What happens if I overdose Tobramycin?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local, or emergency room immediately.
Proper storage of Tobramycin solution:
Store Tobramycin solution in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do not freeze. If necessary, Tobramycin solution may be stored in the foil pouches at room temperature below 77 degrees F (25 degrees C) for up to 28 days. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Tobramycin solution out of the reach of children and away from pets.
Overdose of Tobramycin in details
The maximum tolerated daily dose of Tobramycin has not been established.
In the event of accidental oral ingestion of Tobramycin capsules, systemic toxicity is unlikely as Tobramycin is poorly absorbed. Tobramycin serum concentrations may be helpful in monitoring overdosage.
Acute toxicity should be treated with immediate withdrawal of Tobramycin, and baseline tests of renal function should be undertaken.
Hemodialysis may be helpful in removing Tobramycin from the body.
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.
What should I avoid while taking Tobramycin?
Do not mix Tobramycin solution with dornase alfa (Pulmozyme) in the nebulizer.
Tobramycin warnings
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 apprised of the potential hazard to the fetus.
Ototoxicity
Ototoxicity, as measured by complaints of hearing loss or by audiometric evaluations, did not occur with Tobramycin therapy during clinical studies. However, transient tinnitus occurred in eight Tobramycin-treated patients versus no placebo patients in the clinical studies. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution. Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness.
In postmarketing experience, patients receiving Tobramycin have reported hearing loss. Some of these reports occurred in patients with previous or concomitant treatment with systemic aminoglycosides. Patients with hearing loss frequently reported tinnitus.
Nephrotoxicity
Nephrotoxicity was not seen during Tobramycin clinical studies but has been associated with aminoglycosides as a class. If nephrotoxicity occurs in a patient receiving Tobramycin, Tobramycin therapy should be discontinued until serum concentrations fall below 2 mcg/mL.
Muscular Disorders
Tobramycin should be used cautiously in patients with neuromuscular disorders, such as myasthenia gravis or Parkinson's disease, since aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.
Bronchospasm
Bronchospasm has been reported with inhalation of Tobramycin. In clinical studies of Tobramycin, changes in FEV measured after the inhaled dose were similar in the Tobramycin and placebo groups. Bronchospasm should be treated as medically appropriate.
What should I discuss with my healthcare provider before taking Tobramycin?
Some medical conditions may interact with Tobramycin drops. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
- if you are pregnant, planning to become pregnant, or are breast-feeding
- if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
- if you have allergies to medicines, foods, or other substances
Some MEDICINES MAY INTERACT with Tobramycin drops. Tell your health care provider if you are taking any other medicines, especially any of the following:
- Cephalosporins by injection (eg, ceftazidime) because they may decrease Tobramycin drops's effectiveness
- Cyclosporine, fludarabine, loop diuretics (eg, furosemide), methoxyflurane, nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, indomethacin), nitrosoureas (eg, streptozocin), polypeptide antibiotics (eg, polymyxin B), or vancomycin injection because they may increase the risk of Tobramycin drops's side effects, including increased risk of kidney or hearing problems
- Cephalosporins by injection (eg, ceftazidime), nondepolarizing muscle relaxants (eg, pancuronium), or succinylcholine because their side effects may be increased by Tobramycin drops
This may not be a complete list of all interactions that may occur. Ask your health care provider if Tobramycin drops may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Tobramycin precautions
Ototoxicity
Caution should be exercised when prescribing Tobramycin to patients with known or suspected auditory or vestibular dysfunction.
Findings related to ototoxicity as measured by audiometric evaluations and auditory adverse event reports were similar between Tobramycin and placebo in controlled clinical trials. Hearing loss was reported in two (1.1%) Tobramycin-treated patients and in one (0.9%) placebo-treated patient during clinical studies. Additionally, dizziness and vertigo, both of which may be manifestations of vestibular forms of ototoxicity, were observed in similar numbers of Tobramycin- and placebo-treated patients. Dizziness occurred in two (1.1%) Tobramycin-treated patients and one (0.9%) placebo-treated patient and vertigo occurred in two (1.1%) Tobramycin-treated patients versus no placebo patients in clinical studies. None of the Tobramycin patients discontinued their therapy due to hearing loss, dizziness or vertigo.
Tinnitus may be a sentinel symptom of ototoxicity. No reports of tinnitus occurred in patients during clinical studies with Tobramycin, but because it has been observed with inhaled Tobramycin solutions, onset of this symptom warrants caution. Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness.
Nephrotoxicity
Caution should be exercised when prescribing Tobramycin to patients with known or suspected renal dysfunction.
Nephrotoxicity was not seen during Tobramycin clinical studies but has been associated with aminoglycosides as a class. If nephrotoxicity occurs in a patient receiving Tobramycin, therapy should be discontinued until serum concentrations fall below 2 mcg/mL.
Twenty-six (14%) Tobramycin patients and 15 (13%) placebo patients had increases in serum creatinine of at least 50% over baseline. Follow-up values were obtained for 17 of the 26 Tobramycin patients, all of which decreased to serum creatinine values that were within normal laboratory ranges. Patients who experience an increase in serum creatinine during treatment with Tobramycin should have their renal function closely monitored.
Neuromuscular Disorders
Tobramycin should be used cautiously in patients with muscular disorders, such as myasthenia gravis or Parkinson's disease, since aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.
Bronchospasm
Bronchospasm can occur with inhalation of Tobramycin. In clinical studies with Tobramycin, bronchospasm was observed in one (0.5%) Tobramycin-treated patient and in no placebo-treated patients. Wheezing occurred in ten (5%) Tobramycin-treated patients and four (4%) placebo-treated patients. Bronchospasm and wheezing should be treated as medically appropriate.
Laboratory Tests
Audiograms
Clinical studies of inhaled Tobramycin solutions did not identify hearing loss using audiometric tests which evaluated hearing up to 8000 Hz. Physicians should consider an audiogram for patients who show any evidence of auditory dysfunction, or who are at increased risk for auditory dysfunction. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution.
Serum Concentrations
In patients with normal renal function treated with Tobramycin, serum Tobramycin concentrations range from approximately 0.06-1.89 mcg/mL one hour after dose administration and do not require routine monitoring. Serum concentrations of Tobramycin in patients with renal dysfunction or patients treated with concomitant parenteral Tobramycin should be monitored at the discretion of the treating physician.
Renal Function
The clinical studies of Tobramycin did not reveal any imbalance in the percentage of patients who experienced at least a 50% rise in serum creatinine from baseline in either the Tobramycin group (n=26, 14%) or the placebo group (n=15, 13%). Laboratory tests of urine and renal function should be conducted at the discretion of the treating physician.
Use In Pregnancy
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 apprised of the potential hazard to the fetus.
Patient Counseling Information
Information For Patients
Information on the long term efficacy and safety of Tobramycin is limited. There is no information in patients with severe cystic fibrosis (FEV < 40% predicted).
Patients should be advised to complete a full 28-day course of Tobramycin, even if they are feeling better. After 28 days of therapy, patients should stop Tobramycin therapy for the next 28 days, and then resume therapy for the next 28 day on and 28 day off cycle.
For patients taking several different inhaled medications and/or performing chest physiotherapy, advise the patient regarding the order they should take the therapies. It is recommended that Tobramycin be taken last.
Tobramycin is to be used with the PARI LC PLUS reusable nebulizer and the PARI VIOS air compressor. Refer to the manufacturer's instructions for care and use of the nebulizer and compressor.
Ototoxicity
Inform patients that ototoxicity, as measured by complaints of hearing loss or tinnitus, was reported by patients treated with Tobramycin. Physicians should consider an audiogram at baseline, particularly for patients at increased risk of auditory dysfunction.
If a patient reports tinnitus or hearing loss during Tobramycin therapy, the physician should refer that patient for audiological assessment.
Patients should be reminded that vestibular toxicity may manifest as vertigo, ataxia, or dizziness.
Bronchospasm
Inform patients that bronchospasm can occur with inhalation of Tobramycin.
Risks Associated With Aminoglycosides
Inform patients of adverse reactions associated with aminoglycosides such as nephrotoxicity and neuromuscular disorders.
Laboratory Tests
Inform patients of the need to monitor hearing, serum concentrations of Tobramycin, or renal function as necessary during treatment with Tobramycin.
