Oxaliplatin Hikma 5 mg/ml concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Oxaliplatin Hikma 5 mg/ml concentrate for solution for infusion EFG

Read the entire leaflet carefully before you start using 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, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or nurse, even if these effects are not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Oxaliplatin Hikma is and what it is used for
2. What you need to know before using Oxaliplatin Hikma
3. How to use Oxaliplatin Hikma
4. Possible side effects
5. How to store Oxaliplatin Hikma
6. Contents of the pack and other information

1. What Oxaliplatin Hikma is and what it is used for

Oxaliplatin Hikma is an anticancer medication that contains the active substance oxaliplatin.

Oxaliplatin is used to treat intestinal cancer after it has been surgically removed or when it has already spread.

This medicine is used in combination with other anticancer drugs called 5-fluorouracil (5-FU) and folinic acid (FA).

2. What you need to know before you start using Oxaliplatin Hikma

Do not use Oxaliplatino Hikma:

1. if you are allergic to oxaliplatin or to any of the other ingredients of this medicine (listed in section 6).
2. if you are breastfeeding.
3. if you already have a low number of blood cells.
4. if you already suffer from tingling or numbness in the fingers and toes and have difficulty performing delicate tasks, such as buttoning clothes.
5. if you have a severe kidney disease.

Warnings and precautions

Talk to your doctor or pharmacist before starting treatment with Oxaliplatino Hikma: If you have ever had an allergic reaction to medicines containing platinum, such as carboplatin and cisplatin. Allergic reactions may occur during oxaliplatin infusion.

• If you have a mild or moderate kidney disorder.
• If you have liver problems or abnormal blood test results indicating liver function abnormalities during your treatment.
• If you have or have had heart disorders, such as an abnormal electrical signal known as QT interval prolongation, irregular heartbeat, or a family history of heart problems.
• If you have received or are scheduled to receive any vaccine. During treatment with oxaliplatin, you must not be vaccinated with live or live attenuated vaccines, such as the yellow fever vaccine.

Other medicines and Oxaliplatino Hikma

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding and fertility

Pregnancy

• It is not advisable to become pregnant during treatment with oxaliplatin, and you should use an effective method of contraception. Female patients should use appropriate contraceptive measures during treatment and for 4 months after treatment ends.
• If you are pregnant or planning to become pregnant, it is very important to discuss this with your doctor before starting any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breastfeeding

• Breastfeeding must be discontinued during treatment with oxaliplatin.

Fertility

• Oxaliplatin may permanently affect fertility. Male patients should seek advice about sperm preservation before starting treatment.
• Male patients are advised not to father a child during treatment and for 6 months after treatment ends, and to use appropriate contraceptive measures during this period.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

Treatment with oxaliplatin may increase the risk of dizziness, nausea and vomiting, as well as other neurological symptoms that may affect walking and balance. If you experience any of these symptoms, you must not drive or operate machinery. If you experience vision problems while being treated with oxaliplatin, do not drive, operate heavy machinery, or perform hazardous activities.

3. How to use Oxaliplatin Hikma

This medicine will be administered by medical personnel; do not use it yourself.

Oxaliplatin is indicated only in adults.

Dosage

The dose of oxaliplatin depends on your body surface area, which is calculated from your height and weight.

The usual dose in adults (including elderly patients) is 85 mg/m² of body surface area. The dose you receive may also depend on the results of blood tests and whether you have previously experienced adverse effects with this medicine.

Method and route of administration

• Oxaliplatin will be prescribed by a specialist doctor experienced in cancer treatment.
• You will be treated by a healthcare professional, who will have calculated the dose of medicine you require.
• Oxaliplatin is administered as a slow injection into a vein (intravenous infusion) over a period of 2–6 hours. If you feel discomfort or pain at the injection site, inform healthcare professionals immediately.
• This medicine will be administered at the same time as folinic acid and before the infusion of 5-fluorouracil.

Frequency of administration

In general, you will receive an infusion every 2 weeks.

Duration of treatment

Your doctor will determine the duration of treatment.

Your treatment will last a maximum of 6 months when used after complete resection of the tumour.

If you use more Oxaliplatin Hikma than you should

Since this medicine will be administered by a healthcare professional, it is unlikely that you will receive too much or too little.

In the event of an overdose, you may experience an increase in adverse effects. Your doctor can provide appropriate treatment for these adverse effects.

If you forget to take Oxaliplatin Hikma

Your doctor will decide when you will receive this medicine. If you think a dose has been missed, contact your doctor as soon as possible.

If you have any questions about your treatment, consult your doctor or pharmacist.

