What is Tobramycin

Tobramycin is a parenterally administered, broad spectrum aminoglycoside antibiotic that is widely used in the treatment of moderate to severe bacterial infections in many different parts of the body due to sensitive organisms. Tobramycin works by killing bacteria or preventing their growth. Tobramycin and other aminoglycosides are typically used in combination with a penicillin or cephalosporin for treatment of severe infections with E. coli, Staphylococcus aureus, Enterobacter, Klebsiella, Serratia, Pseudomonas aeruginosa, and other gram negative bacteria resistant to less toxic antibiotics. Tobramycin injection is most commonly used for septicemia, bacterial endocarditis, peritonitis, meningitis, pelvic inflammatory disease and pneumonia. Tobramycin inhalation is used to treat lung infections in patients with cystic fibrosis. It is breathed into the lungs through the mouth to treat infections caused by the Pseudomonas aeruginosa bacteria. However, tobramycin antibiotic will not work for colds, flu, or other virus infections. Tobramycin is available only with your doctor’s prescription.

Tobramycin was approved for use in the United States in 1980 and is available in multiple generic forms in parenteral formulations; typical adult doses are 3 mg/kg per day im or iv, usually in three divided doses, often after an initial loading dose. The dose of tobramycin must be modified based upon renal function and monitoring of drug levels is advisable. Pediatric formulations, nebulizer solutions for inhalation, and topical formulations for ophthalmologic use are also available.

Tobramycin injection is usually used for serious bacterial infections for which other medicines may not work. However, tobramycin antibiotic may also cause some serious side effects, including damage to your hearing, sense of balance, and kidneys. These side effects may be more likely to occur in elderly patients and newborn infants. You and your doctor should talk about the benefits of tobramycin antibiotic as well as the risks.

Tobramycin injection comes as a liquid to be injected intravenously (into a vein) or intramuscularly (into a muscle). Tobramycin injection is to be administered only by or under the immediate supervision of your doctor. When tobramycin is injected intravenously, it is usually infused (injected slowly) over a period of 20 to 60 minutes once every 6 or 8 hours. The length of your treatment depends on the type of infection you have.

You may receive tobramycin injection in a hospital or you may administer the medication at home. If you will be receiving tobramycin injection at home, your healthcare provider will show you how to use the medication. Be sure that you understand these directions, and ask your healthcare provider if you have any questions.

You should begin to feel better during the first few days of treatment with tobramycin injection. If your symptoms do not improve or get worse, call your doctor.

Use tobramycin injection until you finish the prescription, even if you feel better. If you stop using tobramycin injection too soon or skip doses, your infection may not be completely treated and the bacteria may become resistant to antibiotics.

Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.

Tobramycin is a semisynthetic aminoglycoside, similar in spectrum of activity to gentamicin, that is widely used for severe bacterial infections caused by sensitive agents, primarily aerobic gram negative bacteria. Like other aminoglycosides, tobramycin is thought to act by binding to bacterial ribosomes and inhibiting protein synthesis. Nevertheless, tobramycin is considered bacteriocidal as well as bacteriostatic.

Tobramycin common side effects include dizziness, headache, confusion, nausea and skin rash. Important, dose related adverse effects include ototoxicity (toxic to the ear) and nephrotoxicity (toxic to the kidney), which are shared by all aminoglycosides.

Tobramycin mechanism of action

Tobramycin has bactericidal activity in which it binds to the bacteria ribosomal 30S subunit. Specifically, tobramycin is believed to bind to the A-site on the 16S rRNA, a component of the ribosomal 30S subunit. Through this binding, the genetic code gets misread, and the translation is disrupted, leading to the bacteria being unable to carry out protein synthesis ¹.

Tobramycin special precautions

Before using tobramycin:

• tell your doctor and pharmacist if you are allergic to tobramycin injection; other aminoglycoside antibiotics such as amikacin, gentamicin, kanamycin, neomycin, or streptomycin; sulfites; any other medications; or any of the ingredients in tobramycin injection. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements, you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: other antibiotics such as amoxicillin (Amoxil, Larotid, Moxatag, in Augmentin, in Prevpac), ampicillin, or penicillin; dimenhydrinate (Dramamine); meclizine (Bonine); or nonsteroidal anti-inflammatory drugs such as indomethacin (Indocin, Tivorbex). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with tobramycin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor if you are or have or have ever had cystic fibrosis (an inherited condition that affects the lungs and digestive system), problems with your muscles such as myasthenia gravis, or Parkinson’s disease.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using tobramycin injection.

Tobramycin may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention. Call your doctor right away if you or your child have blistering, peeling, or loosening of the skin; itching; hives; hoarseness; shortness of breath; sores, ulcers, or white spots in the mouth or on the lips; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth after you receive tobramycin.

Stop using tobramycin and check with your doctor right away if you or your child have sudden decrease in hearing or loss of hearing, which may be accompanied by dizziness and ringing in the ears. Tell your doctor if you or your child have dizziness or lightheadedness; feeling of constant movement of self or surroundings; or sensation of spinning. These may be symptoms of damage to your hearing or sense of balance.

Check with your doctor right away if you or your child have blood in the urine, change in frequency of urination or amount of urine, difficulty with breathing, drowsiness, increased thirst, loss of appetite, nausea or vomiting, swelling of feet or lower legs, or weakness. These may be symptoms of a serious kidney problem.

This medicine may cause nerve problems. Check with your doctor right away if you or your child have numbness, skin tingling, muscle twitching, or seizures.

Make sure your doctor knows that you or your child are using tobramycin before having a surgery or other procedures that require you to receive a numbing medicine (e.g., anesthetics, neuromuscular blocking agents). Using tobramycin injection together with numbing medicines may increase your risk of having difficulty in breathing, drowsiness, inability to breathe without assistance, or unusual tiredness or weakness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of tobramycin injection in children. However, tobramycin should be used with caution in premature and newborn infants.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of tobramycin injection in the elderly. However, elderly patients are more likely to develop unwanted effects and to have kidney problems, which may require caution and an adjustment in the dose for patients receiving tobramycin injection.

Tobramycin in pregnancy

FDA pregnancy category D. Do not use tobramycin if you are pregnant. Using tobramycin while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Breastfeeding

There are no adequate studies in women for determining infant risk when using tobramycin during breastfeeding. Tobramycin can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby. Weigh the potential benefits against the potential risks before taking tobramycin while breastfeeding.

Tobramycin Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving tobramycin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using tobramycin with any of the following medicines is not recommended. Your doctor may decide not to treat you with tobramycin or change some of the other medicines you take.

• Ataluren

Using tobramycin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alcuronium
• Atracurium
• Cholera Vaccine, Live
• Cidofovir
• Cisatracurium
• Colistimethate Sodium
• Decamethonium
• Doxacurium
• Ethacrynic Acid
• Fazadinium
• Foscarnet
• Furosemide
• Gallamine
• Hexafluorenium
• Lysine
• Mannitol
• Metocurine
• Mivacurium
• Pancuronium
• Pipecuronium
• Rapacuronium
• Rocuronium
• Succinylcholine
• Tubocurarine
• Vancomycin
• Vecuronium

Using tobramycin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cisplatin
• Cyclosporine

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of tobramycin. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma or
• Sulfite allergy, history of—This medicine contains sodium bisulfite which may cause an allergic reaction in patients with these conditions.
• Burns, extensive or
• Cystic fibrosis—Use with caution. Your doctor may need to change your dose if you have these conditions.
• Kidney disease—Higher blood levels of tobramycin may result, which increases the risk of serious side effects.
• Kidney disease, severe or
• Muscle problems or
• Myasthenia gravis (severe muscle weakness) or
• Nerve problems or
• Parkinson’s disease—Use with caution. May make these conditions worse.

