PEMETREXED WAVERLEY 100 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Pemetrexed Waverley 100 mg powder for concentrate for solution for infusion EFG

Pemetrexed Waverley 500 mg powder for concentrate for solution for infusion EFG

pemetrexed

Read all of this leaflet carefully before you start receiving 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.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

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

Pemetrexed Waverley is a medicine used to treat cancer.

Pemetrexed can be given with cisplatin, another anticancer medicine, as a treatment for malignant pleural mesothelioma, a type of cancer that affects the lining of the lungs, in patients who have not received chemotherapy before.

Pemetrexed can also be given, along with cisplatin, for the initial treatment of patients with advanced stages of lung cancer.

Pemetrexed may be prescribed for you if you have advanced lung cancer, if your disease has responded to treatment or if it remains unchanged after initial chemotherapy.

Pemetrexed can also be given for the treatment of patients with advanced stages of lung cancer whose disease has progressed, who have already received other initial chemotherapy treatment.

2. What you need to know before you use Pemetrexed Waverley

Do not use Pemetrexed Waverley

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

• if you are breastfeeding, you must stop breastfeeding during treatment with this medicine, or if you have recently been vaccinated against yellow fever or are going to be vaccinated.

Warnings and precautions

Talk to your doctor or hospital pharmacist before you are given Pemetrexed Waverley.

If you have had or have kidney problems, tell your doctor or hospital pharmacist, as you may not be able to receive this medicine.

Before each infusion, you will need to give blood samples to check if your kidney and liver function is sufficient and to check if you have enough blood cells to receive pemetrexed.

Your doctor may decide to change your dose or delay treatment depending on your general condition and if your blood cell count is too low. If you are also receiving cisplatin, your doctor will make sure you are properly hydrated and receive appropriate treatment before and after receiving cisplatin to prevent vomiting. If you have received or are going to receive radiotherapy, please consult your doctor, as an early or late reaction may occur between the radiation and pemetrexed. If you have been vaccinated recently, please consult your doctor, as this may cause some negative effect with this medicine.

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

If you have fluid accumulated around the lung, your doctor may decide to remove the fluid before administering this medicine to you.

Children and adolescents

There is no relevant data on the use of pemetrexed in the pediatric population.

Using Pemetrexed Waverley with other medicines

Tell your doctor if you are taking medicines for pain or inflammation (swelling), such as medicines called "non-steroidal anti-inflammatory drugs" (NSAIDs), including those purchased without a prescription (such as ibuprofen). There are many classes of NSAIDs with different durations of action. Based on the date of your infusion of this medicine and/or the status of your kidney function, your doctor will advise you which medicines you can use and when you can take them. If you are unsure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID. Tell your doctor or hospital pharmacist if you are using or have recently used other medicines, including those purchased without a prescription.

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, tell your doctor. During pregnancy, the use of this medicine should be avoided. Your doctor will inform you of the possible risks of taking pemetrexed during pregnancy. Women must use effective contraceptive methods during treatment with this medicine.

Breastfeeding

If you are breastfeeding, tell your doctor.

During treatment with this medicine, breastfeeding should be stopped.

Fertility

Male patients are advised not to father a child during and up to 6 months after treatment with this medicine and must use effective contraceptive methods during and up to 6 months after treatment with pemetrexed. If you want to have a child during treatment or in the 6 months following treatment, ask your doctor or pharmacist for advice. You may want to ask for information about sperm preservation before starting your treatment.

Driving and using machines

This medicine may make you feel tired. Be careful when driving a vehicle or using machines.

Pemetrexed Waverley contains sodium

Pemetrexed Waverley 100 mg powder for concentrate for solution for infusion EFG

contains less than 23 mg (1 mmol) of sodium per vial, so it is considered essentially "sodium-free".

Pemetrexed Waverley 500 mg powder for concentrate for solution for infusion EFGcontains 54 mg of sodium (main component of cooking/salt) per vial. This is equivalent to 2.7% of the maximum recommended daily intake of sodium for an adult.

3. How to use Pemetrexed Waverley

The dose of Pemetrexed Waverley 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 surface area to calculate the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell count and general condition. The hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Waverley powder with a sodium chloride solution for injection of 9 mg/ml (0.9%) before it is given to you.

You will always receive Pemetrexed Waverley through an infusion (drip) in one of your veins. The infusion will last at least 10 minutes.

