PEMETREXED Fresenius Kabi 100 mg powder for concentrate for infusion solution

Introduction

Package Leaflet: Information for the User

Pemetrexed Fresenius Kabi 100 mg powder for concentrate for solution for infusion EFG

Pemetrexed Fresenius Kabi 500 mg powder for concentrate for solution for infusion EFG

pemetrexed

Read all of this leaflet carefully before you start using 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 get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

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

1. Contents of the pack and further 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 for the initial treatment of patients with advanced 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 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

Consult 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 need 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 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 there may be an early or late reaction between radiation and Pemetrexed Fresenius Kabi.

If you have recently been vaccinated, please consult your doctor, as this may cause some 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 drain 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, have recently used or might use medicines for pain or inflammation (swelling), such as medicines called “non-steroidal anti-inflammatory drugs” (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 your kidney function status, your doctor will advise which medicines you can use and when you can take them. If you are unsure, 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.

3. How to use Pemetrexed Fresenius Kabi

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 the Pemetrexed Fresenius Kabi powder with 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 about 30 minutes after the Pemetrexed Fresenius Kabi infusion has finished. The cisplatin infusion lasts about 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 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 the 21 days after the last dose of Pemetrexed Fresenius Kabi. You will also 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 blistering (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 in your sputum (uncommon) (may indicate that there is a blood clot in the lungs).

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

Abnormal blood tests showing reduced kidney function

Asthenia (tiredness)

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

Abnormal 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 covering the eyelids and the white part of the eye)

Dry eyes

Tearing

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

Swelling of the eyelids

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

Heart failure (condition affecting 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 resembles a target

Hair loss

Hives

Kidney failure

Reduced kidney function

Fever

Pain

Excess fluid in the 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 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 blood distribution 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 mucosa of the large intestine, 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 filled with fluid

Skin fragility, blisters, and erosions and scarring of the skin

Redness, pain, and swelling mainly of the lower limbs

Inflammation of the skin and subcutaneous fat (pseudocellulitis)

Inflammation of the skin (dermatitis)

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

Intensely itchy patches

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

A type of diabetes derived mainly from kidney disease

Kidney disorder involving the death of the epithelial 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 it is possible side effects 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 vial label and carton after EXP. The expiry date is the last day of the month shown.

This medicine does not require any special storage conditions.

Reconstituted solution and infusion solution: the medicine must be used immediately. The chemical and physical stability of the reconstituted pemetrexed solution has been demonstrated for 24 hours under refrigeration when prepared as directed. For the pemetrexed infusion solution, chemical and physical stability has been demonstrated for 21 days under refrigeration and for 7 days at 25°C.

This medicine must not be used if the solution 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 Contents and Additional Information

Composition of Pemetrexed Fresenius Kabi

The active ingredient is pemetrexed.

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

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

After reconstitution, the solution contains 25 mg/ml of pemetrexed. Prior to administration, it is required that the healthcare professional perform further dilution.

The other components are mannitol, hydrochloric acid, and trometamol.

Product Appearance and Container Contents

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

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

or

Fresenius Kabi France- Louviers

6 rue du Rempart

Louviers, 27400

France

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 for healthcare professionals only:

Instructions for use and handling and disposal

• Use aseptic techniques during the reconstitution and subsequent 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 the administration of the required nominal amount.

• Pemetrexed Fresenius Kabi 100 mg:

Reconstitute each 100 mg vial with 4.2 ml of 5% glucose solution for intravenous infusion, obtaining a solution that contains 25 mg/ml of pemetrexed.

• Pemetrexed Fresenius Kabi 500 mg:

Reconstitute each 500 mg vial with 20 ml of 5% glucose solution for intravenous infusion, obtaining a solution that contains 25 mg/ml of pemetrexed.

• Shake the vial carefully until the powder is completely dissolved. The resulting solution is clear with a color range that may vary from colorless to yellow or yellow-green without affecting the product quality. The pH of the reconstituted solution is between 6.6 and 7.8. Further dilution is required.

• The appropriate volume of the reconstituted pemetrexed solution should be diluted to 100 ml with 5% glucose solution for intravenous infusion and administered as an intravenous infusion over 10 minutes.

• The pemetrexed infusion solution prepared according to the instructions described above 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 should 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 discoloration prior to administration. If particulate matter is observed, the medicinal product should 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 according to 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.