Last Updated on eMC 12-01-2018 View medicine  | Novartis Pharmaceuticals UK Ltd Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 1 - Name of the medicinal product
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:22-12-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 1 – removal of the Own Label Supplier product name

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.2 - Incompatibilities
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:16-08-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



To update sections 4.2 and 5.1 to add the results of study C2304 - Treatment of early infections of P. aeruginosa in cystic fibrosis subjects from 3 months to less than 7 years of age.

Section 4.2 - change Older people to Elderly

Section 6.2 - change compatibilities to compatibility

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:19-02-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.5 - change to the wording for concomitant use with mannitol

TOBI should not be administered concomitantly with ethacrynic acid, furosemide, urea or intravenous mannitol.


Sections 4.1, 4.2, 4.6 and 4.8 - updated in line with current QRD template


Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text
  • Change to section 4.8 - Undesirable effects
  • Change to section 2 - Qualitative and quantitative composition

Date of revision of text on the SPC:08-03-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Sections 2, 4.2, 4.3 and 6.4 updated in  line with QRD.

Section 4.4 - updated wording on monitoring of serum tobramycin concentrations and on ototoxicity.

Section 4.5- addition of 'No interaction studies have been performed with TOBI'.

Section 4.8 - Update to the adverse reactions.

Section 5.1 - addition of information on clinical efficacy

Section 5.2 - addition of information on absorbtion, distribution and elimination.


 

 

 

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC:13-11-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

It was noticed that there was a formatting error in Section 4.2 of the SmPC on eMC. This has now been rectified.

Reasons for adding or updating:

  • Change to section 1 - Name of the medicinal product
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:13-11-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Addition of own label supplier with the product name of Tobramycin 300mg/5ml Nebuliser Solution.

Reasons for adding or updating:

  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 5.3 - Preclinical Safety Data
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:20-09-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

New "Fertility" paragraph added to Section 4.6: 

Fertility

 

No effect on male or female fertility was observed in animal studies after subcutaneous administration (see section 5.3).



Section 5.3 has been updated as shown below:


 

5.3       Preclinical safety data

 

Preclinical data reveal that the main hazard for humans, based on studies of safety pharmacology, repeated dose toxicity, genotoxicity, or toxicity to reproduction, consists of renal toxicity and ototoxicity. In repeated dose toxicity studies, target organs of toxicity are the kidneys and vestibular/cochlear functions. In general, toxicity is seen at higher systemic tobramycin levels than are achievable by inhalation at the recommended clinical dose.

 

Carcinogenicity studies with inhaled tobramycin do not increase the incidence of any variety of tumour.  Tobramycin showed no genotoxic potential in a battery of genotoxicity tests.

 

No reproduction toxicology studies have been conducted with tobramycin administered by inhalation, but subcutaneous administration at doses of 100 mg/kg/day in rats and the maximum tolerated dose of 20 mg/kg/day in rabbits, during organogenesis, was not teratogenic. Teratogenicity could not be assessed at higher parenteral doses (greater than or equal to 40mg/kg/day) in rabbits as they induced maternal toxicity and abortion. Ototoxicity was not evaluated in offspring during nonclinical reproduction toxicity studies with tobramycin. Based on available data from animals a risk of toxicity (e.g. ototoxicity) at prenatal exposure levels cannot be excluded.

 

Subcutaneous administration of up to 100mg/kg of tobramycine did not affect mating behaviour or cause impairment of fertility in male or female rats.



 

 

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.2 - Pharmacokinetic Properties

Date of revision of text on the SPC:26-08-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

In Section 4.2 the following wording as shown has ben deleted under sub-headings "Posology" and "Patients with renal impairment":

For data on the degree of absorption of tobramycin after inhalation treatment, please refer to information in section 5.2.

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 or blood urea nitrogen (BUN) 40 mg/dL or more were not included in clinical studies and

In Section 5.1 under the heading "Other information" the following wording has been deleted/inserted as shown below.

An open-label, uncontrolled study in CF patients aged 6 months and above (including 48 patients below 6 years of age) explored the effect of 28-day and 56-day TOBI treatment on early, non-chronic infection with P.aeruginosa. Both regimens were well-tolerated and resulted in over 90% of the patients being free from P.aeruginosa 1 month after treatment end. Adequately controlled clinical data are not available to date in this population.

 

There are insufficient clinical safety and efficacy data in children < 6 years of age.

In an open-label uncontrolled study, 88 patients with CF (37 patients between 6 months and 6 years, 41 patients  between 6 and18 years of age and 10 patients above 18 years of age) with early (non-chronic) P aeruginosa infection were treated for 28 days with TOBI. After 28 days, patients were randomised 1:1 to either stop (n=45) or to receive a further 28 days treatment (n=43).

Primary outcome was the median time to recurrence of P aeruginosa (any strain ) which was 26.1 and 25.8 months for the 28-day and 56-day groups, respectively. It was found that; 93% and 92% of the patients were free of P aeruginosa infection 1 month after the end of treatment in the 28-day and 56-day groups, respectively. Adequately controlled clinical data are not available to date in this population . The use of TOBI with a dosing regimen longer than 28 days continuous treatment, is not approved.



In Section 5.2 the wording has been amended as shown below.