When using Pemetrexed Waverley in combination with cisplatin:

Your doctor or hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin is also given through an infusion in one of your veins and is given approximately 30 minutes after the infusion of Pemetrexed Waverley has finished. The cisplatin infusion lasts approximately two hours.

Normally, you should receive your infusion once every three weeks.

Additional medication:

Corticosteroids: your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you will need to take the day before, the day of, and the day after treatment with Pemetrexed Waverley. Your doctor gives you this medicine to reduce the frequency and severity of skin reactions you may experience during your cancer treatment.

Vitamin supplement: your doctor will prescribe oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1,000 micrograms) that you should take once a day while taking Pemetrexed Waverley. You should take at least five doses during the seven days before the first dose of Pemetrexed Waverley. You should continue taking folic acid for 21 days after the last dose of Pemetrexed Waverley. You will also receive a vitamin B12 injection (1,000 micrograms) in the week before administration of Pemetrexed Waverley and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Waverley). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

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.

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

• Fever or infection (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 frequent). Infections (sepsis) can be serious and life-threatening.
• If you start to feel chest pain (frequent) or your heart rate is faster (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very frequent).
• Allergic reaction: if you develop a rash (very frequent), burning sensation, or itching (frequent), or fever (frequent). In rare cases, skin reactions can be serious and life-threatening. Contact your doctor if you experience severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you are short of breath or pale (due to having fewer red blood cells than normal, which is very frequent).
• 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 having fewer platelets than normal, which is very frequent).
• If you experience sudden difficulty breathing, severe chest pain, or coughing up blood (uncommon) (may indicate that there is a blood clot in the lungs).

Side effects with Pemetrexed Waverley may include:

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

• Low white blood cell count
• Low hemoglobin levels (anemia)
• Low platelet count
• Diarrhea
• Vomiting
• Pain, redness, swelling, or sores in the mouth
• Nausea
• Loss of appetite
• Asthenia (fatigue)
• Rash
• Hair loss
• Constipation
• Numbness
• Kidney: changes in blood tests

Common (may affect up to 1 in 10 people)

• Allergic reaction: rash/burning sensation or itching
• Infection including sepsis
• Fever
• Dehydration
• Kidney failure
• Skin irritation and itching
• Chest pain
• Muscle weakness
• Conjunctivitis (eye inflammation)
• Upset stomach
• Abdominal pain
• Changes in taste
• Liver: changes in blood tests
• Tearful eyes
• Increased skin pigmentation

Uncommon (may affect up to 1 in 100 people)

• Acute kidney failure
• Fast heart rate
• Inflammation of the esophagus (throat) after combination of pemetrexed and radiotherapy

• Colitis (inflammation of the lining of the large intestine, which may be accompanied by intestinal or rectal bleeding)
• Interstitial pneumonitis (hardening of the walls of the air sacs in the lungs)
• Edema (excess fluid in the body tissues that causes swelling)
• Some patients have experienced a heart attack, embolism, or "mini-stroke" while receiving pemetrexed, usually in combination with other anticancer treatment
• Pancytopenia: combination of low white blood cell count, low red blood cell count, and low platelet count
• Radiation pneumonitis (scarring of the air sacs in the lungs associated with radiotherapy) may occur in patients who are being treated with radiation before, during, or after treatment with pemetrexed
• Pain in the limbs, low temperature, and changes in skin color have been reported
• Blood clots in the lungs (pulmonary embolism)

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

• Late skin toxicity (skin rash similar to severe sunburn) that can appear on skin that has been previously exposed to radiation, from days to years after radiation
• Bullous disorders (diseases with blistering of the skin) including Stevens-Johnson syndrome and toxic epidermal necrolysis
• Immune-mediated hemolytic anemia (destruction of red blood cells by antibodies)
• Hepatitis (inflammation of the liver)
• Anaphylactic shock (severe allergic reaction)

Frequency not known: frequency cannot be estimated from the available data

• Swelling of the lower limbs with pain and redness.
• Increased urine production
• Thirst and increased water intake
• Hypernatremia - elevated sodium in the blood
• Skin inflammation, mainly of the lower limbs with swelling, pain, and redness

You may experience some of these symptoms and/or situations. You should tell your doctor as soon as you start experiencing any of these side effects.

