Tobramycin 300mg/4ml Neb Sol 4ml
It is used in people with cystic fibrosis to treat a certain type of bacterial infection.
Drug Class
Anti-infective
Pharmacologic Class
Aminoglycoside antibiotic
Pregnancy Category
D
FDA Approved
Mar 1997
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tobramycin inhalation solution is an antibiotic medicine used to treat lung infections caused by a specific type of bacteria (Pseudomonas aeruginosa) in people with cystic fibrosis. It is breathed in through a nebulizer directly into the lungs to help kill the bacteria and improve lung function.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. You will inhale this medication through your mouth using a special machine called a nebulizer. Your doctor will show you how to use the nebulizer properly. Be sure to use only the type of nebulizer recommended by your doctor. If you're unsure about the correct nebulizer to use, consult with your doctor.
Continue using this medication as directed by your doctor or healthcare provider, even if you're feeling well. Do not use the medication if the solution appears cloudy, is leaking, or contains particles. Additionally, do not mix other medications in the nebulizer. If you're taking multiple inhaled medications, discuss the best order for taking them with your doctor.
It's essential to follow the cleaning instructions for the nebulizer carefully.
Storage and Disposal
Store this medication in a refrigerator or at room temperature. If stored at room temperature, discard any unused portion after 28 days. Keep unused containers in their foil pouches until you're ready to use them. Do not freeze the medication.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's less than 6 hours until your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses.
To use this medication correctly, follow your doctor's instructions and read all the information provided. You will inhale this medication through your mouth using a special machine called a nebulizer. Your doctor will show you how to use the nebulizer properly. Be sure to use only the type of nebulizer recommended by your doctor. If you're unsure about the correct nebulizer to use, consult with your doctor.
Continue using this medication as directed by your doctor or healthcare provider, even if you're feeling well. Do not use the medication if the solution appears cloudy, is leaking, or contains particles. Additionally, do not mix other medications in the nebulizer. If you're taking multiple inhaled medications, discuss the best order for taking them with your doctor.
It's essential to follow the cleaning instructions for the nebulizer carefully.
Storage and Disposal
Store this medication in a refrigerator or at room temperature. If stored at room temperature, discard any unused portion after 28 days. Keep unused containers in their foil pouches until you're ready to use them. Do not freeze the medication.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's less than 6 hours until your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Administer using a nebulizer (e.g., PARI LC PLUS® Reusable Nebulizer with a suitable air compressor).
- Do not mix with other drugs in the nebulizer.
- Administer in a well-ventilated room.
- Follow the 28-day on, 28-day off dosing cycle strictly.
- Maintain good oral hygiene to reduce risk of oral thrush.
- Stay well-hydrated.
- Report any changes in hearing, balance, or kidney function to your doctor.
Available Forms & Alternatives
Available Strengths:
- Tobramycin 0.3% Oph Sol 5ml
- Tobramycin 40mg/ml Injection 25x2ml
- Tobramycin 80mg/2ml Inj Mdv
- Tobramycin Sulf 40mg/ml Inj, 30ml
- Tobramycin 10mg/ml Inj, 2ml
- Tobramycin 300mg/5ml Inh Sol 5ml
- Tobramycin 80mg/2ml Inj, 2ml
- Tobramycin 1.2/30ml Inj, 30ml
- Tobramycin 300mg/5ml Inh Sol 56x5ml
- Tobramycin 300mg/4ml Neb Sol 4ml
- Tobramycin 40mg/ml Inj, 50ml
- Tobramycin 40mg/ml Inj, 2ml
- Tobramycin 1.2gm Inj, 1 Vial
- Tobramycin 1.2gm Inj 1 Vial
Dosing & Administration
Adult Dosing
Standard Dose:
300 mg (one 4 mL ampule) administered twice daily, every 12 hours, for 28 days. Followed by 28 days off therapy. Repeat cycle.
Dose Range:
300 - 300 mg
Condition-Specific Dosing:
Cystic Fibrosis with Pseudomonas aeruginosa:
300 mg (one 4 mL ampule) administered twice daily, every 12 hours, for 28 days. Followed by 28 days off therapy. Repeat cycle.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established (Safety and efficacy not established in patients under 6 years of age).
