Vantobra (Previously Tobramycin PARI)

Posology The dose of Vantobra is the same for all patients within the approved age range, regardless of age or weight. e. total daily dose is 2 ampoules) for 28 days. The dose interval should be as close as possible to 12 hours and not less than 6 hours.

Vantobra is taken in alternating cycles of 28 days. A cycle of 28 days of active therapy (on-treatment period) and 28 days of rest from treatment (off-treatment period) should be maintained. Missed doses In case of a missed dose with at least 6 hours remaining until the next dose, the patient should inhale the dose as soon as possible.

If less than 6 hours remain to the next planned dose, the patient should wait for the next dose and not inhale more to make up for the missed dose. Duration of treatment Treatment should be continued on a cyclical basis for as long as the physician considers the patient is gaining clinical benefit from the treatment taking into account that long-term safety data are not available for Vantobra.

If clinical deterioration of pulmonary status is evident, additional or alternative anti-pseudomonal therapy should be considered. 1. Special populations Elderly patients (≥65 years) There are insufficient data in this population to support a recommendation for or against dose adjustment.

3 Renal impairment There are no data in this population to support a recommendation for or against dose adjustment with Vantobra. 2. 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 inhaled tobramycin in patients after organ transplantation. No recommendation for or against dose adjustment can be made for patients after organ transplantation.

Paediatric population There is no relevant use of Vantobra in children below 6 years of age. Method of administration Inhalation use. Vantobra is administered by inhalation using the Tolero nebuliser handset provided in the pack. 6. Vantobra must not be administered by any other route or using any other device than the one provided in the pack.

The use of an alternative untested nebuliser system may alter the pulmonary deposition of the active substance. And this in turn may alter efficacy and safety of the product. Where patients are receiving several inhaled medicinal products and chest physiotherapy, it is recommended that Vantobra is used last.

Summary of the safety profile In controlled clinical trials with Vantobra the most frequent adverse reactions in cystic fibrosis patients with P. aeruginosa infection were cough and dysphonia. Other clinical trials with tobramycin nebuliser solution mention dysphonia and tinnitus as the most frequent undesirable events that were reported in significantly more patients compared to those treated with placebo.

The episodes of tinnitus were transient and resolved without discontinuation of tobramycin therapy. 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.

4). 1). Tabulated list of adverse reactions Adverse drug reactions reported for tobramycin nebuliser solution are listed in Table 1. Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category is provided using the following convention: Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000).

Table 1 Adverse reactions System Organ Class Frequency category Adverse Reactions Infections and infestations Rare Laryngitis Very rare Fungal infection Oral candidiasis Blood and lymphatic system disorders Very rare Lymphadenopathy Immune system disorders Very rare Hypersensitivity Metabolism and nutrition disorders Rare Anorexia Nervous system disorders Rare Dizziness Aphonia Headache Very rare Somnolence Ear and labyrinth disorders Rare Hearing loss 7 Tinnitus Very rare Ear pain Ear disorder Vascular disorders Rare Haemoptysis Epistaxis Respiratory, thoracic and mediastinal disorders Uncommon Dyspnoea Dysphonia Pharyngitis Cough Rare Asthma Lung disorder Chest discomfort Productive cough Rhinitis Bronchospasm Very rare Hypoxia Hyperventilation Sinusitis Gastrointestinal disorders Rare Vomiting Mouth ulceration Nausea Dysgeusia Very rare Diarrhoea Abdominal pain Skin and subcutaneous tissue disorders Rare Rash Very rare Urticaria Pruritus Musculoskeletal and connective tissue disorders Very rare Back pain General disorders and administration site conditions Rare Asthenia Pyrexia Pain Chest pain Very rare Malaise Investigations Rare Pulmonary function test decreased Paediatric population There was no difference in the safety profile between pediatric and adult patient population treated with Vantobra.

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.

Auditory toxicity, as measured by complaints of hearing loss or by audiometric evaluations, was observed with parenteral aminoglycosides and may be considered also for the inhalation route of administration. 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.

Physicians should consider the potential for aminoglycosides to cause vestibular and cochlear toxicity and carry out appropriate assessments of auditory function during Vantobra therapy. In patients with a predisposing risk due to previous prolonged systemic aminoglycoside therapy it may be necessary to consider audiological assessment before initiating Vantobra therapy.

If a patient reports tinnitus or hearing loss during aminoglycoside therapy, the physician should consider referring them for audiological assessment. 4 There is an increased risk of ototoxicity in patients with mitochondrial DNA mutations (particularly the nucleotide 1555 A to G substitution in the 12S rRNA gene), even if aminoglycoside serum levels are within the recommended range during treatment.

Alternative treatment options should be considered in such patients. In patients with a maternal history of relevant mutations or aminoglycoside induced deafness, alternative treatments or genetic testing prior to administration, should be considered.

Nephrotoxicity Nephrotoxicity has been associated with parenteral aminoglycoside therapy. There was no evidence of nephrotoxicity during clinical trials with inhaled tobramycin and Vantobra. Caution should be exercised when prescribing Vantobra to patients with known or suspected renal dysfunction.

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