TOBI PODHALER 28 MG

/ Dexcel

The dose of Tobramycin is the same for all patients (adults and children aged 6 years or older) regardless of age or weight. The recommended dosage is four capsules (4 × 28 mg = 112 mg Tobramycin) administered twice daily for 28 days. This medical product is taken in alternating cycles of 28 days on drug followed by 28 days off drug. Each dose of four capsules should be inhaled as close as possible to 12 hours apart and not less than six hours apart. In case of missed dose with at least 6 hours until the next dose, the patient should take the dose as soon as possible. Otherwise, the patient should wait for the next dose and not inhale more capsules to make up for the missed dose. Treatment with Tobramycin should be continued on a cyclical basis for as long as the physician considers the patient is gaining clinical benefit from the treatment with Tobramycin taking into account that long-term safety data are not available for Tobramycin. If clinical deterioration of pulmonary status is evident, additional or alternative anti-pseudomonal therapy should be considered. 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 is 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 Tobramycin.
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 and blood urea nitrogen (BUN) 40mg/dL or more have not been included in clinical studies and there is no data in this population to support a recommendation for or against dose adjustment with this drug. Caution should be exercised when prescribing this drug to patients with known or suspected renal dysfunction. Please also refer to section 6 Warnings and precautions – 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 of this drug in patients after organ transplantation.
Pediatric Population: The safety and efficacy of this drug in children aged under 6 years have not been established.
Method of administration: This medical product is administered only by the oral inhalation route and only using the Podhaler device. It must not be administered by any other route or with any other inhaler. Capsules must not be swallowed. Each capsule should be inhaled in two inhalations with breath-hold manoeuvres, and the capsule should be checked to ensure it is empty after use. Caregivers should assist children initiating treatment, particularly those aged 10 years or younger, and continue supervision until the child is able to use the Podhaler device properly without help. When patients are receiving several different inhaled medications and performing chest physiotherapy, this medicinal product should be taken last.

Suppressive therapy of chronic pulmonary infection due to Pseudomonas aeruginosa in adults and children aged 6 years and older with cystic fibrosis.

Known hypersensitivity to the active substance and any aminoglycoside, or to any of the excipients.

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. Hearing loss and tinnitus were reported by patients in this medical product clinical studies. Caution should be exercised when prescribing Tobramycin 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.
Caution is advised in patients with known or suspected auditory or vestibular dysfunction. Audiograms should be considered in patients with baseline auditory dysfunction or those at increased risk.
Risk of ototoxicity due to mitochondrial DNA variants
Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly the m.1555A>G variant.
Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range. In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, it may be necessary to consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies.
If a patient reports tinnitus or hearing loss during therapy, the physician should refer for audiological assessment.
Nephrotoxicity
Nephrotoxicity has been reported with the use of parenteral aminoglycosides. Nephrotoxicity was not observed during this medical product clinical studies. Caution should be exercised when prescribing Tobramycin to patients with known or suspected renal dysfunction. Baseline renal function should be assessed. Urea and creatinine levels should be reassessed after every 6 complete cycles.
Monitoring of serum tobramycin concentrations
Patients with known or suspected auditory or renal dysfunction should be monitored for serum tobramycin concentrations. If oto- or nephrotoxicity occurs in a patient receiving TOBI Podhaler, tobramycin therapy should be discontinued until serum concentration falls below 2 μg/mL. Serum concentrations greater than 12 μg/ml are associated with tobramycin toxicity and treatment should be discontinued if concentrations exceed this level. 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 this medical product during clinical trials. Bronchospasm should be treated as medically appropriate. The first dose of this medical product should be given under supervision, after using a bronchodilator if this is part of the current regimen for the patient. FEV1 should be measured before and after inhalation of this medical product. If there is evidence of therapy-induced bronchospasm, the physician should carefully evaluate whether the benefits of continued use of this medical product outweigh the risks to the patient. If an allergic response is suspected, this medical product should be discontinued.
Cough
Cough can occur with the use of inhaled medicinal products and was reported with use of this medical product in clinical studies. Based on clinical trial data the inhalation powder tobramycin was associated with a higher reported rate of cough compared with tobramycin nebuliser solution. Cough was not related to bronchospasm. Children below the age of 13 years may be more likely to cough when treated with this medical product compared with older subjects. If there is evidence of continued therapy-induced cough with this medical product, the physician should consider whether an approved tobramycin nebuliser solution should be used as an alternative treatment. Should cough remain unchanged, other antibiotics should be considered.
Haemoptysis
Haemoptysis is a complication in cystic fibrosis and is more frequent in adults. Patients with haemoptysis (>60 ml) were excluded from the clinical studies so no data exist on the use of this medical product in these patients. This should be taken into account before prescribing this medical product, considering the inhalation powder formulation was associated with a higher rate of cough. The use of this medical product in patients with clinically significant haemoptysis should be undertaken or continued only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage.
Other precautions
Patients receiving concomitant parenteral aminoglycoside therapy (or any medication affecting renal excretion, such as diuretics) should be monitored as clinically appropriate taking into account the risk of cumulative toxicity. This includes monitoring of serum concentrations of tobramycin. In patients with a predisposing risk due to previous prolonged, systemic aminoglycoside therapy it may be necessary to consider renal and audiological assessment before initiating therapy with this medical product. Caution should be exercised when prescribing this medical 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. The development of antibiotic-resistant P. aeruginosa and superinfection with other pathogens represent potential risks associated with antibiotic therapy. In clinical studies, some patients on therapy showed an increase in aminoglycoside minimum inhibitory concentrations (MIC) for P. aeruginosa isolates tested. MIC increases observed were in large part reversible during off treatment periods. There is a theoretical risk that patients being treated with this medical product may develop P. aeruginosa isolates resistant to intravenous tobramycin over time. Development of resistance during inhaled tobramycin therapy could limit treatment options during acute exacerbations; this should be monitored.
For full details see prescribing information.

