Pemetrexed Fresenius Kabi 25 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Pemetrexed Fresenius Kabi 25 mg/ml concentrate for solution for infusion EFG pemetrexed

Read the entire leaflet carefully before you start receiving this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Pemetrexed Fresenius Kabi is and what it is used for
2. What you need to know before using Pemetrexed Fresenius Kabi
3. How to use Pemetrexed Fresenius Kabi
4. Possible side effects
5. How to store 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 for the treatment of cancer.

Pemetrexed Fresenius Kabi may be given together with cisplatin, another anticancer medicine, as treatment for malignant pleural mesothelioma, a type of cancer affecting the lining of the lung, in patients who have not received previous chemotherapy.

Pemetrexed Fresenius Kabi may also be given together with cisplatin as initial treatment for patients with advanced-stage lung cancer.

Pemetrexed Fresenius Kabi may be prescribed to you if you have advanced-stage lung cancer, and your disease has responded to treatment or has remained unchanged after initial chemotherapy.

Pemetrexed Fresenius Kabi may also be given for the treatment of patients with advanced-stage lung cancer whose disease has progressed after having received prior initial chemotherapy treatment.

2. What you need to know before using 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 interrupt breastfeeding during treatment with Pemetrexed Fresenius Kabi.
• if you have recently received or are scheduled 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 currently have kidney problems, inform your doctor or hospital pharmacist, as you may not be able to receive Pemetrexed Fresenius Kabi.

Before each infusion, you will need to provide blood samples to assess whether your kidney and liver function are adequate and to evaluate whether you have sufficient blood cells to receive Pemetrexed Fresenius Kabi. Your doctor may decide to adjust 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 ensure that 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 there may be an early or delayed interaction between radiation and Pemetrexed Fresenius Kabi.

If you have recently been vaccinated, please consult your doctor, as this may cause some adverse effects with Pemetrexed Fresenius Kabi.

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

If you have fluid accumulation 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 individuals under 18 years of age.

Use of Pemetrexed Fresenius Kabi with other medicines

Inform your doctor if you are taking pain or anti-inflammatory (swelling) medicines, such as medicines known as “non-steroidal anti-inflammatory drugs” (NSAIDs), including those obtained without a prescription (such as ibuprofen). There are many types 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 you which medicines you can use and when. If you are unsure, consult your doctor or pharmacist to determine whether any medicine you are taking is an NSAID.

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

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

Pregnancy

If you are pregnant, think you might be pregnant, or plan to become pregnant, inform your doctor. Pemetrexed Fresenius Kabi should be avoided during pregnancy. Your doctor will inform you of the potential 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, inform your doctor.

Breastfeeding must be interrupted during treatment with Pemetrexed Fresenius Kabi.

Fertility

Male patients are advised not to father a child during and for up to 3 months after treatment with Pemetrexed Fresenius Kabi, and therefore must use effective contraception during and for 3 months after treatment with Pemetrexed Fresenius Kabi. If you wish to father a child during treatment or within 3 months after treatment, seek advice from your doctor or pharmacist. Pemetrexed Fresenius Kabi may affect your ability to have children. Speak with your doctor for advice on sperm preservation before starting your treatment.

Driving and using machines

Pemetrexed Fresenius Kabi may make you feel tired. Be cautious when driving or operating machinery.

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 administration instructions for this medicine given by your doctor or pharmacist. If in doubt, 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 value to determine the correct dose for you. This dose may be adjusted or the treatment may be delayed depending on your blood cell counts and your general condition. The hospital pharmacist, nurse, or doctor will have mixed Pemetrexed Fresenius Kabi with an injection solution of sodium chloride 9 mg/ml (0.9%) or a 5% glucose intravenous infusion solution before administration.

Pemetrexed Fresenius Kabi will always be administered to you as an intravenous infusion (drip) into 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 administered by intravenous infusion and is given approximately 30 minutes after the Pemetrexed Fresenius Kabi infusion has finished. The cisplatin infusion lasts approximately two hours.

You will normally receive your infusion once every three weeks.

Additional medication:

Corticosteroids: Your doctor will prescribe steroid tablets (equivalent to 4 milligrams of dexamethasone twice daily) that you must take the day before, the day of, and the day after treatment with Pemetrexed Fresenius Kabi. Your doctor prescribes this medication 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 preparation containing folic acid (350 to 1,000 micrograms), to be taken once daily while you are receiving Pemetrexed Fresenius Kabi. You should take at least five doses during the seven days before the first dose of Pemetrexed Fresenius Kabi. You should continue taking folic acid for 21 days after the last dose of Pemetrexed Fresenius Kabi. In addition, you will receive an injection of vitamin B12 (1,000 micrograms) during the week before administration of Pemetrexed Fresenius Kabi and then approximately every 9 weeks (corresponding to 3 treatment cycles with Pemetrexed Fresenius Kabi). Vitamin B12 and folic acid are given to reduce the potential toxic effects of cancer treatment.

