Last Updated on eMC 25-07-2016 View medicine  | Merck Sharp & Dohme Limited 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 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Date of revision of text on the SPC:23-06-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



The changes made to the SmPC are as follows:

·        Section 4.4 Special warnings and precautions for use: The following warning statement has been added, ‘Cases of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported after post marketing use of caspofungin. Caution should apply in patients with history of allergic skin reaction’.
·        Section 4.8 Undesirable effects: New adverse drug reactions of “toxic epidermal necrolysis” and “Stevens-Johnson Syndrome” with the frequency ‘not known’ based on the post-marketing experience have been added. This section has also been updated to include a single table listing all adverse reactions (clinical trials + post-authorisation) with their respective frequency category. A separate table for the paediatric population listing all adverse events has also been created.
·        Sections which details ‘Instructions for use in adults patients’ has been separated per individual strength (50mg and 70mg). 

 

 

Reasons for adding or updating:

  • 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:26-05-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 5.1 Pharmacodynamic properties: Wording has been added on molecular diagnostic methods to detect for the presence of “FkS” mutations together with the EUCAST guidance on the use of anidulafungin and/or micafungin breakpoints as an alternative susceptibility testing for caspofungin.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects

Date of revision of text on the SPC:26-03-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



·        Update of section 4.8 of the SmPC in order to add clinical ADR term, “gamma-glutamyltransferase increased” in the “Paediatric patients” section as the cumulative review of postmarketing reports of GGT increased includes reports from paediatric and adult patients.

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for use

Date of revision of text on the SPC:16-09-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

The following information has been added to 4.4:

“Laboratory abnormalities in liver function tests have been seen in healthy volunteers and adult and paediatric patients treated with caspofungin. In some adult and paediatric patients with serious underlying conditions who were receiving multiple concomitant medications with caspofungin, cases of clinically significant hepatic dysfunction, hepatitis and hepatic failure have been reported; a causal relationship to caspofungin has not been established. Patients who develop abnormal liver function tests during caspofungin therapy should be monitored for evidence of worsening hepatic function and the risk/benefit of continuing caspofungin therapy should be re-evaluated.”

Reasons for adding or updating:

  • 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
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:13-06-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

-  Update to section 4.8 to include the new reporting statement.
-  Update to section 5.1 to include new sub-headings to relect the QRD V.9 template.
-  Update to section 6.6 to include statement on disposal of unused medicinal product.

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:26-04-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4 of the SmPC has been updated  to add a warning on hypersensitivity and anaphylaxis events  and to provide guidance to healthcare professionals if these events occur.

Anaphylaxis has been reported during administration of caspofungin. If this occurs, caspofungin should be discontinued and appropriate treatment administered. Possibly histamine-mediated adverse reactions, including rash, facial swelling, angioedema, pruritus, sensation of warmth, or bronchospasm have been reported and may require discontinuation and/or administration of appropriate treatment.

 

 

 

Section 4.8 was updated accordingly - previous information has been replaced as follows with a reference to the information in 4.4:

 

Hypersensitivity reactions (anaphylaxis and possibly histamine-mediated adverse reactions) have been reported (see section 4.4).

 

 

 

Possible histamine-mediated symptoms have been reported including reports of rash, facial swelling, angio-oedema, pruritus, sensation of warmth, or bronchospasm. Anaphylaxis has been reported during administration of caspofungin.

Reasons for adding or updating:

  • Change to section 9 - Date of first Authorisation/renewal of the Authorisation
  • Change to section 10 date of revision of the text
  • 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 6. 4 - Special Precautions for Storage

Date of revision of text on the SPC:19-07-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Editorial changes only- no change to any meaning.

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 9 - Date of first Authorisation/renewal of the Authorisation

Date of revision of text on the SPC:14-05-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 5.1 Pharmacodynamic properties-Information on susceptibility testing has been added. The updated paragraph in section 5.1 reads as follows :

Susceptibility testing was performed according to a modification of both the Clinical and Laboratory Standards Institute (CLSI, formerly known as the National Committee for Clinical Laboratory Standards [NCCLS]) method M38-A2 (for Aspergillus species) and method M27-A3 (for Candida species). Standardised techniques for susceptibility testing have been established for yeasts by EUCAST. However, interpretive breakpoints for caspofungin have not been approved by EUCAST. Isolates of Candida with reduced susceptibility to caspofungin have been identified in a small number of patients during treatment (MICs for caspofungin >2 mg/L (4- to 30-fold MIC increases) have been reported using standardized MIC testing techniques approved by the CLSI).The mechanism of resistance identified was FKS1/FKS2 gene mutation. These cases have been associated with poor clinical outcomes.

