Nephrotoxicity is a potential adverse effect of tobramycin, which can lead to acute kidney injury and acute renal failure. Factors such as increased serum trough levels, high peak concentrations, cumulative dose, advanced age, volume depletion, and concurrent or sequential use of other nephrotoxic drugs contribute to the risk. It is important to avoid the concurrent or sequential use of other potentially nephrotoxic medications and closely monitor serum tobramycin levels and renal function in all patients receiving the drug. If renal impairment occurs, dosage adjustment or discontinuation of tobramycin may be necessary.
Ototoxicity is another concern associated with tobramycin, characterized by irreversible auditory and vestibular toxicity. This toxicity may continue to develop even after discontinuation of the drug. Risk factors for ototoxicity include high serum concentrations, prolonged therapy, renal impairment, concurrent or sequential use of other ototoxic drugs, and extremes of age. It is crucial to avoid concurrent or sequential use of other potentially ototoxic medications and monitor for signs and symptoms of auditory and vestibular toxicity. If ototoxicity is observed, tobramycin should be discontinued.
Neuromuscular blockade is a potential adverse reaction linked to aminoglycosides, including tobramycin. Close monitoring is necessary during therapy, particularly in high-risk patients with underlying neuromuscular disorders (such as myasthenia gravis) or those receiving neuromuscular-blocking agents concurrently.
Tobramycin and other aminoglycosides have the potential to cause embryo-fetal toxicity when administered to pregnant women. If tobramycin is used during pregnancy or if a patient becomes pregnant while taking the medication, it is important to inform the patient about the potential risks to the fetus.
Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Germany, Japan , Malaysia, India, China, U.S., U.K.,
Tobramycin belongs to the pharmacological class of Macrolide antibiotics.
Tobramycin has been approved to relieve symptoms and also for the treatment and maintenance of Ocular infections, Cystic fibrosis, Non–cystic fibrosis bronchiectasis, Pneumonia, hospital-acquired or ventilator-associated, Bloodstream infection, Cerebrospinal fluid shunt infection, Cystic fibrosis, acute pulmonary exacerbation, Meningitis, bacterial, Peritonitis, treatment, Plague, treatment, Pneumonia, hospital-acquired or ventilator-associated, Sepsis or septic shock, adjunctive empiric gram-negative coverage and Urinary tract infection, complicated.
Tobramycin is readily absorbed after intramuscular or intravenous administration, with peak plasma concentrations (Cmax) achieved within one hour. The bioavailability of tobramycin is approximately 90% when administered intramuscularly. The drug has a large volume of distribution, indicating extensive tissue penetration. Tobramycin is primarily eliminated unchanged by the kidneys through glomerular filtration, with little hepatic metabolism. The half-life of tobramycin is approximately 2 to 3 hours in individuals with normal renal function. In patients with impaired renal function, the elimination half-life may be prolonged. About 80-90% of a dose of tobramycin is excreted unchanged in the urine within 24 hours. Limited data is available regarding the distribution of tobramycin in specific tissues or its metabolism in the body.
The common side effects involved in using Tobramycin are Hematuria, Urinary frequency or volume changes, Respiratory difficulty, Somnolence, Polydipsia, Anorexia, Nausea, Edema, Emesis.
Tobramycin is available in the form of Injectables, Ophthalmic solution , Ophthalmic ointment, Inhalation Solution.
Tobramycin is approved in Germany, Japan, Malaysia, India, the U.K., the U.S, and China.
Tobramycin belongs to the pharmacological class of Macrolide antibiotics.
Tobramycin is an aminoglycoside antibiotic that contains a 4,6-disubstituted 2-deoxystreptamine (DOS) ring structure. It is effective against various Gram-negative bacteria and some Gram-positive bacteria. The precise mechanism of action of tobramycin is not fully understood, and our understanding of its mechanism is based on studies conducted on similar aminoglycosides. Generally, tobramycin is bactericidal, meaning it kills bacteria, and it demonstrates both immediate and delayed killing, which are believed to occur through different mechanisms.
