Last Updated on eMC 04-04-2017 View medicine  | Gilead Sciences 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 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:29-03-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

$0• Update to include a dosing recommendation for mucormycosis.$0$0• Update to sections 3,4.1,4.2,4.3,4.4,4.6,4.8,4.9,5.1,5.2,6.4 to align with the latest version of the QRD template$0$0$0$0

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:02-02-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

• Section 7: Minor correction of the name of the marketing authorisation holder to Gilead Sciences International Ltd
• Section 10: Change to the date of revision to February 2015

Reasons for adding or updating:

  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 10 date of revision of the text
  • Change to section 6. 3 - Shelf Life

Date of revision of text on the SPC:01-08-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



SPC:

Section 6.3- Shelf life extension from 3 to 4 years

Section 6.4- Removal of the statement “Do not Freeze” for the storage of the finished product

Section 10- Date changed for the revision of the text to August 2012

 

 

 

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:01-12-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

- Musculoskeletal pain (arthralgia, back pain or bone pain) listed as a symptom of less frequent infusion related reactions (Section 4.8)

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 5.1 - Pharmacodynamic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-12-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



1. Extension of the indication to first-line treatment of severe systemic or deep mycoses (Section 4.1)


2. Re wording of the dosing requirements in paediatric patients (Section 4.2) to now state:-

"Paediatric Patients: Both systemic fungal infections in children and presumed fungal infections in children with febrile neutropenia have been successfully treated with AmBisome, without reports of unusual adverse events. AmBisome has been studied in paediatric patients aged one month to 18 years old. Doses used in these clinical studies were the same as those used in adults on a mg/kg body weight basis.

 

AmBisome is not recommended for use in children below 1 month old due to lack of data on safety and efficacy. "

3. Inclusion of a paragraph on the pharmacokinetic/pharmacodynamic relationship (Section 5.1):-

"PK/PD relationship

 

Mechanism of resistance

Intrinsic resistance, though rare, maybe primarily due to decrease in ergosterol or a change in the target lipid; Leading to reduced binding of amphotericin B to the cell membrane.

 

Breakpoints

EUCAST breakpoints for AmBisome have not yet been established, however,

susceptibility to AmBisome may differ to that of amphotericin B deoxycholate."

4. Re wording of the list of species that AmBisome is active in vitro against (Section 5.1) to now state:-

"Amphotericin B, the antifungal component of AmBisome is active in vitro against many species of fungi., most strains of Histoplasma capsulatum, Coccidioides immitis, Candida spp, Blastomyces dermatidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenkii and Aspergillus fumigatus, Penicillium marneffi, and members of the mucormycetes group of moulds including Mucor mucedo, Rhizomucor and Rhizopus oryzae.

 

The majority of clinically important fungal species seem to be susceptible to Amphotericin B, although intrinsic resistance has rarely been reported for example, for some strains of S. schenckii, C. glabrata, C.krusei, C. tropicalis, C. lusitaniae, C parapsilosis and Aspergillus terreus.

 

AmBisome has been shown to be effective in animal models of visceral leishmaniasis (caused by Leishmania infantum and Leishmania donovani)."

5. Addition of study data to support the safe and effective first-line use, includes

AmBiLoad, Kuse 2007 paper along with paediatric sub study and data from Pagano 2004 (Section 5.1):

"The efficacy of AmBisome has been established in a number of clinical trials for the treatment of systemic mycotic infections, as empirical therapy for fever of unknown origin in neutropenic patients and for the treatment of visceral leishmaniasis. These studies include comparative randomized studies of AmBisome versus conventional amphotericin B in confirmed Aspergillus and Candida infections where the efficacy of both medicinal products was equivalent. In both adult and paediatric febrile neutropenic patients presumed to have fungal infection, the results of a randomized, double-blind clinical trial demonstrated that AmBisome administered at 3 mg/kg/day is as effective as conventional amphotericin B. The efficacy of AmBisome in the treatment of visceral leishmaniasis has been clearly demonstrated in a large population of immunocompetent and immunocompromised patients.

 

 

Invasive Filamentous Fungal Infections (IFFI) including Aspergillus spp.: The efficacy of AmBisome has been demonstrated in a prospective, randomised, multicentre study as first line treatment in immunocompromised, mainly neutropenic adults and children (> 30 days old) with proven or probable IFFIs (AmBiLoad Study). Patients were monitored for 12 weeks. A standard-dose regimen of 3 mg/kg/day (N=107) was compared to a loading dose regimen of 10 mg/kg/day (N=94) for the first 14 days of treatment. The favourable overall response rates were 50% of subjects in the standard-dose group and 46% of the subjects in the loading-dose group in the modified intent-to-treat analysis set. Differences were not statistically significant. The median time to resolution of fever was similar in the standard-dose and loading-dose groups (6 and 5 days, respectively). Twelve weeks after the first dose of AmBisome, survival was 72% in the standard-dose group and 59% in the loading-dose group, a difference that was not statistically significant.

 

Invasive candidiasis: AmBisome (3 mg/kg/day) was as effective as Micafungin (100 mg/day [Body weight > 40 kg] or 2 mg/kg/day [Body weight ≤ 40 kg]) as first line treatment of candidaemia and invasive candidiasis in a randomised, double-blind, multinational non-inferiority study in adults and children. AmBisome and Micafungin were administered for a median duration of 15 days. The favourable overall response was 89.5% (170/190) in the AmBisome group and 89.6% (181/202) in the Micafungin group (per protocol analysis set). The paediatric sub-study, which enrolled 98 patients  of whom 57 were <2 years old, (including 19 premature infants), showed favourable overall response rates  of : 88.1% (37/42) for AmBisome and 85.4% (35/41) for Micafungin (per protocol analysis set).

