Pemetrexed 25 mg/ml, concentrate for solution for infusion

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.

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 solution with 0.9% sodium chloride or 5% dextrose 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.

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, or very common, respectively): if you have a temperature of 38 ºC or greater, sweating or other signs of infection (since you might have less white blood cells than normal which is common or very common, respectively). Infection (sepsis) may be severe and could lead to death.
• If you start feeling chest pain (common) or having a fast heart rate (uncommon).
• If you have pain, redness, swelling or sores in your mouth (very common).
• Allergic reaction: If you develop a skin rash (very common) / burning or prickling sensations (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).
• If you experience tiredness, feeling faint, becoming easily breathless or if you look pale (since you might have less haemoglobin than normal which is very common).
• If you experience bleeding from the gums, nose or mouth or any bleeding that would not stop, reddish or pinkish urine, unexpected bruising (since you might have less platelets than normal which is common).
• If you experience sudden breathlessness, intense chest pain or a cough with bloody sputum (uncommon) (may indicate a blood clot in the blood vessels of the lungs).

Side effects with pemetrexed may include:

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
• Loss of appetite
• Vomiting
• Diarrhoea
• Nausea
• Flaking skin
• Abnormal blood tests showing reduced functionality of kidneys
• Fatigue (tiredness).

Common (may affect up to 1 in 10 people):

• Blood infections
• Low platelet count
• Loss of body fluids
• Taste changes
• 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 an unsteady gait
• Dizziness
• Inflammation or swelling of the conjunctiva (the membrane that lines the eyelids and covers the white of the eye)
• Dry eyes
• 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 disorders with dryness, tearing, irritation, and/or pain
• Cardiac failure (a 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
• Rashes on the body where each mark resembles a bullseye
• Hair loss
• Hives
• Kidneys stop working
• Reduced functionality of the kidneys
• Pain
• Excess fluid in body tissue, causing swelling
• 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
• 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 lungs 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.

Very rare (may affect up to 1 of 10 000 people):

• Infections of skin and soft tissues
• Toxic Epidermal Necrolysis (a type of severe skin reaction that may be life threatening)
• Autoimmune disorders that result 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 becoming 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

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.

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

Do not use this medicine after the expiry date which is stated on the label after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not freeze.

Diluted solutions: The product should be used immediately.

Chemical and physical in-use stability of infusion solution of pemetrexed diluted with 5% dextrose in a polyvinyl chloride or polyolefin infusion bag and diluted with 0.9% sodium chloride (Saline) solution for infusion in a polyvinyl chloride bag was demonstrated for 24 hours in the dark at refrigerated temperature (2-8 °C).

Chemical and physical in-use stability of infusion solution of pemetrexed diluted with 0.9% sodium chloride (Saline) solution for infusion in a polyolefin infusion bag was demonstrated for 3 days in the dark at refrigerated temperature (2-8 °C).

Chemo spike syringes – in-use shelf life and storage conditions: Chemical and physical in-use stability of Pemetrexed 25 mg/ mL concentrate for solution for infusion inserted with a chemo spike syringe in the vial was demonstrated for 7 days in the dark at refrigerated temperature (2-8 °C).

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