Pemetrexed Sandoz - patient leaflet, side effects, dosage

1. What Pemetrexed Sandoz is and what it is used for

Pemetrexed Sandoz is a medicine used in the treatment of cancer.

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

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

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

Do not use Pemetrexed Sandoz:

• – if you are allergic (hypersensitive) 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 Sandoz.

• – if you 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 Sandoz.

If you currently have or have previously had problems with your kidneys, talk to your doctor or hospital pharmacist as you may not be able to receive Pemetrexed Sandoz.

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 Sandoz. 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, please tell your doctor, as there may be an early or late radiation reaction with Pemetrexed Sandoz.

If you have been recently vaccinated, please tell your doctor, as this can possibly cause bad effects with Pemetrexed Sandoz.

If you have heart disease or a history of heart disease, please tell your doctor.

If you have an accumulation of fluid around your lungs, your doctor may decide to remove the fluid before giving you Pemetrexed Sandoz.

Children and adolescents

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.

Other medicines and Pemetrexed Sandoz

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 Sandoz 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.

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

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, tell your doctor. The use of Pemetrexed Sandoz should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Pemetrexed Sandoz during pregnancy.

Women must use effective contraception during treatment with Pemetrexed Sandoz.

Breast-feeding

If you are breast-feeding, tell your doctor.

Breast-feeding must be discontinued during Pemetrexed Sandoz treatment.

Fertility

Men are advised not to father a child during and up to 6 months following treatment with Pemetrexed Sandoz and should therefore use effective contraception during treatment with Pemetrexed Sandoz 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 Sandoz may make you feel tired. Be careful when driving a car or using machines.

Pemetrexed Sandoz contains sodium

Pemetrexed Sandoz 100 mg powder for concentrate for solution for infusion

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

Pemetrexed Sandoz 500 mg powder for concentrate for solution for infusion

This medicine contains 54 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 2.7% of the recommended maximum daily dietary intake of sodium for an adult.

Pemetrexed Sandoz 1000 mg powder for concentrate for solution for infusion

This medicine contains 108 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 5.4% of the recommended maximum daily dietary intake of sodium for an adult.

3. How to use Pemetrexed Sandoz

The dose of Pemetrexed Sandoz is 500 mg 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 Sandoz powder with 9 mg/ml (0.9 %) sodium chloride solution for injection before it is given to you.

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

When using Pemetrexed Sandoz 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 Sandoz 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 milligram of dexamethasone twice a day) that you will need to take on the day before, on the day of, and the day after Pemetrexed Sandoz 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 Sandoz. You must take at least 5 doses during the seven days before the first dose of Pemetrexed Sandoz. You must continue taking the folic acid for 21 days after the last dose of Pemetrexed Sandoz. You will also receive an injection of vitamin B12 (1000 micrograms) in the week before administration of Pemetrexed Sandoz and then approximately every 9 weeks (corresponding to 3 courses of Pemetrexed Sandoz 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.

4. Possible side effects

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 38°C 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.
• 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 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).
• 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 very common).
• If you experience sudden breathlessness, intense chest pain or cough with bloody sputum (uncommon)(may indicate a blood clot in the blood vessels of the lungs)

Side effects with Pemetrexed Sandoz 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
• Low haemoglobin level
• Diarrhoea
• Vomiting
• Pain, redness, swelling or sores in your mouth
• Nausea
• Loss of appetite
• Fatigue (tiredness)
• Skin rash
• Flaking skin
• Abnormal blood tests showing reduced functionality of kidneys

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 lost 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
• Bleeding inside the skull
• Angina (Chest pain caused by reduced blood flow to the heart)
• Heart attack
• Narrowing or blockage of the coronary arteries
• Abnormal heart rythm
• 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

Very rare (affect up to 1 of 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

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. Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Pemetrexed Sandoz

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 carton and label after EXP.

This medicine does not require any special storage conditions.

