Pemetrexed is a medicine used in the treatment of cancer.

Pemetrexed is given in combination with cisplatin, another anti-cancer medicine, as treatment for malignant pleural mesothelioma, a form of cancer that affects the lining of the lung, to patients who have not received prior chemotherapy.

Pemetrexed is also given in combination with cisplatin for the initial treatment of patients with advanced stage of lung cancer.

Pemetrexed can be prescribed to you if you have lung cancer at an advanced stage if your disease has responded to treatment or it remains largely unchanged after initial chemotherapy.

Pemetrexed is also a treatment for patients with advanced stage of lung cancer whose disease has progressed after other initial chemotherapy has been used.

1.      Do not use Pemetrexed if you:

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

•          you must discontinue breast-feeding during treatment with Pemetrexed

•      have recently received or are about to receive a vaccine against yellow fever.

Warnings and Precautions Talk to your doctor or hospital pharmacist before receiving Pemetrexed if you:

•          currently have or have previously had problems with your kidneys, as you may not be able to receive Pemetrexed

•          have had or are going to have radiation therapy, as there may be an early or late radiation reaction with Pemetrexed

•          have been recently vaccinated, as this can possibly cause bad effects with Pemetrexed

•          have heart disease or a history of heart disease

•          have an accumulation of fluid around your lungs; your doctor may decide to remove the fluid before giving you Pemetrexed.

Blood tests

Before each infusion you will have samples of your blood taken to check you have sufficient kidney and liver function and to check that you have enough blood cells to receive Pemetrexed. Your doctor may decide to change the dose or delay treating you depending on your general condition and if your blood cell counts are too low. If you are also receiving cisplatin, your doctor will make sure that you are properly hydrated and receive appropriate treatment before and after receiving cisplatin to prevent vomiting.

Children and adolescents

Pemetrexed is not used in children.

Other medicines and Pemetrexed

Please tell your doctor if you are taking any medicine for pain or inflammation (swelling), such as medicines called “nonsteroidal anti-inflammatory drugs” (NSAIDs), including medicines purchased without a doctor’s prescription (such as ibuprofen). There are many sorts of NSAIDs. If you are unsure if any of your medicines are NSAIDs, ask your doctor or pharmacist.

Based on the planned date of your infusion of Pemetrexed and/or on the status of your kidney function, your doctor needs to advise you on which medicines you can take and when you can take them.

Tell your doctor or hospital pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Pregnancy, breast-feeding and fertility

Pregnancy

If you are pregnant, or thinking about becoming pregnant, tell your doctor. The use of Pemetrexed should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Pemetrexed during pregnancy. Women must use effective contraception during treatment with Pemetrexed.

Breast-feeding

If you are breast-feeding, tell your doctor. Breast-feeding must be discontinued during Pemetrexed treatment.

Fertility

Men are advised not to father a child during and up to 6 months following treatment with Pemetrexed and should therefore use effective contraception during treatment with Pemetrexed and for up to 6 months afterwards. If you would like to father a child during the treatment or in the 6 months after treatment, seek advice from your doctor or pharmacist. You may want to seek counselling on sperm storage before starting your therapy.

Driving and using machines

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

Pemetrexed powder contains sodium 

Pemetrexed 500 mg contains approximately 52 mg sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

The dose of Pemetrexed is 500 milligrams for every square metre of your body’s surface area. Your height and weight are measured to work out the surface area of your body. Your doctor will use this body surface area to work out the right dose for you.

This dose may be adjusted, or treatment may be delayed depending on your blood cell counts and on your general condition.

A hospital pharmacist, nurse or doctor will have mixed the Pemetrexed powder with 9 mg/ml (0.9%) sodium chloride solution for injection before it is given to you.

You will always receive Pemetrexed by infusion into one of your veins. The infusion will last approximately 10 minutes.

When using Pemetrexed in combination with cisplatin:

The doctor or hospital pharmacist will work out the dose you need based on your height and weight. Cisplatin is also given by infusion into one of your veins, and is given approximately 30 minutes after the infusion of Pemetrexed has finished. The infusion of cisplatin will last approximately 2 hours. You should usually receive your infusion once every 3 weeks.

Additional medicines:

Corticosteriods: Your doctor will prescribe you steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) to take on the day before, on the day of, and the day after Pemetrexed treatment. This will reduce the frequency and severity of skin reactions that you may experience during your anticancer treatment.

Vitamin supplements: Your doctor will prescribe you oral folic acid (vitamin) or a multivitamin containing folic acid (350 to 1000 micrograms) to take once a day while you are taking Pemetrexed. You must also take at least five doses of folic acid during the seven days before the first dose of Pemetrexed and must continue taking folic acid for 21 days after the last dose of Pemetrexed.

You will also have an injection of vitamin B12 (1000 micrograms) in the week before receiving Pemetrexed and then approximately every 9 weeks (corresponding to 3 courses of Pemetrexed treatment). Vitamin B12 and folic acid are given to you to reduce the possible toxic effects of the anticancer treatment.

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

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

•          fever or infection (common): if you have a temperature of 38ºC or greater, sweating or other signs of infection (as this may mean you have less white blood cells than normal which is very common). Infection (sepsis) may be severe and could lead to death

•          chest pain (common) or having a fast heart rate (uncommon)

•          pain, redness, swelling or sores in your mouth (very common)

•          allergic reactions such as skin rash (very common)/ burning or prickling sensation (common), or fever (common). Rarely, skin reactions may be severe and could lead to death. Contact your doctor if you get a severe rash, or itching, or blistering (Stevens-Johnson Syndrome or Toxic epidermal necrolysis)

•          tiredness, feeling faint, becoming easily breathless or if you look pale (as you may have less hemoglobin than normal which is very common)

•          bleeding from the gums, nose or mouth or any bleeding that will not stop, reddish or pinkish urine, unexpected bruising (as you might have less platelets than normal which is very common)

•          sudden breathlessness, intense chest pain or cough with bloody sputum (uncommon). This may indicate a blood clot in the blood vessels of the lungs.

Tell your doctor as soon as possible when you start experiencing any of the following side effects.

Side effects with Pemetrexed may include:

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

•          low white blood cells, low haemoglobin level (anaemia)

•          low platelet count

•          diarrhoea, vomiting, nausea, constipation

•          loss of appetite

•          pain, redness, swelling or sores in your mouth

•          fatigue (tiredness)

•          skin rash, hair loss

•          loss of sensation

•          abnormal kidney function tests

Common (may affect 1 to 10 patients in 100)

•          allergic reaction: skin rash / burning or prickling sensation

•          infection including blood poisoning (sepsis)

•          fever

•          dehydration

•          irritation of the skin and itching

•          chest pain, muscle weakness

•          conjunctivitis (inflamed eye), watery eyes

•          upset stomach, pain in the abdomen

•          taste changes

•          kidney failure

•          abnormal liver function tests

Uncommon (may affect 1 to 10 patients in 1,000)

•          sudden kidney failure

•          fast heart rate

•          inflammation of the lining of the oesophagus (gullet) has been experienced with Pemetrexed/ radiation therapy

•          colitis (inflammation of the lining of the large bowel, which may be accompanied by intestinal or rectal bleeding)

•          scarring of the air sacs of the lung (interstitial pneumonitis)

•          oedema (excess fluid in body tissue, causing swelling)

•          some patients have experienced a heart attack, stroke or “mini-stroke” while receiving Pemetrexed usually in combination with another anticancer therapy

•          low blood counts of white cells, red cells and platelets (pancytopenia)

•          scarring of the air sacs of the lung associated with radiation therapy may occur in patients who are also treated with radiation either before, during or after their Pemetrexed therapy

•          pains in the hands and feet, low temperature and skin discolouration

•          blood clots in the lung blood vessels (pulmonary embolism)

Rare (may affect 1 to 10 patients in 10,000)

•          radiation recall (a skin rash like severe sunburn) can occur on skin that has previously been exposed to radiotherapy, from days to years after the radiation

•          blistering skin diseases including Stevens- Johnson syndrome and Toxic epidermal necrolysis

•          haemolytic anaemia (anaemia due to destruction of red blood cells)

•          hepatitis (inflammation of the liver)

•          anaphylactic shock (severe allergic reaction causing difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and/or throat, which may cause difficulty in swallowing, collapse)

Not known frequency cannot be estimated from the available data 

•          Lower limb swelling with pain and redness 

•          Increased urine output 

•          Thirst and increased water consumption 

•          Hypernatraemia – increased sodium in blood 

•          Inflammation of the skin, mainly of the lower limb with swelling, pain and redness

You might have any of these symptoms and/or conditions. You must tell your doctor as soon as possible  when you start experiencing any of these side effects.

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

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report any side effects directly via the Yellow Card Scheme, website www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

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

Do not use after the expiry date shown on the pack. 

This medicine does not require any special storage conditions.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and 2°C to 8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not be longer than 24 hours at 2°C to 8°C.

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