4. Possible adverse effects

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

If you experience any adverse effect, it is very important that you inform your doctor before starting the next treatment.

Contact your doctor immediately if you experience any of the following symptoms:

• Symptoms of an allergic or anaphylactic reaction, accompanied by sudden signs such as rash, itching or hives on the skin, difficulty swallowing, swelling of the face, lips, tongue or other parts of the body, difficulty breathing, wheezing or breathing problems, extreme tiredness (you may feel like fainting). These symptoms occur in most cases during or immediately after the infusion, but delayed allergic reactions have also been observed hours or even days after the infusion (very common).
• Unusual bruising, bleeding, or signs of infection such as sore throat and fever (very common).
• Persistent or severe diarrhea or vomiting (very common).
• Respiratory symptoms such as dry or wet cough, difficulty breathing or crackling sounds (very common), difficulty breathing and wheezing, as they may indicate a serious lung disease that could be fatal.
• Stomatitis/mucositis (sores on the lips and ulcers in the mouth) (very common).
• Presence of blood or dark brown coffee-ground-like particles in vomit (common).
• A set of symptoms such as headache, altered mental activity, seizures, and abnormal vision (from blurred vision to vision loss) (symptoms of reversible posterior leukoencephalopathy syndrome, a rare neurological disorder) (rare).
• Symptoms of stroke (including sudden and severe headache, confusion, difficulty seeing with one or both eyes, numbness or weakness of the face, arm or leg usually on one side, facial drooping, difficulty walking, dizziness, loss of balance, and difficulty speaking).
• Extreme tiredness, accompanied by a decrease in red blood cells and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelet count, unusual bruising (thrombocytopenia) (rare), and kidney problems resulting in little or no urine output (symptoms of hemolytic uremic syndrome) (frequency not known).
• Tingling and/or numbness in the fingers and toes, around the mouth or in the throat, which may sometimes occur with cramps and may also lead to difficulty performing delicate tasks such as buttoning clothes (symptoms of peripheral neuropathy) (very common).

Other adverse effects of Oxaliplatin Hikmason:

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

• Oxaliplatin may affect the nerves (peripheral neuropathy). You may feel tingling or numbness in the fingers and toes, around the mouth or throat, which may sometimes be accompanied by cramps.

These adverse effects are usually triggered by exposure to cold, such as opening the refrigerator or holding a cold drink. You may also have difficulty performing fine tasks, such as buttoning clothes. Although in most cases these symptoms resolve completely on their own, there is a possibility that symptoms of peripheral sensory neuropathy may persist after treatment has ended.

Some people have experienced a sudden tingling sensation in the arms or trunk when bending the neck.

• Oxaliplatin may cause an unpleasant sensation in the throat, particularly when swallowing, which may feel like difficulty breathing. If this occurs, it usually happens during or shortly after the infusion and may be triggered by exposure to cold.

Although unpleasant, this sensation does not last long and resolves without treatment. Your doctor may decide to modify your treatment as a result.

• Oxaliplatin may cause diarrhea, mild nausea (feeling of queasiness), and vomiting (upset stomach). However, your doctor will provide you with treatment to prevent this discomfort before starting therapy, and it should be continued after treatment.
• Oxaliplatin may cause a temporary reduction in blood cell counts. A decrease in red blood cells may cause anemia (reduced number of red blood cells), unusual bleeding or bruising (due to reduced platelet count). A decrease in white blood cells may increase the risk of infections.

Before starting treatment and before each treatment cycle, your doctor will perform a blood test to ensure you have sufficient blood cell counts.

• Feeling of discomfort around or at the injection site during infusion.
• Fever, chills (shivering), mild or extreme fatigue, body pain.
• Weight changes, loss or lack of appetite, taste disturbances, constipation.
• Headache, back pain.
• Inflammation of muscular nerves, neck stiffness, abnormal sensation in the tongue that may impair speech.
• Stomach pain.
• Unusual bleeding, including nosebleeds.
• Cough, difficulty breathing.
• Allergic reactions, skin rash which may be red and itchy, moderate hair loss (alopecia).
• Abnormal blood test results, including those related to changes in liver function.

Common (may affect up to 1 in 10 people)

• Infection due to decreased white blood cell count.
• Severe blood infection, in addition to decreased white blood cell count (neutropenic sepsis), which may be fatal.
• Decreased white blood cell count accompanied by fever >38.3°C or prolonged fever >38°C for more than one hour (febrile neutropenia).
• Indigestion and heartburn, hiccups, hot flashes, dizziness.
• Increased sweating and nail changes, skin peeling.
• Chest pain.
• Pulmonary disorders and nasal discharge.
• Joint pain and bone pain.
• Pain when urinating and changes in kidney function, changes in frequency of urination, dehydration.
• Blood in urine/stool, inflammation of veins, blood clots in the lung.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Decreased blood calcium levels.
• Falls.

