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Pemetrexed Fresenius Kabi - patient leaflet, side effects, dosage

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Patient leaflet - Pemetrexed Fresenius Kabi

1. What Pemetrexed Fresenius Kabi is and what it is used for

Pemetrexed Fresenius Kabi is a medicine used in the treatment of cancer.

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

Pemetrexed Fresenius Kabi 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 Fresenius Kabi 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 Fresenius Kabi

Do not use Pemetrexed Fresenius Kabi

  • – 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 Fresenius Kabi.

  • – 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 Fresenius Kabi.

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 Fresenius Kabi.

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 Fresenius Kabi. 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 Fresenius Kabi.

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

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 Fresenius Kabi.

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 Fresenius Kabi

Tell your doctor if you are taking, have recently taken or might take 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 Fresenius Kabi 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 Fresenius Kabi should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Pemetrexed Fresenius Kabi during pregnancy. Women must use effective contraception during treatment with Pemetrexed Fresenius Kabi.

Breast-feeding

If you are breast-feeding, tell your doctor.

Breast-feeding must be discontinued during treatment with Pemetrexed Fresenius Kabi.

Fertility

Men are advised not to father a child during and up to 6 months following treatment with Pemetrexed Fresenius Kabi and should therefore use effective contraception during treatment with Pemetrexed

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

3. How to use Pemetrexed Fresenius Kabi

The dose of Pemetrexed Fresenius Kabi 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 Fresenius Kabi powder with 5% glucose intravenous infusion before it is given to you.

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

When using Pemetrexed Fresenius Kabi 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 Fresenius Kabi has finished. The infusion of cisplatin will last approximately 2 hours.

You should usually receive your infusion once every 3 weeks.

Additional medicines:

Corticosteroids: 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 Fresenius Kabi 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 Fresenius Kabi. You must take at least 5 doses during the seven days before the first dose of Pemetrexed Fresenius Kabi. You must continue taking the folic acid for 21 days after the last dose of Pemetrexed Fresenius Kabi. You will also receive an injection of vitamin B12 (1000 micrograms) in the week before administration of Pemetrexed Fresenius Kabi and then approximately every 9 weeks (corresponding to 3 courses of Pemetrexed Fresenius Kabi 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)

Other 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

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 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

Increased 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 may 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 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 Fresenius Kabi

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 vial label and carton after ‘EXP’. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Reconstituted and infusion solutions: The product should be used immediately. When prepared as directed, chemical and physical in-use stability of reconstituted solution of pemetrexed was demonstrated for 24 hours at refrigerated temperature. For infusion solution of pemetrexed, chemical and physical in-use stability was demonstrated for 21 days at refrigerated temperature and 7 days at 25°C.

This medicine should not be used if there are any signs of particles.

This medicine is for single use only.

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

6. Contents of the pack and other information

What Pemetrexed Fresenius Kabi contains

The active substance is pemetrexed.

Pemetrexed Fresenius Kabi 100 mg : Each vial contains 100 milligrams of pemetrexed (as pemetrexed diacid)..

Pemetrexed Fresenius Kabi 500 mg : Each vial contains 500 milligrams of pemetrexed (as pemetrexed diacid).

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 trometamol.

What Pemetrexed Fresenius Kabi looks like and contents of the pack

Pemetrexed Fresenius Kabi is a powder for concentrate for solution for infusion in a glass vial. It is a white to off-white lyophilised powder or solid.

It is available in packs of 1 vial.

Marketing Authorisation Holder

Fresenius Kabi Deutschland GmbH

Else-Kröner-Straße 1,

61352 Bad Homburg v.d.Höhe

Germany

Manufacturer

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

Fresenius Kabi Polska Sp. z o.o.

ul. Sienkiewicza 25, Kutno, 99–300, Poland

Fresenius Kabi France- Louviers

  • 6 rue du Rempart

Louviers, 27400

France

For any information about this medicine, please contact the Marketing Authorisation Holder.

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the website of European Medicines

Agency

The following information is intended for medical or healthcare professionals only:

Instructions for use, handling and disposal.

  • – Use aseptic techniques during the reconstitution and further dilution of pemetrexed

for intravenous infusion administration.

  • – Calculate the dose and the number of Pemetrexed Fresenius Kabi vials needed. Each vial

contains an excess of pemetrexed to facilitate delivery of the label amount.

  • - Pemetrexed Fresenius Kabi 100 mg:

  • – Reconstitute each 100 mg vial with 4.2 ml of 5% glucose intravenous infusion resulting in a solution containing 25 mg/ml pemetrexed.

  • - Pemetrexed Fresenius Kabi 500 mg:

  • – Reconstitute each 500 mg vial with 20 ml of 5% glucose intravenous infusion 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 yellow or green-yellow without adversely affecting product quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

  • – The appropriate volume of reconstituted pemetrexed solution must be further diluted to

100 ml with 5% glucose intravenous infusion and administered as an intravenous infusion over 10 minutes.

  • – 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.

Pemetrexed Fresenius Kabi contains trometamol as an excipient. Trometamol is incompatible with cisplatin resulting in degradation of cisplatin. This medicinal product must not be mixed with other medicinal products. Intravenous lines should be flushed after administration of Pemetrexed Fresenius Kabi

  • – Parenteral medicinal products should be inspected visually for particulate matter and

discolouration prior to administration. If particulate matter is observed, do not administer.

  • – Pemetrexed solutions are for single use only. Any unused product or waste material should