PLENADREN 5 mg MODIFIED-RELEASE TABLETS

Introduction

Patient Information: Summary of Product Characteristics

Plenadren 5 mg modified-release tablets

Plenadren 20 mg modified-release tablets

Hydrocortisone

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Plenadren and what is it used for
2. What you need to know before you take Plenadren
3. How to take Plenadren
4. Possible side effects
5. Storing Plenadren
6. Contents of the pack and other information

1. What is Plenadren and what is it used for

Plenadren contains a substance called hydrocortisone (sometimes also called cortisol). Hydrocortisone is a glucocorticoid. It belongs to a group of medicines called corticosteroids. Glucocorticoids are produced naturally in the body and help to maintain general health and well-being.

Plenadren is used in adults to treat a disease known as adrenal insufficiency or cortisol deficiency. This occurs when the adrenal glands (located just above the kidneys) do not produce enough cortisol. Patients with long-term (chronic) adrenal insufficiency need replacement therapy to survive.

Plenadren replaces the missing natural cortisol in adrenal insufficiency. It provides hydrocortisone to the body throughout the day. Cortisol levels in the blood increase rapidly to a peak about 1 hour after taking the tablet in the morning; then decrease during the day, with little or no cortisol in the blood in the late afternoon and evening, when levels are supposed to be low.

2. What you need to know before you take Plenadren

Do not take Plenadren:

• if you are allergicto hydrocortisone or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Plenadren

• When you have any disease that prevents you from taking the medicine or it is not absorbed correctly in your stomach. This situation may occur in case of gastrointestinal problems with vomiting or diarrhea. In such situations, you must immediately consult your doctor to receive treatment with hydrocortisone injections and fluid administration.

• If you have any short-term or temporary condition, such as an infection, fever, or physical stress, such as surgery: your dose of hydrocortisone should be temporarily increased. Ask your doctor without delay to inform you about the best way to handle these situations. If you are going to have surgery, tell your doctor or dentist that you are taking this medicine.

• If, for any other reason, your general health worsens despite taking the medicine as prescribed, consult your doctor immediately.

• If your thyroid does not function normally, tell your doctor, as you may need to adjust your dose of Plenadren.

Children and adolescents

The use of Plenadren is not recommended in children and adolescents under 18 years of age, as it has not been studied in these patients.

Other medicines and Plenadren

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. During long-term treatment with medicines for the treatment of infections (antibiotics), your doctor may need to adjust your dose of Plenadren. If used with mifepristone, a medicine used to interrupt pregnancy, the effect of Plenadren may be reduced.

Also, consult your doctor or pharmacist if you are using any of the following medicines, as it may be necessary to change your dose of Plenadren:

• Phenytoin, carbamazepine, and barbiturates: used to treat epilepsy
• Rifampicin or rifabutin: used to treat tuberculosis
• Ritonavir, efavirenz, and nevirapine: used to treat HIV infection
• St. John's Wort: used to treat depression and other diseases
• Ketoconazole, itraconazole, posaconazole, and voriconazole: used to treat fungal infections
• Erythromycin, telithromycin, and clarithromycin: used to treat bacterial infections

Taking Plenadren with food and drinks

Do not take the medicine with grapefruit juice, as it will interfere with its action.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

It is important that you continue treatment with Plenadren during pregnancy. It is unlikely that treatment in pregnant women with adrenal insufficiency will produce harmful effects in the mother or the child. If you become pregnant, tell your doctor, as your dose of Plenadren may need to be adjusted.

You can breastfeed while taking Plenadren. Hydrocortisone is excreted in breast milk. The doses of hydrocortisone used as replacement therapy are unlikely to have any effect on the child. However, tell your doctor if you plan to breastfeed.

Fertility in women with adrenal insufficiency or cortisol deficiency may be reduced. There are no signs that Plenadren, at the doses used for replacement therapy, affects fertility.

Driving and using machines

The influence of this medicine on the ability to drive and use machines is small. Extreme fatigue and brief episodes of dizziness (vertigo) have been reported. Untreated or poorly treated adrenal insufficiency reduces the ability to concentrate and affects the ability to drive and use machines. Therefore, it is important that you take this medicine as your doctor tells you when driving or using machines. If you feel affected, do not drive or operate machines until you have discussed the problem with your doctor.

3. How to take Plenadren

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again. The dose is specific for you and has been decided by your doctor.

• When you wake up in the morning, swallow the Plenadren tablets whole with a glass of water and at least 30 minutes before breakfast, preferably between 6:00 and 8:00 in the morning.
• It is preferable to do this in an upright position.
• Do not break, crush, or chew the tablets. These tablets provide hydrocortisone to your body throughout the day. If they are broken, crushed, or chewed, the dose of hydrocortisone from the tablet may not last all day, as it should.

Need for additional doses of Plenadren

During short-term or temporary conditions, such as infections, fever, or physical stress, such as surgery, you will need more hydrocortisone, as the body cannot produce the additional amount of cortisol needed in these situations. Therefore, the dose should be temporarily increased, and your doctor may advise you to take other hydrocortisone tablets instead of or in addition to Plenadren. Consult your doctor and follow their instructions on how to handle these situations.

The daily dose of Plenadren may need to be doubled or tripled in mild conditions, such as an infection or minor stress. In such cases, you should take a second dose of this medicine 6 to 10 hours after the morning dose. If doubling the daily dose is not sufficient, you should take a third dose 6 to 10 hours after the second dose (with intervals of 6-10 hours between doses). When the condition has ended, return to the normal maintenance dose of this medicine.

The following signs and symptoms may indicate that you need to take additional doses of Plenadren or other medicines that contain hydrocortisone: fatigue, weight loss, stomach upset, feeling of dizziness when standing up from a sitting position or dizziness when standing up, darkening of the skin, especially in skin folds and exposed areas. Contact your doctor as soon as possible if you notice any of these signs or symptoms.

Seek medical attention immediatelyif you experience any of the following signs or symptoms: severe weakness, fainting, abdominal pain, nausea, vomiting, back pain, confusion, decreased level of consciousness, delirium (a state of great mental confusion).

If you take more Plenadren than you should

Taking too high a dose of this medicine for more than a few days can be harmful to your health. It can cause high blood pressure, weight gain, and high blood sugar. Sometimes it is necessary to increase the dose to help the body cope with certain stressful situations, such as fever. If you need extra doses frequently and periodically, you should consult your doctor to reconsider your maintenance dose.

If you forget to take Plenadren

If you forget to take the morning tablet, take it as soon as possible. Do not take a double dose to make up for forgotten doses. If you experience any signs or symptoms mentioned in the section "Need for additional doses of Plenadren", contact your doctor immediately.

If you stop taking Plenadren

Stopping the use of Plenadren can be life-threatening. Therefore, it is important that you continue to take this medicine as your doctor has prescribed. Do not stop treatment without consulting your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you switch from taking other hydrocortisone tablets to taking Plenadren, you may experience side effects during the first few weeks. These can be: stomach pain, feeling of nausea, and fatigue. They usually disappear with time; if not, consult your doctor.

The side effects of this medicine are:

Very common (may affect more than 1 in 10 people)

• Dizziness
• Headache
• Diarrhea
• Fatigue

Common (may affect up to 1 in 10 people)

• Stomach pain/burning, nausea
• Joint pain
• Rash
• Itching

Other side effects have been observed with other hydrocortisone medicines. These medicines have also been administered for different indications than the treatment of adrenal insufficiency, often in higher doses. The frequency of these possible side effects is not known (cannot be estimated from the available data). Consult your doctor if you experience any of them:

• Increased susceptibility to infections
• Diabetes or problems with blood sugar levels (checked with blood tests)
• Retention of salts and water, which can cause edema and high blood pressure (checked during clinical examination), and low potassium levels in the blood
• Changes in mood, such as excessive excitement or loss of contact with reality.
• Difficulty sleeping
• Increased eye pressure (glaucoma), clouding of the lens of the eye (cataract)
• Burning, worsening of existing stomach ulcers
• Weakening of bones: can cause bone fractures
• Stretch marks, bruising, acne-like rash, excessive growth of facial hair, slow wound healing.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Plenadren

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after "EXP". The expiry date is the last day of the month stated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

Composition of Plenadren

• The active substance is hydrocortisone.

Plenadren 5 mg: Each modified-release tablet contains 5 mg of hydrocortisone.

Plenadren 20 mg: Each modified-release tablet contains 20 mg of hydrocortisone.

• The other ingredients are hypromellose (E464), microcrystalline cellulose (E460), pregelatinized starch (maize), colloidal anhydrous silica (E551), and magnesium stearate. The coating system is a mixture of macrogol (3350), polyvinyl alcohol, talc (E553b), and titanium dioxide (E171). The 5 mg tablets also contain red iron oxide (E172), yellow iron oxide (E172), and black iron oxide (E172).

Appearance and packaging

The modified-release tablets are round (8 mm in diameter) and convex.

The 5 mg tablets are pink. The 20 mg tablets are white.

Plenadren is available in bottles with a screw cap containing 50 tablets.

Package sizes:

Box containing 1 bottle of 50 modified-release tablets.

Box containing 2 bottles of 50 modified-release tablets (100 tablets).

Not all pack sizes may be marketed in your country.

Marketing authorisation holder

Shire Services BVBA

Rue Montoyer 47

B - 1000 Brussels

Belgium

Tel: +44(0)1256 894 959

E-mail: medinfoEMEA@shire.com

Manufacturer

Shire Pharmaceuticals Ireland Limited

Block 2 & 3 Miesian Plaza

50 – 58 Baggot Street Lower

Dublin 2

Ireland

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.