Plenadren

Package leaflet: Information for the patient

Plenadren 5 mg modified-release tablets, 20 mg modified-release tablets

hydrocortisone
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Plenadren is and what it is used for

Plenadren contains a substance called hydrocortisone (sometimes referred to as cortisol). Hydrocortisone is a glucocorticoid belonging to a group of medicines known as corticosteroids. Glucocorticoids occur naturally in our body and contribute to our well-being and general state of health.
Plenadren is used in adults for the treatment of a condition known as adrenal insufficiency, or cortisol deficiency. Adrenal insufficiency occurs when the adrenal glands (located above the kidneys) do not produce a sufficient amount of the hormone cortisol. Patients with long-term (chronic) adrenal insufficiency require replacement therapy to survive.
Plenadren replaces the naturally missing cortisol in adrenal insufficiency. The medicine provides hydrocortisone to the body throughout the day. Cortisol levels in the blood rise rapidly, reaching a peak approximately 1 hour after taking the morning tablet, then gradually decrease during the day, reaching very low or zero blood levels in the late evening and at night, when levels should naturally be low.

2. What you need to know before taking Plenadren

Do not take Plenadren

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Plenadren

• if your condition prevents you from taking this medicine or when the medicine is not adequately absorbed from the stomach. This may occur if there are stomach problems
  involving vomiting and/or diarrhoea. In these situations, you must consult a doctor immediately for treatment with hydrocortisone injections and additional fluid administration.

• In case of short-term or transient illnesses such as infections, fever, or situations causing significant physical stress, such as surgery: the dose of hydrocortisone should be temporarily increased. Immediately consult your doctor for advice on how best to manage such situations. If undergoing surgery, inform your doctor/dentist before the procedure that you are taking this medicine.

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

• If you have phaeochromocytoma (a rare tumour of the adrenal glands).

• If your thyroid gland is not functioning normally, inform your doctor, as your Plenadren dose may need to be adjusted.

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

Other medicines and Plenadren
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. During long-term treatment with medicines used to treat infections (antibiotics), your doctor may consider adjusting the dose of Plenadren. If taken together with mifepristone, a medicine used to terminate pregnancy, the effect of Plenadren may be reduced.
Also inform your doctor or pharmacist if you are taking any of the following medicines, as your Plenadren dose may need to be adjusted:

• Phenytoin, carbamazepine, and barbiturates – for the treatment of epilepsy
• Rifampicin or rifabutin – for the treatment of tuberculosis
• Ritonavir, efavirenz, and nevirapine – for the treatment of HIV infections
• St John’s wort – for the treatment of depression and other conditions
• Ketoconazole, itraconazole, posaconazole, voriconazole – for the treatment of fungal infections
• Erythromycin, telithromycin, clarithromycin – for the treatment of bacterial infections

Plenadren with food and drink
Do not take this medicine with grapefruit juice, as grapefruit juice affects the action of this medicine.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
It is important to continue treatment during pregnancy. It is unlikely that treatment with Plenadren in pregnant women with adrenal insufficiency will cause adverse effects on the mother and/or the baby. Inform your doctor if you become pregnant, as your Plenadren dose may need to be adjusted.
Breastfeeding during treatment with Plenadren is possible. Hydrocortisone is excreted in breast milk. It is unlikely that the doses of hydrocortisone used in replacement therapy will have any effect on the infant. However, inform your doctor if you intend to breastfeed.
Fertility in women with adrenal insufficiency or cortisol deficiency may be reduced. There are no indications that Plenadren, at the doses used for replacement therapy, has an effect on fertility.

Driving and using machines
This medicine may have a slight influence on the ability to drive and use machines. Brief episodes of dizziness and extreme fatigue have been reported. Untreated or inadequately treated adrenal insufficiency reduces concentration ability and affects the capacity to drive and use machines. It is therefore important to take this medicine exactly as directed by your doctor when driving or operating machinery. If you have this condition, do not drive or operate machinery before consulting a doctor.

