similar numbers of Tobramycin Inhalation Solution- and placebo-treated patients. Dizziness occurred in two (1.1%) Tobramycin Inhalation Solution-treated patients and one (0.9%) placebo-treated patient and vertigo occurred in two (1.1%) Tobramycin Inhalation Solution-treated patients versus no placebo patients in clinical studies. None of the Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution, 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 Tobramycin Inhalation Solution. 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 Tobramycin Inhalation Solution. 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 Tobramycin Inhalation Solution to patients with known or suspected renal dysfunction. Nephrotoxicity was not seen during Tobramycin Inhalation Solution clinical studies but has been associated with aminoglycosides as a class. Patients with known or suspected renal dysfunction or taking concomitant nephrotoxic dru…

🤒 Adverse Reactions ~3 min read

6 ADVERSE REACTIONS Common adverse reactions (more than 5%) occurring more frequently in Tobramycin Inhalation Solution patients are forced expiratory volume decreased, rales, red blood cell sedimentation rate increased, and dysphonia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories at 1-866-525-0688 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 Tobramycin Inhalation Solution in two placebo-controlled studies in 305 cystic fibrosis patients. Patients receiving Tobramycin Inhalation Solution ranged in age from 6 to 31 years.

In Study 1, an eight week study, 29 patients received Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution group (23% [7/30] vs 3.4% [1/29], respectively).

Five patients in the placebo group compared to none in the Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution group (9.4% [8/85] vs 4.3% [7/161], respectively). Of these, 3 patients in the Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution- and placebo-treated patients. The following adverse reactions were reported in at least 5% of Tobramycin Inhalation Solution-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 Tobramycin Inhalation Solution Patients Adverse Reactions Tobramycin Inhalation Solution 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…

🔄 Drug Interactions 119 words

7 DRUG INTERACTIONS Concurrent and/or sequential use of Tobramycin Inhalation Solution with other drugs with neurotoxic, nephrotoxic or ototoxic potential should be avoided. ( 7.1 ) Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution 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, Tobramycin Inhalation Solution should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. The interaction between inhaled mannitol and Tobramycin Inhalation Solution has not been evaluated.

👥 Use in Specific Populations ~3 min read

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 Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution. 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 Tobramycin Inhalation Solution and any potential adverse effects on the breastfed child from Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution have not been studied in pediatric cystic fibrosis patients under six years of age.

8.5Geriatric Use Clinical studies of Tobramycin Inhalation Solution 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…

🤰 Pregnancy ~1 min read

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 Tobramycin Inhalation Solution 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 25 words

8.4Pediatric Use The safety and efficacy of Tobramycin Inhalation Solution have not been studied in pediatric cystic fibrosis patients under six years of age.

🧓 Geriatric Use 75 words

8.5Geriatric Use Clinical studies of Tobramycin Inhalation Solution 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 107 words

10 OVERDOSAGE No overdoses have been reported with Tobramycin Inhalation Solution 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 ~2 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Tobramycin Inhalation Solution is an aminoglycoside antibacterial [see Clinical Pharmacology ( 12.4 )] .

12.3Pharmacokinetics Tobramycin Inhalation Solution contains tobramycin, a cationic polar molecule that does not readily cross epithelial membranes. 1 The bioavailability of Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution, 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 Tobramycin Inhalation Solution average mean sputum tobramycin concentrations obtained 10 minutes following administration were 717 mcg/g.

Distribution Following administration of Tobramycin Inhalation Solution, 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 Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution 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 Quantit…

🧬 Mechanism of Action 18 words

12.1Mechanism of Action Tobramycin Inhalation Solution is an aminoglycoside antibacterial [see Clinical Pharmacology ( 12.4 )] .

📦 How Supplied / Storage and Handling ~1 min read

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Tobramycin Inhalation Solution 300 mg/4 mL is supplied as a sterile, clear, colorless to pale yellow, non-pyrogenic, aqueous solution and is available as follows: NDC 66993-195-94: 4 mL single-use ampule (carton of 14 foil pouches each containing four ampules)

16.2Storage and Handling Tobramycin Inhalation Solution should be stored under refrigeration at 2°C ‑ 8°C (36°F ‑ 46°F). Upon removal from the refrigerator, or if refrigeration is unavailable, Tobramycin Inhalation Solution pouches (opened or unopened) may be stored at room temperature [up to 25°C (77°F)] for up to 28 days. Tobramycin Inhalation Solution 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)].

Tobramycin Inhalation Solution ampules should not be exposed to intense light. Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution 300 mg/4 mL is supplied as a sterile, clear, colorless to pale yellow, non-pyrogenic, aqueous solution and is available as follows: NDC 66993-195-94: 4 mL single-use ampule (carton of 14 foil pouches each containing four ampules)

📦 Storage and Handling 162 words

16.2Storage and Handling Tobramycin Inhalation Solution should be stored under refrigeration at 2°C ‑ 8°C (36°F ‑ 46°F). Upon removal from the refrigerator, or if refrigeration is unavailable, Tobramycin Inhalation Solution pouches (opened or unopened) may be stored at room temperature [up to 25°C (77°F)] for up to 28 days. Tobramycin Inhalation Solution 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)].

Tobramycin Inhalation Solution ampules should not be exposed to intense light. Tobramycin Inhalation Solution 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 120 words

11 DESCRIPTION Tobramycin Inhalation Solution is a sterile, clear, colorless to pale yellow, non-pyrogenic, aqueous solution with pH and salinity adjusted. Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution 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 ~3 min read

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 Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution, even if they are feeling better. After 28 days of therapy, patients should stop Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution be taken last. Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution.

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 Tobramycin Inhalation Solution: In case a dose of Tobramycin Inhalation Solution is missed and there are at least 6 hours until the next dose, patients should be instructed to take the prescribed dose of Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution ampules in a refrigerator (36-46 °F or 2-8 °C). However, when you don’t have a refrigerator available (e.g., transporting your Tobramycin Inhalation Solution), you may store the foil pouches (opened or unopened) at room temperature (up to 77 °F/25 °C) for up to 28 days. Tobramycin Inhalation Solution is light sensitive; unopened ampules should be returned to the foil pouch.

Avoid exposing Tobramycin Inhalation Solution ampules to intense light. Unrefrigerated Tobramycin Inhalation Solution, 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 Tobramycin Inhalation Solution 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 Tobramycin Inhalation Solution beyond the expiration date stamped on the ampule. Nebulizers and Compressors: 1-800-327-8632 Tobramycin Inhalation Solution: 1-866-525-0688 U.S. Patent 6,987,094.

Manufactured for Prasco L…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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