Tobramycin has been approved to relieve symptoms and also for the treatment and maintenance of Ocular infections, Cystic fibrosis, Non–cystic fibrosis bronchiectasis, Pneumonia, hospital-acquired or ventilator-associated, Bloodstream infection, Cerebrospinal fluid shunt infection, Cystic fibrosis, acute pulmonary exacerbation, Meningitis, bacterial, Peritonitis, treatment, Plague, treatment, Pneumonia, hospital-acquired or ventilator-associated, Sepsis or septic shock, adjunctive empiric gram-negative coverage and Urinary tract infection, complicated.
Tobramycin is found to be available in the form of Injectables, Ophthalmic solution , Ophthalmic ointment, Inhalation Solution.
Tobramycin can be used in the following treatment:
● Ocular infections
● Cystic fibrosis
● Non–cystic fibrosis bronchiectasis
● Pneumonia, hospital-acquired or ventilator-associated
● Bloodstream infection
● Cerebrospinal fluid shunt infection
● Cystic fibrosis, acute pulmonary exacerbation
● Meningitis, bacterial
● Peritonitis, treatment
● Plague, treatment
● Pneumonia, hospital-acquired or ventilator-associated
● Sepsis or septic shock, adjunctive empiric gram-negative coverage
● Urinary tract infection, complicated
Tobramycin can help to relieve symptoms and also for the treatment and maintenance of Ocular infections, Cystic fibrosis, Non–cystic fibrosis bronchiectasis, Pneumonia, hospital-acquired or ventilator-associated, Bloodstream infection, Cerebrospinal fluid shunt infection, Cystic fibrosis, acute pulmonary exacerbation, Meningitis, bacterial, Peritonitis, treatment, Plague, treatment, Pneumonia, hospital-acquired or ventilator-associated, Sepsis or septic shock, adjunctive empiric gram-negative coverage and Urinary tract infection, complicated.
Tobramycin is approved for use in the following clinical indications:
● Ocular infections
● Cystic fibrosis
● Non–cystic fibrosis bronchiectasis
● Pneumonia, hospital-acquired or ventilator-associated
● Bloodstream infection
● Cerebrospinal fluid shunt infection
● Cystic fibrosis, acute pulmonary exacerbation
● Meningitis, bacterial
● Peritonitis, treatment
● Plague, treatment
● Pneumonia, hospital-acquired or ventilator-associated
● Sepsis or septic shock, adjunctive empiric gram-negative coverage
● Urinary tract infection, complicated
- Ocular Infections:
Ophthalmic ointment: 0.3% (3 mg/g)
Ophthalmic solution: 0.3% (3 mg/mL) or 0.6% (6 mg/mL)
- Cystic Fibrosis:
Inhalation solution: 300 mg/5 mL
- Non-Cystic Fibrosis Bronchiectasis:
Inhalation solution: Dosage strengths may vary.
- Pneumonia, Hospital-acquired or Ventilator-associated:
Intravenous (IV) solution: Various strengths available, such as 40 mg/mL, 80 mg/2 mL, 120 mg/2 mL, 150 mg/2 mL, 200 mg/2 mL, and 300 mg/2 mL. The specific dosage strength will depend on the severity of the infection and patient factors.
- Bloodstream Infection:
IV solution: Dosage strengths may vary.
- Cerebrospinal Fluid Shunt Infection:
Intrathecal/Intraventricular solution: Dosage strengths may vary.
- Acute Pulmonary Exacerbation in Cystic Fibrosis:
Inhalation solution: 300 mg/5 mL
- Bacterial Meningitis:
IV solution: Dosage strengths may vary.
- Peritonitis:
IV solution: Dosage strengths may vary.
- Plague:
IV solution: Dosage strengths may vary.