The median serum concentration of tobramycin 1 hour after inhalation of a single 300 mg dose of TOBI by CF patients was 0.95 mg/mL (range: below limit of quantitation [BLQ] – 3.62μg/mL). After 20 weeks of therapy on the TOBI regimen, the median serum tobramycin concentration 1 hour after dosing was 1.05 mg/mL (range: BLQ- 3.41μg/mL). by amean

The median serum concentration of tobramycin 1 hour after inhalation of a single 300 mg dose of TOBI by CF patients was 0.95 µg/mL (range: below limit of quantitation [BLQ] – 3.62µg/mL). After 20 weeks of therapy on the TOBI regimen, the median serum tobramycin concentration 1 hour after dosing was 1.05 µg/mL (range: BLQ- 3.41µg/mL).For comparison. the  peak concentrations after intravenous or intramuscular administration of a single tobramycin dose of 1.5 to 2mg/kg typically range from 4 to 12 µg/mL.  

 

 

 

Elimination

 

The elimination of tobramycin administered by the inhalation route has not been studied. Tobramycin is primarily excreted unchanged in the urine and renal function is expected to affect the exposure to tobramycin, however data are not available as .p atients with serum creatinine 2 mg/dL (176,8 mmol/L) or more or blood urea nitrogen (BUN) 40 mg/dL or more were not included in clinical studies.


 

 

 

Reasons for adding or updating:

  • Change to section 4.3 - Contraindications
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6.2 - Incompatibilities
  • Change to section 6. 3 - Shelf Life
  • Change to section 9 - Date of first Authorisation/renewal of the Authorisation
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:23-09-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.3

Administration of TOBI is contraindicated in any patient with known hypersensitivity to any aminoglycoside or any of the excipients (section 6.1)..


Section 4.8

In controlled clinical trials, voice alterationdysphonia and tinnitus were the only undesirable effects reported in significantly more patients treated with TOBI; (13% TOBI vs 7% control) and (3% TOBI vs 0% control) respectively. These episodes of tinnitus were transient and resolved without discontinuation of TOBI therapy, and were not associated with permanent loss of hearing on audiogram testing. The risk of tinnitus did not increase with repeated cycles of exposure to TOBI.

 

Additional undesirable effects, some of which are common sequelae of the underlying disease, but where a causal relationship to TOBI could not be excluded were: sputum discolouredation, respiratory tract infection, myalgia, nasal polyps and otitis media.

 

In the POSTMARKETING phase, undesirable effects have been reported at the following frequencies:

 

 

 

 

Body as a Whole

 

 

 

Rare:

Chest pain, Asthenia, Fever, Headache, Pain,

Very Rare:

Abdominal pain, Fungal infection, Malaise, Back pain, Allergic reactions including urticaria and pruritus

Infections and infestations

 

Rare:

Laryngitis

Very Rare:

Oral candidiasis, fungal infection

Blood and lymphatic system disorders

 

Very Rare:

Lymphadenopathy

Immune system disorders

 

Very Rare:

Hypersensitivity

Metabolism and nutrition disorders

 

Rare:

Anorexia

Nervous system disorders

 

 

Rare:

Headache, Ddizziness, aphonia

 

Very Rare:

Somnolence

 

Ear and labyrinth disorders

 

 

 

Rare:

Tinnitus, Taste perversion, Hhearing loss, Aphonia

Very Rare:

Ear disorder, Eear pain

Respiratory, thoracic and mediastinal disorders

 

 

Uncommon:

Voice alteration, Dysphonia, dyspnoea, Ccough increased, Ppharyngitis

Rare:

Bronchospasm, chest discomfort, tightness, cough, shortness of breath, Llung disorder, productive cough, Sputum Increased, Hhaemoptysis, Lung function decreased, Laryngitis, Eepistaxis, Rrhinitis, Aasthma

Very Rare:

Hyperventilation, Hhypoxia, Ssinusitis

Digestive SystemGastrointestinal disorders

 

Rare:

Dysgeusia, Nnausea, Anorexia, Mmouth ulceration, Vvomiting

Very Rare:

Diarrhoea, abdominal painOral moniliasis

 

Skin and subcutaneous tissue disorders

 

Rare:

Rash

Very Rare:

Urticaria, pruritus

Musculoskeletal, connective tissue and bone disorders

Very Rare:

Back pain

General disorders and administration site conditions

Rare:

Asthenia, pyrexia, chest pain, pain

Very Rare:

Malaise

Investigations

 

Rare:

Pulmonary function test decreased

Haemic and Lymphatic System

 

 

 

Very Rare:

Lymphadenopathy

 

Nervous System

 

 

 

Rare:

Dizziness

 

 

Very Rare:

Somnolence

 

 

Respiratory System

 

 

 

Uncommon:

Voice alteration (including hoarseness), Dyspnoea, Cough increased, Pharyngitis

Rare:

Bronchospasm, chest tightness, cough, shortness of breath, Lung disorder, Sputum Increased,

 

Haemoptysis, Lung function decreased, Laryngitis, Epistaxis,

 

Rhinitis, Asthma

 

 

Very Rare:

Hyperventilation, Hypoxia, Sinusitis

 

Special Senses

 

 

 

Rare:

Tinnitus, Taste perversion, Hearing loss, Aphonia

 

Very Rare:

Ear disorder, Ear pain

 

Skin and Appendages

 

 

 

Rare:

Rash

 

 

 

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 (see 4.4). Parenteral aminoglycosides have been associated with hypersensitivity, ototoxicity and nephrotoxicity (see 4.3, 4.4).


Section 6.2

TOBI should not be diluted or In the absence of compatibilities studies, this medicinal product must not be mixed with any other medicinal product in the nebuliser.


Section 6.3

For single use. The contents of the whole ampoule should be used immediately after opening (see section 6.6). Discard any remaining contents.


Section 9

Include 9th December 2009 for the date of renewal.

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Date of revision of text on the SPC:01-09-2006

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

 
 Change in Market Authorisation Holder from Chiron to Novartis

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC