PEMETREXED PFIZER 25 mg/mL concentrate for infusion solution

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

Do not use Pemetrexed Pfizer:

• if you are allergic (hypersensitive) 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 Pemetrexed Pfizer.
• if you have recently received or are going to receive the yellow fever vaccine.

Warnings and precautions

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

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

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 Pfizer. 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 between radiation and Pemetrexed Pfizer may occur.

If you have recently been vaccinated, please consult your doctor, as this may cause a negative effect with Pemetrexed Pfizer.

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 drain the fluid before administering Pemetrexed Pfizer.

Children and adolescents

This medicine must not be used in children or adolescents, as there is no experience with this medicine in children and adolescents under 18 years.

Using Pemetrexed Pfizer with other medicines

Tell your doctor if you are taking medicines for pain or inflammation (swelling), such as non-steroidal anti-inflammatory medicines (NSAIDs), including those bought without a prescription (such as ibuprofen). There are many classes of NSAIDs with different durations of action. Based on the date of your pemetrexed infusion 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 taking or have recently taken any other medicines, including those bought without a prescription.

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, tell your doctor.Pemetrexed should be avoided during pregnancy. Your doctor will inform you of the possible risks of taking pemetrexed during pregnancy. Women must use effective contraceptive methods during treatment with pemetrexed and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, tell your doctor.

During treatment with pemetrexed, breastfeeding should be stopped.

Fertility

Male patients are advised not to father a child during and up to 3 months after treatment with pemetrexed, and to use effective contraceptive methods during and up to 3 months after treatment with pemetrexed. If you wish to have a child during treatment or in the 3 months following treatment, consult your doctor or pharmacist. Pemetrexed Pfizer may affect your ability to have children. Talk to your doctor about sperm conservation before starting your treatment.

Driving and using machines

Pemetrexed Pfizer may make you feel tired. Be careful when driving a vehicle or using machines.

Pemetrexed Pfizer contains sodium

A 4 ml vial contains less than 1 mmol of sodium (23 mg); this is essentially "sodium-free".

A 20 ml vial contains approximately 54 mg of sodium (a major component of table salt/cooking salt). This is equivalent to 2.7% of the maximum recommended daily sodium intake for an adult.

A 40 ml vial contains approximately 108 mg of sodium (a major component of table salt/cooking salt). This is equivalent to 5.4% of the maximum recommended daily sodium intake for an adult.

3. How to use Pemetrexed Pfizer

The dose of Pemetrexed Pfizer 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 your general condition. The hospital pharmacist, nurse, or doctor will have mixed the Pemetrexed Pfizer concentrate with a sodium chloride solution for injection (9 mg/ml, 0.9%) before it is given to you.

You will always receive Pemetrexed Pfizer through an infusion into one of your veins. The infusion will last at least 10 minutes.

When using Pemetrexed Pfizer 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 into one of your veins and is given about 30 minutes after the Pemetrexed Pfizer infusion has finished. The cisplatin infusion lasts about 2 hours.

You should normally receive your infusion once every 3 weeks.

Additional medication:

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

Vitamin supplement: your doctor will prescribe oral folic acid (vitamin) or a multivitamin that contains folic acid (350 to 1,000 micrograms) that you should take once a day while you are taking Pemetrexed Pfizer. You should take at least 5 doses during the 7 days before the first dose of Pemetrexed Pfizer. You should continue taking folic acid during the 21 days after the last dose of Pemetrexed Pfizer. You will also receive a vitamin B12 injection (1,000 micrograms) in the week before Pemetrexed Pfizer administration and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Pfizer). 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:

• Fever or infection (frequent or very frequent, respectively): 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 beats faster (uncommon).
• If you have pain, redness, swelling, or sores in your 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 (because you have less hemoglobin than normal, which is very frequent).
• If you experience bleeding from your gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising (because you have fewer platelets than normal, which is 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 may include:

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

Infection

Pharyngitis (sore throat)

Low neutrophil count (a type of white blood cell)

Low white blood cell count

Low hemoglobin levels

Pain, redness, swelling, or sores in the mouth

Lack of appetite

Vomiting

Diarrhea

Nausea

Rash

Scaly skin

Changes in blood tests that show reduced kidney function

Weakness (fatigue)

Common (may affect up to 1 in 10 people)

Blood infection

Fever with low neutrophil count (a type of white blood cell)

Low platelet count

Allergic reaction

Loss of body fluids

Changes in taste

Nerve damage that can cause muscle weakness and wasting (primarily in arms and legs)

Nerve damage that can cause loss of sensation, burning (pain), and unsteady walking

Dizziness

Inflammation or swelling of the conjunctiva (membrane that covers the eyelids and the white part of the eye)

Dry eyes

Watery eyes

Dryness of the conjunctiva (membrane inside the eyelids and covering the white part of the eye) and the cornea (transparent layer in front of the iris and pupil).

Swelling of the eyelids

Eyelid disorder with dryness, tearing, irritation, and/or pain

Heart failure (a condition that affects the heart's pumping ability)

Irregular heartbeat

Indigestion

Constipation

Abdominal pain

Liver: increase in chemicals in the blood produced by the liver

Increased skin pigmentation

Itching of the skin

Rash on the body where each lesion looks like a target

Hair loss

Hives

Kidney failure

Reduced kidney function

Fever

Pain

Excess fluid in the body tissue that causes swelling

Chest pain

Inflammation and ulceration of the mucous membranes that line the digestive tract

Uncommon (may affect up to 1 in 100 people)

Decrease in the number of red blood cells, white blood cells, and platelets

Ischemia or lack of blood flow

Ischemia due to blockage of a cerebral artery

Intracranial bleeding

Angina (chest pain caused by reduced blood flow to the heart)

Heart attack

Narrowing or blockage of the coronary arteries

Increased heart rate

Poor distribution of blood to the limbs

Blockage in one of the pulmonary arteries in the lungs

Inflammation and scarring of the lung mucosa with respiratory problems

Loss of bright red blood through the anus

Bleeding in the gastrointestinal tract

Perforation of the intestine

Inflammation of the esophagus mucosa

Inflammation of the mucosa of the large intestine, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin)

Inflammation, edema, redness, and erosion of the mucous membrane surface of the esophagus caused by radiotherapy

Inflammation of the lung 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

Redness of the skin

Rash on the skin that develops in a previously irradiated area

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

Infections of the skin and soft tissues

Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that can be life-threatening)

Toxic epidermal necrolysis (a type of severe skin reaction that can be life-threatening)

Autoimmune disorder that causes skin rashes and blisters on the legs, arms, and abdomen

Inflammation of the skin characterized by the presence of blisters that are filled with fluid

Frailty of the skin, blisters, and erosions and scarring of the skin

Redness, pain, and swelling mainly of the lower limbs

Inflammation of the skin and the fat under the skin (pseudocellulitis)

Inflammation of the skin (dermatitis)

The skin becomes inflamed, itchy, red, cracked, and rough

Itchy patches

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

A type of diabetes derived mainly from kidney disease

Kidney disorder that involves the death of the epithelial cells that form the renal tubules

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, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Pemetrexed Pfizer

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Solution for infusion: the chemical and physical stability of the infusion solution of pemetrexed has been demonstrated for 24 hours at a temperature of 2°C to 8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage time and conditions are the responsibility of the user and should not exceed 24 hours at 2°C to 8°C.

Parenteral medicines should be inspected visually for particles and discoloration before administration. If particles are observed, do not administer.

This medicine is for single use only. The unused solution should be discarded in accordance with local requirements.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container contents and additional information

Pfizer Pemetrexed composition

The active ingredient is pemetrexed. One ml of concentrate contains pemetrexed disodium equivalent to 25 mg of pemetrexed. Before administration, it is required that the healthcare professional perform another dilution.

A 4 ml vial of concentrate contains pemetrexed disodium equivalent to 100 mg of pemetrexed.

A 20 ml vial of concentrate contains pemetrexed disodium equivalent to 500 mg of pemetrexed.

A 40 ml vial of concentrate contains pemetrexed disodium equivalent to 1,000 mg of pemetrexed.

The other components are monothioglycerol, sodium hydroxide (for pH adjustment), and water for injectable preparations. See section 2 "Pfizer Pemetrexed contains sodium".

Product appearance and container contents

Pfizer Pemetrexed concentrate for solution for infusion (sterile concentrate) is a clear, colorless to pale yellow or yellowish-green solution practically free of visible particles in a glass vial.

Each container contains a vial of 100 mg/4 ml, 500 mg/20 ml, or 1,000 mg/40 ml of pemetrexed (as pemetrexed disodium).

Only some pack sizes may be marketed.

Marketing authorization holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

Belgium

Manufacturer

Pfizer Service Company BV

Hoge Wei 10

1930 Zaventem

Belgium

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

Date of last revision of this leaflet: MM/AAAA

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

This leaflet can be found in all languages of the European Union / European Economic Area on the European Medicines Agency website.

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This information is intended only for healthcare professionals:

Instructions for use, handling, and disposal

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

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

1. The appropriate volume of pemetrexed should be diluted to 100 ml with a 0.9% (9 mg/ml) sodium chloride injection solution 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 drugs should be inspected visually for particulate matter and discoloration prior to administration. If particles are observed, the drug should not be administered.

1. Pemetrexed solutions are for single use. The drug 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.