Vantobra

Each single-dose ampoule of 1.7 ml contains 170 mg tobramycin.

For the full list of excipients, see section 6.1.

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or Each ampoule of 1.7 ml contains 170 mg tobramycin.

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Each ampoule of 1.7 ml contains 170 mg tobramycin.

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Each ampoule of 1.7 ml contains 170 mg tobramycin.

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PARI Pharma GmbH

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or Nebuliser solution.

th A clear to slightly yellow solution.

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Excipients: sodium chloride, calcium chloride, magnesium sulphate, water for injections,

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sulphuric acid and sodium hydroxide for pH adjustment.

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Excipients: sodium chloride, calcium chloride, magnesium sulphate, water for injections, sulphuric acid and sodium hydroxide for pH adjustment.

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au Excipients: sodium chloride, calcium chloride, magnesium sulphate, water for injections, sulphuric acid and sodium hydroxide for pH adjustment.

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EXP

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ng Vantobra is indicated for the management of chronic pulmonary infection due to Pseudomonas aeruginosa in patients aged 6 years and older with cystic fibrosis lo (CF).

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

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Posology

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The dose of Vantobra is the same for all patients within the approved age range, regardless of age or weight.

The recommended dose ro is one ampoule (170 mg/1.7 ml) administered twice daily (i.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 p 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.

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Missed doses

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In case of a missed dose with at least 6 hours remaining until the next dose, the patient should inhale the dose as soon ic 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.

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Duration of treatment

Treatment should be continued on a cyclical basis for as long as the physician considers the patient is gaining

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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. See also information on clinical benefit and tolerability in sections 4.4, 4.8 and 5.1.

Special populations

Elderly patients (≥65 years)

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

Renal impairment

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

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 ed 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.

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Paediatric population

or There is no relevant use of Vantobra in children below 6 years of age.

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Method of administration

au Inhalation use.

Vantobra is administered by inhalation using the Tolero nebuliser handset provided in the pack. For detailed er instructions on use see section 6.6.

ng 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 lo of the product.

Where patients are receiving several inhaled medicinal products and chest physiotherapy, it is recommended

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that Vantobra is used last.

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Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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Ototoxicity

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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.

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Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution.

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Auditory toxicity, as measured by complaints of hearing loss or by audiometric evaluations, was observed ed 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

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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.

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. According to current clinical practice baseline renal function should be assessed. Urea and creatinine levels should be reassessed after every 6 complete cycles of Vantobra therapy (180 days of nebulised aminoglycoside therapy).

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 Vantobra, tobramycin therapy should ed be discontinued until serum concentration falls below 2 µg/ml.

Serum concentrations greater than 12 µg/ml are associated with tobramycin toxicity and treatment is should be discontinued if concentrations exceed this level.

or The serum concentration of tobramycin should only be monitored using validated methods. Finger prick blood sampling is not recommended due to the risk of contamination of the sample. th

au Bronchospasm

Bronchospasm can occur with inhalation of medicinal products and has been reported with the use of nebulised tobramycin. Bronchospasm should be treated as medically appropriate.

er The first dose of Vantobra should be used under supervision of a physician, after taking a bronchodilator if this is part of the current regimen for the patient. FEV 1 should ng be measured before and after nebulisation.

If there is evidence of therapy-induced bronchospasm, the physician should carefully evaluate whether the

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benefits of continued use of Vantobra outweighs the risks to the patient. If an allergic response is suspected, Vantobra should be discontinued.

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Neuromuscular disorders

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

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Haemoptysis

Inhalation of nebulised tobramycin solutions may induce a cough reflex. The treatment with Vantobra in ro

patients with active, severe haemoptysis should be initiated only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage.

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Development of resistance

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The development of antibiotic-resistant P. aeruginosa and superinfection with other pathogens represent potential risks associated with antibiotic therapy. Development of resistance during inhaled tobramycin in

therapy could limit treatment options during acute exacerbations; this should be monitored.

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Other precautions

ed Patients receiving concomitant parenteral aminoglycoside therapy (or any medicine 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.

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Safety and efficacy have not been studied in patients colonised with Burkholderia cepacia.

No interaction studies have been performed. Based on the interaction profile for tobramycin following intravenous and aerosolised administration, concurrent and/or sequential use of Vantobra is not recommended with other medicinal products with nephrotoxic or ototoxic potential, such as:

• - amphotericin B, cefalotin, ciclosporin, tacrolimus, polymyxins (risk of increased nephrotoxicity);
• - platinum compounds (risk of increased nephrotoxicity and ototoxicity);

Concurrent use of Vantobra with diuretic compounds (such as ethacrynic acid, furosemide, urea or mannitol) is not recommended. Such compounds can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue (see section 4.4).

