Thiotepa Riemser - patient leaflet, side effects, dosage

1. What Thiotepa Riemser is and what it is used for

Thiotepa Riemser contains the active substance thiotepa, which belongs to a group of medicines called alkylating agents.

Thiotepa Riemser is used to prepare patients for bone marrow transplantation. It works by destroying bone marrow cells. This enables the transplantation of new bone marrow cells (haematopoietic progenitor cells), which in turn enable the body to produce healthy blood cells.

Thiotepa Riemser can be used in adults and children and adolescents.

2. What you need to know before you use Thiotepa Riemser

Do not use Thiotepa Riemser

• – if you are allergic to thiotepa,

• – if you are pregnant or think you may be pregnant,

• – if you are breast-feeding,

• – if you are receiving yellow fever vaccination, live virus and bacterial vaccines.

Warning and precautions

You should tell your doctor if you have:

• – liver or kidney problems,

• – heart or lung problems,

• – seizures/fits (epilepsy) or have had them in the past (if treated with phenytoin or fosphenytoin).

Because Thiotepa Riemser destroys bone marrow cells responsible for producing blood cells, regular blood tests will be taken during treatment to check your blood cell counts.

In order to prevent and manage infections, you will be given anti-infectives.

Thiotepa Riemser may cause another type of cancer in the future. Your doctor will discuss this risk with you.

Other medicines and Thiotepa Riemser

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy, breast-feeding and fertility

You must tell your doctor if you are pregnant or you think you may be pregnant before you receive Thiotepa Riemser. You must not use Thiotepa Riemser during pregnancy.

Both women and men using Thiotepa Riemser must use effective contraceptive methods during treatment. Men should not father a child while treated and during the year after cessation of treatment.

It is not known whether this medicinal product is excreted in breast milk. As a precautionary measure, women must not breast-feed during treatment with Thiotepa Riemser.

Thiotepa Riemser can impair male and female fertility. Male patients should seek advice for sperm preservation before therapy is started.

Driving and using machines

It is likely that certain side effects of thiotepa like dizziness, headache and blurred vision could affect your ability to drive and use machines. If you notice such side effects, do not drive or use machines.

3. How to use Thiotepa Riemser

Your doctor will calculate the dose according to your body surface or weight and your disease.

How Thiotepa Riemser is given

Thiotepa Riemser is administered by a qualified healthcare professional as an intravenous infusion (drip in a vein) after dilution of the individual vial. Each infusion will last 2 – 4 hours.

Frequency of administration

You will receive your infusions every 12 or 24 hours. The duration of treatment can last up to 5 days. Frequency of administration and duration of treatment depend on your disease.

4. Possible side effects

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

The most serious side effects of Thiotepa Riemser therapy or the transplant procedure may include

• – decrease in circulating blood cell counts (intended effect of the medicine to prepare you for your transplant infusion)

• – infection

• – liver disorders including blocking of a liver vein

• – the graft attacks your body (graft versus host disease)

• – respiratory complications

Your doctor will monitor your blood counts and liver enzymes regularly to detect and manage these events.

Other side effects of Thiotepa Riemser, which may occur with certain frequencies, are listed as follows:

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

• – increased susceptibility to infection

• – whole-body inflammatory state (sepsis)

• – decreased counts of white blood cells, platelets and red blood cells (anaemia)

• – the transplanted cells attack your body (graft versus host disease)

• – dizziness, headache, blurred vision

• – uncontrolled shaking of the body (convulsion)

• – sensation of tingling, pricking or numbness (paraesthesia)

• – partial loss of movement

• – cardiac arrest

• – nausea, vomiting, diarrhoea

• – inflammation of the mucosa of the mouth (mucositis)

• – irritated stomach, gullet, intestine

• – inflammation of the colon

• – anorexia, decreased appetite

• – high glucose in the blood

• – skin rash, itching, shedding

• – skin colour disorder (do not confuse with jaundice – see below)

• – redness of the skin (erythema)

• – hair loss

• – back and abdominal pain, pain

• – muscle and joint pain

• – abnormal electrical activity in the heart (arrhythmia)

