Tobi Solution for Inhalation

/ Dexcel

The dose of TOBI is the same for all patients regardless of age or weight. The recommended dosage for adults and children 6 years of age and older is one single-use ampoule (300 mg/5 mL) administered twice daily (BID) for 28 days. this product is taken in alternating cycles of 28 days on drug followed by 28 days off drug. Each dose should be inhaled as close as possible to 12 hours apart and not less than six hours apart. Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with FEV1 (Forced Expiratory Volume in 1 second) <25% or >75% predicted, or patients colonized with Burkholderia cepacia.
Dosing in special populations
Elderly patients (≥ 65 years): There are insufficient data in this population to support a recommendation for or against dose adjustment. Renal function in elderly patients should be taken into account while using this product.
Patients with renal impairment: Tobramycin is primarily excreted unchanged in the urine and renal function is expected to affect the exposure to tobramycin. Patients with serum creatinine 2 mg/dL or more or blood urea nitrogen (BUN) 40 mg/dL or more were not included in clinical studies and there are no data in this population to support a recommendation for or against dose adjustment with this product. Please also refer to Warnings and precautions section on nephrotoxicity.
Patients with hepatic impairment: No studies have been performed on patients with hepatic impairment. As tobramycin is not metabolized, an effect of hepatic impairment on the exposure to tobramycin is not expected.
Patients after organ transplantation: Adequate data do not exist for the use in patients after organ transplantation.

Cystic fibrosis with P. aeruginosa under 6 years of age, Fevi, <25% or >75% predicted, patients colonized with Burkholderia cepacia.

Known hypersensitivity to aminoglycosides, children under 6 years.

Ototoxicity: Ototoxicity, manifested as both auditory toxicity (hearing loss) and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia, or dizziness. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution. Ototoxicity, as measured by complaints of hearing loss or by audiometric evaluations, did not occur with this product therapy during clinical studies. In postmarketing experience, patients receiving this product 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. Caution should be exercised when prescribing to patients with known or suspected auditory or vestibular dysfunction. Physicians should consider an audiogram for patients who show any evidence of auditory dysfunction, or who are at increased risk for auditory dysfunction. If a patient reports tinnitus or hearing loss during therapy, the physician should refer them for audiological assessment. Also see prescribing information for monitoring of serum tobramycin concentrations.
Nephrotoxicity: Nephrotoxicity has been reported with the use of parenteral aminoglycosides. Nephrotoxicity was not observed during TOBI clinical studies. Caution should be exercised when prescribing to patients with known or suspected renal dysfunction. See Laboratory Test section below for monitoring of serum tobramycin concentrations. Laboratory tests of renal function should be monitored as clinically appropriate.
Laboratory tests and monitoring: serum concentrations Serum tobramycin concentrations should be monitored in patients with known or suspected auditory or renal dysfunction. If oto- or nephrotoxicity occurs in a patient receiving this product, tobramycin therapy should be discontinued until serum concentration falls below 2 µg/mL. In patients with normal renal function treated with this product, serum tobramycin concentrations are approximately 1 µg/mL one hour after dose administration. Serum concentrations of tobramycin should be monitored in patients receiving concomitant parenteral aminoglycoside therapy (or other medications that can affect renal excretion). These patients should be monitored as clinically appropriate.
The serum concentration of tobramycin should only be monitored through venipuncture and not finger prick blood sampling. Contamination of the skin of the fingers with tobramycin may lead to falsely increased measurements of serum levels of the drug. This contamination cannot be completely avoided by hand washing before testing.
Bronchospasm: Bronchospasm can occur with the inhalation of medicinal products and has been reported with this product. Bronchospasm should be treated as medically appropriate.
Neuromuscular dysfunction: Caution should be exercised when prescribing this product to patients with known or suspected neuromuscular disorders such as myasthenia gravis or Parkinson’s disease. Aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.

Cough, pharyngitis, sputum increased and discoloured, asthenia, rhinitis, dyspnea, fever, lung disorder, headache, chest pain, hemoptysis, anorexia, decreased lung function, asthma, vomiting, abdominal pain, voice alteration, nausea, weight loss.
For full details see prescribing information.

No clinical drug interaction studies have been performed with this product. Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. this product should not be administered concomitantly with ethacrynic acid, furosemide, urea, or mannitol. Concurrent and/or sequential use of this product with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided.
Absence of interactions: In clinical studies of this product, patients taking this product concomitantly with dornase alfa, ß-agonists, inhaled corticosteroids, other anti-pseudomonal antibiotics, or parenteral aminoglycosides demonstrated adverse experience profiles similar to the study population as a whole.

Pregnancy: There are no adequate data from the use of tobramycin administered by inhalation in pregnant women. Aminoglycosides can cause fetal harm (e.g. congenital deafness) when high systemic concentrations are achieved in a pregnant woman.
Treatment with this product during pregnancy should be undertaken only if the benefits to the mother outweigh the risks to the fetus or baby. Patients who use this product during pregnancy, or become pregnant while taking this product , should be apprised of the potential hazard to the fetus.
Breastfeeding: The amount of tobramycin excreted in human breast milk after administration by inhalation is not known. Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate nursing or discontinue treatment with this product , taking into account the importance of the drug to the mother.
Fertility: Data in animals from subcutaneous administration of tobramycin did not reveal a problem or potential problem concerning fertility in either males or females.
For full details see prescribing information.

The maximum tolerated daily dose has not been established. Tobramycin serum concentrations may be helpful in monitoring overdose. Acute toxicity should be treated with immediate withdrawal, and baseline tests of renal function should be undertaken. In the event of accidental oral ingestion, systemic toxicity is unlikely as tobramycin is poorly absorbed from an intact gastrointestinal tract. In the event of inadvertent administration by the intravenous route, signs and symptoms of parenteral tobramycin overdose may occur that include dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory distress, neuromuscular blockade, and renal impairment. Hemodialysis may be helpful in removing tobramycin from the body.