Mepact 4mg powder for suspension for infusion

  • Name:

    Mepact 4mg powder for suspension for infusion

  • Company:
    info
  • Active Ingredients:

    Mifamurtide

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 26/03/19

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Summary of Product Characteristics last updated on medicines.ie: 8/3/2019

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Takeda Products Ireland Ltd

Takeda Products Ireland Ltd

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1 - 0 of 26 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 26 March 2019 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 2 - excipient warnings
  • Change to section 4 - possible side effects
  • Change to section 5 - how to store or dispose
  • Change to section 6 - what the product contains
  • Change to section 6 - date of revision

Updated on 8 March 2019 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

The EMA have approved the Mepact renewal and as a consequence, the product information has been updated. The changes are largely administrative in nature, to align with the QRD template.

Updated on 12 May 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 8 November 2016 PIL

Reasons for updating

  • New PIL for new product

Updated on 8 November 2016 PIL

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 21 July 2015 SmPC

Reasons for updating

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

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

SPC and PIL to change the name of the IMB to the HPRA in the adverse event reporting sections

Updated on 21 July 2015 PIL

Reasons for updating

  • Addition of information on reporting a side effect.

Updated on 21 July 2015 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 13 January 2014 SmPC

Reasons for updating

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

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Date of revision  of the text has been changed to '18/12/2013'

Updated on 20 December 2013 PIL

Reasons for updating

  • Change to product name
  • Addition of information on reporting a side effect.

Updated on 19 December 2013 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

1     Name of the medicinal product

Changed:

‘’MEPACT 4mg Powder for suspension for infusion’’ to ‘’MEPACT 4mg Powder for concentrate for dispersion for infusion’’

3.    Pharmaceutical form

Changed:

‘’Powder for suspension for infusion’’ to ‘’Powder for concentrate for dispersion for infusion’’

4.2  Posology and method of administration

 

Changed:

‘Elderly patients’ to ‘’Adults >30 years’’

 

 

4.6  Fertility, pregnancy and lactation

 

Added: “Fertility” to the section heading “Fertility, pregnancy and lactation”

 

Changed: “Lactation” heading to “Breastfeeding”

 

Added:

Fertility

No dedicated fertility studies have been conducted with mifamurtide (see section 5.3).

 

4.8   Undesirable effects

 

 

 

 

 

 

 

 

 

 

4.8 Description of selected adverse reactions

 

 

Changed:

Summary of the safety profile

Mifamurtide was studied as a single agent in 248 patients with mostly advanced malignancies during the early, single arm phase I and II clinical studies. The most frequent adverse reactions, occurring in >50% of patients, were chills, pyrexia, fatigue, nausea, tachychardia and headache. Many of the very commonly reported adverse reactions.

 

 

 

 

Added:

Nervous system disorders

One patient in the phase III study experienced 2 episodes of Grade 4 seizure while on study therapy with chemotherapy and mifamurtide. The second episode involved multiple grand mal seizures over the course of days. Mifamurtide treatment was continued for the remainder of the study without seizure recurrence.

 

Investigations:

An osteosarcoma patient in a phase II study who had high creatinine level at enrolment showed an increase in blood urea and blood creatinine which was associated with mifamurtide use.

 

Immune system disorders:

In a phase I study, there was one report of severe allergic reaction occurring after the first infusion of mifamurtide at 6 mg/m2 dose level. The patient experienced shaking, chills, fever, nausea, vomiting, uncontrollable coughing, shortness of breath, cyanotic lips, dizziness, weakness, hypotension, tachycardia, hypertension and hypothermia leading to study discontinuation. There was also one report of a grade 4 allergic reaction (hypertension) requiring hospitalization in the phase III study (see section 4.4).

 

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, IRL – Dublin 2. Tel: +353 1 6764971, Fax: +353 1 6767836, Website: www.imb.ie. e-mail:imbpharmacovigilance@imb.ie.

 

10      DATE OF REVISION OF THE TEXT

 

Changed to:

12th December 2013

 

Updated on 7 October 2013 PIL

Reasons for updating

  • Change to marketing authorisation holder

Updated on 4 October 2013 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In Section 7. Marketing authorisation holder- has the name change approval to the following:      

 

Takeda France SAS

Immeuble Pacific

11-13 cours Valmy

92800 Puteaux

France

               

Updated on 14 June 2013 PIL

Reasons for updating

  • Change to name of manufacturer

Updated on 4 April 2013 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.9 - Overdose
  • Change to section 5.2 - Pharmacokinetic properties

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Additional wording to section 4.2:

Patients with impaired renal or hepatic function

There are no clinically meaningful effects of mild to moderate renal (creatinine clearance (CrCL) ≥ 30ml/min) or hepatic impairment (Child-Pugh class A or B) on the pharmacokinetics of mifamurtide; therefore, dose adjustments are not necessary for these patients. However, as the variability in pharmacokinetics of mifamurtide is greater in subjects with moderate hepatic impairment (see Section 5.2), and safety data in patients with moderate hepatic impairment is limited, caution when administering mifamurtide to patients with moderate hepatic impairment is recommended.

