TYMBRINEB Nebuliser solution Ref.[49977] Active ingredients: Tobramycin

Tymbrineb Nebuliser Solution is for inhalation use and is not intended for parenteral use.

Posology

The recommended dose for adults and children is one ampoule twice daily for 28 days. The dose interval should be as close as possible to 12 hours and not less than 6 hours. After 28 days of therapy, patients should stop tobramycin therapy for the next 28 days. A cycle of 28 days of active therapy and 28 days of rest from treatment should be maintained.

Dosage is not adjusted for weight. All patients should receive one ampoule of tobramycin 300 mg twice daily.

Controlled clinical studies, conducted for a period of 6 months using the following tobramycin dosage regimen, have shown that improvement in lung function was maintained above baseline during the 28 day rest periods.

Tymbrineb Dosing Regimen in Controlled Clinical Studies:

Safety and efficacy for long-term management of chronic pulmonary infection due to Pseudomonas aeruginosa have been assessed in controlled and open label studies for up to 96 weeks (12 cycles), but have not been studied in patients under the age of 6 years, in patients with forced expiratory volume in 1 second (FEV1) <25% or >75% predicted, or in patients colonised with Burkholderia cepacia.

Therapy should be initiated by a physician experienced in the management of cystic fibrosis. Tobramycin treatment should be continued on a cyclical basis for as long as the physician considers the patient is gaining clinical benefit from the inclusion of tobramycin in their treatment regimen. If clinical deterioration of the pulmonary status is evident, additional anti-pseudomonal therapy should be considered. Clinical studies have shown that a microbiological report indicating in vitro drug resistance does not necessarily preclude a clinical benefit for the patient.

Special populations

Elderly (≥65 years)

There are insufficient data in this population to support a recommendation for or against dose adjustment.

Patients with renal impairment

There are no data in this population to support a recommendation for or against dose adjustment with tobramycin. Please also refer to nephrotoxicity information in section 4.4 and excretion information in section 5.2.

Patients with hepatic impairment

No studies have been performed on patients with hepatic impairment. As tobramycin is not metabolised, 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 tobramycin in patients after organ transplantation.

Paediatric population

The safety and efficacy of tobramycin in children aged less than 6 years have not yet been established. Currently available data are described in section 5.1 but no recommendation on a posology can be made.

Method of administration

The contents of one ampoule should be emptied into the nebuliser and administered by inhalation over approximately a 15-minute period using a hand-held PARI LC PLUS reusable nebuliser with a suitable compressor. Suitable compressors are those which, when attached to a PARI LC PLUS nebuliser, deliver a flow rate of 4–6 L/min and/or a back pressure of 110–217 kPa. The manufacturers' instructions for the care and use of the nebuliser and compressor should be followed.

Tobramycin is inhaled whilst the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebuliser. Nose clips may help the patient breathe through the mouth. The patient should continue their standard regimen of chest physiotherapy. The use of appropriate bronchodilators should continue as thought clinically necessary. Where patients are receiving several different respiratory therapies it is recommended that they are taken in the following order: bronchodilator, chest physiotherapy, other inhaled medicinal products, and finally tobramycin.

Maximum tolerated daily dose

The maximum tolerated daily dose of tobramycin has not been established.

Administration by inhalation results in low systemic bioavailability of tobramycin. Symptoms of aerosol overdose may include severe hoarseness.

In the event of accidental ingestion of Tymbrineb Nebuliser Solution, toxicity is unlikely as tobramycin is poorly absorbed from an intact gastrointestinal tract.

In the event of inadvertent administration of Tymbrineb Nebuliser Solution by the intravenous route, signs and symptoms of parenteral tobramycin overdose may occur, that include dizziness, tinnitus, vertigo, loss of hearing acuity, respiratory distress and/or neuromuscular blockade and renal impairment.

Acute toxicity should be treated with immediate withdrawal of tobramycin and baseline tests of renal function should be undertaken. Tobramycin serum concentrations may be helpful in monitoring overdose. In the case of any overdosage, the possibility of drug interactions with alterations in the elimination of tobramycin or other medicinal products should be considered.

3 years

The foil pouches (intact or opened) may be stored at up to 25°C for up to 28 days.

The contents of the whole ampoule should be used immediately after opening (see section 6.6).

Store in a refrigerator (2°C–8°C). Do not freeze. Store in the original package in order to protect from light.

For storage conditions after first opening of the medicinal product, see section 6.3.

Tymbrineb solution may be slightly yellow and some variability in colour may be observed; this does not indicate loss of activity providing the solution has been stored as recommended.

Tymbrineb Nebuliser Solution is supplied in 5 mL single-dose low density polyethylene ampoules.

4 ampoules are packed and sealed in a foil pouch. Each carton comprises 14 (56 ampoules), 28 (112 ampoules) or 42 (168 ampoules) foil pouches.

Not all pack sizes may be marketed.

This medicinal product is a sterile, non-pyrogenic, aqueous preparation for single-use only. As it is preservative-free, the contents of the whole ampoule should be used immediately after opening and any unused solution discarded. Opened ampoules should never be stored for re-use.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.