Prospect: 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 this prospect carefully before starting to receive this medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Pemetrexed Waverley is a medication used for the treatment of cancer.

Pemetrexed can be administered along with cisplatin, another anticancer medication, as treatment for malignant pleural mesothelioma, a form of cancer that affects the lung lining, in patients who have not received prior chemotherapy.

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

Pemetrexed may be prescribed 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 administered for the treatment of patients in advanced stages of lung cancer whose disease has progressed, who have already received initial chemotherapy treatment.

No use Pemetrexed Waverley

• If you are allergic to pemetrexed or any of the other components of this medication (listed in section 6).

• If you are breastfeeding, you must stop breastfeeding during treatment with this medicationIf you have recently received or are to receive the yellow fever vaccine.

Warnings and precautions

Consult your doctor or hospital pharmacist before Pemetrexed Waverley is administered to you.

If you have or have had kidney problems, tell your doctor or hospital pharmacist as it may be possible that you cannot receivethis medication.

Before each infusion, you will need to give blood samples to evaluate if your renal and hepatic function is sufficient and to evaluate if you have enough blood cells to receive pemetrexed.

Your doctor may decide to change your dose or delay treatment depending on your overall condition and if your blood cell count is too low. If you are also receiving cisplatin, your doctor will ensure that you are properly hydrated and receive the appropriate treatment before and after receiving cisplatin to prevent vomiting. If you have received or are to receive radiation therapy, please consult with your doctor, as there may be an early or late reaction between the radiation and . If you have recently been vaccinated, please consult with your doctor, as it may cause some negative effect with this medication.

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

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

Children and adolescents

No relevant data is available on the use of pemetrexed in the pediatric population.

Use of Pemetrexed Waverley with other medications

Inform your doctor if you are using pain or anti-inflammatory medications (such as non-steroidal anti-inflammatory drugs, or NSAIDs), including those obtained 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 medication and/or your renal function status, your doctor will advise you on which medications you can use and when. If you are unsure, consult your doctor or hospital pharmacist to see if any medication you are taking is an NSAID. Inform your doctor or hospital pharmacist if you are using or have recently used other medications, including those obtained without a prescription.

Pregnancy

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

Breastfeeding

If you are breastfeeding, inform your doctor.

During treatment with this medication, breastfeeding should be interrupted.

Fertility

Men are advised not to father a child during and for 6 months after treatment with this medication, and therefore, should use effective contraceptive methods during and for 6 months after treatment with pemetrexed. If you wish to have a child during treatment or in the 6 months following treatment, please consult your doctor or pharmacist. You may wish to request information on sperm preservation before starting your treatment.

Driving and operating machinery

This medication may make you feel tired. Be careful when driving a vehicle or operating machinery.

Pemetrexed Waverley contains sodium

Pemetrexed Waverley 100 mg powder for concentrate forinfusion solution EFG

contains less than 23 mg (1 mmol) of sodium per vial, which is considered essentially “sodium-free”.

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

The dose of Pemetrexed Waverley is 500 milligrams per square meter of the surface area of your body.

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 overall condition. The hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Waverley powder with a 9 mg/ml sodium chloride solution (0.9%) before administration.

You will always receive Pemetrexed Waverley through a vein infusion (drip). 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 administered through a vein infusion and is given approximately 30 minutes after the Pemetrexed Waverley infusion is completed. The cisplatin infusion lasts approximately two hours.

You should normally receive your infusion once every three weeks.

Additional medication:

Corticosteroids: Your doctor will prescribe some steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you will need to take the day before, on the day of, and the day after treatment with Pemetrexed Waverley. Your doctor gives you this medication 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 will need to 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 an injection of vitamin B12 (1,000 micrograms) the week before Pemetrexed Waverley administration and approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Waverley). Vitamin B12 and folic acid are given to reduce possible toxic effects of cancer treatment.

If you have any other questions about using this product, ask your doctor or pharmacist.

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

You must inform 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 (since you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be serious and cause death.
• If you start to feel chest pain (frequent) or your heart rate is faster (rare).
• If you have pain, redness, swelling, or sores in your mouth (very frequent).
• Allergic reaction: if you develop hives (very frequent), burning or itching sensation (frequent), or fever (frequent). In rare cases, skin reactions can be severe and may cause death. Contact your doctor if you present severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you lack breath or are pale (because you have fewer hemoglobin than normal, which is very frequent).
• If you experience bleeding gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, or unexpected bruises (because you have fewer platelets than normal, which is very frequent).
• If you experience sudden difficulty breathing, intense chest pain, or coughing up blood in your sputum (rare) (which may indicate that there is a blood clot in the veins of the lungs).