Tobramycin uses

Tobramycin injection is used to treat certain serious infections that are caused by bacteria such as meningitis (infection of the membranes that surround the brain and spinal cord) and infections of the blood, abdomen (stomach area), lungs, skin, bones, joints, and urinary tract. Tobramycin may be inhaled using a nebulizer for cystic fibrosis patients experiencing pulmonary exacerbation from infection ². Tobramycin injection works by killing bacteria.

Use: Labeled Indications

• Cystic fibrosis: Management of cystic fibrosis in adults and pediatric patients ≥6 years of age with Pseudomonas aeruginosa.

Limitations of use: Safety and efficacy have not been demonstrated in patients with FEV1 <40% or >80% predicted (Bethkis) or FEV1 <25% or >80% predicted (TOBI Podhaler) or FEV1 <25% or >75% predicted (Kitabis Pak; TOBI), or in patients colonized with Burkholderia cepacia.

Off Label Uses

Non-cystic fibrosis bronchiectasis

According to a national consensus summary and international guidelines, aerosolized tobramycin should not be used for the treatment and prevention of non-cystic fibrosis bronchiectasis. Aerosolized antibiotics may be considered in patients who have experienced 3 or more exacerbations requiring antibiotic therapy per year; organism sensitivity should be considered when choosing an antibiotic. The risk of adverse events, cost of therapy, and patient status should be considered prior to initiating aerosolized tobramycin because the efficacy of aerosolized tobramycin in the treatment of non-cystic fibrosis bronchiectasis has not been well documented.

Tobramycin dosage

Serious infections: 1 mg/kg IM or IV infusion (over 20 to 60 minutes) every 8 hours

Duration of therapy: 7 to 10 days

Life-threatening infections:

• Initial dose: Up to 5 mg/kg IM or IV infusion (over 20 to 60 minutes), given in equally divided doses 3 to 4 times a day
• Maintenance dose: 3 mg/kg IM or IV infusion (over 20 to 60 minutes), given in equally divided doses 3 to 4 times a day
• Maximum dose: 5 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Maintenance doses should be used as soon as clinically indicated.
• Doses exceeding 5 mg/kg/day should be avoided unless serum levels are closely monitored for toxicity.
• Tobramycin is not routinely indicated in the initial treatment of uncomplicated urinary tract infections UNLESS the organism is resistant to other less toxic antibacterial agents.
• Empiric treatment may begin prior to obtaining susceptibility results.

Uses:

• Serious staphylococcal infections for which penicillin or other less potentially toxic drugs are contraindicated and when bacterial susceptibility testing and clinical judgement indicate its use
• Treatment of septicemia caused by Pseudomonas aeruginosa, Klebsiella species, and Escherichia coli
• Treatment of serious lower respiratory tract infections caused by P aeruginosa, Klebsiella species, Enterobacter species, Serratia species, E coli, and Staphylococcus aureus (penicillinase and non-penicillinase-producing strains)
• Treatment of serious skin, bone, and skin structure infections caused by P aeruginosa, Proteus species, E coli, Klebsiella species, Enterobacter species, S aureus
• Treatment of complicated and recurrent urinary tract infections caused by P aeruginosa, Proteus species (indole-positive/-negative), E coli, Klebsiella species, Enterobacter species, Serratia species, S aureus, Providencia species, and Citrobacter species

Infectious Diseases Society of America (IDSA) Recommendations:

• 5 to 7 mg/kg IV every 24 hours PLUS cefepime, imipenem, meropenem, OR piperacillin/tazobactam

Use: Treatment of catheter-related infections caused by Pseudomonas aeruginosa

Comment: The susceptibility of strains varies.

For Pseudomonas lung infections

For inhalation dosage form (solution):

• Adults and children 6 years of age and older—One ampule or container with 300 milligrams (mg) of tobramycin 2 times a day for 28 days in the nebulizer. Then, stop using this medicine and wait 28 days, and repeat the cycle (28-day on, 28-day off cycle). You should space the doses at least 6 hours apart.
• Children younger than 6 years of age—Use and dose must be determined by your doctor.