After reconstitution and infusion:

Chemical and physical in-use stability of reconstituted solutions of Pemetrexed Sandoz has been demonstrated for 4 days at 2°C to 8°C and for 4 days below 25°C.

Chemical and physical in-use stability of infusion solutions of Pemetrexed Sandoz has been demonstrated for 4 days at 2°C to 8°C and for 2 days below 25°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 normally not be longer than 24 hours at 2°C to 8°C, unless reconstitution / dilution has taken place in controlled and validated aseptic conditions.

Do not use this medicine if you notice particles or a discolouration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measurements will help protect the environment.

6. Contents of the pack and other information

What Pemetrexed Sandoz contains

The active substance is pemetrexed.

Pemetrexed Sandoz 100 mg: Each vial contains 100 milligrams of pemetrexed (as disodium).

Pemetrexed Sandoz 500 mg: Each vial contains 500 milligrams of pemetrexed (as disodium). Pemetrexed Sandoz 1000 mg: Each vial contains 1000 milligrams of pemetrexed (as disodium).

After reconstitution, the solution contains 25 mg/ml of pemetrexed.

The other ingredients are mannitol (E421), hydrochloric acid (for pH adjustment) and sodium hydroxide (for pH adjustment) (see section 2 “Pemetrexed Sandoz contains sodium”).

What Pemetrexed Sandoz looks like and contents of the pack

Pemetrexed Sandoz is a powder for concentrate for solution for infusion in a glass vial. It is a white to pale yellow lyophilised powder.

Each pack of Pemetrexed Sandoz consists of one vial with protective plastic overwrap, containing 100 mg, 500 mg or 1000 mg of pemetrexed.

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestrasse 10

A-6250 Kundl

Austria

Manufacturer

Ebewe Pharma Ges.m.b.H

Nfg.KG

Mondseestrasse 11,

Unterach

4866 Austria

Fareva Unterach GmbH

Mondseestraße 11

4866 Unterach

Austria

Lek Pharmaceuticals d.d.

Verovskova 57

1526 Ljubljana

Slovenia

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

1407 Co$ua

Ten.: + 359 2 970 47 47

Tél: + 33 1 4964 4800

Tel: + 385 1 2353111

e-mail:

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

The following information is intended for healthcare professionals only:

Special precautions for disposal and other handling

• 1. Use aseptic technique during the reconstitution and further dilution of pemetrexed for intravenous infusion administration.

• 2. Calculate the dose and the number of Pemetrexed Sandoz vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of label amount.

• 3. Pemetrexed Sandoz 100 mg:

Reconstitute 100-mg vials with 4.2 ml of sodium chloride 9 mg/ml (0.9%) solution for injection (without preservative), resulting in a solution containing 25 mg/ml pemetrexed.

Pemetrexed Sandoz 500 mg:

Reconstitute 500-mg vials with 20 ml of sodium chloride 9 mg/ml (0.9%) solution for injection (without preservative), resulting in a solution containing 25 mg/ml pemetrexed.

Pemetrexed Sandoz 1000 mg:

Reconstitute 1000-mg vials with 40 ml of sodium chloride 9 mg/ml (0.9%) solution for injection (without preservative), resulting in a solution containing 25 mg/ml pemetrexed.

Gently swirl each vial until the powder is completely dissolved. The resulting solution is clear and ranges in colour from colourless to pale yellow without adversely affecting product quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

• 4. The appropriate volume of reconstituted pemetrexed solution must be further diluted to 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection (without preservative) or with glucose 50 mg/ml (5%) solution for injection (without preservative) and administered as an intravenous infusion over 10 minutes.

• 5. Pemetrexed infusion solutions prepared as directed above are compatible with polyvinyl chloride and polyolefin lined administration sets and infusion bags. Pemetrexed is incompatible with diluents containing calcium, including lactated Ringer’s Injection and Ringer’s Injection.

• 6. Parenteral medicinal products must be inspected visually for particulate matter and discolouration prior to administration. If particulate matter is observed, do not administer.

• 7. Pemetrexed solutions are for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.