Patient leaflet - Zepzelca 4 mg powder for concentrate for solution for infusion
1. What ZEPZELCA is and what it is used for
ZEPZELCA is a cancer medicine that contains the active substance lurbinectedin.
ZEPZELCA is used in adults for the treatment of a type of small cell lung cancer (SCLC) that has spread within the lung or to other parts of the body (extensive-stage SCLC). It is used together with atezolizumab as maintenance treatment in adults whose cancer has not progressed following treatment with atezolizumab, carboplatin and etoposide (other cancer medicines).
The active substance in ZEPZELCA, lurbinectedin, works by attaching to the genetic material (DNA) inside cancer cells. This damages the DNA and interferes with the cell growth and multiplication, leading to cancer cell death. It also reduces the activity of certain immune cells that help tumours grow.
ZEPZELCA may be given in combination with other anticancer medicine. It is important that you also read the package leaflets for the other anticancer medicine you may be receiving. If you have any questions about these medicines, ask your doctor.
2. What you need to know before you use ZEPZELCA
Do not use ZEPZELCA
-If you are allergic to lurbinectedin or any of the other ingredients of this medicine (listed in section 6). -If you are breastfeeding.
Warnings and precautions
Talk to your doctor before using ZEPZELCA if you have liver problems.
If you are not sure, talk to your doctor before you are given ZEPZELCA.
Decreased blood cell counts
ZEPZELCA can cause severe and life-threatening myelosuppression (a condition in which the bone marrow cannot make enough blood cells). This can lead to febrile neutropenia (a decrease in neutrophils, white blood cells that fight infections, with fever) and a decrease in blood platelets, components that help the blood to clot. Your doctor will do blood tests to check your blood counts before you start treatment with ZEPZELCA and before each treatment cycle.
Tell your healthcare provider if you develop signs of infection such as:
- fever,
- chills,
- fatigue,
- body ache,
- cough;
or signs of low blood platelets such as:
- bruising,
- bleeding from gums or nose,
- blood in urine or stools,
- cuts that bleed for a long time.
Liver problems
ZEPZELCA can cause an increase in liver enzymes which can be a sign of liver problems. Your doctor will do blood tests to check your liver function before and during treatment with ZEPZELCA.
Severe muscle problems (rhabdomyolysis).
ZEPZELCA may cause damage to your muscle which increases the level of an enzyme in your blood called creatine phosphokinase (CPK). You should seek medical attention immediately if you experience severe muscle pain or weakness.
Your doctor will do a blood test to check these enzyme levels before you start and periodically during treatment with ZEPZELCA.
Infusion leaking out of your vein (extravasation)
You should seek medical attention immediately if you notice that ZEPZELCA infusion leaks out of your vein while you are being given it, or if you notice any redness, swelling, itching or discomfort at the injection site at any time. It could lead to damage and death of your tissue cells around the injection site (tissue necrosis, see also section 4) which may require surgery.
Tumour Lysis Syndrome
ZEPZELCA can cause cancer cells to break down too quickly. When many cells break down at once, they release substances into the blood that can throw off the body’s normal balance. This can harm the kidneys and may cause a life-threatening problem such as abnormal heart rhythms and seizures.
Children and adolescents
Do not give this medicine to children and adolescents between the ages of 0 and 18 years because there is no relevant use of ZEPZELCA in the treatment of SCLC in this population. Other medicines and ZEPZELCA
Tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription and herbal medicines.
The following medicines may reduce the effectiveness of ZEPZELCA by decreasing the level of ZEPZELCA in your body:
- phenytoin, phenobarbital or carbamazepine (for seizures);
- rifampicin, rifapentine and rifabutin (for tuberculosis);
- St. John’s wort (Hypericum perforatum, a herbal remedy for depression and low mood).
