Pemetrexed Krka - patient leaflet, side effects, dosage

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

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

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

Pemetrexed Krka 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 Krka 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 Krka

Do not use Pemetrexed Krka

• – 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 Krka.

• – 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 using Pemetrexed Krka.

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 Krka.

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

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 Krka.

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 Krka

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 Krka 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 Krka should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Pemetrexed Krka during pregnancy. Women must use effective contraception during treatment with Pemetrexed Krka.

Breast-feeding

If you are breast-feeding, tell your doctor.

Breast-feeding must be discontinued during treatment with Pemetrexed Krka.

Fertility

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

Pemetrexed Krka contains sodium

Pemetrexed Krka 100 mg contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially “sodium-free”.

Pemetrexed Krka 500 mg contains 54 mg sodium (main component of cooking/table salt) per vial. This is equivalent to 2.7% of the recommended maximum daily dietary intake of sodium for an adult.

3. How to use Pemetrexed Krka

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

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

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

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

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

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

5. How to store Pemetrexed Krka

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

This medicine does not require any special storage conditions.

Chemical and physical in-use stability of reconstituted and infusion solutions of pemetrexed were demonstrated for 24 hours at 2°C to 8°C (and 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 not be longer than 24 hours at 2°C to 8°C.

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 Krka contains

• – The active substance is pemetrexed.

Pemetrexed Krka 100 mg: Each vial contains 100 mg pemetrexed (as pemetrexed disodium hemipentahydrate).

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

Pemetrexed Krka 500 mg: Each vial contains 500 mg pemetrexed (as pemetrexed disodium hemipentahydrate).

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

• – The other ingredients are mannitol, hydrochloric acid (for pH adjustment), sodium hydroxide

(for pH adjustment) (E524). See section 2 „Pemetrexed Krka contains sodium“.

What Pemetrexed Krka looks like and contents of the pack

Pemetrexed Krka is a powder for concentrate for solution for infusion (powder for concentrate). It is a white to either light yellow or green yellow lyophilized cake or powder.

Pemetrexed Krka is available in transparent glass vials containing either 100 mg or 500 mg pemetrexed. Each box contains one vial.

Marketing Authorisation Holder and Manufacturer

KRKA, d.d., Novo mesto, Smarjeska cesta 6, 8501 Novo mesto, Slovenia

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

België/Belgiqu­e/Belgien

KRKA Belgium, SA.

Tél/Tel: + 32 (0) 487 50 73 62

Luxembourg/Lu­xemburg

KRKA Belgium, SA.

Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika KRKA ČR, s.r.o. Tel: + 420 (0) 221 115 150	Magyarország KRKA Magyarország Kereskedelmi Kft. Tel.: + 36 (1) 355 8490
Danmark KRKA Sverige AB Tlf: + 46 (0)8 643 67 66 (SE)	Malta E. J. Busuttil Ltd. Tel: + 356 21 445 885
Deutschland TAD Pharma GmbH Tel: + 49 (0) 4721 606–0	Nederland KRKA Belgium, SA. Tel: + 32 (0) 487 50 73 62 (BE)
Eesti KRKA, d.d., Novo mesto Eesti filiaal Tel: + 372 (0) 6 671 658	Norge KRKA Sverige AB Tlf: + 46 (0)8 643 67 66 (SE)
EZZáóa KRKA EAAAS EnE Tni: + 30 2100101613	Österreich KRKA Pharma GmbH, Wien Tel: + 43 (0)1 66 24 300
España KRKA Farmacéutica, S.L. Tel: + 34 911 61 03 81	Polska KRKA-POLSKA Sp. z o.o. Tel.: + 48 (0)22 573 7500
France KRKA France Eurl Tél: + 33 (0)1 57 40 82 25	Portugal KRKA Farmacéutica, Sociedade Unipessoal Lda. Tel: + 351 (0)21 46 43 650
Hrvatska KRKA – FARMA d.o.o. Tel: + 385 1 6312 100	Romania KRKA Romania S.R.L., Bucharest Tel: + 4 021 310 66 05
Ireland KRKA Pharma Dublin, Ltd. Tel: + 353 1 293 91 80	Slovenija KRKA, d.d., Novo mesto Tel: + 386 (0) 1 47 51 100
Ísland LYFIS ehf. Sími: + 354 534 3500	Slovenská republika KRKA Slovensko, s.r.o. Tel: + 421 (0) 2 571 04 501
Italia KRKA Farmaceutici Milano S.r.l. Tel: + 39 02 3300 8841	Suomi/Finland KRKA Finland Oy Puh/Tel: + 358 20 754 5330
Kúnpoc KI.PA. (PHARMACAL) LIMITED Tni: + 357 24 651 882	Sverige KRKA Sverige AB Tel: + 46 (0)8 643 67 66 (SE)
Latvija KRKA Latvija SIA Tel: + 371 6 733 86 10	United Kingdom Krka UK Ltd. Tel: +44 (0)207 400 3352

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:

Instructions for use, handling and disposal.

• 1. Use aseptic techniques during the reconstitution and further dilution of pemetrexed for

intravenous infusion administration.

• 2. Calculate the dose and the number of Pemetrexed Krka vials needed. Each 100 mg vial contains an excess of pemetrexed to facilitate delivery of the label amount.

• 3. Pemetrexed Krka 100 mg:

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

Pemetrexed Krka 500 mg:

Reconstitute each 500 mg vial with 20 ml of 9 mg/ml (0.9%) sodium chloride 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 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.

• 4. The appropriate volume of reconstituted pemetrexed solution must be further diluted to 100 ml with 9 mg/ml (0.9%) sodium chloride 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 should 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 product or waste material should be disposed of in accordance with local requirements.