 

Section 9 of the SmPC has also been updated to reflect the date of the last renewal

of the SmPC has also been updated to reflect the date of the last renewal

 

Reasons for adding or updating:

  • Change to section 3 - Pharmaceutical form
  • 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 4.6 - 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 - Instructions for use, handling and disposal

Date of revision of text on the SPC:07-09-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 3: Description updated to make clear it is the description of the pharmaceutical form prior to reconstitution.

Section 4.2: 'CANCIDAS' has been changed to 'caspofungin throughout this section. Sub-heading names have been added to make the text clearer (i.e. 'Posology', 'Special populations', 'Method of administration'). Administration details have been re-located to the bottom of section 4.2 and made more concise, with a cross reference to section 6.6.

Section 4.2: 'hepatic insufficiency' has been changed to 'hepatic impairment' throughout this section

Section 4.2: The following text has been added

"The safety information on treatment durations longer than 4 weeks is limited. However, available data suggest that caspofungin continues to be well tolerated with longer courses of therapy (up to 162 days in adult patients and up to 87 days in paediatric patients."  

Section 4.4: '

 

CANCIDAS' has been changed to 'caspofungin throughout this section. In addition, 'hepatic insufficiency' has been changed to 'hepatic impairment' throughout this section. A cross reference to section 2 has been added at the end of the section. 

Section 4.5:
'
CANCIDAS' has been changed to 'caspofungin throughout this section.  

 

 

Section 4.6: section heading has changed from 'Pregnancy and lactation' to 'Fertility, pregnancy and lactation' in line with current QRD template. This section has been re-wording as follows:

 

Pregnancy

 

 

 

 

For CANCIDAS, no clinical data on exposed pregnancies are available There are no or limited data from the use of caspofungin in pregnant women. Caspofungin should not be used during pregnancy unless clearly necessary. Animal studies have shown developmental toxicity (see section 5.3). There are no adequate data from the use of caspofungin in pregnant women. Developmental studies in animals have shown adverse effects (see section 5.3). Caspofungin has been shown to cross the placental barrier in animal studies. The potential risk to the human foetus is unknown.   

Breastfeeding
It is unknown whether caspofungin is excreted in human milk. Available pharmacodynamic/ toxicological data in animals have shown excretion of caspofungin in milk. Caspofungin is excreted in milk of lactating animals. It is not known whether it is excreted in human milk. Women receiving caspofungin should not breast-feed.

Fertility
For caspofungin, there were no effects on fertility in studies conducted in male and female rats (see section 5.3). There are no clinical data for caspofungin to assess its impact on fertility.  


Section 4.8: The following information has been re-located to the start of this section:
Possible histamine-mediated symptoms have been reported including reports of rash, facial swelling, angio-oedema, pruritus, sensation of warmth, or bronchospasm. Anaphylaxis has been reported during administration of caspofungin.
Also reported in patients with invasive aspergillosis were pulmonary oedema, adult respiratory distress syndrome (ARDS), and radiographic infiltrates.

 

Section 4.8: The information concerning paediatric patients has been updated as follows:

Data from 5 clinical studies completed in 171 paediatric patients suggest that the overall incidence of clinical adverse experiences (26.3%; 95% CI -19.9, 33.6) is not worse than reported for adults treated with caspofungin (43.1%; 95% CI -40.0, 46.2). However, paediatric patients probably have a different adverse event profile compared to adult patients. The most common drug-related clinical adverse experiences reported in paediatric patients treated with caspofungin were pyrexia (11.7%), rash (4.7%) and headache (2.9%)

 

 

In clinical studies, 171 paediatric patients received single or multiple doses of CANCIDAS: 104 febrile, neutropenic patients; 56 patients with invasive candidiasis; 1 patient with esophageal candidiasis; and 10 patients with invasive aspergillosis. The overall safety profile of CANCIDAS in paediatric patients is generally comparable to that in adult patients.

 Section 4.8 and 4.9: 'adverse event' has been changes to 'adverse reactions'

Section 5.1: '

 

CANCIDAS' has been changed to 'caspofungin' in this section. Information has been updated as follows:

Development of in vitro resistance to caspofungin by Aspergillus species has not been identified. In limited clinical experience, resistance to caspofungin in patients with invasive aspergillosis has not been observed. 
T
he mechanism of resistance has not been established. The incidence of resistance to caspofungin by various clinical isolates of Candida and Aspergillus is unknownrare.  