Pregnancy
Inform patients that aminoglycosides can cause fetal harm when administered to a pregnant woman. Advise them to inform their doctor if they are pregnant, become pregnant, or plan to become pregnant.
Storage Instructions
You should store Tobramycin ampules in a refrigerator (36-46 °F or 2-8 °C). However, when you don't have a refrigerator available (e.g., transporting your Tobramycin), you may store the foil pouches (opened or unopened) at room temperature (up to 77 °F/25 °C) for up to 28 days.
Tobramycin is light sensitive; unopened ampules should be returned to the foil pouch. Avoid exposing Tobramycin ampules to intense light. Unrefrigerated Tobramycin, which is normally colorless to pale yellow, may darken with age; however, the color change does not indicate any change in the quality of the product.
You should not use Tobramycin 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. You should not use Tobramycin beyond the expiration date stamped on the ampule.
Additional Information
Nebulizers and Compressors: 1-800-327-8632.
Tobramycin: 1-888-661-9260
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
A two-year rat inhalation toxicology study to assess carcinogenic potential of an inhaled solution of Tobramycin has been completed. Rats were exposed to Tobramycin for up to 1.5 hours per day for 95 weeks. Serum levels of Tobramycin up to 35 mcg/mL were measured in rats, 35x the average 1 mcg/mL exposure levels observed in cystic fibrosis patients in clinical trials. There was no drug-related increase in the incidence of any variety of tumors.
Additionally, Tobramycin has been evaluated for genotoxicity in a battery of in vitro and in vivo tests. The Ames bacterial reversion test, conducted with five tester strains, failed to show a significant increase in revertants with or without metabolic activation in all strains. Tobramycin was negative in the mouse lymphoma forward mutation assay, did not induce chromosomal aberrations in Chinese hamster ovary cells, and was negative in the mouse micronucleus test.
Subcutaneous administration of up to 100 mg/kg of Tobramycin did not affect mating behavior or cause impairment of fertility in male or female rats.
Use In Specific Populations
Pregnancy
Teratogenic Effects
Pregnancy Category D
No reproduction toxicology studies have been conducted with inhaled Tobramycin. However, subcutaneous administration of Tobramycin at doses of 100 mg or 20 mg/kg/day during organogenesis was not teratogenic in rats or rabbits, respectively. Subcutaneous doses of Tobramycin ≥ 40mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of teratogenicity. Aminoglycosides can cause fetal harm (e.g., congenital deafness) when administered to a pregnant woman. Ototoxicity was not evaluated in offspring during nonclinical reproduction toxicity studies with Tobramycin. If Tobramycin is used during pregnancy, or if the patient becomes pregnant while taking Tobramycin, the patient should be apprised of the potential hazard to the fetus.
Labor And Delivery
The safety and efficacy of Tobramycin have not been studied in the puerperal patient.
Nursing Mothers
It is not known if Tobramycin will reach sufficient concentrations after administration by inhalation to be excreted in human breast milk. Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate nursing or discontinue Tobramycin therapy, taking into account the importance of the drug to the mother.
Pediatric Use
The safety and efficacy of Tobramycin have not been studied in pediatric cystic fibrosis patients under six years of age.
Geriatric Use
The safety and efficacy of Tobramycin have not been studied in adult cystic fibrosis patients over 31 years of age.
Renal Impairment
Tobramycin is primarily excreted unchanged in the urine and renal function is expected to affect the exposure of Tobramycin. The risk of adverse reactions to this drug may be greater in patients with impaired renal function. Patients with serum creatinine > 2mg/dL and blood urea nitrogen (BUN) > 40mg/dL have not been included in clinical studies and there are no data in this population to support a recommendation for or against dose adjustment.
Serum concentrations of Tobramycin in patients with renal dysfunction, or patients treated with concomitant parenteral Tobramycin should be monitored at the discretion of the treating physician.
What happens if I miss a dose of Tobramycin?
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.
For Tobramycin: Skip the missed dose if your next dose is less than 6 hours away. Do not use extra medicine to make up the missed dose.
References
- DailyMed. "TOBRAMYCIN SULFATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DrugBank. "tobramycin". http://www.drugbank.ca/drugs/DB00684 (accessed September 17, 2018).
- MeSH. "Anti-Bacterial Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
Reviews
Consumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