- Sepsis or Septic Shock (Adjunctive Empiric Gram-negative Coverage):
IV solution: Dosage strengths may vary.
- Complicated Urinary Tract Infection:
IV solution: Dosage strengths may vary.
Following a single dose of 112 mg, the maximum concentration (Cmax) in serum was 1.02 ± 0.53 μg/mL, reached within one hour (Tmax). In contrast, the Cmax in sputum was 1048 ± 1080 μg/g. For a 300 mg dose, the serum Cmax was 1.04 ± 0.58 μg/mL, also achieved within one hour, while the sputum Cmax was 737 ± 1028 μg/g. The overall exposure to the drug (AUC0-12) was similar for both doses, measuring at 4.6 ± 2.0 μg∙h/mL for the 112 mg dose and 4.8 ± 2.5 μg∙h/mL for the 300 mg dose. When tobramycin was administered twice daily at a dose of 112 mg over a four-week cycle, the Cmax observed one hour after dosing ranged from 1.48 ± 0.69 μg/mL to 1.99 ± 0.59 μg/mL.
- Dosage Adjustments in Pediatric Patients:
- For Intramuscular (IM) administration: Tobramycin can be given without dilution.
For Intravenous (IV) administration: Tobramycin should be administered by intermittent infusion over a period of 20 to 60 minutes. In pediatric patients, including preterm and term neonates, receiving doses of ≤4 mg/kg, shorter infusion times of ≤5 minutes have been reported (Ref). If possible, avoid simultaneous infusion with penicillins or cephalosporins. For more information, please consult the drug interactions database.
- For Intrathecal/Intraventricular administration: Only use preservative-free preparations of tobramycin, and dilute the solution before administration. There is no specific information available on the administration technique. However, it has been suggested that instilling small volumes of less than 3 mL over a period of 1 to 2 minutes is safe (Ref). When administered through a ventricular drain, clamp the drain for 15 to 60 minutes to allow the tobramycin solution to equilibrate in the cerebrospinal fluid (CSF) (Ref).
- Treatment for eradicating new or initial Pseudomonas aeruginosa airway culture in patients with cystic fibrosis:
Limited data is available for the following age groups:
Infants aged 6 months and older, children, and adolescents:
Inhalation: 300 mg every 12 hours for a duration of 28 days
- Maintenance of chronic lung infection caused by Pseudomonas aeruginosa colonization:
For patients with cystic fibrosis:
Bethkis, Kitabis Pak, Tobramycin: Children and adolescents (limited data available for children under 6 years):
Inhalation: 300 mg every 12 hours; administer in repeated cycles of 28 days on the drug followed by 28 days off the drug .
Tobramycin Podhaler: Children aged 6 years and older, and adolescents:
Inhalation: 112 mg (4 x 28 mg capsules) every 12 hours; administer in repeated cycles of 28 days on the drug followed by 28 days off the drug (manufacturer's labeling).
For patients without cystic fibrosis:
Limited data is available. Please note that the doses mentioned are from initial studies conducted on patients with cystic fibrosis (CF) using the intravenous (IV) product as inhalation .
Children and adolescents:
Inhalation: 80 mg per dose, administered 2 to 3 times daily.
- For ocular infections:
Ophthalmic treatment for infants aged 2 months and older, children, and adolescents:
Ointment:
Mild to moderate infections: Apply a 1/2 inch ribbon of ointment into the affected eye(s) 2 to 3 times daily.
Severe infections: Apply a 1/2 inch ribbon of ointment into the affected eye(s) every 3 to 4 hours initially until improvement, then reduce the frequency of application before discontinuing.
- Solution:
Mild to moderate infections: Instill 1 to 2 drops into the affected eye(s) every 4 hours.
Severe infections: Instill 2 drops into the affected eye(s) every hour initially until improvement, then reduce the frequency of application before discontinuing.
- Dosage Adjustments in Kidney impairment:
Conventional dosing:
CrCl>60 mL/minute : Administer every 8 hours.