As no pharmacokinetic data of mifamurtide is available in patients with severe renal or hepatic impairment, caution when administering mifamurtide to these patients is recommended. Continued monitoring of the kidney and liver function is recommended if MEPACT is used beyond completion of chemotherapy until all therapy is completed.

 
Additonal wording to section 4.9
No case of overdose has been reported within the approved indication

A healthy adult volunteer accidentally received a single dose of 6.96 mg mifamurtide and experienced a reversible treatment-related event of orthostatic hypotension

 

Additional wording and changes to Section 5.2:

The pharmacokinetics of mifamurtide have been characterized in healthy adult subjects following a 4 mg intravenous  infusion and in paediatric and adult patients with osteosarcoma following a 2 mg/m2 intravenous infusion.

In 21 healthy adult subjects mifamurtide was cleared rapidly from  serum (minutes) with a half-life of 2.05 ± 0.40 hours, resulting in a very low  serum concentration of total (liposomal and free) mifamurtide. The mean AUC was 17.0 ± 4.86 h x nM and Cmax was 15.7 ± 3.72 nM.

In 28 osteosarcoma patients aged 6 to 39 years serum total (liposomal and free) mifamurtide concentrations declined rapidly with a mean half-life of 2.04 ± 0.456 hours. BSA-normalized clearance and half-life were similar across the age range and consistent with that determined in healthy adult subjects, supporting the recommended dose of 2 mg/m2.

In a separate study in 14 patients, mean serum concentration‑time curves of total and free mifamurtide that were assessed after the first infusion of MEPACT and after a last infusion 11 or 12 weeks later, were almost superimposable and the mean AUC values of the free mifamurtide after the first and last infusion were similar. These data indicate that neither total nor free mifamurtide accumulated during the treatment period.

At 6 hours after injection of radiolabelled liposomes containing 1 mg mifamurtide, radioactivity was found in liver, spleen, nasopharynx, thyroid, and, to a lesser extent, in lung. The liposomes were phagocytosed by cells of the reticuloendothelial system. In 2 of 4 patients with lung metastases, radioactivity was associated with lung metastases.

 

Special Populations

 

Renal Impairment

 

The pharmacokinetics of a single 4mg dose of mifamurtide following a 1 hour intravenous infusion were evaluated in adult volunteers with mild (n=9) or moderate (n=8) renal impairment and in age- ,sex-, and weight-matched healthy adults with normal renal function (n=16). There was no effect of mild (50 mL/min £ CLcr £80 mL/min) or moderate (30 mL/min £ CLcr < 50 mL/min) renal insufficiency on the clearance of total MTP-PE, when compared with that observed in healthy adult subjects with normal renal function (CLcr > 80 mL/min). Additionally, the systemic exposures (AUCinf) of free (non-liposome associated) MTP-PE in mild or moderate renal insufficiency were similar to those observed in healthy adult subjects with normal renal function.

Hepatic Impairment

The pharmacokinetics of a single 4mg dose of mifamurtide following a 1 hour intravenous infusion were evaluated in adult volunteers with mild (Child‑Pugh class A; n=9) or moderate (Child-Pugh class B; n=8) hepatic impairment and in age- ,sex-, and weight-matched healthy adults with normal hepatic function (n=19). There was no effect of mild hepatic impairment on the systemic exposure (AUCinf) of total MTP-PE. Moderate hepatic impairment resulted in a small increase in AUCinf of total MTP-PE, with the geometric least square mean ratio (expressed as %) for moderate hepatic impairment in reference to the matched normal hepatic function group being 119% (90% CI: 94.1%‑151%). Pharmacokinetic variability was higher in the moderate hepatic impairment group (co-efficient of variation in systemic exposure [AUCinf] was 50% versus <30% in the other hepatic function groups).

 

Mean half-lives of total and free MTP-PE in mild hepatic impairment were 2.02 hours and 1.99 hours, respectively, and were comparable to those in subjects with normal hepatic function (2.15 hours and 2.26 hours, respectively). Mean half-lives of total and free MTP-PE in moderate hepatic impairment were 3.21 hours and 3.15 hours, respectively. Additionally, the geometric mean plasma AUCinf of free (non-liposome associated) MTP-PE in mild and moderate hepatic impairment were 47% higher than the corresponding values in the matched normal hepatic function groups.These changes were not considered to be clinically meaningful as the maximum tolerated dose (4-6 mg/m2) of mifamurtide is 2-3 times the recommended dose (2 mg/m2).

Updated on 4 April 2013 PIL

Reasons for updating

  • Change to improve clarity and readability

Updated on 7 September 2012 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.8 febrile neutropenia has been added

Updated on 5 September 2012 PIL

Reasons for updating

  • Change to side-effects

Updated on 8 March 2011 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 6.3, the shelf-life has been changed from 2 years to 3months

Updated on 11 November 2010 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

None provided

Updated on 9 November 2010 PIL

Reasons for updating

  • New PIL for medicines.ie