For inhalation dosage form (capsule):

• Adults and children 6 years of age and older—Four capsules with 28 milligrams (mg) of tobramycin 2 times a day for 28 days in the Podhaler™ device. Then, stop using this medicine and wait 28 days, and repeat the cycle (28-day on, 28-day off cycle). You should space the doses at least 6 hours apart.
• Children younger than 6 years of age—Use and dose must be determined by your doctor.

Adult dose for Pneumonia with Cystic Fibrosis

INHALATION:

• Inhalation capsules: 112 mg (4 capsules) inhaled via Podhaler (R) 2 times a day
• Inhalation solution: 300 mg inhaled via nebulizer 2 times a day
• Duration of therapy: 28 days

PARENTERAL:

• Serious infections: 1 mg/kg IM or IV infusion (over 20 to 60 minutes) every 8 hours
• Duration of therapy: 7 to 10 days

Life-threatening infections:

• Initial dose: Up to 5 mg/kg IM or IV infusion (over 20 to 60 minutes), given in equally divided doses 3 to 4 times a day
• Maintenance dose: 3 mg/kg IM or IV infusion (over 20 to 60 minutes), given in equally divided doses 3 to 4 times a day
• Maximum dose: 5 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Safety and efficacy of the inhalation solution have not been demonstrated in patients with a predicted forced expiratory volume in 1 second (FEV1) of 25% or less OR greater than 75% at screening, or those colonized with Burkholderia cepacia.
• Doses should be given as close to 12 hours apart as possible; doses should not be given less than 6 hours apart.
• Parenteral formulations should be limited to short-term use.
• After 28 days of treatment with an inhalation formulation, patients should stop treatment for 28 days before restarting treatment for additional 28-day on/28-day off cycles.
• Maintenance doses should be used as soon as clinically indicated.
• Doses exceeding 5 mg/kg/day should be avoided unless serum levels are closely monitored for toxicity.
• In patients with cystic fibrosis, altered pharmacokinetics may result in reduced serum levels of aminoglycosides; measurement of serum levels is recommended as the basis for dose adjustments.
• In patients with severe cystic fibrosis, an initial dosing regimen of 10 mg/kg/day in 4 equally divided doses is suggested by the manufacturer.
• The serum levels should be measured directly during therapy due to wide interpatient variability.

Uses:

• Management of cystic fibrosis in patients with Pseudomonas aeruginosa infections
• Serious staphylococcal infections for which penicillin or other less potentially toxic drugs are contraindicated and when bacterial susceptibility testing and clinical judgement indicate its use
• Treatment of serious lower respiratory tract infections caused by Pseudomonas aeruginosa, Klebsiella species, Enterobacter species, Serratia species, E coli, and Staphylococcus aureus (penicillinase and non-penicillinase-producing strains)

Pediatric dose for Pneumonia with Cystic Fibrosis

INHALATION:

• 6 years and older:
  • Inhalation capsules: 112 mg (4 capsules) inhaled via Podhaler (R) 2 times a day
  • Inhalation solution: 300 mg inhaled via nebulizer 2 times a day
  • Duration of therapy: 28 days

PARENTERAL:

• Premature and full-term neonates 1 week of age or less: Up to 4 mg/kg IM or IV infusion (over 20 to 60 minutes) every 12 hours
• Pediatric patients greater than 1 week of age: 2 to 2.5 mg/kg IM or IV infusion (over 20 to 60 minutes) every 8 hours OR 1.5 to 1.89 mg/kg IM or IV infusion (over 20 to 60 minutes) every 6 hours
• Duration of therapy: 7 to 10 days

Comments:

• Safety and efficacy of the inhalation solution have not been demonstrated in patients with a predicted FEV1 of 25% or less OR greater than 75% at screening, or those colonized with B cepacia.
• Doses should be given as close to 12 hours apart as possible; doses should not be given less than 6 hours apart.
• Parenteral formulations should be limited to short-term use.
• After 28 days of treatment with an inhalation formulation, patients should stop treatment for 28 days before restarting treatment for additional 28-day on/28-day off cycles.
• In patients with cystic fibrosis, altered pharmacokinetics may result in reduced serum levels of aminoglycosides; measurement of serum levels is recommended as the basis for dose adjustments.
• In patients with severe cystic fibrosis, an initial dosing regimen of 10 mg/kg/day in 4 equally divided doses is suggested by the manufacturer.
• The serum levels should be measured directly during therapy due to wide interpatient variability.

