o

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMEA/H/C/002185

EPAR summary for the public

Plenadren

hydrocortisone

This is a summary of the European public assessment report (EPAR) for Plenadren. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Plenadren.

What is Plenadren?

Plenadren is a medicine that contains the active substance hydrocortisone. It is available as modified-release tablets (5 mg and 20 mg).

What is Plenadren used for?

Plenadren is used to treat adrenal insufficiency in adults. Adrenal insufficiency (including primary insufficiency or Addison's disease) is a condition where the adrenal glands (located just above the kidneys) do not produce enough of a steroid hormone called cortisol (also known as the stress hormone because it is released in response to stress). Symptoms include weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin. Adrenal insufficiency can require life-long treatment to replace the missing cortisol.

Because the number of patients with adrenal insufficiency is low, the disease is considered 'rare', and Plenadren was designated an 'orphan medicine' (a medicine used in rare diseases) on 22 May 2006.

The medicine can only be obtained with a prescription.

How is Plenadren used?

Plenadren tablets are taken once per day early in the morning, swallowed whole with a glass of water at least 30 minutes before food. The usual daily dose ranges from 20 to 30 mg, but this will need to be individually adjusted according to how the patient responds. In situations of excessive physical or mental stress or illness, patients may need further doses of hydrocortisone. This may be given

7 Westferry Circus • Canary Wharf • London E14 4HB • United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail info@ema.europa.eu Website www.ema.europa.eu

© European Medicines Agency, 2011. Reproduction is authorised provided the source is acknowledged.

Plenadren tablets twice or three times daily or conventional immediate-release tablets or injections, either alone or in combination with Plenadren.

How does Plenadren work?

The active substance in Plenadren, hydrocortisone, is the pharmaceutical form of cortisol, the main steroid hormone secreted by the adrenal gland. Hydrocortisone replaces the natural cortisol that is missing in patients with adrenal insufficiency. It has been used in medicines for several decades.

Because it is available as a modified-release tablet, Plenadren releases hydrocortisone over a longer period of time allowing for a once daily dosing. It is taken early in the morning since the amount of cortisol in the blood normally increases early in the morning in healthy people.

How has Plenadren been studied?

The applicant presented data on experimental models from the scientific literature.

The effects of Plenadren were investigated in one main study involving 64 patients with adrenal insufficiency. Plenadren, given once per day, was compared with conventional hydrocortisone treatment, which is given three times per day. The study looked at the levels of cortisol in the patients' blood during a 24 hour period following three months of treatment.

What benefit has Plenadren shown during the studies?

In patients taking Plenadren the cortisol levels achieved were considered to be satisfactory for patients with adrenal insufficiency. The overall amount of cortisol absorbed into the blood was around 20% lower in patients taking Plenadren compared with patients taking conventional hydrocortisone treatment.

What is the risk associated with Plenadren?

The most common side effect with Plenadren (seen in more than 1 patient in 10) was fatigue. For the full list of all side effects reported with Plenadren, see the package leaflet.

Plenadren must not be used in people who are hypersensitive (allergic) to hydrocortisone or any of the other ingredients.

Why has Plenadren been approved?

The CHMP noted that Plenadren achieved satisfactory levels of cortisol during the treatment of patients with adrenal insufficiency. The Committee also noted that with Plenadren there is the convenience of once daily dosing. Although once daily dosing comes with a risk of cortisol levels being too low in the afternoon, this can be managed by adding further doses of hydrocortisone if needed.

The CHMP concluded that the benefits of Plenadren were greater than its risks and recommended that it be granted marketing authorisation.

Other information about Plenadren

The European Commission granted a marketing authorisation valid throughout the European Union for Plenadren on 03 November 2011.

The full EPAR for Plenadren can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about

Plenadren treatment with Plenadren, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

The summary of the opinion of the Committee for Orphan Medicinal Products for Plenadren can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/Rare disease designations.

This summary was last updated in 08-2011.

Plenadren

Page 3/3