CrCl 40 to 60 mL/minute: Administer every 12 hours.
CrCl 20 to 39 mL/minute: Administer every 24 hours.
CrCl<20 mL/minute: Loading dose, then monitor levels.
- Dosage strengths of Tobramycin
- Intravenous (IV) Solution: Tobramycin IV solution is available in various strengths, including 40 mg/mL, 80 mg/2 mL, 120 mg/2 mL, 150 mg/2 mL, 200 mg/2 mL, and 300 mg/2 mL.
- Inhalation Solution: Tobramycin inhalation solution is commonly available as 300 mg/5 mL strength.
- Ophthalmic Ointment:Tobramycin ophthalmic ointment is typically available in a strength of 0.3% (3 mg/g).
- Ophthalmic Solution:Tobramycin ophthalmic solution is commonly available in strengths of 0.3% (3 mg/mL) and 0.6% (6 mg/mL).
Injectables, Ophthalmic solution , Ophthalmic ointment, Inhalation Solution.
There are no specific dietary restrictions related to the use of Tobramycin. However, it is generally recommended to follow a balanced and healthy diet while undergoing treatment with any medication, including Tobramycin. Eating a nutritious diet can support overall health and aid in the recovery process.
It is important to maintain adequate hydration during treatment with Tobramycin and in general. Drinking an adequate amount of water and fluids can help support kidney function and prevent dehydration.
Tobramycin may be contraindicated under the following conditions:
Patients with a known allergy to Tobramycin or any of its components should avoid using it. Additionally, if a patient has a history of hypersensitivity or serious toxic reactions to aminoglycosides, it may also be contraindicated to use any other aminoglycoside due to the possibility of cross-sensitivities that can occur within this class of drugs.
- Caution should be exercised when prescribing Tobramycin to patients with known or suspected renal, auditory, vestibular, or neuromuscular dysfunction. Patients receiving concomitant parenteral aminoglycoside therapy should be monitored as clinically appropriate.
- 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. Patients who use Tobramycin during pregnancy, or become pregnant while taking Tobramycin should be informed about the potential risk to the fetus.
- Gastrointestinal:
- Clostridium difficile-associated disease (CDAD) has been reported with the use of many antibacterial agents, including tobramycin. CDAD can range in severity from mild diarrhea to fatal colitis. Healthcare providers should consider CDAD in patients presenting with diarrhea or symptoms of colitis after antibacterial administration. CDAD can occur even after 2 months of antibacterial therapy. Appropriate measures should be initiated if CDAD is suspected or confirmed.
- The use of Tobramycin may alter the normal flora of the colon, leading to the overgrowth of Clostridium difficile. This can result in CDAD, which may require specific therapeutic interventions.
- Prescribing Tobramycin without a proven or strongly suspected bacterial infection is unlikely to provide benefit and may lead to the development of drug-resistant bacteria.
- The use of Tobramycin may promote the growth of non-susceptible organisms. If superinfection occurs during therapy, appropriate measures should be taken.
- Aminoglycosides, including Tobramycin, can cause auditory and vestibular toxicity. Symptoms may include vertigo, ataxia, dizziness, and tinnitus. Patients experiencing tinnitus should exercise caution.
- Transient tinnitus has been reported in some patients treated with Tobramycin.
- Severe hearing loss has been reported in some patients who received Tobramycin therapy in combination with parenteral aminoglycosides. Tobramycin therapy should be discontinued if ototoxicity occurs until serum concentrations fall below 2 μg/mL.
- While nephrotoxicity was not observed during Tobramycin therapy in clinical studies, it has been associated with aminoglycosides. Tobramycin therapy should be discontinued if nephrotoxicity occurs until serum concentrations fall below 2 μg/mL.
- Tobramycin should be used with caution in patients with neuromuscular disorders like myasthenia gravis or Parkinson's disease, as aminoglycosides may worsen muscle weakness due to their potential curare-like effect on neuromuscular function.