Uses:

• Management of cystic fibrosis in patients with P aeruginosa infections
• Serious staphylococcal infections for which penicillin or other less potentially toxic drugs are contraindicated and when bacterial susceptibility testing and clinical judgement indicate its use
• Treatment of serious lower respiratory tract infections caused by P aeruginosa, Klebsiella species, Enterobacter species, Serratia species, E coli, and S aureus (penicillinase and non-penicillinase-producing strains)

What happens if I miss a dose?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Tobramycin side effects

The main noted adverse effects of tobramycin are ototoxicity, nephrotoxicity, and neuromuscular blockade. Therefore, patients should be educated to look out for warning signs of these adverse effects before the initiation of tobramycin therapy ³.

Tobramycin-induced ototoxicity has been reported to occur in 2 to 45% of adults ⁴. The ototoxicity can be vestibular and/or cochlear and is typically dose-dependent. Tobramycin more commonly cause vestibular damage ⁵. Studies have found that tobramycin seem to create reactive oxygen species within the inner ear; this, in turn, causes damage to the vestibular and cochlear sensory cells along with cochlear neurons. Often the vestibular loss is salvageable while hearing loss is irreversible ⁶.

Nephrotoxicity due to tobramycin may appear in up to 10 to 25% of patients ⁴. In patients receiving tobramycin therapy, renal tubular toxicity, decreased blood flow to the kidneys, and reduced GFR most commonly causes the nephrotoxicity seen. Renal effects with tobramycin generally are reversible. Furthermore, there are risk factors associated with the development of tobramycin-induced nephrotoxicity including dehydration, pregnancy, and hepatic dysfunction. Taking other medications concurrently with tobramycin that can cause nephrotoxicity, such as nonsteroidal anti-inflammatory drugs (NSAIDs), cyclosporine, and diuretics, also put a patient at risk for renal problems. It is important to monitor patient renal function when taking tobramycin ⁷.

Aminoglycosides have also demonstrated correlations with neuromuscular blockade. Although this is less common than ototoxicity and nephrotoxicity, patients with diseases affecting the neuromuscular junction and patients using medications prolonging neuromuscular blockade, most notably calcium channel blockers, should be cautious when using tobramycin ⁸.

There is no antidote for tobramycin toxicities. However, agents with protective effects on the ear and kidney may help prevent tobramycin-induced toxicity. In particular, N-acetylcysteine demonstrates promising protective effects on patients using tobramycin ⁹.

Tobramycin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• vomiting
• diarrhea
• pain at the injection site
• headache
• fever

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• rash
• peeling or blistering of the skin
• itching
• hives
• swelling of the eyes, face, throat, tongue, or lips
• difficulty breathing or swallowing
• hoarseness

Incidence not known:

• black, tarry stools
• bleeding gums
• blood in the urine or stools
• chills
• cloudy urine
• clumsiness
• continuing ringing or buzzing or other unexplained noise in the ears
• cough
• cracks in the skin
• decrease in the amount of urine
• dizziness or lightheadedness
• feeling of constant movement of self or surroundings
• feeling of fullness in the ears
• fever
• loss of balance
• loss of heat from the body
• loss or change in hearing
• nausea
• pale skin
• pinpoint red spots on the skin
• red, swollen skin
• scaly skin
• sensation of spinning
• shortness of breath
• sore throat
• trouble in hearing
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unsteadiness
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting

Tobramycin may cause other side effects. Call your doctor if you have any unusual problems while taking tobramycin.

Symptoms of tobramycin overdose may include the following:

• hearing loss
• ringing in the ears
• dizziness
• decreased urination
• swelling of the face, arms, hands, feet, ankles, or lower legs
• unusual tiredness or weakness
• inability to breath without assistance.

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