The following medicines may increase the risk of side effects with ZEPZELCA since they increase the level of ZEPZELCA in your body:
- ketoconazole, itraconazole, posaconazole, fluconazole or voriconazole (for fungal infections);
- clarithromycin, erythromycin, telithromycin, ciprofloxacin (for bacterial infections);
- indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, atazanavir, boceprevir, telaprevir (for HIV infection);
- aprepitant (a medicine used to prevent nausea and vomiting);
- ciclosporin (a medicine used to inhibit the defensive system of the body);
- verapamil, diltiazem (for hypertension);
- fluvoxamine (a medicine used to treat depression).
The use of any of these medicines together with ZEPZELCA should be avoided, if possible.
Pregnancy, breastfeeding and fertility
ZEPZELCA should not be used during pregnancy. This is because studies in animals have shown that ZEPZELCA may cause damage to the unborn baby. If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
You must stop breastfeeding before you start your treatment with ZEPZELCA and you must not begin breastfeeding again until your doctor has confirmed that it is safe to do so. This is because it is not known if ZEPZELCA passess into breast milk. Therefore a risk to newborns/infants cannot be ruled out.
If you are a woman who could become pregnant, you will need to have a pregnancy test before you start treatment with ZEPZELCA.
If you are a woman who could become pregnant, you must use effective contraception (birth control) during treatment with ZEPZELCA and for 7 months after your last dose.
If you are a man with a female partner who could become pregnant, you must use effective contraception during treatment with ZEPZELCA and for 4 months after your last dose.
Talk to your doctor or nurse about suitable methods of contraception for you and your partner.
ZEPZELCA may affect your ability to have a baby as it can cause damage to cells (cytotoxic) and may cause changes in genetic materials (mutagenic). Talk to your doctor for advice about options to preserve eggs or sperm before using ZEPZELCA.
Driving and using machines
During your treatment with ZEPZELCA you may experience tiredness, dizziness, vertigo and nausea. Do not drive or use any tools or machines if you are experiencing any of these side effects.
ZEPZELCA contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.
3. How to use ZEPZELCA
Treatment with ZEPZELCA should be started and supervised in a hospital or clinic by a healthcare professional experienced in the use of cancer medicines.
The dose of ZEPZELCA is based on your body surface area, which is calculated using your height and weight. The recommended dose is 3.2 mg/m2 of body surface.
ZEPZELCA is given as an infusion (drip) into a vein over a period of one hour. To reduce the risk of infusion leaking out of your vein (extravasation) and inflammation of veins causing a blood clot (thrombophlebitis), this medicine should be given through a central venous line (a thin, flexible tube placed into a large vein, usually in the chest or neck, which allows medicines to be delivered directly into the bloodstream).
It is given once every 21 days. Before each dose your doctor will carefully test your blood counts, liver and kidney functions, and iron levels; based on the results of these tests your doctor may recommend dose delays to ensure that you receive the most appropriate dose of this medicine. Treatment can continue until the patient’s cancer progresses or they experience serious side effects.
ZEPZELCA should be given after atezolizumab when both medicines are given on the same day.
If you develop serious side effects treatment may be withheld or permanently discontinued.
You will be given another medicine such as corticosteroids and serotonin antagonist before treatment with ZEPZELCA to prevent you feeling sick (nausea) and vomiting. If needed, treatment with these medicines can be continued after treatment with ZEPZELCA.
You will be given another medicine such as with granulocyte colony-stimulating factor (G-CSF) after treatment with ZEPZELCA to prevent fever associated with lower-than-normal number of white blood cells (neutropenia).
If you stop receiving ZEPZELCA
Do not stop treatment with this medicine unless you have discussed this with your doctor. This is because stopping treatment may stop the effect of the medicine.
If you have any further questions on the use of this medicine, ask your doctor.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you are not sure what the side effects below are, you should ask your doctor to explain them to you in more detail.
Tell your doctor immediately if you develop any of the following serious side effects:
Very common (may affect more than 1 in 10 people):
- difficulty breathing (dyspnoea).
Common (may affect up to 1 in 10 people):
- low levels of white blood cells with fever due to infection (febrile neutropenia),
- infusion leaking out of your vein (extravasation) while you are being given the medicine, causing redness, swelling, itchiness and discomfort at the infusion site,
It could cause tissue damage and death around the injection site (tissue necrosis), which may require surgery. Some of the symptoms or signs of extravasation may not be visible until several hours after it has occurred. There may be blistering, peeling and darkening of the skin over the site. It is possible for it to take a few days before the full extent of tissue damage is visible,
- lung infection (pneumonia) and cough.
Uncommon (may affect up to 1 in 100 people):
- blood poisoning (sepsis).
Frequency not known (cannot be estimated from the available data):
- breakdown of muscles often leading to kidney damage (rhabdomyolysis),
- rapid and massive destruction of cancer cells which release substances into the blood that can throw off the body’s normal balance. This can harm the kidneys and may cause a life-threatening problem such as abnormal heart rhythms and seizures (tumour lysis syndrome).
Talk to your doctor if you get any of the following other side effects
Very common (may affect more than 1 in 10 people):
- tiredness (fatigue),
- low levels of red blood cells which can cause tiredness and pale skin (anaemia),
- low levels of blood platelets which can lead to bleeding and bruising (thrombocytopenia),
- low levels of neutrophils, a type of white blood cell that fights infection (neutropenia),
- low levels of white blood cells (leukocytes),
- feeling sick (nausea),
- vomiting,
- diarrhoea,
- constipation,
- decreased appetite,
- pain in muscle and bones (musculoskeletal pain).
Common (may affect up to 1 in 10 people):
- high blood levels of creatinine, a sign of kidney problems,
increased blood levels of liver enzymes (transaminases and gamma-glutamyl transferase), indicating problems with liver function,
- increased level of creatine phosphokinase in the blood,
- infection of the parts of the body that collect and pass out urine (urinary tract infection),
- low levels of thyroid hormone (hypothyroidism) which can cause tiredness, weight gain, and skin and hair changes,
- joint pain (arthralgia),
- nerve damage in arms and legs causing pain or numbness, burning and tingling (peripheral neuropathy),
- low levels of a type of white blood cell called lymphocytes (lymphopenia),
- low blood levels of magnesium (hypomagnesaemia),
- low blood levels of calcium (hypocalcaemia),
- belly (abdominal) pain,
- headache,
- inflammation of a vein (phlebitis),
- inflammation of veins causing a blood clot to form and block one of your vein, leading to redness, swelling and pain in the area affected (thrombophlebitis),
- fever (pyrexia),
- swelling due to fluid retention (oedema),
- peripheral swelling,
- rash,
- itching (pruritus),
- infection,
- skin infection,
- taste disturbance (dysgeusia),
- pain or burning in the stomach, bloating, excessive belching or nausea (dyspepsia),
- inflammation of the lining of the mouth (stomatitis),
- cough or productive cough,
- inflammation in the lungs causing shortness of breath and cough (pneumonitis),
- mucosal inflammation, and
- weight decreased.
Uncommon (may affect up to 1 in 100 people):
- low levels of all types of blood cells (pancytopenia).
Reporting of side effects
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.
5. How to store ZEPZELCA
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 the vial label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2ºC – 8ºC).
Information on storage of the reconstituted and diluted solutions is included in the section for healthcare professionals.
Do not use this medicine if you notice visible particles after the reconstitution or dilution of the medicine.
Any unused medicine or waste material should be disposed of in accordance with local requirements for cytotoxic medicines.
6. Contents of the pack and other information
What ZEPZELCA contains
ZEPZELCA 4 mg powder for concentrate for solution for infusion
- The active substance is lurbinectedin. Each vial contains 4 mg of lurbinectedin.
- The other excipients are sucrose, lactic acid and sodium hydroxide (see section 2).
