PEMETREXED Fresenius Kabi 25 mg/ml concentrate for infusion solution

Introduction

Package Leaflet: Information for the User

Pemetrexed Fresenius Kabi 25 mg/ml Concentrate for Solution for Infusion EFGpemetrexed

Read all of this leaflet carefully before you start receiving 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, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

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

Pemetrexed Fresenius Kabi is a medicine used to treat cancer.

Pemetrexed Fresenius Kabi can be given with cisplatin, another anticancer medicine, as a treatment for malignant pleural mesothelioma, a type of cancer that affects the lining of the lungs, in patients who have not received chemotherapy before.

Pemetrexed Fresenius Kabi can also be given, with cisplatin, as an initial treatment for patients with advanced stages of lung cancer.

Pemetrexed Fresenius Kabi may be prescribed for you if you have advanced lung cancer, if your disease has responded to treatment or if it remains unchanged after initial chemotherapy.

Pemetrexed Fresenius Kabi can also be given for the treatment of patients with advanced stages of lung cancer whose disease has progressed, who have already received other initial chemotherapy treatment.

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 to any of the other ingredients of this medicine (listed in section 6).
• if you are breastfeeding, you must stop breastfeeding during treatment with Pemetrexed Fresenius Kabi.
• if you have recently received or are going to receive the yellow fever vaccine.

Warnings and precautions

Talk to your doctor or hospital pharmacist before you are given Pemetrexed Fresenius Kabi.

If you have had or have kidney problems, tell your doctor or hospital pharmacist, as you may not be able to receive Pemetrexed Fresenius Kabi.

Before each infusion, you will have to give blood samples to check if your kidney and liver function is sufficient and to check if you have enough blood cells to receive Pemetrexed Fresenius Kabi. Your doctor may decide to change your dose or delay treatment depending on your general condition and if your blood cell count is too low. If you are also receiving cisplatin, your doctor will make sure you are properly hydrated and will receive appropriate treatment before and after receiving cisplatin to prevent vomiting.

If you have received or are going to receive radiotherapy, please consult your doctor, as an early or late reaction may occur between radiation and Pemetrexed Fresenius Kabi.

If you have been vaccinated recently, please consult your doctor, as this may cause a negative effect with Pemetrexed Fresenius Kabi.

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

If you have fluid accumulated around the lung, your doctor may decide to remove the fluid before administering Pemetrexed Fresenius Kabi.

Children and adolescents

This medicine must not be used in children or adolescents, as there is no experience with this medicine in children and adolescents under 18 years.

Using Pemetrexed Fresenius Kabi with other medicines

Tell your doctor if you are using pain or inflammation medicines (swelling), such as medicines called “non-steroidal anti-inflammatory medicines” (NSAIDs), including those bought without a prescription (such as ibuprofen). There are many classes of NSAIDs with different durations of action. Based on the date of your Pemetrexed Fresenius Kabi infusion and/or the status of your kidney function, your doctor will advise you which medicines you can use and when you can take them. If you are not sure, consult your doctor or pharmacist to see if any medicine you are taking is an NSAID.

Tell your doctor if you are taking medicines called proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) used to treat stomach acid and acid reflux.

Tell your doctor or hospital pharmacist if you are using or have recently used other medicines, including those bought without a prescription.

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, tell your doctor. During pregnancy, the use of Pemetrexed Fresenius Kabi should be avoided. Your doctor will inform you of the possible risks of taking Pemetrexed Fresenius Kabi during pregnancy. Women must use effective contraceptive methods during treatment with Pemetrexed Fresenius Kabi and for 6 months after receiving the last dose.

Breastfeeding

If you are breastfeeding, tell your doctor.

During treatment with Pemetrexed Fresenius Kabi, breastfeeding must be stopped.

Fertility

Male patients are advised not to father a child during and up to 3 months after treatment with Pemetrexed Fresenius Kabi and, therefore, must use effective contraceptive methods during and up to 3 months after treatment with Pemetrexed Fresenius Kabi. If you wish to have a child during treatment or in the 3 months following treatment, ask your doctor or pharmacist for advice. Pemetrexed Fresenius Kabi may affect your ability to have children. Talk to your doctor about sperm preservation before starting your treatment.

Driving and using machines

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

Pemetrexed Fresenius Kabi contains 964 mg of hydroxypropylbetadex per 100 mg of pemetrexed.

If you have kidney disease, consult your doctor before you are given this medicine.

3. How to use Pemetrexed Fresenius Kabi

Follow exactly the instructions for administration of this medicine given by your doctor or pharmacist. If you are not sure, consult your doctor or pharmacist again.