- Bronchospasm can occur with the inhalation of Tobramycin. In clinical studies, a decrease in lung function was observed in a small percentage of Tobramycin-treated patients. Medically appropriate treatment should be provided for bronchospasm.
- Development of Drug-Resistant Bacteria
- Potential for Microbial Overgrowth
- Ototoxicity
- Nephrotoxicity
- Muscular Disorders
- Bronchospasm
Alcohol Warning
There is no specific alcohol warning for Tobramycin. However, it is generally advisable to avoid consuming alcohol while undergoing treatment with any medication, including Tobramycin. Alcohol can have various effects on the body and may interact with medications, potentially leading to adverse reactions or reducing the effectiveness of the treatment.
Additionally, alcohol can strain the liver and kidneys, which are organs involved in the elimination of medications from the body. Since Tobramycin can have potential side effects on these organs, alcohol consumption may exacerbate these effects.
Breast Feeding Warning
Limited information is available regarding the effects of tobramycin on lactating mothers. However, aminoglycosides, including tobramycin, can be excreted into breast milk in small amounts. Although the concentration of tobramycin in breast milk is generally low, there is a potential risk of adverse effects on the nursing infant.
If a lactating mother requires treatment with tobramycin, it is important to weigh the potential benefits against the potential risks to the infant.
Pregnancy Warning
Pregnancy Category B:
The administration of aminoglycosides to pregnant women can pose a risk of fetal harm. These antibiotics are capable of crossing the placenta, and there have been documented cases of irreversible bilateral congenital deafness in children whose mothers were treated with streptomycin during pregnancy. However, no serious side effects to the mother, fetus, or newborn have been reported with the use of other aminoglycosides in pregnant women. If tobramycin is prescribed during pregnancy or if a patient becomes pregnant while taking tobramycin, it is important to inform the patient about the potential risks to the fetus.
Food Warning
There are no specific food warnings related to the use of Tobramycin. However, it is generally recommended to follow a balanced and healthy diet while undergoing treatment with any medication, including Tobramycin. Eating a nutritious diet can support overall health and aid in the recovery process.
The adverse reactions related to Tobramycin can be categorized as follows:
Common:
- Epistaxis (bloody nose)
- Difficulty breathing
- Sputum discoloration
- Fever
- Rhinorrhea (runny nose)
- Sneezing
- Nasal congestion
- Voice changes
Less Common :
- Melena (black, tarry stools)
- Chest pain or tightness
- Chills
- Persistent ringing or buzzing in the ears
- Feeling of fullness in the ears
- Hearing loss
- Loss of balance
- Painful or difficult urination
- Sore throat
- Oral ulcers or white spots
- Swollen glands
- Trouble hearing
- Unusual bleeding or bruising
- Unusual fatigue or weakness
Rare :
- Cough
- Rapid heartbeat
- Hives, itching, or skin rash
- Hoarseness
- Irritation
- Joint pain, stiffness, or swelling
- Mouth or throat pain
- Noisy breathing
- Skin redness
- Swelling of the eyelids, face, lips, hands, or feet
- Difficulty swallowing
Loop Diuretics: Concurrent use of loop diuretics (e.g., furosemide) with tobramycin may increase the risk of kidney damage. Close monitoring of kidney function is advised when these medications are used together.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs, such as ibuprofen or naproxen, may increase the risk of kidney toxicity when used along with tobramycin. Kidney function should be monitored if these medications are used concomitantly.
Neuromuscular Blocking Agents: Tobramycin may enhance the effects of neuromuscular blocking agents, leading to increased muscle weakness or paralysis. Caution is advised when using these medications together, particularly in patients with neuromuscular disorders.
Other Nephrotoxic or Ototoxic Drugs: Concurrent use of other medications that can cause kidney or ear toxicity, such as cisplatin or vancomycin, may increase the risk of these side effects when used with tobramycin. Close monitoring and dose adjustments may be necessary.
