Tobramycin Inhalation
FDA Drug Information • Also known as: Tobramycin Inhalation
- Brand Names
- Tobramycin Inhalation
- Drug Class
- Aminoglycoside Antibacterial [EPC]
- Route
- RESPIRATORY (INHALATION)
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
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
What Is Tobramycin Inhalation Used For?
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
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 ) 2.1 Dosage 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. 2.2 Administration 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.
Side Effects (Adverse Reactions)
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. 6.1 Clinical 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
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 ) 7.1 Drugs 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. 7.2 Diuretics 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.
Contraindications
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 )
Pregnancy and Breastfeeding
8.1 Pregnancy 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....
Overdosage
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.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How 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) 16.2 Storage 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. 16.1 How 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)
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.