Pemetrexed 25mg/ml concentrate for solution for infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
  See section 4.

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

• if you are allergic to pemetrexed or any of the other ingredients of this medicine (listed in section 6).
• if you are breast-feeding; you must discontinue breast-feeding during treatment with Pemetrexed.
• if you have recently received or are about to receive a vaccine against yellow fever.

Talk to your doctor or hospital pharmacist before using Pemetrexed.

• if you currently have or have previously had problems with your kidneys, as you may not be able to receive Pemetrexed.
  Before each infusion you will have samples of your blood taken to evaluate if 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.
• if you have had or are going to have radiation therapy, as there may be an early or late radiation reaction with Pemetrexed.
• if you have been recently vaccinated, as this can possibly cause bad effects with Pemetrexed.
• if you have heart disease or a history of heart disease.
• if you have an accumulation of fluid around your lungs, your doctor may decide to remove the fluid before giving you Pemetrexed.

This medicine should not be used in children or adolescents, since there is no experience with this medicine in children and adolescents under 18 years of age.

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

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 with different durations of activity.

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. If you are unsure, ask your doctor or pharmacist if any of your medicines are NSAIDs.

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, 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 and for 6 months after receiving the last dose.

Breast-feeding

If you are breast-feeding, tell your doctor.

Breast-feeding must be discontinued during treatment with Pemetrexed.

Fertility

Men are advised not to father a child during and up to 3 months following treatment with Pemetrexed and should therefore use effective contraception during treatment with Pemetrexed and for up to 3 months afterwards. If you would like to father a child during the treatment or in the 3 months following receipt of treatment, seek advice from your doctor or pharmacist. Pemetrexed can affect your ability to have children. Talk to your doctor to seek advice about sperm storage before starting your therapy.

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

This medicine contains 140mg propylene glycol in each 4ml vial which is equivalent to 35mg/ml.

This medicine contains 700mg propylene glycol in each 20ml vial which is equivalent to 35mg/ml.

This medicine contains 1400mg propylene glycol in each 40ml vial which is equivalent to 35mg/ml.

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.

Corticosteroids

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

Vitamin supplementation

Your doctor will prescribe you oral folic acid (vitamin) or a multivitamin containing folic acid (350 to 1000 micrograms) that you must take once a day while you are taking Pemetrexed. You must take at least 5 doses during the seven days before the first dose of Pemetrexed. You must continue taking the folic acid for 21 days after the last dose of Pemetrexed. You will also receive an injection of vitamin B12 (1000 micrograms) in the week before administration of 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.

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

• infection
• pharyngitis (a sore throat)
• low number of neutrophil granulocytes (a type of white blood cell)
• low white blood cells
• low haemoglobin level
• pain, redness, swelling or sores in your mouth
• loss of appetite
• vomiting
• diarrhoea
• nausea
• skin rash
• flaking skin
• abnormal blood tests showing reduced functionality of kidneys
• fatigue (tiredness)

Common side effects (may affect up to 1 in 10 people)

• blood infection
• fever with low number of neutrophil granulocytes (a type of white blood cell)
• low platelet count
• allergic reaction
• loss of body fluids
• taste change
• damage to the motor nerves which may cause muscle weakness and atrophy (wasting) primarily in the arms and legs
• damage to the sensory nerves that may cause loss of sensation, burning pain and unsteady gait
• dizziness
• inflammation or swelling of the conjunctiva (the membrane that lines the eyelids and covers the white of the eye)
• dry eye
• watery eyes
• dryness of the conjunctiva (the membrane that lines the eyelids and covers the white of the eye) and cornea (the clear layer in front of the iris and pupil)
• swelling of the eyelids
• eye disorder with dryness, tearing, irritation, and/or pain
• cardiac failure (condition that affects the pumping power of your heart muscles)
• irregular heart rhythm
• indigestion
• constipation
• abdominal pain
• liver: increases in the chemicals in the blood made by the liver
• increased skin pigmentation
• itchy skin
• rash on the body where each mark resembles a bullseye
• hair loss
• hives
• kidney stops working
• reduced functionality of kidney
• fever
• pain
• excess fluid in body tissue, causing swelling
• chest pain
• inflammation and ulceration of the mucous membranes lining the digestive tract

Uncommon side effects (may affect up to 1 in 100 people)

• reduction in the number of red, white blood cells and platelets
• stroke
• type of stroke when an artery to the brain is blocked
• bleeding inside the skull
• angina (chest pain caused by reduced blood flow to the heart)
• heart attack
• narrowing or blockage of the coronary arteries
• increased heart rhythm
• deficient blood distribution to the limbs
• blockage in one of the pulmonary arteries in your lungs
• inflammation and scarring of the lining of the lungs with breathing problems
• passage of bright red blood from the anus
• bleeding in the gastrointestinal tract
• ruptured bowel
• inflammation of the lining of the oesophagus
• inflammation of the lining of the large bowel, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin)
• inflammation, oedema, erythema, and erosion of the mucosal surface of the oesophagus caused by radiation therapy
• inflammation of the lung caused by radiation therapy

Rare side effects (may affect up to 1 in 1000 people)

• destruction of red blood cells
• anaphylactic shock (severe allergic reaction)
• inflammatory condition of the liver
• redness of the skin
• skin rash that develops throughout a previously irradiated area

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

• infection of skin and soft tissues
• Stevens-Johnson syndrome (a type of severe skin and mucous membranes reaction that may be life threatening)
• toxic epidermal necrolysis (a type of severe skin reaction that may be life threatening)
• autoimmune disorder that results in skin rashes and blistering on the legs, arms, and abdomen
• inflammation of the skin characterised by the presence of bullae which are filled with fluid
• skin fragility, blisters and erosions and skin scarring
• redness, pain and swelling mainly of the lower limbs
• inflammation of the skin and fat beneath the skin (pseudocellulitis)
• inflammation of the skin (dermatitis)
• skin to become inflamed, itchy, cracked and rough
• intensely itchy spots

Not known side effects (frequency cannot be estimated from the available data)

• form of diabetes primarily due to pathology of the kidney
• disorder of the kidneys involving the death of tubular epithelial cells that form the renal tubules

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.

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 side effects directly via: Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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

The active substance is pemetrexed.

One vial of 4ml concentrate contains 100mg pemetrexed (as pemetrexed diarginine).

One vial of 20ml concentrate contains 500mg pemetrexed (as pemetrexed diarginine).

One vial of 40ml concentrate contains 1000mg pemetrexed (as pemetrexed diarginine).

The solution contains 25mg/ml of pemetrexed. Further dilution by a healthcare provider is required prior to administration.

The other ingredients are L-Arginine, L-Cysteine, propylene glycol, citric acid and water for injections.

Pemetrexed is a clear, colourless to slightly yellow to brown, brown yellow or green yellow solution. It is provided in glass vials.

Each pack contains:

1 x 4ml vial (100mg/4ml) or

1 x 20ml vial (500mg/20ml) or

1 x 40ml vial (1000mg/40ml)

The vials are closed with a rubber stopper (bromobutyl), a cap and a flip-top.

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