Child:
For patients 6 years and older: 300 mg (one 4 mL ampule) administered twice daily, every 12 hours, for 28 days. Followed by 28 days off therapy. Repeat cycle.
Adolescent:
300 mg (one 4 mL ampule) administered twice daily, every 12 hours, for 28 days. Followed by 28 days off therapy. Repeat cycle.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor renal function.
Moderate:
Use with caution. Monitor renal function and serum tobramycin levels. Consider extending dosing interval or reducing dose if systemic accumulation occurs.
Severe:
Use with caution. Monitor renal function and serum tobramycin levels. Consider extending dosing interval or reducing dose if systemic accumulation occurs. Systemic exposure is low with inhalation, but risk of accumulation increases.
Dialysis:
Not specifically studied for inhaled form. For systemic use, dose adjustment is required. Monitor serum levels if systemic absorption is a concern.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
No specific dose adjustment recommended.
Pharmacology
Mechanism of Action
Tobramycin is an aminoglycoside antibiotic. It exerts its bactericidal effect by irreversibly binding to the 30S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. This leads to misreading of the mRNA code, premature termination of protein synthesis, and incorporation of incorrect amino acids, ultimately resulting in bacterial cell death.
Pharmacokinetics
Absorption:
Bioavailability:
Low systemic bioavailability (typically <10% of inhaled dose reaches systemic circulation).
Tmax:
Approximately 1 hour (in sputum), 1-2 hours (in serum).
FoodEffect:
Not applicable for inhaled formulation.
Distribution:
Vd:
Not directly applicable for inhaled form due to primary local action. For systemic tobramycin, Vd is 0.26 L/kg.
ProteinBinding:
Low (<10%).
CnssPenetration:
Limited (poor penetration into CSF even with systemic administration; negligible with inhaled form).
Elimination:
HalfLife:
Approximately 2-3 hours (systemic), but much longer in sputum (up to 12 hours or more).
Clearance:
Primarily renal clearance for systemically absorbed drug.
ExcretionRoute:
Renal (unchanged drug).
Unchanged:
>90% (systemically absorbed portion).
Pharmacodynamics
OnsetOfAction:
Rapid (within minutes of inhalation for local effect).
PeakEffect:
Within 1-2 hours (sputum concentration).
DurationOfAction:
Sustained high concentrations in sputum for up to 12 hours.
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of kidney problems, including:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Changes in balance
Dizziness or fainting
Fever
Muscle weakness
Ringing in the ears, hearing loss, or other changes in hearing
Wheezing
Persistent cough
Coughing up blood
New or worsening breathing difficulties
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Headache
Cough
Increased sputum production
Mouth pain
Throat pain
Sore throat
Changes in taste
Noisy breathing
Changes in voice
Stuffy nose
Upset stomach or vomiting
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of kidney problems, including:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Changes in balance
Dizziness or fainting
Fever
Muscle weakness
Ringing in the ears, hearing loss, or other changes in hearing
Wheezing
Persistent cough
Coughing up blood
New or worsening breathing difficulties
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Headache
Cough
Increased sputum production
Mouth pain
Throat pain
Sore throat
Changes in taste
Noisy breathing
Changes in voice
Stuffy nose
Upset stomach or vomiting
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Increased coughing, wheezing, or shortness of breath immediately after inhalation (bronchospasm)
- Hoarseness or voice changes
- Sore throat or white patches in the mouth (oral thrush)
- Ringing in the ears (tinnitus)
- Difficulty hearing
- Dizziness or feeling off balance
- Changes in how much you urinate, or swelling in your ankles/feet (signs of kidney problems)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are currently taking or have recently taken any of the following medications: Ethacrynic acid, furosemide, mannitol, or urea.
If you are taking or have recently taken any medications that may cause nerve, kidney, or hearing problems, such as:
+ Amphotericin B
+ Bacitracin
+ Cephaloridine
+ Cisplatin
+ Colistin
+ Cyclosporine
+ Paromomycin
+ Polymyxin B
+ Vancomycin
+ Viomycin
+ Other similar medications
Please note that this is not an exhaustive list, and there may be other medications that can interact with this drug. If you are unsure, consult your doctor or pharmacist.