 

Invasive zygomycosis: A retrospective  analysis covering  a 15-year period included 59 patients with haematological malignancies with proven or probable mucormycosis. Therapy was successful in 16 patients (37%): 9 of 39 patients who received conventional amphotericin B (23%) and 7 of the 12 patients who received AmBisome (58%) responded to therapy."

6. Date changed for the revision of the text (Section 10)

Reasons for adding or updating:

  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:03-05-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



1. Addition of an alternative 20ml size Ph.Eur Type I glass tubing vial (Section 6.5)

2. Date changed for the revision of the text (Section 10)

Reasons for adding or updating:

  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 6 - Instructions for use, handling and disposal
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:07-04-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



  • Clarifying the dosing and reconstitution information in sections 6.3 (shelf life) and 6.6 (special precautions for disposal and other handling)
  • In section 10, date of the revision of the text has changed

Reasons for adding or updating:

  • Change to section 6. 6 - Instructions for use, handling and disposal
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:22-07-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.6

  • Addition of a warning that AmBisome is not interchangeable with other amphotericin products
  • Correcting information regarding reconstitution and dilution prior to infusion
  • Inclusion of a cross reference between section 6.6 and 4.4

Section 10

  • Date of the revision of the text- 22nd July 2010 

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-07-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

The changes to the SPC are all in section 4.8 (undesirable effects) and include the following

1. Addition of rhabdomyolysis (associated with hypokalaemia)

2. Addition of information regarding the interference with phosphorus chemistry assays

3. Other amendments include bringing the SPC in line with CIOMS and EU SPC guidelines i.e. a reordering of the information in section 4.8


Section 10 has been updated from May 2010 to July 2010

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:04-05-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

- In section 4.2 the following statement has been added:-

Hepatic impairment: No data are available on which to make a dose recommendation for patients with hepatic impairment (See section 4.4).


-In section 10, the date of the revision of the text has changed to May 2010.

Reasons for adding or updating:

  • Change to section 1 -Name of the Medicinal product
  • Change to section 3 - Pharmaceutical form
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:21-01-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



  • In section 1- Amended to AmBisome 50 mg powder for solution for infusion.
  • In section 3- Rewording of the dosage form to state AmBisome is a sterile, powder for solution for infusion.
  • In section 10- Date changed for the revision of the text to 21/01/2009.

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.3 - Preclinical Safety Data
  • Change to section 6.1 - List of Excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 6. 6 - Instructions for use, handling and disposal
  • Change to section 10 date of revision of the text
  • Change to section 1 -Name of the Medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • 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 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose

Date of revision of text on the SPC:20-08-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 1
- Name amended to AmBisome 50 mg lyophilisate for solution for infusion.

Section 2
The following statement added:
- After reconstitution, the concentrate contains 4 mg/mL amphotericin B.

Section 3
-
Rewording of dosage form.

Section 4.2
-
Information added regarding the recommended duration of intravenous infusion in doses greater than 5mg/kg/day.
- Inclusion of adult patients subheading and “B” following amphotericin.
- Statement that AmBisome is not recommended for use in children below 1 month.
- Statement alteration in elderly patients section.

Section 4.3
-
Amendment to contraindication statement.

Section 4.4
-
Changes to this section with additional information included with regards special warnings and precautions.

Section 4.5
- Changes to this section with additional information included with regards to interaction.

Section 4.7
-
Statement alteration on the effects of AmBisome on the ability to drive/or use machines.

Section 4.8
- Changes with additional information on undesirable effects.
- Amendment to the frequency definitions.
- Addition of “not known” incidences in the disorders section.

Section 4.9
- Inclusion of the word “acute” to overdose.

Section 5.1
Addition of a subheading and “B” after amphotericin.

Section 5.3
Statement amendments to doses in dogs, rabbits and rats and non-mutagenic in bacterial and mammalian systems.

Section 6.1
- Excipients listed.

Section 6.2
-
Statement alteration with regards incompatibility and mixing with other drugs and electrolytes.

Section 6.3
-
Minor amendments with shelf life information.

Section 6.4
- Statement “Keep container in outer carton” added.
- Statement of Referral to section 6.3 for storage conditions.

Section 6.5
-
Statement on the marketing of pack sizes.

Section 6.6
-
Addition of yellow dispersion after reconstitution with water for injections statement.
- Includes statements on unused product and waste disposal.

Section 10
-
Date changed for the revision of the text.

Reasons for adding or updating:

  • Change to MA holder contact details

Date of revision of text on the SPC:01-07-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change to MAH postcode from CB2 6GT to CB21 6GT

Reasons for adding or updating:

  • Change to section 6. 4 - Special Precautions for Storage

Date of revision of text on the SPC:01-08-2006

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.4 - change in the storage conditions of the finished product to remove the requirement to protect the product from light.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects

Reasons for adding or updating:

  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 4 - Special Precautions for Storage

Reasons for adding or updating:

  • Correction of spelling/typing errors

Reasons for adding or updating:

  • Change to section 2 - qualitative and quantitative composition
  • Change to section 6. 5 - Nature and Contents of Container

Reasons for adding or updating:

  • Change to section 3 - pharmaceutical form
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • No reasons supplied