• – inflammation of lung tissue

• – enlarged liver

• – altered organ function

• – blocking of a liver vein (veno-occlusive sisease, VOD)

• – yellowing of the skin and eyes (jaundice)

• – hearing impaired

• – lymphatic obstruction

• – high blood pressure

• – increased liver, renal and digestive enzymes

• – abnormal blood electrolytes

• – weight gain

• – fever, general weakness, chills

• – bleeding (haemorrhage)

• – nasal bleeding

• – general swelling due to fluid retention (oedema)

• – pain or inflammation at the injection site

• – eye infection (conjunctivitis)

• – decreased sperm cell count

• – vaginal bleeding

• – absence of menstrual periods (amenorrhea)

• – memory loss

• – delaying in weight and height increase

• – bladder disfunction

• – underproduction of testosterone

• – insufficient production of thyroid hormone

• – deficient activity of the pituitary gland

• – confusional state

Common side effects (may affect up to 1 in 10 people)

• – anxiety, confusion

• – abnormal bulging outward of one of the arteries in the brain (intracranial aneurysm)

• – creatinine elevated

• – allergic reactions

• – occlusion of a blood vessel (embolism)

• – heart rhythm disorder

• – heart inability

• – cardiovascular inability

• – oxygen deficiency

• – fluid accumulation in the lungs (pulmonary oedema)

• – pulmonary bleeding

• – respiratory arrest

• – blood in the urine (haematuria) and moderate renal insufficiency

• – inflammation of the urinary bladder

• – discomfort in urination and decrease in urine output (disuria and oliguria)

• – increase in the amount of nitrogen components in the blood stream

• – cataract

• – inability of the liver

• – cerebral haemorrhage

• – cough

• – constipation and upset stomach

• – obstruction of the bowel

• – perforation of stomach

• – changes in muscle tone

• – gross lack of coordination of muscle movements

• – bruises due to a low platelet count

• – menopausal symptoms

• – cancer (second primary malignancies)

• – abnormal brain function

• – male and female infertility

Uncommon side effects (may affect up to 1 in 100 people)

• – inflammation and exfoliation of the skin (erythrodermic psoriasis)

• – delirium, nervousness, hallucination, agitation

• – gastrointestinal ulcer

• – inflammation of the muscular tissue of the heart (myocarditis)

• – abnormal heart condition (cardiomyopathy)

Not known (frequency cannot be estimated from the available data)

• – increased blood pressure in the arteries (blood vessels) of the lungs (pulmonary arterial hypertension)

• – severe skin damage (e.g. severe lesions, bullae, etc.) potentially involving the full body surface which can be even life-threatening

• – damage to a component of the brain (the so-called white matter) which can be even lifethreatening (leukoencepha­lopathy)

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. 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 By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Thiotepa Riemser

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 carton and vial label, after EXP.

The expiry date refers to the last day of that month.

Store and transport refrigerated (2 °C – 8 °C).

Do not freeze.

After reconstitution the product is stable for 8 hours when stored at 2 °C – 8 °C.

After dilution the product is stable for 24 hours when stored at 2 °C – 8 °C and for 4 hours when stored at 25 °C. From a microbiological point of view, the product should be used immediately.

Any unused product or waste material should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Thiotepa Riemser contains

Thiotepa Riemser 15 mg powder for concentrate for solution for infusion

• – The active substance is thiotepa. One vial contains 15 mg thiotepa. After reconstitution, each mL contains 10 mg thiotepa (10 mg/mL).

Thiotepa Riemser 100 mg powder for concentrate for solution for infusion

• – The active substance is thiotepa. One vial contains 100 mg thiotepa. After reconstitution, each mL contains 10 mg thiotepa (10 mg/mL).

• – Thiotepa Riemser does not contain any other ingredients.

What Thiotepa Riemser looks like and contents of the pack

Thiotepa Riemser 15 mg powder for concentrate for solution for infusion

Thiotepa Riemser is a white crystalline powder supplied in a glass vial containing 15 mg thiotepa.

