Last Updated on eMC 22-11-2016 View medicine  | Celgene 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 5.2 - Pharmacokinetic properties
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Date of revision of text on the SPC:11-11-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



·         Annual PSUR in Europe covering 07 Jan 2015 to 06 Jan 2016 to add “clopidogrel” to Section 4.5 of the SmPC and section 2 of the PIL as an example of drugs known to interact with Cytochrome P450 isoenzymes inhibitors and inducers. In addition, minor editorial changes were made to section 4.5

·         Correction in section 5.2 of the smPC (range = 3.21%-37.70%).-37.70% replaced 27.70%

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC:28-07-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Update of section 4.2 to ammend dose reduction recommendations for NSCLC patients with hepatic impairment

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 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling

Date of revision of text on the SPC:26-02-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



·          sections 4.1, 4.2, 4.4, 4.5, 4.8, 5.1 and 6.6 to add the new indication below and an instruction to flush the infusion line following ABX administration.

 

Abraxane in combination with carboplatin is indicated for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy.

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 5.2 - Pharmacokinetic properties
  • Change to section 6.4 - Special precautions for storage

Date of revision of text on the SPC:27-10-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



The following sections of the SPC have been changed:

·         Section 4.2 (dose adjustment in special populations)

·         Section 4.4 (warning for hepatic impairment)

·         Section 5.2 (added pharmacokinetic data)

·         Section 6.4 (additional information on special precautions for storage)

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects - how to report a side effect

Date of revision of text on the SPC:20-03-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Minor re-phrasing and free telephone number added

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 6.6 - Special precautions for disposal and other handling

Date of revision of text on the SPC:20-03-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.2 - additional information regarding method of administration using an infusion set incorporating a 15 µm filter.

Section 6.6 - additional information regarding method of administration using an infusion set incorporating a 15 µm filter.

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • 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 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • 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:16-01-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 2 -  update to the amount of sodium on the excipients section

Section 4.1 -  update to the therapeutic indications, now including metastatic adencarcinoma of the pancreas

Section 4.2

-         units change in breast cancer posology

-          Section added for pancreatic cancer posology

-          Pancreatic info added for pancreatic cancer indication in special populations, specifically older people and the paediatric  population

Section 4.3

-          Units change in neutrophil counts

Section 4.4

-          Units change in haematology section

-          Pancreatic combination dosing with gemcitabine added for neuropathy section

-          Sepsis section added and and pnemonitis section mover higher up

-          Patients ≥ 75 years section added

-          ‘Other’ section has been added comprising of pancreatic cancer info

-          Excipients section has been updated regarding the amount of sodium

Section 4.5

-          Section added regarding paclitaxel and gemcitabine, as these are used in combination in our pancreatic licence.

Section 4.8

-          The summary info has been updated to partition abraxane monotherapy (table 4) and abraxane with gemcitabine (table 5) for the breast cancer and pancreatic cancer indications respectively.

-          The skin and subcutaneous tissue disorder section has been updated with respect to info on alopecia

Section 5.1

-          Clinical data has been added for pancreatic cancer

Section  7

-          Manufacturing has been removed

Section 10

-          Date of revision of the text has been updated to 16/01/2014

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects
  • Change to section 7 - Marketing authorisation holder

Date of revision of text on the SPC:25-07-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



In section 4.2 "elderly population" has been replaced with "older people"
In section 4.8 (undesirable effects), atrioventricular block has been added, and the section "reporting of suspected adverse reactions" have been added.
In section 7 title "and manufacturer" has been added.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects

Date of revision of text on the SPC:14-01-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

in section 4.8 cystoid macular edema and sepsis, neutropenic sepsis has been added as rare and uncommon respectively

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • 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 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 - Special precautions for disposal and other handling
  • 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:14-01-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

section 2

Each vial contains 100 mg of paclitaxel formulated as albumin bound nanoparticles. [as opposed to "paclitaxel albumin"
Excipients "with known effect" added. "the full list" amended to "a full list"
section 4.2

"Abraxane should only be administered under the supervision of a qualified oncologist in units specialised in the administration of cytotoxic agents. It should not be substituted for or with other paclitaxel formulations." removed from the end of paragraph and added to the start

"impaired renal function" replaced with "renal impairment"
modified section on elderly population.
Paediatric population
"and adolescent aged 0-17 years" added
section 4.3
excipients - "listed in section 6.1" added
Lactation - "see section 4.6" added
 Cardiotoxicity section:"drugs" replaced with "medicinal products"
section 4.6 "treatment" added.
section 4.8
title added "summary of the safety profile"
this text was added: 

Tabulated summary of adverse reactions

this text was deleted: from "blood and lymphatic system disorders" up to 6 paragraphs down "general disorders...40% of the patients"
this section was added after the table:

Description of selected adverse reactions

 

Blood and lymphatic system disorders

Neutropenia was the most notable important haematological toxicity (reported in 79% of patients), and was rapidly reversible and dose dependent; leukopenia was reported in 71% of patients. Grade 4 neutropenia (< 0.5 x 109/l) occurred in 9% of patients treated with Abraxane. Febrile neutropenia occurred in four patients on Abraxane. Anaemia (Hb < 10 g/dl) was observed in 46% of patients on Abraxane, and was severe (Hb < 8 g/dl) in three cases. Lymphopenia was observed in 45% of the patients.