Anticoagulants: Tobramycin may potentiate the effects of anticoagulant medications, such as warfarin, leading to an increased risk of bleeding. Frequent monitoring of blood clotting parameters is recommended in patients receiving both medications.
Muscle Relaxants: Tobramycin may enhance the effects of muscle relaxants, such as succinylcholine, leading to prolonged muscle paralysis. Extra caution is needed when these medications are used together.
The following are the side effects involving Tobramycin:
● Nausea
● Vomiting
● Diarrhea
● Loss of appetite
● Abdominal pain or discomfort
● Headache
● Dizziness
● Rash or itching
● Injection site reactions (pain, redness, swelling)
● Changes in kidney function (increased or decreased urine output)
● Changes in hearing (ringing in the ears or hearing loss)
● Irritation or redness of eyes
Pregnancy:
Pregnancy Category B:
The administration of aminoglycosides to pregnant women can pose a risk of fetal harm. These antibiotics are capable of crossing the placenta, and there have been documented cases of irreversible bilateral congenital deafness in children whose mothers were treated with streptomycin during pregnancy. However, no serious side effects to the mother, fetus, or newborn have been reported with the use of other aminoglycosides in pregnant women. If tobramycin is prescribed during pregnancy or if a patient becomes pregnant while taking tobramycin, it is important to inform the patient about the potential risks to the fetus.
Lactation:
Limited information is available regarding the effects of tobramycin on lactating mothers. However, aminoglycosides, including tobramycin, can be excreted into breast milk in small amounts. Although the concentration of tobramycin in breast milk is generally low, there is a potential risk of adverse effects on the nursing infant.
If a lactating mother requires treatment with tobramycin, it is important to weigh the potential benefits against the potential risks to the infant.
Pediatric Use:
The pediatric use of tobramycin in specific populations requires special consideration, particularly regarding potential risks and appropriate dosage adjustments. Tobramycin is an aminoglycoside antibiotic commonly used to treat various infections in children. However, certain factors should be taken into account:
1. Nephrotoxicity and Ototoxicity: Children, especially neonates and infants, may be more susceptible to the nephrotoxic and ototoxic effects of tobramycin. Monitoring renal function and hearing should be a priority during treatment.
2. Dose Adjustment: Pediatric patients with impaired renal function or low glomerular filtration rate may require dosage adjustments to avoid potential toxicity. The dosage should be carefully determined based on the child's age, weight, and renal function.
3. Safety and Efficacy: The safety and efficacy of tobramycin in premature infants, particularly those with extremely low birth weight, need to be carefully evaluated. The benefits of treatment should outweigh the potential risks.
4. Pharmacokinetic Variability: Pediatric patients may exhibit variability in the pharmacokinetics of tobramycin due to factors such as age, weight, and developmental changes. Therapeutic drug monitoring may be necessary to ensure appropriate drug levels.
5. Interaction with Other Drugs: Concomitant use of other nephrotoxic or ototoxic medications should be closely monitored and evaluated for potential interactions and cumulative toxicity.
Geriatric Use:
Elderly individuals may face an increased risk of developing nephrotoxicity and ototoxicity while receiving tobramycin. Several factors can contribute to these adverse effects, including elevated trough levels, excessive peak concentrations, dehydration, concomitant use of other neurotoxic or nephrotoxic drugs, and cumulative dose. It is recommended to periodically measure peak and trough serum levels during therapy to ensure appropriate levels and prevent potentially toxic levels. Tobramycin is primarily eliminated by the kidneys, and patients with impaired renal function are at a higher risk of experiencing toxic reactions. Therefore, dose reduction is necessary for individuals with impaired renal function. It's important to note that elderly patients may have reduced renal function that may not be easily detectable through routine screening tests such as blood urea nitrogen (BUN) or serum creatinine levels. In such cases, a creatinine clearance determination may provide more accurate information. Monitoring renal function during aminoglycoside treatment is particularly crucial in the elderly population.
Furthermore, it should be noted that each vial of tobramycin 20 mg/2 mL contains 1.56 mg (0.068 mEq) of sodium.
Physicians should be knowledgeable as well as vigilant about the treatment and identification of over dosage of Tobramycin.
Signs and symptoms of excessive intravenous (IV) tobramycin dosing may include dizziness, tinnitus, vertigo, reduced high-tone hearing acuity, respiratory failure, neuromuscular blockade, and renal impairment. When tobramycin is administered via inhalation, its systemic bioavailability is low. Oral administration does not result in significant absorption of tobramycin. Monitoring tobramycin serum concentrations can be useful in assessing overdose situations.
In cases of acute toxicity, it is crucial to immediately discontinue the use of TOBI (tobramycin) and perform baseline tests to evaluate renal function. If an overdose is suspected, healthcare professionals should contact the Regional Poison Control Center to obtain information regarding appropriate treatment options. It is important to consider the potential for drug interactions and alterations in drug disposition in cases of overdose. Hemodialysis may be beneficial in eliminating tobramycin from the body.
Pharmacodynamics
Tobramycin, derived from Streptomyces tenebrarius, is an aminoglycoside antibiotic known for its broad spectrum of activity against various Gram-negative bacteria. This includes Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Moraxella lacunata, Proteus spp., Haemophilus spp., Acinetobacter spp., Neisseria spp., and notably, Pseudomonas aeruginosa. It also retains effectiveness against Yersinia pestis and Francisella tularensis, which are biothreat agents. Additionally, tobramycin exhibits activity against certain Gram-positive bacteria such as Staphylococcus spp. (including methicillin-resistant and vancomycin-resistant strains), Streptococcus spp., and Mycobacterium spp.
Similar to other aminoglycosides, tobramycin is taken up and retained by proximal tubule cells in the kidney and cochlear cells in the ear. Consequently, it carries a risk of nephrotoxicity and ototoxicity. There is also a potential for neuromuscular block, particularly in individuals with preexisting neuromuscular disorders like myasthenia gravis or Parkinson's disease. When administered during pregnancy, aminoglycosides can cross the placenta and cause irreversible bilateral congenital deafness in newborns. However, the risk of these adverse effects is generally more significant with injected tobramycin compared to inhaled and topical formulations, which have lower systemic absorption. Nevertheless, all formulations of tobramycin come with the potential for hypersensitivity reactions, including severe cutaneous reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis.
Pharmacokinetics
Absorption
Tobramycin inhalation in cystic fibrosis patients demonstrated higher variability in sputum concentrations compared to serum. After a single 112 mg dose, the maximum serum concentration (Cmax) reached 1.02 ± 0.53 μg/mL within one hour (Tmax), whereas the sputum Cmax was 1048 ± 1080 μg/g. For a 300 mg dose, the serum Cmax was 1.04 ± 0.58 μg/mL, also achieved within one hour, while the sputum Cmax was 737 ± 1028 μg/g. The systemic exposure (AUC0-12) was similar between the two doses, with values of 4.6 ± 2.0 μg∙h/mL for the 112 mg dose and 4.8 ± 2.5 μg∙h/mL for the 300 mg dose. When administered twice daily over a four-week cycle at 112 mg, the Cmax measured one hour after dosing ranged from 1.48 ± 0.69 μg/mL to 1.99 ± 0.59 μg/mL.
Volume of Distribution:
Tobramycin exhibited an apparent volume of distribution in the central compartment of 85.1 L in a typical cystic fibrosis patient.
Protein Binding:
Tobramycin demonstrated negligible binding to serum proteins.
Metabolism:
Tobramycin showed minimal metabolic activity.
Route of Elimination:
The primary route of elimination for tobramycin was renal, with the drug being excreted primarily unchanged in the urine.
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