Very common: Haemoptysis, Dyspnoea, Dysphonia, Productive cough, Cough, Oropharyngeal pain, Pyrexia.
Common: Hearing loss, Tinnitus, Epistaxis, Wheezing, Rales, Chest discomfort, Nasal congestion, Bronchospasm, Aphonia, Vomiting, Diarrhoea, Throat irritation, Nausea, Dysgeusia, Rash, Musculoskeletal chest pain,
For full details see prescribing information

No clinical drug interaction studies have been performed with this drug. Based on the interaction profile for tobramycin following intravenous and aerosolised administration, concurrent and/or sequential use of TOBI Podhaler is not recommended with other medicinal products with nephrotoxic or ototoxic potential. Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue, should not be administered concomitantly with ethacrynic acid, furosemide, urea, or mannitol.
For full details see prescribing information

Pregnancy: There is a limited amount of data on the use of inhaled Tobramycin in pregnant patients. Treatment with this medical product during pregnancy should be undertaken only if the expected benefits to the mother outweigh the potential risks to the fetus or baby.
Lactation: Tobramycin is excreted in human breast milk after systemic administration. The amount of Tobramycin excreted in human breast milk after administration by inhalation is not known, though it is estimated to be very low considering the low systemic exposure. Because of the potential for ototoxicity and nephrotoxicity in infants, a decision should be made whether to terminate nursing or discontinue treatment, taking into account the importance of the drug to the mother.
For full details see prescribing information.

Adverse reactions specifically associated with overdose of Tobramycin have not been identified. The maximum tolerated daily dose of this drug has not been established. Tobramycin serum concentrations may be helpful in monitoring overdose. Acute toxicity should be treated with immediate withdrawal of this drug, and baseline tests of renal function should be undertaken. In the event of accidental oral ingestion of this drug, systemic toxicity is unlikely as Tobramycin is poorly absorbed. Hemodialysis may be helpful in removing Tobramycin from the body.

Incompatibilities: The Podhaler device is the only inhaler to be used with TOBI Podhaler capsules; this inhaler must not be used for any drug product other than TOBI Podhaler.
Storage: Store below 30°C; Store in the original package to protect from moisture. Store the inhaler in its tightly closed case when not in use.