 

Nervous system disorders

In general, the frequency and severity of neurotoxicity was dose‑dependent in patients receiving Abraxane. Peripheral neuropathy (mostly Grade 1 or 2 sensory neuropathy) was observed in 68% of patients on Abraxane with 10% being Grade 3, and no cases of Grade 4.

 

Gastrointestinal disorders

Nausea occurred in 29% of the patients and diarrhoea in 25% of the patients.

 

Skin and subcutaneous tissue disorders

Alopecia was observed in 90% of the patients treated with Abraxane.

 

Musculoskeletal and connective tissue disorders

Arthralgia occurred in 32% of patients on Abraxane and was severe in 6% of cases. Myalgia occurred in 24% of patients on Abraxane and was severe in 7% of cases. The symptoms were usually transient, typically occurred three days after Abraxane administration and resolved within a week.

 

General disorders and administration site conditions

Asthenia/Fatigue was reported in 40% of the patients.

start of section 5.1 was modified as follows:

Pharmacotherapeutic group: Antineoplastic agents, plant alkaloids and other natural products, taxanes, ATC Code: L01CD01

 

Mechanism of action

 

Paclitaxel is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilises microtubules by preventing depolymerisation. This stability results in the inhibition of the normal dynamic reorganisation of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.

 

Abraxane contains human serum albumin‑paclitaxel nanoparticles of approximately 130 nm in size, where the paclitaxel is present in a non-crystalline, amorphous state. Upon intravenous administration, the nanoparticles dissociate rapidly into soluble, albumin bound paclitaxel complexes of approximately 10 nm in size. Albumin is known to mediate endothelial caveolar transcytosis of plasma constituents, and in vitro studies demonstrated that the presence of albumin in Abraxane enhances transport of paclitaxel across endothelial cells. It is hypothesised that this enhanced transendothelial caveolar transport is mediated by the gp‑60 albumin receptor, and that there is enhanced accumulation of paclitaxel in the area of tumour due to the albumin‑binding protein Secreted Protein Acidic Rich in Cysteine (SPARC).

 

Clinical efficacy and safety

 

Breast cancer ("carcinoma" deleted)

"229" patients replaced with number in letters: "Two hundred and twenty nine"
section 6.3
"3 years" formatting change only
section 6.4
"this medicinal does not require... conditions" replaced with "keep the vial in the outer carton in order to protect from light"
section 6.5
"(as paclitaxel albumin)" modified to "formulated as albumin bound nanoparticles"
section 6.6
"drug" to "medicinal product"
"(as paclitaxel albumin)" modified to "formulated as albumin bound nanoparticles"
last paragraph modified to:
"

The exact total dosing volume of 5 mg/ml suspension required for the patient should be calculated and the appropriate amount of reconstituted Abraxane should be injected into an empty, sterile, PVC or non‑PVC type intravenous bag. The use of specialized di(2-ethylhexyl)phthalate (DEHP)‑free solution containers or administration sets is not necessary to prepare or administer Abraxane infusions. In‑line filters should not be used.

"

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • 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:17-07-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

- Update of Section 4.4 to extend the hypersensitivity warning, specifically mentioning rare cases of anaphylactic reactions
- Update of Section 7 to remove the county name "Middlesex" from the address of the MAH Celgene Europe Ltd
- Update of Section 10 to include date of revision of the text

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:20-04-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.4 (Special warnings and precautions for use) - paragraph added about pneumonitis
Section 4.8 (Undesirable effects) - section added after Table 1 regarding the incidence and occurance of pneumonitis

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 6. 6 - Instructions for use, handling and disposal
  • 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:01-07-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.8 - Addition of Stevens-Johnson syndrome, toxic epidermal necrolysis as very rare side effects. Addition of Extravasation as a rare side effect.
Footnote under Table 1 added to state: "As reported in the postmarketing surveillance of Abraxane"

section 6.5 - Addition of generic drug name.

Section 6.6 - Addition of paragraph regarding extravasation and addition of generic drug name in third paragraph.

Section7.0 - Change of address

Section 10.0 - update to 07/2011

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Date of revision of text on the SPC:31-03-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change to marketing authorisation holder from Abraxis to Celgene Europe Limited

Reasons for adding or updating:

  • Change to section 5.2 - Pharmacokinetic Properties
  • Extra statutory information

Date of revision of text on the SPC:01-09-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



In Section 4.2 Posology and method of administration

The information has been reworded/ formatted to comply with current requirements.

 

In Section 4.6 Fertility, pregnancy and lactation

The information has been reworded/ formatted to comply with current requirements.

 

In Section 5.1 Pharmacodynamic properties

The information has been reworded/ formatted to comply with current requirements.

 

In Section 5.2 Pharmacokinetic properties

The text has been updated to include information relating to drug exposure in low bodyweight patients

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 - Pregnancy and Lactation
  • Change to section 4.8 - Undesirable Effects
  • Addition of link to EMEA website

Date of revision of text on the SPC:01-06-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



In Section 4.2 Posology and method of administration

The information has been reworded/ formatted to comply with current requirements.

 

In Section 4.4 Special Warnings and Precautions for Use
Cardiotoxicity information has been updated to acknowledge some cardiotoxicity is associated with Abraxane.

 

In Section 4.6 Fertility, pregnancy and lactation

The information has been reworded/ formatted to comply with current requirements.

 

In Section 4.8 Undesirable effects Table 1 has been updated to include the following rare effects: pancytopenia, left ventricular dysfunction, congestive heart failure

 

The website address of the EMA has been updated at the end of the document

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 5.2 - Pharmacokinetic Properties
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 6. 3 - Shelf Life
  • Change to section 6. 4 - Special Precautions for Storage
  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 10 date of revision of the text
  • Addition of link to EMEA website
  • Change to section 4.4 - Special warnings and precautions for Use

Date of revision of text on the SPC:01-08-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



In Section 4.4 Special Warnings and Precautions for Use
An additional warning has been added advising that Abraxane should not be substituted for or with other paclitaxel formulations.

In Section 4.5 Interactions with other medicinal products and other forms of interaction

The examples of drugs known to inhibit either CYP2C8 or CYP3A4 have been expanded to include ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir)

 

In Section 4.8 Undesirable effects Table 1 has been updated to include the following effects:

bone marrow supression (very common)

severe hypersensitivity (rare)

keratitis (uncommon)

arrhythmia, supraventricular tachycardia (common)

bradycardia, cardiac arrest (rare)

pulmonary emboli, pulmonary thromboembolism (uncommon)

nail pigmentation, nail changes (common)

radiation pneumonitis (rare)

Additionally, hyperbilirubinaemia has been removed from the hepatobiliary disorders SOC and appears as increased bilirubin in the Investigations SOC

 

In Section 5.2 Pharmacokinetic properties the following information has been added:

 

In a repeat dose study with 12 patients receiving Abraxane administered intravenously at the approved dose, intrapatient variability in systemic paclitaxel exposure (AUCinf) was 19% (range = 3.21%-27.70%). There was no evidence for accumulation of paclitaxel with multiple treatment courses.

 

The protein binding of paclitaxel following Abraxane was evaluated by ultrafiltration. The fraction of free paclitaxel was significantly higher with Abraxane (6.2%) than with solvent-based paclitaxel (2.3%). This resulted in significantly higher exposure to unbound paclitaxel with Abraxane compared with solvent-based paclitaxel, even though the total exposure is comparable.  This is possibly due to paclitaxel not being trapped in Cremophor EL micelles as with solvent-based paclitaxel.

 

In Section 6.3 Shelf life

The shelf-life of the unopened vials has been increased from 2 to 3 years.

For the storage of the reconstituted solution in the vial, where health care practitioners were advised to store the vials in the original carton in order to protect the product from light, a clarifying statement has been added: "Alternative light-protection may be used in the clean room."

 

In Section 6.4 Special precautions for storage

For the unopened vials the following text has been added:

"This medicinal product does not require any special temperature storage conditions"

 

In Section 7 Marketing Authorisation Holder the address has been updated

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 5.2 - Pharmacokinetic Properties

Date of revision of text on the SPC:01-04-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



In section 4.2, the text relating to doses for patients with hepatic impairment has been clarified.

 

In section 4.4, under hepatic impairment, the following caution has been added

"Because the toxicity of paclitaxel can be increased with hepatic impairment, administration of Abraxane in patients with hepatic impairment should be performed with caution."
Additionally, physicians are advised to contemplate a dose reduction in patients whose blood bilirubin exceeds twice the limit of normal, since paclitaxel clearance is decreased in patients with high bilirubin levels.

 

In section 5.2, Figure 1 shows the relationship between paclitaxel clearance and blood bilirubin following administration of Abraxane to patients with hepatic impairment.

Reasons for adding or updating:

  • New SPC for new product

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): NO