Thiotepa Riemser 100 mg powder for concentrate for solution for infusion

Thiotepa Riemser is a white crystalline powder supplied in a glass vial containing 100 mg thiotepa.

Each carton contains 1 vial.

Marketing Authorisation Holder

Esteve Pharmaceuticals GmbH

Hohenzollerndamm 150–151

14199 Berlin

Germany

Manufacturer

HWI development GmbH

Straßburger Str. 77

77767 Appenweier

Germany

For any information about this medicine, please

Authorisation Holder:

België/Belgiqu­e/Belgien

Eurocept Pharmaceuticals

Pays-Bas/Nederland/Ni­ederlande

Tél/Tel: +31 35 528 8377

Etarapuu

Thrive Pharma Ltd.

Euarapua

Tea.: +359 2 878 05 43

contact the local representative of the Marketing

Lietuva

UAB ARMILA

Lietuva

Tel: +370– (0) 5 2777596

Luxembourg/Lu­xemburg

Eurocept Pharmaceuticals

Pays-Bas/Nederland/Ni­ederlande

Tel/Tel: +31 35 528 8377

Česká republika LERAM pharmaceuticals s.r.o. Česká republika Tel: +420 513 035 442	Magyarorszag SANATIS Europe Kft. Magyarorszag Tel.: +36– (0) 23 367 673
Danmark CampusPharma AB Sverige Tlf: +46 31 205020	Malta Esteve Pharmaceuticals GmbH Il-Germanja Tel: +49-(0) 30 338427–0
Deutschland Esteve Pharmaceuticals GmbH Deutschland Tel: +49-(0) 30 338427–0	Nederland Eurocept Pharmaceuticals Nederland Tel: +31 35 528 8377
Eesti AUXILIA Pharma OÜ Eesti Tel: +372 605 00 05	Norge CampusPharma AB Sverige Tlf: +46 31 205020
EMáSa Esteve Pharmaceuticals GmbH reptaría Tql: +49-(0) 30 338427–0	Österreich AGEA Pharma GmbH Österreich Tel: +43– (0) 1 336 01 41
España Esteve Pharmaceuticals, S.A. España Tel: +34 93 446 60 00	Polska COPHARMA JOSEPH RAKOTO Polska Tel.: +48 691 702 426
France KEOCYT France Tél: +33 1 42 31 07 10	Portugal Esteve Pharmaceuticals GmbH Alemanha Tel: +49-(0) 30 338427–0
Hrvatska MEDIS Adria d.o.o. Hrvatska Tel: +385 1 2303 446	România SANATIS Europe Kft. Ungaria Tel: +36– (0) 23 367 673
Ireland Esteve Pharmaceuticals GmbH Germany Tel: +49-(0) 30 338427–0	Slovenija MEDIS d.o.o. Slovenija Tel: +386– (0) 1 589 69 00

Slovenská republika

LERAM pharmaceuticals s.r.o.

Česká republika

Tel: +420 513 035 442

Suomi/Finland

CampusPharma AB

Ruotsi

Puh/Tel: +46 31 205020

Sverige

CampusPharma AB

Sverige

Tel: +46 31 205020

United Kingdom (Northern Ireland)

Esteve Pharmaceuticals GmbH

Germany

Tel: +49-(0) 30 338427–0

This leaflet was last revised in {MM/YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:.

The following information is intended for healthcare professionals only:

PREPARATION GUIDE

Thiotepa Riemser 15 mg powder for concentrate for solution for infusion

Thiotepa Riemser 100 mg powder for concentrate for solution for infusion

thiotepa

Read this guide prior to the preparation and administration of Thiotepa Riemser.

• 1. PRESENTATION

Thiotepa Riemser 15 mg powder for concentrate for solution for infusion

Thiotepa Riemser is supplied as 15 mg powder for concentrate for solution for infusion.

Thiotepa Riemser 100 mg powder for concentrate for solution for infusion

Thiotepa Riemser is supplied as 100 mg powder for concentrate for solution for infusion.

Thiotepa Riemser must be reconstituted and diluted prior to administration.

• 2. SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING