Pemetrexed Stadagen 25 mg/ml concentrate for infusion solution

Patient Information Leaflet

Introduction

Patient Information Leaflet

Pemetrexed STADAGEN 25 mg/ml concentrate for solution for infusion

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

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Pemetrexed Stadagen is and what it is used for

2. What you need to know before using Pemetrexed Stadagen

3. How to use Pemetrexed Stadagen

4. Possible side effects

5. Storage of Pemetrexed Stadagen

6. Contents of the pack and other information

1. What Pemetrexed Stadagen is and what it is used for

Pemetrexed is a medicine used to treat cancer.

Pemetrexed may be given together with cisplatin, another anticancer medicine, as treatment for malignant pleural mesothelioma, a type of cancer affecting the lining of the lung, in patients who have not received previous chemotherapy.

Pemetrexed may also be given together with cisplatin as initial treatment for patients with advanced-stage lung cancer.

Pemetrexed may be prescribed if you have advanced-stage lung cancer and your disease has responded to treatment or remained stable after initial chemotherapy.

Pemetrexed may also be administered for the treatment of patients with advanced-stage lung cancer whose disease has progressed after having received prior initial chemotherapy treatment.

2. What you need to know before using Pemetrexed Stadagen

Do not use pemetrexed:

• if you are allergic to pemetrexed or to any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding, you must interrupt breastfeeding during treatment with pemetrexed.
• if you have recently received or are scheduled to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor, hospital pharmacist, or nurse before starting treatment with pemetrexed.

If you have had or currently have kidney problems, inform your doctor or hospital pharmacist, as you may not be able to receive pemetrexed.

Before each infusion, you will need to provide blood samples to assess whether your kidney and liver function are adequate and to evaluate whether you have enough blood cells to receive pemetrexed. Your doctor may decide to adjust your dose or delay treatment depending on your general condition and whether your blood cell count is too low.

If you are also receiving cisplatin, your doctor will ensure that you are properly hydrated and will administer appropriate treatment before and after cisplatin to prevent vomiting.

If you have received or are scheduled to receive radiotherapy, please consult your doctor, as there may be an early or delayed interaction between radiation and pemetrexed.

If you have recently been vaccinated, please consult your doctor, as this could potentially cause a negative interaction with pemetrexed.

If you have heart disease or a history of heart disease, please consult your doctor.

If you have fluid accumulation around the lung, your doctor may decide to drain the fluid before administering pemetrexed.

Children and adolescents

This medicine should not be given to children and adolescents, as there is no experience with this medicine in individuals under 18 years of age.

Other medicines and Pemetrexed Stadagen

Inform your doctor if you are taking any other medicines for pain or inflammation (swelling), such as medicines known as “non-steroidal anti-inflammatory drugs” (NSAIDs), including those obtained without a prescription (such as ibuprofen). There are many types of NSAIDs with different durations of action. Based on the date of your scheduled pemetrexed infusion and/or your kidney function status, your doctor will advise you which medicines you can use and when. If you are unsure, consult your doctor or pharmacist to determine whether any medicine you are taking is an NSAID.

Inform your doctor if you are taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lansoprazol, pantoprazole, and rabeprazole) used to treat stomach acid and acid reflux.

Inform your doctor or hospital pharmacist if you are taking, have recently taken, or might need to take any other medicine.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Pemetrexed should be avoided during pregnancy. Your doctor will inform you of the potential risks of taking pemetrexed during pregnancy. Women must use effective contraception during treatment with pemetrexed and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, inform your doctor.

Breastfeeding must be interrupted during treatment with pemetrexed.

Fertility

Male patients are advised not to father a child during and for 3 months after treatment with pemetrexed, and therefore must use effective contraception during and for 3 months after treatment with pemetrexed. If you wish to father a child during treatment or within 3 months after treatment, seek advice from your doctor or pharmacist. Pemetrexed may affect your ability to have children. Consult your doctor for advice on sperm preservation before starting treatment.

Driving and using machines

Pemetrexed may cause tiredness. Be cautious if you drive or operate machinery.

Pemetrexed Stadagen contains sodium

This medicine contains 110.03 mg of sodium (main component of table/cooking salt) in each 500 mg dose of pemetrexed per square meter of body surface area. This corresponds to 5.51% of the maximum daily recommended sodium intake for an adult.

3. How to use Pemetrexed Stadagen

Dose

The dose of pemetrexed is 500 milligrams per square meter of your body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor will use this value to determine the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell counts and your overall condition.

The hospital pharmacist, nurse, or doctor will have diluted Pemetrexed Stadagen with 9 mg/ml (0.9%) sodium chloride injection solution before administration.

Method of administration

You will always receive Pemetrexed Stadagen as an intravenous infusion into one of your veins. The infusion will last at least 10 minutes.

Duration of use

You will normally receive your infusion once every three weeks.

When using pemetrexed in combination with cisplatin:

Your doctor or hospital pharmacist will calculate your required dose based on your height and weight. Cisplatin is also administered by intravenous infusion and is given approximately 30 minutes after the pemetrexed infusion has finished. The cisplatin infusion lasts approximately two hours.

Additional medication:

Corticosteroids: Your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice daily) to be taken the day before, the day of, and the day after pemetrexed treatment. Your doctor prescribes this medication to reduce the frequency and severity of skin reactions that may occur during your cancer treatment.

Vitamin supplementation:

• Folic acid: Your doctor will prescribe oral folic acid (vitamin) or a multivitamin preparation containing folic acid (350 to 1,000 micrograms), to be taken once daily while receiving pemetrexed. You should take at least five doses during the seven days prior to your first dose of pemetrexed. You must continue taking folic acid for 21 days after your last dose of pemetrexed.
• Vitamin B12: Additionally, you will receive a vitamin B12 injection (1,000 micrograms) in the week prior to pemetrexed administration, and then approximately every 9 weeks (corresponding to 3 treatment cycles of pemetrexed).

Vitamin B12 and folic acid are given to reduce potential toxic effects of cancer treatment.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

You must inform your doctor immediately if you notice any of the following symptoms:

• fever or infection (respectively, frequent or very frequent): if you have a temperature of 38°C or higher, sweating, or other signs of infection (as you may have fewer white blood cells than normal, which is very common). Infections (sepsis) can be severe and may cause death.
• if you start experiencing chest pain (frequent) or your heart rate increases (uncommon).
• if you have pain, redness, swelling, or sores in the mouth (very common).
• allergic reaction: if you develop a rash (very common), burning sensation or itching (common), or fever (common). Skin reactions may rarely be severe and may cause death. Contact your doctor if you develop severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• if you feel tired or dizzy, are short of breath, or look pale (due to lower than normal hemoglobin levels, which is very common).
• if you experience bleeding from the gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising (due to lower than normal platelet counts, which is very common).
• if you suddenly experience difficulty breathing, severe chest pain, or coughing up blood (uncommon) (this may indicate a blood clot in the veins of the lungs).

Adverse effects with pemetrexed may include:

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

• infection
• pharyngitis (sore throat)
• low neutrophil granulocyte count (a type of white blood cell)
• low white blood cell count
• low hemoglobin levels
• pain, redness, swelling, or sores in the mouth
• loss of appetite
• vomiting
• diarrhea
• nausea
• skin rash
• scaly skin
• blood test abnormalities showing reduced kidney function
• asthenia (tiredness)

Common (may affect up to 1 in 10 people)

• blood infection
• fever with low neutrophil granulocyte count (a type of white blood cell)
• low platelet count
• allergic reaction
• loss of body fluids
• changes in taste sensation
• motor nerve damage that may cause muscle weakness and atrophy (wasting, mainly in arms and legs)
• sensory nerve damage that may cause loss of sensation, burning pain, and unsteady gait
• dizziness
• inflammation or swelling of the conjunctiva (the membrane lining the eyelids and covering the white part of the eye)
• dry eyes
• watery eyes
• dryness of the conjunctiva (the inner membrane of the eyelids and covering the white part of the eye) and cornea (transparent layer in front of the iris and pupil)
• eyelid swelling
• eye disorder with dryness, tearing, irritation, and/or pain
• heart failure (a condition affecting the pumping ability of the heart muscles)
• irregular heart rate
• indigestion
• constipation
• abdominal pain
• liver: increased levels of chemicals in the blood produced by the liver
• increased skin pigmentation
• skin itching
• body rash where each lesion resembles a target (bull's-eye)
• hair loss
• hives
• kidney failure
• reduced kidney function
• fever
• pain
• excess fluid in body tissues causing swelling
• chest pain
• inflammation and ulceration of mucous membranes lining the digestive tract internally

Uncommon (may affect up to 1 in 100 people)

• reduction in red blood cells, white blood cells, and platelets
• ischemia
• type of ischemia due to blockage of a cerebral artery
• intracranial bleeding
• angina (chest pain caused by reduced blood flow to the heart)
• infarction
• narrowing or blockage of coronary arteries
• increased heart rate
• poor blood distribution to the limbs
• obstruction in one of the pulmonary arteries in the lungs
• inflammation and scarring of the lung mucosa with breathing difficulties
• passage of bright red blood from the anus
• gastrointestinal tract bleeding
• intestinal perforation
• inflammation of the esophageal mucosa
• inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (observed only in combination with cisplatin)
• inflammation, edema, erythema, and erosion of the esophageal mucosal surface caused by radiotherapy
• lung inflammation caused by radiotherapy

Rare (may affect up to 1 in 1,000 people)

• destruction of red blood cells
• anaphylactic shock (severe allergic reaction)
• inflammatory liver disease
• skin redness
• skin rash developing in a previously irradiated area

Very rare (may affect up to 1 in 10,000 people)

• skin and soft tissue infections
• Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that may be fatal)
• toxic epidermal necrolysis (a type of severe skin reaction that may be fatal)
• autoimmune disorder causing skin rashes and blisters on the legs, arms, and abdomen
• skin inflammation characterized by the presence of fluid-filled blisters
• skin fragility, blistering, erosions, and scarring of the skin
• redness, pain, and swelling, mainly in the lower limbs
• inflammation of the skin and underlying fat (pseudocellulitis)
• skin inflammation (dermatitis)
• skin becomes inflamed, itchy, red, cracked, and rough
• intensely itchy spots

Not known (frequency cannot be estimated from available data)

• a type of diabetes resulting mainly from kidney disease
• kidney disorder involving death of tubular epithelial cells forming the renal tubules

You may experience one or more of these symptoms and/or conditions. You should inform your doctor as soon as you begin to experience any of these adverse effects.

If you are concerned about any adverse effect, consult your doctor.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Pemetrexed Stadagen

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

Do not use this medicine after the expiry date stated on the labelling after EXP. The expiry date refers to the last day of the month indicated.

Store the unopened vial in a refrigerator (2°C – 8°C).

Do not freeze.

After first opening, use immediately.

Perfusion solution: the medicine should be used immediately. Once prepared as recommended, the in-use chemical and physical stability of pemetrexed has been demonstrated for 72 hours under refrigerated conditions (2°C – 8°C).

The solution is clear and may display a range of colour from colourless to slightly yellow or yellowish-green, without this indicating that the quality of the product has been affected.

Do not use if particles are observed.

This medicine is for single use only; any unused medicine and all materials that have come into contact with it must be disposed of in accordance with local regulations for cytotoxic medicines.

This medicine is for single use only; any unused solution must be discarded in accordance with local requirements for cytotoxic medicines.

6. Contents of the container and other information

Composition of Pemetrexed Stadagen

• The active substance is pemetrexed.

Each ml of concentrate for solution for infusion contains 25 mg of pemetrexed (as 30.21 mg of pemetrexed disodium hemipentahydrate).

A 4 ml vial of concentrate contains 100 mg of pemetrexed (as 120.83 mg of pemetrexed disodium 2.5 hydrate).

A 20 ml vial of concentrate contains 500 mg of pemetrexed (as 604.13 mg of pemetrexed disodium 2.5 hydrate).

A 40 ml vial of concentrate contains 1,000 mg of pemetrexed (as 1,208.26 mg of pemetrexed disodium 2.5 hydrate).

The other components are mannitol, acetylcysteine, sodium hydroxide (to adjust pH), hydrochloric acid (to adjust pH) and water for injections.

Further dilution by a healthcare professional is required before administration.

Appearance of Pemetrexed Stadagen and contents of the pack

This medicine is a concentrate for solution for infusion.

The concentrate solution is clear, colourless or slightly yellow or yellowish-green. It is packaged in clear glass vials sealed with a chlorobutyl/butyl rubber stopper coated with fluoropolymer, Type I, and aluminium flip-off caps.

Each vial is contained within a transparent tamper-evident polycarbonate (PC) container with a hinged polypropylene (PP) lid that can be re-closed.

Each vial contains 25 mg/ml of pemetrexed.

Each pack contains 1 vial of 4 ml.

Each pack contains 1 vial of 20 ml.

Each pack contains 1 vial of 40 ml.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Laboratorio STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Manufacturer

STADA Arzneimittel AG

Stadastrasse 2-18

61118 Bad Vilbel

Germany

This medicinal product is authorised in the European Economic Area member states under the following names:

Date of last review of this package leaflet: April 2025

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicinal Products and Health Products (AEMPS) (http://www.aemps.gob.es/)

This information is intended for healthcare professionals only:

Instructions for use, handling, and disposal

1. Use aseptic techniques when reconstituting pemetrexed for intravenous infusion administration.

2. Calculate the required dose and number of pemetrexed vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of the labeled amount.

3. The appropriate volume of pemetrexed concentrate should be diluted to 100 ml with 0.9 mg/ml (0.9%) sodium chloride solution for injection, preservative-free, and administered as an intravenous infusion over 10 minutes.

4. The pemetrexed infusion solution prepared as described above is compatible with polyolefin-coated and polyvinyl chloride infusion bags and administration systems. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer's injection and Ringer's injection.

5. Parenteral medicinal products should be visually inspected for particulate matter and discoloration prior to administration. Do not administer if particles are observed.

6. Chemical and physical in-use stability of the infusion solution has been demonstrated for 72 hours at 2°C to 8°C. From a microbiological standpoint, the infusion solution should be administered immediately. If not used immediately, storage time and conditions prior to use are the responsibility of the user and should normally not exceed 24 hours at 2°C–8°C, unless the dilution was prepared under controlled and validated aseptic conditions.

7. Pemetrexed solutions are for single use only. Unused medicinal product and waste material should be disposed of in accordance with local regulations for cytotoxic agents.

Precautions in preparation and administration: As with any other potentially toxic antineoplastic agent, special care should be taken in handling and preparing pemetrexed infusion solutions. Glove use is recommended during handling. If pemetrexed solutions come into contact with the skin, wash immediately and thoroughly with soap and water. If pemetrexed solutions contact mucous membranes, rinse thoroughly with water. Pemetrexed is not a vesicant. There is no specific antidote for pemetrexed extravasation. Cases of pemetrexed extravasation have been reported, none of which were considered serious by the investigator. Extravasation should be managed according to standard clinical practice for non-vesicant drugs.