Pemetrexed Waverley 100 mg powder for concentrate for infusion solution EFG

Package leaflet: Information for the user

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 the entire leaflet carefully before you start receiving 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 or pharmacist.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are not adverse reactions listed in this leaflet. See section 4.

Leaflet contents

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

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

Pemetrexed Waverley is a medicine used for the treatment of 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 previously received 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, if your disease has responded to initial treatment, or if it remains 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 Waverley

Do not use Pemetrexed Waverley

• 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 stop breastfeeding during treatment with this medicine.

• if you have recently received or are scheduled to receive the yellow fever vaccine.

Warnings and precautions

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

Tell your doctor or hospital pharmacist if you have had or currently have kidney problems, as this may mean you cannot receive this medicine.

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 sufficient blood cells to receive pemetrexed.

Your doctor may decide to adjust your dose or delay treatment depending on your overall 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 due to receive radiotherapy, please consult your doctor, as there may be an early or delayed interaction between radiation and pemetrexed. If you have been recently vaccinated, please consult your doctor, as this may potentially cause a negative interaction with this medicine.

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 this medicine.

Children and adolescents

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

Use of Pemetrexed Waverley with other medicines

Inform your doctor if you are taking pain or anti-inflammatory medicines (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 infusion of this medicine and/or your kidney function status, your doctor will advise you which medicines you may take 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 or hospital pharmacist if you are currently taking or have recently taken any other medicines, including those obtained without a prescription.

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, inform your doctor. This medicine 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 this medicine.

Breastfeeding

If you are breastfeeding, inform your doctor.

Breastfeeding must be discontinued during treatment with this medicine.

Fertility

Male patients are advised not to father a child during and for 6 months after treatment with this medicine, and should therefore use effective contraception during and for 6 months after treatment with pemetrexed. If you wish to father a child during treatment or within 6 months after treatment, seek advice from your doctor or pharmacist. You may wish to request information about sperm preservation before starting treatment.

Driving and using machines

This medicine may make you feel tired. Be cautious when driving or operating machinery.

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 and is therefore considered essentially “sodium-free”.

Pemetrexed Waverley 500 mg powder for concentrate for solution for infusion EFG contains 54 mg of sodium (the main component of cooking salt/table salt) per vial. This is equivalent to 2.7% of the maximum daily recommended 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 determine the correct dose for you. This dose may be adjusted or the treatment may be delayed depending on your blood cell count and your general condition. The hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Waverley powder with a 9 mg/ml (0.9%) sodium chloride injection solution before administration.

You will always receive Pemetrexed Waverley as an intravenous infusion (drip) into 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 administered by intravenous 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 steroid tablets (equivalent to 4 milligrams of dexamethasone twice daily) that you must take the day before, the day of, and the day after treatment with Pemetrexed Waverley. Your doctor prescribes 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 preparation containing folic acid (350 to 1,000 micrograms) to be taken once daily while you are receiving Pemetrexed Waverley. You should take at least five doses during the seven days prior to your first dose of Pemetrexed Waverley. You must continue taking folic acid for 21 days after your last dose of Pemetrexed Waverley. In addition, you will receive an injection of vitamin B12 (1,000 micrograms) during the week before administration of Pemetrexed Waverley, and then approximately every 9 weeks (corresponding to 3 treatment cycles of Pemetrexed Waverley). Vitamin B12 and folic acid are given to reduce the potential toxic effects of cancer treatment.

If you have any further questions about the use of this product, 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 (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 begin to feel chest pain (frequent) or your heartbeat becomes faster (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 (frequent), or fever (frequent). 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 appear pale (due to lower than normal hemoglobin levels, which is very common).
• If you experience bleeding from gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising (due to lower than normal platelet count, which is very common).
• If you suddenly experience difficulty breathing, severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the lung veins).

Adverse 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 (tiredness)
• Skin rash
• Hair loss
• Constipation
• Loss of sensation
• Kidney: changes in blood tests

Common (may affect up to 1 in 10 people)

• Allergic reaction: rash/burning or itching sensation
• 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 sensation
• Liver: changes in blood tests
• Watery eyes
• Increased skin pigmentation

Uncommon (may affect up to 1 in 100 people)

• Acute kidney failure
• Increased heart rate
• Inflammation of the esophageal mucosa (throat) following combination of pemetrexed and radiotherapy
• Colitis (inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding)
• Interstitial pneumonitis (hardening of the walls of the lung alveoli)
• Edema (excess fluid in body tissues causing swelling)
• Some patients have experienced heart attack, embolism, or "mini-embolism" while receiving pemetrexed, usually in combination with other anticancer therapy
• Pancytopenia: combination of low white blood cell, red blood cell, and platelet counts
• Radiation pneumonitis (scarring of the lung air sacs associated with radiotherapy) may occur in patients receiving radiation either before, during, or after treatment with pemetrexed
• Pain in the limbs, low body temperature, and changes in skin coloration have been reported
• Blood clots in the lung veins (pulmonary embolism)

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

• Delayed skin toxicity (sunburn-like skin rash) that may appear on skin previously exposed to radiation, from days to years after such radiation
• Bullous disorders (skin diseases with blister formation), 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)

Frequency not known: frequency cannot be estimated from available data

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

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 Waverley

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

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

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, chemical and physical in-use stability of pemetrexed reconstituted and infusion solutions has been demonstrated for 24 hours under refrigerated conditions.

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

6. Contents of the container and other information

Composition of PemetrexedWaverley

The active substance 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. Prior to administration, a further dilution must be performed by the healthcare professional.

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

Appearance of the product and contents of the container

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

Each pack of Pemetrexed Waverley consists of one vial containing pemetrexed powder for concentrate for infusion solution.

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 Münster
Germany

Or

Wessling Hungary KFT
Anonymus u. 6
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, 7th Floor
28045 Madrid
Spain

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

Date of the most recent review of this summary: September 2021.

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

This information is intended solely for physicians or healthcare professionals:

Instructions for use, handling, and disposal

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

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

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

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

Gently shake the vial until the powder is completely dissolved. The resulting solution is clear, with a color range varying from colorless to yellow or yellow-green, without negatively affecting the product's quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

4. The appropriate volume of the reconstituted pemetrexed solution must be diluted to 100 ml with 0.9 % sodium chloride (9 mg/ml) injection solution without preservatives and should be administered as an intravenous infusion over 10 minutes.

5. The pemetrexed infusion solution prepared as described above 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.

6. Parenteral medicines should be inspected visually before administration to check for particulate matter or discoloration. If particulates are observed, the medicine must not be administered.

7. Pemetrexed solutions are for single use only. Unused medicine and materials 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 handling and preparing pemetrexed infusion solutions. The use of gloves is recommended. If pemetrexed solutions come into contact with the skin, wash immediately and thoroughly with water and soap. If pemetrexed solutions contact mucous membranes, rinse thoroughly with water. Pemetrexed is not a vesicant drug. There is no specific antidote for pemetrexed extravasation. Some 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.

Marketing Authorization Holder

Waverley Pharma Europe Limited

Alexandra House, Office # 234, The Sweepstakes,

Ballsbridge, Dublin 4, D04 C7H2, Ireland.