The dose of Pemetrexed Fresenius Kabi is 500 milligrams per square meter of your body surface area. Your height and weight will be measured to calculate your body surface area. Your doctor will use this surface area to calculate the correct dose for you. This dose may be adjusted or treatment may be delayed depending on your blood cell count and your general condition. The hospital pharmacist, nurse, or doctor will have mixed Pemetrexed Fresenius Kabi with a sodium chloride 9 mg/ml (0.9%) solution for injection or a 5% glucose solution for intravenous infusion before it is given to you.

You will always receive Pemetrexed Fresenius Kabi through an infusion (drip) in one of your veins. The infusion will last at least 10 minutes.

When using Pemetrexed Fresenius Kabi in combination with cisplatin:

Your doctor or hospital pharmacist will calculate the dose you need based on your height and weight. Cisplatin is also given through an infusion in one of your veins and is given approximately 30 minutes after the Pemetrexed Fresenius Kabi infusion has finished. The cisplatin infusion lasts approximately 2 hours.

You should normally receive your infusion once every 3 weeks.

Additional medication:

Corticosteroids: your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice a day) that you must take the day before, the day of, and the day after treatment with Pemetrexed Fresenius Kabi. Your doctor gives you this medicine to reduce the frequency and severity of skin reactions you may experience during your cancer treatment.

Vitamin supplement: your doctor will prescribe oral folic acid (vitamin) or a multivitamin complex containing folic acid (350 to 1,000 micrograms) that you must take once a day while you are taking Pemetrexed Fresenius Kabi. You must take at least 5 doses during the 7 days before the first dose of Pemetrexed Fresenius Kabi. You must continue taking folic acid during 21 days after the last dose of Pemetrexed Fresenius Kabi. Additionally, you will receive a vitamin B12 injection (1,000 micrograms) in the week before administration of Pemetrexed Fresenius Kabi and then approximately every 9 weeks (corresponding to 3 cycles of treatment with Pemetrexed Fresenius Kabi). Vitamin B12 and folic acid are given to reduce the possible toxic effects of cancer treatment.

If you have any further questions on the use of this product, 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 tell your doctor immediately if you notice any of the following symptoms:

• Fever or infection (frequent or very frequent, respectively): if you have a temperature of 38°C or higher, sweating, or other signs of infection (as you may have fewer white blood cells than normal, which is very frequent). Infections (sepsis) can be serious and life-threatening.
• If you start to feel chest pain (frequent) or your heart rate is faster (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very frequent).
• Allergic reaction: if you develop a rash (very frequent), burning sensation, or itching (frequent), or fever (frequent). In rare cases, skin reactions can be serious and life-threatening. Contact your doctor if you have a severe rash, itching, or blisters (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, if you are short of breath or are pale (due to having fewer red blood cells than normal, which is very frequent).
• If you experience bleeding from the gums, nose, or mouth, or any bleeding that does not stop, red or pink urine, or unexpected bruising (due to having fewer platelets than normal, which is very frequent).
• If you experience sudden difficulty breathing, severe chest pain, or coughing up blood (uncommon) (may indicate that there is a blood clot in the lungs).

Other side effects with pemetrexed may include:

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

Infection

Pharyngitis (sore throat)

Low neutrophil count (a type of white blood cell)

Low white blood cell count

Low hemoglobin levels

Pain, redness, swelling, or sores in the mouth

Lack of appetite

Vomiting

Diarrhea

Nausea

Rash

Scaly skin

Changes in blood tests that show reduced kidney function

Asthenia (fatigue)

Common (may affect up to 1 in 10 people)

Blood infection

Fever with low neutrophil count

Low platelet count

Allergic reaction

Loss of body fluids

Changes in taste

Nerve damage that can cause muscle weakness and wasting (mainly in arms and legs)

Nerve damage that can cause loss of sensation, burning (pain), and unsteady gait

Dizziness

Inflammation or swelling of the conjunctiva (membrane that covers the eyelids and the white part of the eye)

Dry eyes

Watery eyes

Dryness of the conjunctiva (membrane inside the eyelids) and the cornea (transparent layer in front of the iris and pupil)

Swelling of the eyelids

Eye disorder with dryness, tearing, irritation, and/or pain

Heart failure (a condition that affects the heart's pumping ability)

Irregular heartbeat

Indigestion

Constipation

Abdominal pain

Liver: increased levels of chemicals in the blood produced by the liver

Increased skin pigmentation

Itching of the skin

Rash on the body where each lesion looks like a target

Hair loss

Hives

Kidney failure

Reduced kidney function

Fever

Pain

Excess fluid in the body tissue that causes swelling

Chest pain

Inflammation and ulceration of the mucous membranes that line the digestive tract

Uncommon (may affect up to 1 in 100 people)

Reduction in the number of red blood cells, white blood cells, and platelets

Ischemia or lack of blood flow

Ischemia due to blockage of a cerebral artery

Intracranial bleeding

Angina (chest pain caused by reduced blood flow to the heart)