To ensure your safety, it is crucial to inform your doctor and pharmacist about:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
Your medical history and any existing health problems
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to confirm that it is safe to do so.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are currently taking or have recently taken any of the following medications: Ethacrynic acid, furosemide, mannitol, or urea.
If you are taking or have recently taken any medications that may cause nerve, kidney, or hearing problems, such as:
+ Amphotericin B
+ Bacitracin
+ Cephaloridine
+ Cisplatin
+ Colistin
+ Cyclosporine
+ Paromomycin
+ Polymyxin B
+ Vancomycin
+ Viomycin
+ Other similar medications
Please note that this is not an exhaustive list, and there may be other medications that can interact with this drug. If you are unsure, consult your doctor or pharmacist.
To ensure your safety, it is crucial to inform your doctor and pharmacist about:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
Your medical history and any existing health problems
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to confirm that it is safe to do so.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regularly undergo blood work, hearing tests, and other laboratory tests as directed by your doctor to monitor your condition. Do not exceed the prescribed duration of treatment, as this may increase the risk of a second infection.
If you are pregnant or become pregnant while taking this drug, it is crucial to notify your doctor immediately, as it may cause harm to the unborn baby. Additionally, if you are breast-feeding, consult your doctor to discuss potential risks to your baby and determine the best course of action.
If you are pregnant or become pregnant while taking this drug, it is crucial to notify your doctor immediately, as it may cause harm to the unborn baby. Additionally, if you are breast-feeding, consult your doctor to discuss potential risks to your baby and determine the best course of action.
Overdose Information
Overdose Symptoms:
- Severe bronchospasm
- Hoarseness
- Systemic toxicity (if significant absorption occurs): ototoxicity (hearing loss, tinnitus, vertigo), nephrotoxicity (decreased urine output, elevated BUN/creatinine), neuromuscular blockade (muscle weakness, respiratory depression).
What to Do:
Discontinue drug. Provide supportive care. For severe bronchospasm, administer a bronchodilator. In cases of significant systemic absorption and toxicity, hemodialysis may be considered to remove tobramycin from the blood. Call 1-800-222-1222 (Poison Control Center).
Drug Interactions
Major Interactions
- Other aminoglycosides (e.g., amikacin, gentamicin, streptomycin): Increased risk of nephrotoxicity and ototoxicity.
- Amphotericin B, cisplatin, cyclosporine, loop diuretics (e.g., furosemide), vancomycin: Increased risk of nephrotoxicity and/or ototoxicity.
- Neuromuscular blocking agents (e.g., succinylcholine, rocuronium): Potentiation of neuromuscular blockade, leading to respiratory depression or paralysis.
Moderate Interactions
- Cephalosporins (especially cephaloridine): Increased risk of nephrotoxicity (less common with newer cephalosporins).
- Polymyxins (e.g., colistin): Increased risk of nephrotoxicity and neuromuscular blockade.
- Digoxin: Aminoglycosides may increase digoxin levels by altering gut flora, though less likely with inhaled form.
Monitoring
Baseline Monitoring
Pulmonary function tests (FEV1)
Rationale: To establish baseline lung function and monitor response to therapy.
Timing: Prior to initiation of therapy.
Renal function (serum creatinine, BUN)
Rationale: To assess baseline kidney function due to potential for systemic absorption and nephrotoxicity.
Timing: Prior to initiation of therapy.
Audiometry
Rationale: To establish baseline hearing function due to potential for ototoxicity.
Timing: Prior to initiation of therapy.
Routine Monitoring
Pulmonary function tests (FEV1)
Frequency: Every 3-6 months or as clinically indicated.
Target: Improvement or stabilization of FEV1.
Action Threshold: Significant decline in FEV1 may indicate lack of efficacy or worsening disease, requiring re-evaluation.
Renal function (serum creatinine, BUN)
Frequency: Periodically (e.g., every 6-12 months or more frequently if risk factors for nephrotoxicity are present).
Target: Within normal limits for age.
Action Threshold: Significant increase in creatinine or BUN may indicate nephrotoxicity, requiring discontinuation or dose adjustment.
Audiometry
Frequency: Periodically (e.g., every 12-24 months or more frequently if symptoms of ototoxicity occur).
Target: No significant change from baseline.
Action Threshold: Significant hearing loss (especially high-frequency) or vestibular dysfunction may indicate ototoxicity, requiring discontinuation.
Serum tobramycin levels
Frequency: Generally not routinely recommended due to low systemic absorption, but may be considered if there is concern for systemic accumulation (e.g., renal impairment, concomitant nephrotoxic drugs, or unexplained toxicity).
Target: Peak < 2 mcg/mL, Trough < 1 mcg/mL (for inhaled form, these are general guidelines for systemic toxicity avoidance, not efficacy targets).
Action Threshold: Elevated levels may indicate systemic accumulation and increased risk of toxicity, requiring dose adjustment or discontinuation.
Symptom Monitoring
- Bronchospasm (cough, wheezing, shortness of breath) immediately after inhalation
- Hoarseness
- Sore throat
- Oral thrush
- Tinnitus (ringing in ears)
- Hearing loss
- Vertigo or dizziness
- Changes in urine output or swelling (signs of kidney problems)
Special Patient Groups
Pregnancy
Category D. Tobramycin can cause fetal harm when administered systemically to a pregnant woman. Aminoglycosides cross the placenta and have been associated with total, irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. While systemic exposure from inhaled tobramycin is low, the potential for fetal harm cannot be excluded. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity, though data specifically for inhaled form is limited. Risk of ototoxicity to fetus.
Second Trimester:
Risk of ototoxicity to fetus (irreversible congenital deafness).
Third Trimester:
Risk of ototoxicity to fetus (irreversible congenital deafness). Risk of neuromuscular blockade in neonate if administered close to delivery.
Lactation
L3 (Moderately Safe). Tobramycin is excreted in human milk after systemic administration. While systemic absorption from inhaled tobramycin is low, and infant exposure is expected to be minimal, caution should be exercised. Monitor breastfed infant for diarrhea, candidiasis, and potential effects on gut flora. The benefits of breastfeeding should be weighed against the potential risks.
Infant Risk:
Low risk of adverse effects due to poor oral absorption by the infant and low levels in milk. Potential for alteration of infant gut flora or allergic sensitization.
Pediatric Use
Safety and efficacy have not been established in patients under 6 years of age. In patients 6 years and older, the dosing is the same as for adults. Close monitoring for systemic toxicity (renal, auditory) is important, especially in younger children who may have higher systemic absorption relative to body weight.
Geriatric Use
No specific dose adjustment is recommended based on age alone. However, elderly patients are more likely to have decreased renal function, which could increase systemic exposure and risk of toxicity. Monitor renal function and auditory function closely.
Clinical Information
Clinical Pearls
- Tobramycin inhalation solution is specifically for *Pseudomonas aeruginosa* infections in cystic fibrosis patients, not for general respiratory infections.
- Pre-treatment with a bronchodilator (e.g., albuterol) is recommended for patients who experience bronchospasm with tobramycin inhalation.
- Administer tobramycin after other nebulized medications (e.g., dornase alfa) and chest physiotherapy.
- The 28-day on, 28-day off cycle is crucial to minimize the development of bacterial resistance and reduce the risk of toxicity.
- Patients should be instructed on proper nebulizer technique and maintenance.
- Hoarseness and voice changes are common side effects, often reversible upon discontinuation or during the off-cycle.
Alternative Therapies
- Aztreonam for inhalation solution (Cayston)
- Colistimethate sodium for inhalation
- Oral antibiotics (e.g., azithromycin, ciprofloxacin) for chronic suppression
- IV antibiotics (e.g., IV tobramycin, ceftazidime, meropenem) for acute exacerbations
Cost & Coverage
Average Cost:
Varies widely, typically $2,000 - $5,000+ per 28-day supply (56 ampules)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.