If you are concerned about any side effect, talk to your doctor.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Pemetrexed Waverley

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 after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Reconstituted and infusion solutions: the product should be used immediately. When prepared according to the instructions, the chemical and physical stability of the reconstituted and infusion solutions of pemetrexed has been demonstrated for 24 hours at refrigerated temperature.

This medicine is for single use; any unused solution should be disposed of in accordance with local requirements.

6. Container Content and Additional Information

Pemetrexed CompositionWaverley

The active ingredient is pemetrexed.

Pemetrexed Waverley 100 mg powder for concentrate for solution for infusion EFG:Each vial contains 100 mg of pemetrexed (as pemetrexed disodium)

Pemetrexed Waverley 500 mg powder for concentrate for solution for infusion EFG:Each vial contains 500 mg of pemetrexed (as pemetrexed disodium)

After reconstitution, the solution contains 25 mg/ml of pemetrexed. Before administration, it is required that the healthcare professional perform another dilution.

The other components are mannitol (E421), hydrochloric acid (E507), (for pH adjustment) and sodium hydroxide (E524), (for pH adjustment).

Product Appearanceand Container Content

Pemetrexed Waverley is a powder for concentrate for solution for infusion in a vial. It is a white to light yellow or yellow-green lyophilized powder.

Each package of Pemetrexed Waverley consists of a pemetrexed powder for concentrate for solution for infusion vial.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder

Waverley Pharma Europe Limited

Alexandra House, Office # 234, The Sweepstakes,

Ballsbridge, Dublin 4, D04 C7H2, Ireland

Manufacturer:

Wessling GmbH

Johann-Krane-Weg 42

48149 Munster

Germany

Or

Wessling Hungary KFT

Anonymus u. 6

Hungary, Budapest 1045

Hungary

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Viso Farmacéutica, S.L.U

c/ Retama 7, 7ª Planta

28045 Madrid

Spain

This medicinal product is authorized in the EEA Member States with the following names:

Date of last revision of this leaflet:September 2021.

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

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This information is intended only for healthcare professionals:

Instructions for use and handling and disposal

1. Use aseptic techniques during the reconstitution and subsequent dilution of pemetrexed for intravenous infusion administration.

1. Calculate the dose and the number of Pemetrexed Waverley vials needed. Each vial contains an excess of pemetrexed to facilitate the administration of the necessary nominal amount.

1. Pemetrexed Waverley 100 mg powder for concentrate for solution for infusion EFG:

Reconstitute each 100 mg vial with 4.2 ml of a 0.9% sodium chloride injection solution (9 mg/ml), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Pemetrexed Waverley 500 mg powder for concentrate for solution for infusion EFG:

Reconstitute each 500 mg vial with 20 ml of a 0.9% sodium chloride injection solution (9 mg/ml), without preservatives, to obtain a solution containing 25 mg/ml of pemetrexed.

Shake the vial carefully until the powder is completely dissolved. The resulting solution is transparent with a color range that can vary from colorless to yellow or yellow-green without affecting the product quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

1. The appropriate volume of the reconstituted pemetrexed solution should be diluted to 100 ml with a 0.9% sodium chloride injection solution (9 mg/ml) without preservatives and should

be administered as an intravenous infusion over 10 minutes.

1. The prepared pemetrexed infusion solution is compatible with polyvinyl chloride and polyolefin infusion systems and bags. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer's injection and Ringer's injection.

1. Parenteral medicinal products should be inspected visually for particulate matter or color change prior to administration. If particles are observed, the medicinal product should not be administered.

1. Pemetrexed solutions are for single use. The medicinal product and unused material should be discarded according to local requirements.

Precautions in preparation and administration:As with any other potentially toxic antineoplastic agent, special care should be taken in the handling and preparation of pemetrexed infusion solutions. The use of gloves is recommended. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and thoroughly with water and soap. If pemetrexed solutions come into contact with mucous membranes, they should be rinsed with plenty of water. Pemetrexed is not a vesicant drug. There is no specific antidote for pemetrexed extravasation. Some cases of pemetrexed extravasation have been reported, which were not considered serious by the investigator. Extravasation should be treated according to standard clinical practice with other non-vesicant drugs.

Marketing Authorization Holder

Waverley Pharma Europe Limited

Alexandra House, Office # 234, The Sweepstakes,

Ballsbridge, Dublin 4, D04 C7H2, Ireland.