Heart attack

Narrowing or blockage of the coronary arteries

Increased heart rate

Poor distribution of blood to the limbs

Blockage in one of the pulmonary arteries in the lungs

Inflammation and scarring of the lung mucosa with respiratory problems

Bright red blood loss through the anus

Bleeding in the gastrointestinal tract

Perforation of the intestine

Inflammation of the esophagus mucosa

Inflammation of the large intestine mucosa, which may be accompanied by intestinal or rectal bleeding (seen only in combination with cisplatin)

Inflammation, edema, erythema, and erosion of the mucous membrane surface of the esophagus caused by radiotherapy

Inflammation of the lung caused by radiotherapy

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

Destruction of red blood cells

Anaphylactic shock (severe allergic reaction)

Inflammatory liver disease

Redness of the skin

Rash on the skin that develops in a previously irradiated area

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

Infections of the skin and soft tissues

Stevens-Johnson syndrome (a type of severe skin and mucous membrane reaction that can be life-threatening)

Toxic epidermal necrolysis (a type of severe skin reaction that can be life-threatening)

Autoimmune disorder that causes skin rashes and blisters on the legs, arms, and abdomen

Inflammation of the skin characterized by the presence of blisters that are filled with fluid

Frailty of the skin, blisters, and erosions and scarring of the skin

Redness, pain, and swelling mainly of the lower limbs

Inflammation of the skin and the fat under the skin (pseudocellulitis)

Inflammation of the skin (dermatitis)

The skin becomes inflamed, itchy, red, cracked, and rough

Itchy patches

Frequency not known: frequency cannot be estimated from the available data

A type of diabetes derived mainly from kidney disease

Kidney disorder that involves the death of the epithelial tubular cells that form the renal tubules

You may experience some of these symptoms and/or situations. You must inform your doctor as soon as you start experiencing any of these side effects.

If you are concerned about any side effect, talk to your doctor.

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through 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. Storage of 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 label and on the carton after EXP. The expiry date is the last day of the month shown.

Store below 25°C.

Keep the vial in the outer packaging to protect it from light.

Solution for infusion: the medicine must be used immediately. When prepared as indicated, the chemical and physical stability of the diluted pemetrexed solution has been demonstrated for 21 days in the refrigerator and for 7 days at room temperature.

Do not use this medicine if it contains particles.

This medicine is for single use only.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Pemetrexed Fresenius Kabi

The active ingredient is pemetrexed.

One ml of concentrate contains 25 mg of pemetrexed.

After dilution, a vial of 4 ml concentrate contains 100 mg of pemetrexed (as pemetrexed disodium).

A vial of 20 ml concentrate contains 500 mg of pemetrexed (as pemetrexed disodium).

A vial of 40 ml concentrate contains 1,000 mg of pemetrexed (as pemetrexed disodium).

The other components are hydroxypropylbetadex, hydrochloric acid, trometamol, and water for injectable preparations.

Appearance of the Product and Container Content

Pemetrexed Fresenius Kabi is a concentrate for solution for infusion (sterile concentrate) in a glass vial. It is a transparent to slightly yellowish or greenish-yellow solution.

It is available in packs of 1 vial.

Marketing Authorization 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

Or

Fresenius Kabi Polska Sp. z o.o.

ul. Sienkiewicza 25, Kutno, 99-300

Poland

Further information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

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This information is intended only for healthcare professionals:

Instructions for use and handling and disposal

• Use aseptic techniques during the dilution of pemetrexed for administration by intravenous infusion.

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

• Dilute the appropriate volume of Pemetrexed Fresenius Kabi to 100 ml with sodium chloride 9 mg/ml (0.9%) injectable solution or 5% glucose solution for intravenous infusion and administer as an intravenous infusion over 10 minutes.

• The prepared pemetrexed infusion solution is compatible with polyvinyl chloride and polyolefin infusion systems and 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, as it causes degradation. This medicinal product must not be mixed with other medicinal products. Intravenous lines must be flushed after administration of Pemetrexed Fresenius Kabi.

• Parenteral medicinal products must be inspected visually for particulate matter and discoloration prior to administration. If particulate matter is observed, the medicinal product must not be administered.

• Pemetrexed solutions are for single use. Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.

Precautions in preparation and administration:As with any other potentially toxic antineoplastic agent, special care should be taken in the handling and preparation of pemetrexed infusion solutions. The use of gloves is recommended. If pemetrexed solutions come into contact with the skin, the skin should be washed immediately and thoroughly with water and soap. If pemetrexed solutions come into contact with mucous membranes, they should be rinsed with plenty of water. Pregnant women should avoid contact with cytostatic drugs. Pemetrexed is not a vesicant drug. There is no specific antidote for pemetrexed extravasation. Some cases of pemetrexed extravasation have been reported, which were not considered serious by the investigator. Extravasation should be treated according to standard clinical practice for non-vesicant drugs.