 

 

Section 5.2: The sub-heading name 'Metabolism' has been changed to 'Biotransformation'. 'Hepatic insufficiency' has also been changed to 'Hepatic impairment' throughout this section.

Section 5.3: The following sentence has been added: "

 

For caspofungin, there were no effects on fertility in studies conducted in male and female rats up to 5 mg/kg/day".    

 

Section 6.6: Section heading changed from "Special precautions for disposal" to "Special precautions for disposal and other handling". The text "No special requirements" has been deleted.

Section 6.6: Reconstitution instructions at the end of the SmPC in adult patients and paediatric patients - this section has been updated throughout, so that it is now only recommended to reconstitute Cancidas with water for injection. Typographical errors in the figures in the table have been corrected.

Reasons for adding or updating:

  • Removal of Black Triangle

Date of revision of text on the SPC:14-01-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Black triangle removed- Intensive monitoring no longer required.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects

Date of revision of text on the SPC:26-11-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



Section 4.8: The following change has been made: "Possible histamine-mediated symptoms have been reported including reports of rash, facial swelling,

angio-oedema, pruritus, sensation of warmth, or bronchospasm. Anaphylaxis has been reported during administration of CANCIDAS."

 

Reasons for adding or updating:

  • 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 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic Properties

Date of revision of text on the SPC:01-07-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



The following changes have been made to the SmPC:

Section 4.2: Under the sub-heading "Dosage in adult patients", removal of the sentence "Doses higher than 70 mg daily have not been adequately studied"

Section 4.5: Included paragraph stating "All adult drug-drug interaction studies described above were conducted at a 50 or 70 mg daily caspofungin dose. The interaction of higher doses of caspofungin with other medications has not been formally studied"

Section 4.8: Extensive changes to side effects section. New side effects added. Information about a study which evaluated Cancidas at 150 mg daily has been added.

Section 4.9: 140 mg changed to 400 mg with regards to dosage of caspofungin inadvertently administered in one day (up to 400 mg).

Section 5.1: Paragraph added describing study involving patients with invasive candidiasis receiving daily doses of caspofungin at 50 mg/day (following a 70-mg loading dose on Day 1) or caspofungin at 150 mg/day (see section 4.8).

Reasons for adding or updating:

  • Change to section 1 -Name of the Medicinal product

Date of revision of text on the SPC:27-03-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



In Section 1, the MHRA have approved that the reinstated black triangle marking this product may be put into context by the addition of the following 

 

explanatory sentence

'* Intensive monitoring is requested only when used for the recently-licensed indication extension to paediatric patients.' 

 

 

 

Reasons for adding or updating:

  • Addition of Black Triangle

Date of revision of text on the SPC:02-12-2008

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Following the extension of the indications of this product to the paediatric population in early December 2008, the MHRA have confirmed that Cancidas should be subject to Black triangle intensive monitoring.

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 5.2 - Pharmacokinetic Properties

Date of revision of text on the SPC:26-11-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Extensive changes have been made to the SmPC to add information concerning paediatric patients, as follows:

Section 4.1: All indications now also apply to paediatric patients

Section 4.2: Paediatric dosing added; inclusion of sub-headings

Section 4.4: Statement concerning no clinical experience in paediatric patients with hepatic insufficiency has been added

Section 4.5: Results from studies with paediatric patients have been included

Section 4.8: Undesirable effects specifically reported in paediatric patients have been included

Section 5.1: Information from studies concerning paediatric patients has been added

Section 5.2: Information specific to paediatric patients has been added

Reconstitution details - Instructions for use in paediatric patients has been added

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 4.4 - Special warnings and precautions for Use
  • 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 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:01-01-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 2: We only give the quantity of caspofungin in each vial and not the quantity of caspofungin acetate. Also, we now state the amount of sucrose in each vial.

Section 4.2: The statement on children has been changed to "The experience in children is limited."

Section 4.4; The header has been revised slightly. The statement "However, available data suggest that caspofungin continues to be well tolerated with longer courses of therapy (up to 162 days)." has been deleted. We have added in a statement about the product containing sucrose.

Section 5.1: An editorial change has been made to the ATC code.

Section 6.3: The statement "Cancidas contains no preservatives." has been added.

Section 6.4: The storage statement has been revised editorially. The last three paragraphs have been deleted as this information appears in section 6.3. A statement cross-referring to section 6.3 has been added.

Section 9: The renewal date has been added.

Section 10: The revision date has been added.

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.5 - Interactions with other Medicaments and other forms of Interaction

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic Indications
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Removal of Black Triangle

Reasons for adding or updating:

  • Correction of spelling/typing errors

Reasons for adding or updating:

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