Pemetrexed SUN 1000 mg powder for concentrate for solution for infusion

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

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

What is in this leaflet

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

You should NOT be given Pemetrexed

• 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.

Warnings and precautions

Talk to your doctor before you are given 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 see 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 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.

Children and adolescents

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

Other medicines and Pemetrexed

Tell your doctor if you are taking, have recently taken or might take 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 SUN 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, breast-feeding and fertility

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine. The use of Pemetrexed should be avoided during pregnancy. Your doctor will discuss with you the potential risk of receiving 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 treatment with Pemetrexed.

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 following receipt of 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 contains sodium

Pemetrexed 100 mg contains 11 mg sodium (≤ 1 mmol) per vial, i.e. it is essentially “sodium-free”.

Pemetrexed 500 mg contains approximately 54 mg (2.35 mmol) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

Pemetrexed 1000 mg contains approximately 108 mg (4.70 mmol) sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

Serious side effects

Tell your doctor straight away about any of the following serious side effects:

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

• pain, redness, swelling or sores in mouth
• allergic reaction: skin rash. Rarely, skin reactions may be severe and could lead to death
• low level of haemoglobin (anaemia). You could experience tiredness, feeling faint, becoming easily breathless or you could look pale
• low counts of platelets. You could experience bleeding from the gums, nose or mouth or any bleeding that would not stop, reddish or pinkish urine, unexpected bruising

Common (may affect up to 1 in 10 people)

• fever or infection: if you have a temperature of 38ºC or greater, sweating or other signs of infection (since you might have less white blood cells than normal which is very common). Infection (sepsis) may be severe and could lead to death
• chest pain
• allergic reaction: burning or prickling sensation and fever

Uncommon (may affect up to 1 in 100 people)

• fast heart rate
• blood clots in the blood vessels of the lungs (pulmonary embolism). You could experience sudden breathlessness, intense chest pain or cough with bloody sputum

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

• allergic reaction: severe rash, or itching, or blistering (Stevens-Johnson Syndrome or Toxic epidermal necrolysis).

Other side effects

Tell your doctor as soon as possible about any of the following side effects:

Very common (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 (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) primary 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 stop 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 (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
• angina (chest pain caused by reduced blood flow to the heart)
• heart attack
• narrowing or blockage of the coronary arteries
• abnormal 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, edema, erythema, and erosion of the mucosal surface of the esophagus caused by radiation therapy
• inflammation of the lung caused by radiation therapy

Rare (may affect up to 1 in 1,000 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
• radiation recall (a skin rash like severe sunburn) which can occur on skin that has previously been exposed to radiotherapy, from days to years after the radiation
• immune mediated haemolytic anaemia (antibody-mediated destruction of red blood cells)

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

• infections 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 characterized 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, red, cracked, and rough
• intensely itchy spots

Not known (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.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: 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.

What Pemetrexed contains

• The active substance is pemetrexed. Each vial contains 100, 500 or 1000 milligrams of pemetrexed (as pemetrexed disodium heptahydrate). After reconstitution, the solution contains 25 mg/ml of pemetrexed. Further dilution by a healthcare provider is required prior to administration.
• The other ingredients are mannitol, hydrochloric acid and/or sodium hydroxide (for pH adjustment) (see section 2 for further information).

What Pemetrexed looks like and contents of the pack

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

Pemetrexed is supplied in packs containing one vial.

Marketing Authorisation Holder and Manufacturer