A Need to Harmonise the Prescribing Information for Etoposide in the EU

Outcome of a procedure under Article 30 of Directive 2001/83/EC

On 21 April 2017, the European Medicines Agency (EMA) completed a review of Etopophos and Vepesid. The EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that there is a need to harmonise the prescribing information for Etopophos and Vepesid and associated names in the European Union (EU).

Questions and answers on Etopophos and associated names (etoposide, 100 and 1000 mg powder for solution for infusion)

Etopophos is a cancer medicine used to treat testicular cancer, lung cancer, ovarian cancer, gestational trophoblastic neoplasia, Hodgkin’s and non-Hodgkin’s lymphoma and acute myeloid leukaemia.

Etopophos contains the active substance etoposide (as etoposide phosphate) and is available as a powder to be made into a solution for infusion into a vein.

Etopophos is marketed in the following EU member States: France, Germany, Sweden and the United Kingdom. It is also available in the EU under the trade name Etopofos.

The company that markets these medicines is Bristol-Myers Squibb.

Why was Etopophos reviewed?

Etopophos is authorised in the EU via national procedures. This has led to divergences across Member States in the way the medicine can be used, as seen in the differences in the summaries of product characteristics (SmPCs), labelling and package leaflets in the countries where the medicine is marketed.

Etopophos was identified as needing harmonisation by the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh).

On 14 October 2015, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Etopophos in the EU.

What are the conclusions of the CHMP?

The CHMP, in the light of the data submitted and the scientific discussion within the Committee, was of the opinion that the SmPCs and package leaflets should be harmonised across the EU.

The areas of the SmPC harmonised include:

4.1 Therapeutic indications

The CHMP recommended that Etopophos should be used in combination with other cancer treatments to treat the following cancers:

  • testicular cancer, including cancer that is resistant to treatment or has come back;
  • small-cell lung cancer;
  • Hodgkin’s and non-Hodgkin’s lymphoma;
  • acute myeloid leukaemia;
  • high-risk gestational trophoblastic neoplasia as first- and second-line treatments;
  • non-epithelial ovarian cancer.

In addition, the CHMP recommended Etopophos for treating epithelial ovarian cancer that is resistant to treatments with platinum-containing medicines, with no specification that it should be used in combination with other medicines.

For Hodgkin’s and non-Hodgkin’s lymphoma and acute myeloid leukaemia, Etopophos is recommended for both adults and children, while its other uses are for adults only.

4.2 Posology and method of administration

Etopophos is given as a slow intravenous infusion. The recommended dose for adults is 50 to 100 mg per m2 of body surface area for 5 days in a row or 100 to 120 mg/m2 on days 1, 3 and 5. The course of treatment may be repeated but not sooner than 21 days after the start of the first course.

4.3 Contraindications

Etopophos should not be administered during vaccination with yellow fever or other live vaccines in patients with weakened immune systems and should not be given to breast-feeding women.

Other changes

Other sections of the SmPC harmonised include section 4.4 (special warnings and precautions), section 4.6 (fertility, pregnancy and lactation) and section 4.8 (undesirable effects).

The amended information to doctors and patients is available here.

A European Commission decision on this opinion will be issued in due course.

Questions and answers on Vepesid and associated names (etoposide, 50 and 100 mg capsules)

On 21 April 2017, the EMA completed a review of Vepesid. The CHMP concluded that there is a need to harmonise the prescribing information for Vepesid in the European Union (EU).

Vepesid is a cancer medicine used to treat testicular cancer, lung cancer, ovarian cancer and Hodgkin’s and non-Hodgkin’s lymphoma and acute myeloid leukaemia.

Vepesid contains the active substance etoposide and is available as capsules to be taken by mouth.

Vepesid is marketed in 16 EU member States (Austria, Belgium, Croatia, Denmark, Estonia, Finland, Germany, Ireland, Italy, Luxembourg, the Netherlands, Romania, Slovenia, Spain, Sweden and the United Kingdom) as well as in Norway. It is also available in the EU under the trade name Vepesid K.

The company that markets these medicines is Bristol-Myers Squibb.

Why was Vepesid reviewed?

Vepesid is authorised in the EU via national procedures. This has led to divergences across Member States in the way the medicine can be used, as seen in the differences in the SmPCs, labelling and package leaflets in the countries where the medicine is marketed.

Vepesid was identified as needing harmonisation by the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh).

On 14 October 2015, the European Commission referred the matter to the CHMP in order to harmonise the marketing authorisations for Vepesid in the EU.

What are the conclusions of the CHMP?

The CHMP, in the light of the data submitted and the scientific discussion within the Committee, was of the opinion that the SmPCs and package leaflets should be harmonised across the EU.

The areas of the SmPC harmonised include:

4.1 Therapeutic indications

The CHMP recommended that Vepesid should be used in combination with other cancer treatments to treat the following cancersin adults:

  • testicular cancer that is resistant to treatment or has come back;
  • small-cell lung cancer;
  • Hodgkin’s lymphoma as second-line treatment;
  • non-Hodgkin’s lymphoma that is resistant to treatment or has come back;
  • acute myeloid leukaemia that is resistant to treatment or has come back;
  • non-epithelial ovarian cancer.

In addition, the CHMP recommended Vepesid for treating epithelial ovarian cancer that is resistant to treatments with platinum-containing medicines, with no specification that it should be used in combination with other medicines.

4.2 Posology and method of administration

The dose of Vepesid is based on the recommended dose for the intravenous etoposide medicines, with a 100 mg oral dose being comparable to a 75 mg intravenous one. The usual dose of Vepesid is 100 to 200 mg per m2 of body surface area for 5 days in a row or 200 mg/m2/day on days 1, 3 and 5 every 3 to 4 weeks. Vepesid capsules should be taken on an empty stomach.

4.3 Contraindications

Vepesid should not be taken at the same time as vaccination with yellow fever or other live vaccines in patients with weakened immune systems and should not be taken by breast-feeding women.

Other changes

Other sections of the SmPC harmonised include section 4.4 (special warnings and precautions), section 4.6 (fertility, pregnancy and lactation) and section 4.8 (undesirable effects).

The amended information to doctors and patients is available here.

A European Commission decision on this opinion will be issued in due course.