Other medicinal products that have been reported to increase the potential toxicity of parenterally administered aminoglycosides include:

• - anticholinesterases, botulinum toxin (neuromuscular effects).

ed In clinical studies patients using inhaled tobramycin continued to take dornase alfa, bronchodilators, inhaled corticosteroids and macrolides. No evidence of drug interactions with these medicines was identified. is

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Vantobra ic has no or negligible influence on the ability to drive and use machines.

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

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In the event of accidental ingestion of Vantobra, toxicity is unlikely as tobramycin is poorly absorbed from ic

an intact gastrointestinal tract.

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In the event of inadvertent administration of Vantobra by the intravenous route, signs and symptoms of parenteral tobramycin overdose may occur, including dizziness, tinnitus, vertigo, loss of hearing acuity,

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respiratory distress and/or neuromuscular blockage and renal impairment.

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

Pharmacotherapeutic group: Antibacterials for systemic use, Aminoglycoside antibacterials.

ATC code: J01GB01

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Sodium chloride

Calcium chloride

Magnesium sulphate ct

Sulphuric acid (for pH adjustment)

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Sodium hydroxide (for pH adjustment)

Water for injections

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In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products in the al nebuliser.

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3 years

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The contents of a single-dose ampoule should be used immediately after opening (see section 6.6).

M Stability after opening of the pouch: 4 weeks when stored below 25 °C

Store in a refrigerator (2 °C – 8 °C).

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

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.

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ANNEX II

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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

ng B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

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C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING

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AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE ct

USE OF THE MEDICINAL PRODUCT

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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release

PARI Pharma GmbH

Lochhamer Schlag 21

82166 Graefelfing

GERMANY

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B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

is Medicinal products subject to medical prescription.

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C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING

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AUTHORISATION

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Periodic safety update reports

The requirements for submission of periodic safety update reports er for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC ng and any subsequent updates published on the European medicines web-portal.

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The marketing authorisation holder shall submit the first periodic safety update report for this product within 12 months following authorisation.

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D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT

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Risk Management Plan du (RMP)

The MAH shall perform ro the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent updates of the RMP. p

An updated al RMP should be submitted:

in At the request of the European Medicines Agency;

Whenever the risk management system is modified, especially as the result of new information ic

being received that may lead to a significant change to the benefit/risk profile or as the result of an ed important (pharmacovigilance or risk minimisation) milestone being reached.

M If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same time.

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ANNEX III

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LABELLING AND PACKAGE LEAFLET

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A. LABELLING

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

PARI Pharma GmbH

Moosstrasse 3

D-82319 Starnberg

Germany

• 12. MARKETING AUTHORISATION NUMBER(S) ed

EU/1/14/932/001

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13. BATCH NUMBER

th Lot

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14. GENERAL CLASSIFICATION FOR SUPPLY

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15. INSTRUCTIONS ON USE

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16. INFORMATION IN BRAILLE

Vantobra 170 mg no

17. UNIQUE IDENTIFIER – 2D BARCODE

ct 2D barcode carrying the unique identifier included.

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18. UNIQUE IDENTIFIER _ HUMAN READABLE DATA

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PC: {number}

SN: {number} p

NN: {number}

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING INNER CARTON CONTAINING THE MEDICINE

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

PARI Pharma GmbH

Moosstrasse 3

D-82319 Starnberg

Germany

• 12. MARKETING AUTHORISATION NUMBER(S) ed EU/1/14/932/001

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• 13. BATCH NUMBER or

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Lot

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14. GENERAL CLASSIFICATION FOR SUPPLY

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15. INSTRUCTIONS ON USE

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16. INFORMATION IN BRAILLE

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Vantobra 170 mg

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING

POUCH

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

PARI Pharma GmbH

Moosstrasse 3

D-82319 Starnberg

Germany ed

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12. MARKETING AUTHORISATION NUMBER(S)

or EU/1/14/932/001

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13. BATCH NUMBER

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Lot

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14. GENERAL CLASSIFICATION FOR SUPPLY

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15. INSTRUCTIONS ON USE

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• 16. INFORMATION IN BRAILLE no

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

AMPOULE