Package leaflet: Information for the user

Pemetrexed PharmaSwiss 100 mg powder for concentrate for solution for infusion

Pemetrexed PharmaSwiss 500 mg powder for concentrate for solution for infusion.

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.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

2. What you need to know before you use Pemetrexed PharmaSwiss

3. How to use Pemetrexed PharmaSwiss

4. Possible side effects

6. Contents of the pack and other information

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

Pemetrexed PharmaSwiss 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 PharmaSwiss is also given in combination with cisplatin for the initial treatment of patients with

advanced stage of lung cancer.

Pemetrexed PharmaSwiss 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 PharmaSwiss is also a treatment for patients with advanced stage of lung cancer whose disease has

progressed after other initial chemotherapy has been used.

Do not use Pemetrexed PharmaSwiss

- 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 PharmaSwiss.

- if you have recently received or are about to receive a vaccine against yellow fever.

Warnings and precautions

Talk to your doctor or pharmacist using Pemetrexed PharmaSwiss

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 PharmaSwiss.

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 PharmaSwiss. 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 PharmaSwiss.

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

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 PharmaSwiss.

Children and adolescents

There is no relevant use of pemetrexed in the paediatric population.

Other medicines and Pemetrexed PharmaSwiss

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 PharmaSwiss 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.

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

Pregnancy, breast-feeding and fertility

Pregnancy

If you are pregnant, or thinking about becoming pregnant, tell your doctor. The use of Pemetrexed PharmaSwiss should be avoided during pregnancy. Your doctor will discuss with you the potential risk of taking Pemetrexed PharmaSwiss during pregnancy. Women must use effective contraception during treatment with Pemetrexed PharmaSwiss.

Breast-feeding

If you are breast-feeding, tell your doctor.

Breast-feeding must be discontinued during Pemetrexed PharmaSwiss treatment.

Fertility

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

Pemetrexed PharmaSwiss contains sodium

Pemetrexed PharmaSwiss 100 mg vial contains approximately 10.3 mg sodium.

Pemetrexed PharmaSwiss 500 mg vial contains approximately 51.5 mg sodium. To be taken into consideration by patients on a controlled sodium diet.

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

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

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

The frequency of possible side effects listed below is defined as follows:

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

Common (may affect 1 to 10 patients in 100)

Uncommon (may affect 1 to 10 patients in 1,000)

Rare (may affect 1 to 10 patients in 10,000)

Very rare (may affect less than 1 patient in 10,000)

Side effects with pemetrexed may include:

Very common

Low white blood cells

Low haemoglobin level (anaemia)

Low platelet count

Diarrhoea

Vomiting

Pain, redness, swelling or sores in your mouth

Nausea

Loss of appetite

Fatigue (tiredness)

Skin rash

Hair loss

Constipation

Loss of sensation

Kidney: abnormal blood tests

Common

Allergic reaction: skin rash / burning or prickling sensation

Infection including sepsis

Fever

Dehydration

Kidney failure

Irritation of the skin and itching

Chest pain

Muscle weakness

Conjunctivitis (inflamed eye)

Upset stomach

Pain in the abdomen

Taste change

Liver: abnormal blood tests

Watery eyes

Uncommon

Acute renal failure

Fast heart rate

Inflammation of the lining of the oesophagus (gullet) has been experienced with pemetrexed/ radiation therapy.

Colitis (inflammation of the lining of the large bowel, which may be accompanied by intestinal or rectal bleeding)

Interstitial pneumonitis (scarring of the air sacs of the lung)

Oedema (excess fluid in body tissue, causing swelling)

Some patients have experienced a heart attack, stroke or “mini-stroke” while receiving pemetrexed usually in combination with another anticancer therapy.

Pancytopenia- combined low counts of white cells, red cells and platelets

Radiation pneumonitis (scarring of the air sacs of the lung associated with radiation therapy) may occur in patients who are also treated with radiation either before, during or after their Pemetrexed PharmaSwiss therapy.

Extremity pain, low temperature and discolouration have been reported.

Blood clots in the lung blood vessels (pulmonary embolism)

Rare

Radiation recall (a skin rash like severe sunburn) which can occur on skin that has previously been exposed to radiotherapy, from days to years after the radiation.

Bullous conditions (blistering skin diseases)-including Stevens-Johnson syndrome and Toxic epidermal necrolysis

Immune mediated haemolytic anaemia (antibody-mediated destruction of red blood cells)

Hepatitis (inflammation of the liver)

Anaphylactic shock (severe allergic reaction)

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 PharmaSwiss

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

Store the medicine in the original packaging to protect from light.

Chemical and physical in-use stability of the reconstituted solution 25 mg Pemetrexed /ml in 0.9 % NaCl solution for injection has been demonstrated for 24 hours when stored refrigerated (2-8°C) or stored below 30°C.

After dilution: Chemical and physical in-use stability of the diluted solution 4.5 and 10 mg Pemetrexed/ml in 0.9% NaCl has been demonstrated for 24 hours when stored refrigerated (2-8°C) or stored below 30°C.

From a microbiological point of view, the reconstituted or diluted 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.

This medicine is for single use only; any unused solution must be disposed of in accordance with local requirements.

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 PharmaSwiss contains

• The active substance is pemetrexed.

• The other excipients are mannitol, hydrochloric acid and sodium hydroxide.

What Pemetrexed PharmaSwiss looks like and contents of the pack

Pemetrexed PharmaSwiss is a powder for concentrate for solution for infusion in a vial. It is a sterile, pyrogen free, white to yellow or greenish-yellow lyophilisate powder of 100 mg/vial or 500 mg/vial.

Marketing Authorisation Holder and Manufacturer

Marketing authorisation holder:

<[To be completed nationally]>

Manufacturer:

Actavis Group PTC ehf.

Reykjavíkurvegur 76-78

IS-220 Hafnarfjörður

Iceland

and

S.C. SINDAN-PHARMA S.R.L.

11th Ion Mihalache Boulevard

011171, Bucharest 1

Romania

<This medicinal product is authorised in the Member States of the EEA under the following names:>

<{Name of the Member State}> <{Name of the medicinal product}>

<{Name of the Member State}> <{Name of the medicinal product}>

This leaflet was last revised in 2016-03-16

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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 PharmaSwiss vials needed. Each vial contains an excess of pemetrexed to facilitate delivery of the label amount.

3. Pemetrexed PharmaSwiss 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 PharmaSwiss 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.

Preparation and administration precautions: As with other potentially toxic anticancer agents,

care should be exercised in the handling and preparation of pemetrexed infusion solutions. The use of

gloves is recommended. If a pemetrexed solution contacts the skin, wash the skin immediately and

thoroughly with soap and water. If pemetrexed solutions contact the mucous membranes, flush

thoroughly with water. Pemetrexed is not a vesicant. There is not a specific antidote for extravasation

of pemetrexed. There have been a few reported cases of pemetrexed extravasation, which were not

assessed as serious by the investigator. Extravasation should be managed by local standard practice as

with other non-vesicants.