Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

General Warnings
For information on pregnancy and lactation see section 4.6.

TOBI should be used with caution in patients with known or suspected renal, auditory, vestibular or neuromuscular dysfunction, or with severe, active haemoptysis.

Monitoring of serum tobramycin 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 TOBI, tobramycin therapy should be discontinued until serum concentration falls below 2 μg/ml.

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 inhalation of medicinal products and has been reported with nebulised tobramycin. The first dose of TOBI should be given under supervision, using a pre- nebulisation bronchodilator if this is part of the current regimen for the patient. FEV1 should be measured before and after nebulisation. If there is evidence of therapy-induced bronchospasm in a patient not receiving a bronchodilator the test should be repeated, on a separate occasion, using a bronchodilator. Evidence of bronchospasm in the presence of bronchodilator therapy may indicate an allergic response. If an allergic response is suspected TOBI should be discontinued. Bronchospasm should be treated as medically appropriate.

Neuromuscular disorders

TOBI should be used with great caution in patients with known or suspected neuromuscular disorders such as parkinsonism or other conditions characterised by myasthenia, including myasthenia gravis, as aminoglycosides may aggravate muscle weakness due to a potential curare-like effect on neuromuscular function.

Nephrotoxicity

Although nephrotoxicity has been associated with parenteral aminoglycoside therapy, there was no evidence of nephrotoxicity during clinical trials with TOBI.

The product should be used with caution in patients with known or suspected renal dysfunction and serum concentrations of tobramycin should be monitored. Patients with severe renal impairment, i.e., serum creatinine >2 mg/dl (176.8 mol/l), were not included in the clinical studies.

Current clinical practice suggests baseline renal function should be assessed. Urea and creatinine levels should be reassessed after every 6 complete cycles of TOBI therapy (180 days of nebulised aminoglycoside therapy).

See also “Monitoring of serum tobramycin concentrations” above.

Ototoxicity
Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness. Ototoxicity, as measured by complaints of hearing loss or by audiometric evaluations, did not occur with TOBI therapy during controlled clinical studies. In open label studies and post-marketing experience, some patients with a history of prolonged previous or concomitant use of intravenous aminoglycosides have experienced hearing loss. Patients with hearing loss frequently reported tinnitus. Physicians should consider the potential for aminoglycosides to cause vestibular and cochlear toxicity and carry out appropriate assessments of auditory function during TOBI therapy. In patients with a predisposing risk due to previous prolonged, systemic aminoglycoside therapy it may be necessary to consider audiological assessment before initiating TOBI therapy. The onset of tinnitus warrants caution as it is a sentinel symptom of ototoxicity.

Caution should be exercised when prescribing TOBI to patients with known or suspected auditory or vestibular dysfunction. Physicians should consider an audiological assessment 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 aminoglycoside therapy the physician should consider referring them for audiological assessment.
See also “Monitoring of serum tobramycin concentrations” above.

Haemoptysis

Inhalation of nebulised solutions may induce a cough reflex. The use of TOBI in patients with active, severe haemoptysis should be undertaken only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage.

Microbial Resistance

In clinical studies, some patients on TOBI therapy showed an increase in aminoglycoside Minimum Inhibitory Concentrations for P. aeruginosa isolates tested. There is a theoretical risk that patients being treated with nebulised tobramycin may develop P. aeruginosa isolates resistant to intravenous tobramycin (see 5.1).

Effects on Driving

4.7     Effects on ability to drive and use machines

On the basis of reported adverse drug reactions, TOBI is presumed to be unlikely to produce an effect on the ability to drive and use machinery.