ADMINISTRATION ROUTES:
IV, IM
ALTERNATIVE NAMES:
DBL Tobramycin, Nebcin, Tobra-day
ICU INDICATIONS:
- Treatment of infections caused by susceptible organisms
- Pseudomonas and other gram negative infections (e.g. Burkholderia cepacia complex) susceptible to tobramycin, especially in patients with cystic fibrosis
PRESENTATION AND ADMINISTRATION:
IV:
80 mg in 2 mL solution
Add required dose to 100 mL compatible IV fluid and administer over 30 minutes. Store at room temperature and protect from light. Compatible with the following IV fluids: Normal saline, 5% dextrose
IM:
Not recommended by this route in ICU
DOSAGE:
7 - 10 mg/kg OD. Max 680 mg
Round dose to nearest 40 mg. Dose at 1800 daily for ease of monitoring. Given over 30 mins by infusion.
For patients with high BMI, consult ICU pharmacist. Dose weight for such patients is calculated based on Ideal Body Weight (IBW) & Actual Body Weight (ABW) thus:
Dose weight = IBW + 0.4 (ABW-IBW)
Subsequent dosing is determined by serum level monitoring which requires both peak and trough levels.
Collect specimens in SST (yellow) or Plain (red) tube for peak & trough levels
- Peak level: taken 30 minutes after finishing infusion (1 hour after starting it)
- Trough level: taken 18 hours after start of infusion (6 hours before second dose)
Level interpretation:
Peak level:
Aim for peak level 20 - 30 mcg/mL. Adjust subsequent doses using the table below:
| Peak level (mcg/mL) | Action |
|---|---|
| > 35 | Ensure trough < 1 mcg/mL. Reduce next dose by 25% |
| 31 - 35 | Reduce next dose by 15% |
| 20 - 30 | Continue current dose |
| 15 - 19 | Increase next dose by 20% |
| < 15 | Increase next dose by 30% |
Trough level:
Aim for trough level < 1 mcg/mL. Change dosing interval rather than dose using the table below:
| Trough level (mcg/mL) | Action |
|---|---|
| < 1.0 | Continue dosing OD. If undetectable, ensure adequate peak |
| 1.0 - 1.5 | Repeat trough after next dose. If trough level higher, increase dosing interval to 36 hourly |
| > 1.5 | Withhold dose. Repeat trough every 12 hours until < 1.0, then restart dosing 48 hourly |
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose in renal impairment
| GFR (ml/min) | DOSE |
|---|---|
| <30 | not recommended |
| 30-39 | 7 mg/kg every 48 hrs. Measure trough, ensuring < 1 mcg/mL |
| 40-59 | 7 mg/kg every 36 hrs. Measure trough, ensuring < 1 mcg/mL |
| ≥ 60 | 7 mg/kg every 24 hrs. Measure trough, ensuring < 1 mcg/mL |
Dose in renal replacement therapy
| MODALITY | DOSE |
|---|---|
| CAPD | 2 mg/kg every 48 hours & measure levels |
| HD | 2 mg/kg post dialysis & measure levels |
| CVVHDF | 2 mg/kg every 48 hours & measure levels OR consider alternative antibiotics |
Tobramycin is removed by dialysis
DOSAGE IN PAEDIATRICS:
7 - 10 mg/kg OD
Reduce dose to 5 mg/kg in first week of life
CLINICAL PHARMACOLOGY:
Tobramycin is a bactericidal aminoglycoside antibiotic with concentration dependent bacterial killing & good post antibiotic effect. Its antibacterial action is by various mechanisms including inhibition of protein synthesis by binding to 30S and 50S ribosomal sub-units.
It is active against a variety of bacteria including:
- Pseudomonas aeruginosa
- Proteus sp (including Proteus mirabilis, morganii, rettgeri and vulgaris)
- Escheria coli
- Klebseilla-Enterobacter-Serratia group
- Citrobacter sp
- Providencia sp
- Staphylococci (including Staphylococci aureus - coagulase-positive & coagulase-negative)
Aminoglycosides have a low order of activity against most gram positive organisms including Streptococcus pyogenes, pneumoniae & enterococci
CONTRAINDICATIONS:
- Hypersensitivity to or previous toxic effects from tobramycin or other aminoglycoside antibiotics
WARNINGS:
Nephrotoxicity & ototoxicity
As with other aminoglycosides, tobramycin is nephro & ototoxic which is more likely with prolonged peak levels > 12mcg/L or trough levels > 2 mcg/L. Concurrent use of other nephrotoxic agents should be avoided. Ototoxicity may manifest with both auditory and vestibular effects. The auditory changes are irreversible, usually bilateral and may be partial or total. Patients with pre-existing renal impairment are at higher risk, as are those exposed to higher doses or longer duration of tobramycin therapy.
PRECAUTIONS:
General:
Tobramycin sulphate contains sodium bisulphite, a sulphite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.
Aminoglycosides should be used with caution in patients with neuromuscular disorders, such as myasthenia gravis, since these drugs may aggravate muscle weakness because of their potential curare-like effects on the neuromuscular junction. They may also be absorbed in significant quantities from body surfaces after local irrigation or application.
Drug/Laboratory Test Interactions:
None reported
Pregnancy:
Avoid due to placental transfer causing toxicity. Total irreversible bilateral congenital deafness has been described in children whose mothers received aminoglycosides during pregnancy.
Nursing Mothers:
Likely to be safe though may alter neonatal gut flora
IMPORTANT DRUG INTERACTIONS IN ICU:
Concurrent and/or sequential use of other potentially neurotoxic and/or nephrotoxic drugs, such as cisplatin, amikacin, neomycin, polymyxin B, colistin, and vancomycin, should be avoided. There is increased risk of nephrotoxicity when co-administered with cyclosporin or tacrolimus.
The concurrent use of tobramycin with potent diuretics, such as frusemide, should be avoided, since certain diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering the antibiotic concentration in serum and tissue.
When used with muscle relaxants (non-depolarising agents and suxamethonium), there is an enhanced relaxant effect. Tobramycin will also cause antagonism of neostigmine and pyridostigmine effects.
ADVERSE REACTIONS:
Neurological:
Headache, lethargy, confusion, disorientation, convulsions, dizziness, hearing loss
Renal:
Nephrotoxicity occurs in 2 - 10% of patients. Predisposing factors include advanced age, pre-existing renal impairment, dehydration and concomitant use of other potentially nephrotoxic medication
Respiratory:
Risk of bronchospasm with nebulised therapy
Cardiovascular:
None known
Gastrointestinal:
Nausea & vomiting, diarrhoea, may alter liver function tests
Skin:
Rash, dermatitis, itching, urticaria
Haematological System:
Anaemia, granulocytopaenia, thrombocytopenia