If you have any further questions about the use of this product, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

You should inform your doctor immediately if you notice any of the following symptoms:

• Fever or infection (frequent or very common, 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 common). Infections (sepsis) can be severe and may cause death.
• If you begin to feel chest pain (frequent) or your heartbeat becomes faster (uncommon).
• If you have pain, redness, swelling, or sores in the mouth (very common).
• Allergic reaction: if you develop a rash (very common), burning sensation or itching (frequent), or fever (frequent). Rarely, skin reactions can be severe and may cause death. Contact your doctor if you develop a severe rash, itching, or blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis).
• If you feel tired or dizzy, are short of breath, or look pale (due to having lower than normal hemoglobin levels, which is very common).
• If you experience bleeding from the gums, nose, or mouth, or any bleeding that does not stop, pink or red urine, or unexpected bruising (due to having fewer platelets than normal, which is very common).
• If you suddenly experience difficulty breathing, severe chest pain, or cough up blood (uncommon) (this may indicate a blood clot in the lung veins).

Other adverse effects with pemetrexed may include:

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

Infection

Pharyngitis (sore throat)

Low neutrophil granulocyte count (a type of white blood cell)

Low white blood cell count

Low hemoglobin levels

Pain, redness, swelling, or sores in the mouth

Loss of appetite

Vomiting

Diarrhea

Nausea

Skin 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 granulocyte count (a type of white blood cell)

Low platelet count

Allergic reaction

Loss of body fluids

Changes in taste sensation

Nerve damage causing muscle weakness and atrophy (mainly in arms and legs)

Sensory nerve damage causing loss of sensation, burning pain, and unsteady gait

Dizziness

Inflammation or swelling of the conjunctiva (the membrane lining the eyelids and covering the white part of the eye)

Dry eyes

Watery eyes

Dryness of the conjunctiva (the inner membrane of the eyelids covering the white part of the eye) and cornea (the 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 affecting the heart muscle's ability to pump)

Irregular heartbeat

Indigestion

Constipation

Abdominal pain

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

Increased skin pigmentation

Itchy skin

Rash where each lesion resembles a target (bull's-eye)

Hair loss

Hives

Kidney failure

Reduced kidney function

Fever

Pain

Excess fluid in body tissues 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 red blood cells, white blood cells, and platelets

Ischemia or reduced blood supply

Cerebral artery blockage causing ischemia

Intracranial bleeding

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

Infarction

Narrowing or blockage of the coronary arteries

Increased heart rate

Poor blood distribution to the extremities

Blockage in one of the pulmonary arteries in the lungs

Inflammation and scarring of the lung mucosa causing breathing problems

Bright red blood loss from the anus

Bleeding in the gastrointestinal tract

Intestinal perforation

Inflammation of the esophageal mucosa

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

Inflammation, edema, erythema, and erosion of the esophageal mucosal surface caused by radiotherapy

Lung inflammation 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

Skin rash developing in a previously irradiated area

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

Skin and soft tissue infections

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

Toxic epidermal necrolysis (a severe type of skin reaction that can be fatal)

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

Skin inflammation characterized by the presence of fluid-filled blisters

Skin fragility, blistering, erosions, and scarring

Redness, pain, and swelling mainly in the lower limbs

Inflammation of the skin and underlying fat (pseudocellulitis)

Skin inflammation (dermatitis)

Skin becomes inflamed, itchy, red, cracked, and rough

Intensely itchy spots

Frequency not known: frequency cannot be estimated from available data

A type of diabetes primarily resulting from kidney disease

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

You may experience one or more of these symptoms and/or conditions. You should inform your doctor as soon as you begin to experience any of these adverse effects.

If you are concerned about any adverse effect, consult your doctor.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 stated on the label and the carton after EXP. The expiry date refers to the last day of the month indicated.

Store below 25°C.

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

Infusion solution: the medicine should be used immediately. When reconstituted as directed, chemical and physical in-use stability of the diluted pemetrexed solution has been demonstrated for 21 days under refrigeration and for 7 days at room temperature.

Do not use this medicine if particles are present.

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 and packaging no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Pemetrexed Fresenius Kabi

The active substance is pemetrexed.

One ml of concentrate contains 25 mg of pemetrexed.

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

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

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

The other components are hydroxypropylbetadex, hydrochloric acid, tromethamine and water for injections.

Appearance of the product and contents of the pack

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

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

or

Fresenius Kabi Polska Sp. z o.o.
ul. Sienkiewicza 25, Kutno, 99-300
Poland

Further information on this medicine can be requested from the marketing authorisation holder.

Date of the most recent review of this summary:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/

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This information is intended for healthcare professionals only:

Instructions for use, handling and disposal

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

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

• The appropriate volume of Pemetrexed Fresenius Kabi should be diluted to 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose solution for intravenous infusion, and administered as an intravenous infusion over 10 minutes.

• The pemetrexed infusion solution prepared as described above is compatible with polyvinyl chloride and polyolefin infusion sets and bags. Pemetrexed is incompatible with diluents containing calcium, including injection lactated Ringer's solution and injection Ringer's solution.

Pemetrexed Fresenius Kabi contains tromethamine as an excipient. Tromethamine is incompatible with cisplatin, as it causes its degradation. This medicine must not be mixed with other medicinal products. Intravenous lines should be flushed after administration of Pemetrexed Fresenius Kabi.

• Parenteral medicinal products should be visually inspected 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 only. Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.

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