What ZEPZELCA looks like and contents of the pack
ZEPZELCA is a powder for concentrate for solution for infusion.
ZEPZELCA 4 mg powder for concentrate for solution for infusion
The powder has a white to off-white colour and comes in a 30 mL glass vial with blue coloured aluminium overseal.
Each carton contains one vial.
Marketing Authorisation Holder and Manufacturer
Pharma Mar, S.A.
Avda. de los Reyes 1
Polígono Industrial La Mina
28770 Colmenar Viejo (Madrid)
Spain
Tel: +34 91 846 60 00
Fax: +34 91 846 60 01
This leaflet was last revised in 05/2026.
Other sources of information
Detailed information on this medicine is available on the MHRA Products website: https://products.mhra.gov.uk. There are also links to other websites about rare diseases and treatments.
The following information is intended for healthcare professionals only:
Instructions for use, preparation, handling and disposal
Appropriate procedures for proper handling and disposal of cytotoxic medicines must be followed.
You should have received training on the correct techniques to reconstitute and dilute ZEPZELCA and you should wear protective clothing including mask, goggles and gloves during the reconstitution and dilution. Accidental contact with the skin, eyes or mucous membranes must be treated immediately with copious amounts of water. You should not work with this medicine if you are pregnant.
Preparation for intravenous infusion
ZEPZELCA must be reconstituted and further diluted prior to
infusion (see also section 3). Appropriate aseptic techniques must be used.
ZEPZELCA must not be administered as a mixture with other medicines in the same infusion apart from the diluent. No incompatibilities have been observed between ZEPZELCA and polyolefin containers (polyethylene, polypropylene and mixtures), PVC (non-DEHP-containing), polyurethane and polyolefin infusion sets (polyethylene, polypropylene and polybutadiene), polyethersulfone in-line filters with pore sizes of 0.22 micron, and implantable venous access systems with titanium and plastic resin ports and with polyurethane or silicone intravenous catheters.
Infusion lines containing nylon membrane filters should not be used when the reconstituted ZEPZELCA solution is diluted with sodium chloride 9 mg/mL (0.9%) solution for infusion.
Instructions for reconstitution
Inject 8 mL (for 4 mg strength) of water for injections into the vial.
A syringe is used to inject the correct amount of water for injections into the vial. Shake the vial until complete dissolution. The reconstituted solution results in a clear, colourless or slightly yellowish solution, essentially free of visible particles.
This reconstituted solution contains 0.5 mg/mL of lurbinectedin which requires further dilution. It is for single use only.
Instructions for dilution
Calculate the required volume as follows:
Volume (mL) = Body Surface Area (m2) x Individual Dose (mg/m2)
0.5 mg/mL
Withdraw the appropriate amount of reconstituted solution from the vial.
If intravenous administration is to be made via a central venous line, add the reconstituted solution to an infusion bag containing at least 100 mL of diluent (sodium chloride 9 mg/mL (0.9%) solution for infusion or glucose 50 mg/mL (5%) solution for infusion).
If central venous access is not feasible and a peripheral venous line has to be used, add the reconstituted solution to an infusion bag containing at least 250 mL of diluent (sodium chloride 9 mg/mL (0.9%) solution for infusion or glucose 50 mg/mL (5%) solution for infusion).
Inspect the parenteral solution visually for particles prior to intravenous administration. Once the infusion is prepared, it should be administered immediately.
In-use stability of the solutions
Chemical and physical in-use stability has been demonstrated for 24 hours at either 2°C to 8°C or 25°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless reconstitution / dilution has taken place in controlled and validated aseptic conditions. If reconstitution / dilution has taken place in controlled and validated aseptic conditions the prepared, ready-to-administer product can be stored up to 24 hours at either +2°C to +8°C or +25°C.
Disposal
Any unused medicine or waste material should be disposed of in accordance with local requirements for cytotoxic medicines.