3. How to take Plenadren

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist. The prescribed dose is specific to your needs and has been determined by your doctor.

• In the morning, as soon as you wake up, take the Plenadren tablets whole with a glass of water, at least 30 minutes before breakfast, preferably between 6:00 a.m. and 8:00 a.m.
• The medicine should preferably be taken while in an upright position.
• Swallow the tablet whole, without dividing, breaking, or crushing it. These tablets release hydrocortisone into the body over the entire course of the day. If the tablet is divided, broken, or crushed, the hydrocortisone it contains may not last the full day.

Need for additional doses of Plenadren
In case of short-term or transient illnesses such as infections, fever, or situations causing significant physical stress (e.g. surgery), your body cannot produce the extra cortisol needed. Therefore, you will need to take additional hydrocortisone. Your dose should be temporarily increased, and your doctor will advise whether to take additional hydrocortisone tablets instead of or in addition to Plenadren. Consult your doctor and follow the appropriate instructions.
You may need to double or triple the daily dose of Plenadren in milder conditions, such as a minor infection or mild stress. In such cases, take the second dose of this medicine 6 to 10 hours after the morning dose. If doubling the daily dose is not sufficient, take a third dose 6 to 10 hours after the second dose (with intervals of 6–10 hours between doses). Once the illness has resolved, return to your normal maintenance dose of this medicine.
The following signs and symptoms may indicate the need for additional doses of Plenadren or other forms of hydrocortisone: fatigue, weight loss, stomach discomfort, feeling faint when moving from sitting to standing, dizziness upon standing, or darkening of the skin, particularly in skin folds and sun-exposed areas. Contact your doctor immediately if you experience any of these signs or symptoms.
However, seek immediate medical attention if you experience any of the following: severe weakness, fainting, abdominal pain, nausea, vomiting, back pain, confusion, reduced level of consciousness, or delirium (a state of severe confusion).

If you take more Plenadren than you should
Taking an excessive dose of this medicine for more than a few days may be harmful to your health. It could lead to high blood pressure, weight gain, and elevated blood glucose levels. Occasionally, the dose may need to be increased so your body can cope with periods of increased stress, such as fever. If additional doses are frequently and regularly required, contact your doctor to reassess your maintenance dose.

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

If you stop taking Plenadren
Stopping treatment with Plenadren may be life-threatening. It is therefore essential to continue taking this medicine exactly as prescribed by your doctor. Do not discontinue treatment without consulting your doctor.

If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
If you switch treatment from other hydrocortisone tablets to Plenadren, you may experience side effects during the first few weeks. These may include stomach pain, nausea, and fatigue. Normally these effects disappear over time; if they do not, consult your doctor.

List of side effects with this medicine:
Very common (may affect more than 1 in 10 people)

• Dizziness
• Headache
• Diarrhoea
• Fatigue

Common (may affect up to 1 in 10 people)

• Stomach pain/acid reflux, feeling unwell or nausea
• Joint pain
• Skin rash
• Itching

Other side effects have been reported with other hydrocortisone-containing medicines. These medicines have also been used for indications different from replacement therapy for adrenal insufficiency, often at higher doses. The frequency of such side effects is unknown (cannot be estimated based on the available data). If you notice any of these side effects, consult your doctor.

• Increased susceptibility to infections
• Diabetes or problems with blood glucose levels (based on blood test data)
• Fluid and salt retention leading to swelling and increased blood pressure (observed during medical examination) and low blood potassium levels
• Mood changes, for example, excitement or loss of contact with reality
• Sleep disorders
• Increased intraocular pressure (glaucoma), clouding of the lens (cataract)
• Acid reflux, worsening of existing gastric ulcers
• Bone weakening, which may lead to bone fractures
• Stretch marks, bruising, acne-like rash, excessive facial hair growth, delayed wound healing

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Plenadren

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the box after Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Plenadren contains

• 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 components are hypromellose (E464), microcrystalline cellulose (E460), pregelatinized starch (maize), anhydrous colloidal 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).

Description of the appearance of Plenadren and contents of the pack

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 supplied in screw-cap bottles containing 50 modified-release tablets.
Pack sizes:
Box containing one bottle of 50 modified-release tablets.
Box containing two bottles of 50 modified-release tablets each (100 tablets).
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Takeda Pharmaceuticals International AG Ireland Branch
Block 2 Miesian Plaza
50-58 Baggot Street Lower
Dublin 2
D02 HW68
Ireland

Manufacturer
Takeda Pharmaceuticals International AG Ireland Branch
Block 2 Miesian Plaza
50-58 Baggot Street Lower
Dublin 2
D02 HW68
Ireland
Shire Pharmaceuticals Ireland Limited
Block 2 & 3 Miesian Plaza
50-58 Baggot Street Lower
Dublin 2
Ireland

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Takeda Belgium NV Takeda, UAB
Tél/Tel: +32 2 464 06 11 Tel: +370 521 09 070
[email protected] [email protected]

България Luxembourg/Luxemburg
Такеда България ЕООД Takeda Belgium NV
Тел.: +359 2 958 27 36 Tél/Tel: +32 2 464 06 11
[email protected] [email protected]

Česká republika Magyarország
Takeda Pharmaceuticals Czech Republic s.r.o. Takeda Pharma Kft.
Tel: +420 234 722 722 Tel.: +36 1 270 7030
[email protected] [email protected]

Danmark Malta
Takeda Pharma A/S Takeda HELLAS S.A.
Tlf: +45 46 77 10 10 Tel: +30 210 6387800
[email protected] [email protected]

Deutschland Nederland
Takeda GmbH Takeda Nederland B.V.
Tel: +49 (0)800 825 3325 Tel: +31 20 203 5492
[email protected] [email protected]

Eesti Norge
Takeda Pharma AS Takeda AS
Tel: +372 6177 669 Tlf: +47 800 800 30
[email protected] [email protected]

Ελλάδα Österreich
Takeda ΕΛΛΑΣ Α.Ε. Takeda Pharma Ges.m.b.H.
Tηλ: +30 210 6387800 Tel: +43 (0) 800-20 80 50
[email protected] [email protected]

España Polska
Takeda Farmacéutica España S.A. Takeda Pharma Sp. z o.o.
Tel: +34 917 90 42 22 Tel.: +48223062447
[email protected] [email protected]

France Portugal
Takeda France SAS Takeda Farmacêuticos Portugal, Lda.
Tél: +33 1 40 67 33 00 Tel: +351 21 120 1457
[email protected] [email protected]

Hrvatska România
Takeda Pharmaceuticals Croatia d.o.o. Takeda Pharmaceuticals SRL
Tel: +385 1 377 88 96 Tel: +40 21 335 03 91
[email protected] [email protected]

Ireland Slovenija
Takeda Products Ireland Ltd Takeda Pharmaceuticals farmacevtska družba d.o.o.
Tel: 1800 937 970 Tel: +386 (0) 59 082 480
[email protected] [email protected]

Ísland Slovenská republika
Vistor hf. Takeda Pharmaceuticals Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 (2) 20 602 600
[email protected] [email protected]

Italia Suomi/Finland
Takeda Italia S.p.A. Takeda Oy
Tel: +39 06 502601 Puh/Tel: 0800 774 051
[email protected] [email protected]

Κύπρος Sverige
Takeda ΕΛΛΑΣ Α.Ε. Takeda Pharma AB
Τηλ: +30 210 6387800 Tel: 020 795 079
[email protected] [email protected]

Latvija United Kingdom (Northern Ireland)
Takeda Latvia SIA Takeda UK Ltd
Tel: +371 67840082 Tel: +44 (0) 2830 640 902
[email protected] [email protected]

Other sources of information
More detailed information about this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and their treatments are also provided.