The side effects of Pemetrexed Waverley may include:

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

• Low white blood cell count
• Low hemoglobin levels (anemia)
• Low platelet count
• Diarrhea
• Vomiting
• Mouth pain, redness, swelling, or sores
• Nausea
• Loss of appetite
• Weakness (asthenia)
• Skin rash
• Hair loss
• Constipation
• Loss of sensation
• Kidney: alterations in blood tests

Frequent (may affect up to 1 in 10 people)

• Allergic reaction: hives or burning sensation
• Infection, including sepsis
• Fever
• Dehydration
• Renal failure
• Skin irritation and itching
• Chest pain
• Muscle weakness
• Conjunctivitis (eye inflammation)
• Upset stomach
• Abdominal pain
• Changes in taste
• Liver: alterations in blood tests
• Runny eyes
• Pigmentation increase in the skin

Rare (may affect up to 1 in 100 people)

• Acute renal failure
• Aceeleration of heart rate
• Inflammation of the esophageal mucosa (throat) after the combination of pemetrexed and radiation therapy

• Colitis (inflammation of the intestinal mucosa, which may be accompanied by intestinal or rectal bleeding)
• Interstitial pneumonitis (hardening of the walls of the lung alveoli)
• Edema (excess fluid in the body tissues causing swelling)
• Some patients have experienced a heart attack, embolism, or "small embolism" while receiving pemetrexed, usually in combination with another anticancer treatment
• Pancitopenia: combination of low white blood cell, red blood cell, and platelet counts
• Radiation pneumonitis (scar tissue in the lung air sacs associated with radiation therapy) may occur in patients being treated with radiation either before, during, or after their treatment with pemetrexed
• There have been reports of pain in the limbs, low temperature, and changes in skin color
• Blood clots in the lungs (pulmonary embolism)

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

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

Unknown frequency: the frequency cannot be estimated from available data

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

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

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

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Usehttps://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and vial after CAD.The expiration date is the last day of the month indicated.

This medication does not require special conservation conditions.

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

This medication is for single use; any unused solution must be disposed of according to local requirements.

Composition of PemetrexedWaverley

The active ingredient is pemetrexed.

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

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

After reconstitution, the solution contains 25 mg/ml of pemetrexed. Before administration, a healthcare professional must perform another dilution.

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

Appearanceof the productand contents of the package

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

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

Marketing Authorization Holder and Responsible for Manufacturing:

Marketing Authorization Holder

Waverley Pharma Europe Limited

Alexandra House, Office # 234, The Sweepstakes,

Ballsbridge, Dublin 4, D04 C7H2,Ireland

Responsible for Manufacturing:

Wessling GmbH

Johann-Krane-Weg 42

48149 Munster

Germany

Or

Wessling Hungary KFT

Anonymus u. 6

Hungary, Budapest 1045

Hungary

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Viso Farmacéutica, S.L.U

c/ Retama 7, 7ª Planta

28045 Madrid

Spain

This medication is authorized in the EEA member states with the following names:

Last review date of this leaflet:September 2021.

The detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS):http://www.aemps.gob.es/.

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This information is intended only for doctors or healthcare professionals:

Instructions for use and handling and disposal

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

2.Calculate the dose and the number of vials of Pemetrexed Waverly needed. Each vial contains an excess of pemetrexed to facilitate the administration of the nominal amount required.

3.Pemetrexed Waverley 100 mg powder for concentrate forsolution for infusion EFG:

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

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

Reconstitute each vial of 500 mg with 20 ml of a sodium chloride 0.9% 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 quality of the product. The pH of the reconstituted solution is between 6.6 and 7.8.Further dilution is required.

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

be administered as an intravenous infusion over 10 minutes.

5.The pemetrexed solution for infusion prepared according to the above instructions is compatible with polyvinyl chloride and polyolefin infusion systems and bags. Pemetrexed is incompatible with calcium-containing diluents, including lactated Ringer's injection and Ringer's injection.

6.Parenteral medications must be visually inspected before administration to discard the appearance of particles or color change. If particles are observed, the medication should not be administered.

7.The pemetrexed solutions are for single use. The medication and unused material must be disposed of according to local requirements.

Precautions in preparation and administration:As with any other potentially toxic antineoplastic agent, special care must be taken in the handling and preparation of pemetrexed solutions for infusion. The use of gloves is recommended for handling. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and abundantly with water and soap. If pemetrexed solutions come into contact with mucous membranes, wash with abundant water. Pemetrexed is not a vesicant. 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 non-vesicant drugs.

Marketing Authorization Holder

Waverley Pharma Europe Limited

Alexandra House, Office # 234, The Sweepstakes,

Ballsbridge, Dublin 4, D04 C7H2, Ireland.