Uncommon (may affect up to 1 in 100 people)

• Severe blood infection (sepsis), which may be fatal.
• Bowel obstruction or inflammation.
• Nervousness.

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

• Hearing loss.
• Lung scarring and thickening, accompanied by difficulty breathing, sometimes fatal (interstitial lung disease).
• Reversible, temporary vision loss.
• Unexpected bleeding or bruising due to widespread blood clotting in small blood vessels throughout the body (disseminated intravascular coagulation), which may be fatal.

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

• Kidney problems causing very little or no urine output (symptoms of acute renal failure).
• Vascular disorders of the liver.

Frequency not known (cannot be estimated from available data)

• Allergic vasculitis (inflammation of blood vessels).
• Autoimmune reaction causing a decrease in all blood cell lines (autoimmune pancytopenia), pancytopenia.
• Severe blood infection or low blood pressure (septic shock), which may be fatal.
• Seizures (uncontrolled body shaking).
• Throat spasm that may cause difficulty breathing.
• Extreme tiredness, accompanied by a decrease in red blood cells and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in platelet count, and kidney problems causing little or no urine output (symptoms of hemolytic uremic syndrome), which may be fatal.
• Abnormal heart rhythm (QT interval prolongation), which may be seen on an electrocardiogram (ECG) and may be fatal.
• Myocardial infarction (heart attack), angina (chest pain or discomfort).
• Muscle pain and swelling, accompanied by weakness, fever, or reddish-brown urine (symptoms of muscle damage known as rhabdomyolysis), which may be fatal.
• Esophagitis (inflammation of the inner lining of the esophagus—the tube connecting the mouth to the stomach—causing pain and difficulty swallowing).
• Abdominal pain, nausea, vomiting with blood or "coffee-ground" vomit, dark/black stools with blood (symptoms of gastrointestinal ulcer, with possible bleeding or perforation), which may be fatal.
• Reduced blood flow to the intestine (intestinal ischemia), which may be fatal.
• Risk of new cancers. Leukemia, a type of blood cancer, has been reported in patients after taking oxaliplatin in combination with certain other medicines. Talk to your doctor about the potential risk of increased incidence of this type of cancer when taking oxaliplatin with certain other medicines.
• Abnormal, non-cancerous liver nodules (focal nodular hyperplasia).

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Oxaliplatin Hikma

Keep this medicine out of the sight and reach of children.

Oxaliplatin must not come into contact with the eyes or skin. In the event of accidental spillage, inform the doctor or nurse immediately.

Before mixing this medicine, it should be stored in its original packaging to protect it from light and must not be frozen. Store below 25°C.

Do not use this medicine after the expiry date stated on the carton and vial label after EXP. The expiry date refers to the last day of the month indicated.

Once the infusion is complete, the doctor or nurse will dispose of this medicine using appropriate safety measures.

6. Contents of the pack and other information

Composition of Oxaliplatin Hikma

• The active substance is oxaliplatin.
• The other component is water for injections.

Appearance of the product and contents of the container

The solution is clear, colourless and free from visible particles in suspension.

Each millilitre of solution contains 5 mg of the active substance oxaliplatin.

This medicine is a concentrate for solution for infusion.

Each 10 ml vial of concentrate for solution for infusion contains 50 mg of oxaliplatin.

Each 20 ml vial of concentrate for solution for infusion contains 100 mg of oxaliplatin.

Each 40 ml vial of concentrate for solution for infusion contains 200 mg of oxaliplatin.

Pack sizes:

50 mg/10 ml: 1 vial
100 mg/20 ml: 1 vial
200 mg/40 ml: 1 vial

With or without protective plastic overwrap.

Only some pack sizes may be marketed.

Marketing Authorisation Holder

Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó n.º 8, 8A and 8B, Fervença
2705-906 Terrugem SNT
Portugal

Manufacturer

Thymoorgan Pharmazie GmbH
Schiffgraben 23
38690 Goslar
Germany

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

Hikma España, S.L.U.
Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2
28108 - Alcobendas, Madrid
Spain

This medicine is authorised in the European Economic Area member states under the following names:

Germany/ Austria	Oxaliplatin Hikma 5 mg/ ml Concentrate for Solution for Infusion
Spain	Oxaliplatin Hikma 5 mg/ ml Concentrate for infusion solution EFG
France	Oxaliplatin Hikma 5 mg/ ml Solution for dilution for infusion
Italy	Oxaliplatin Hikma 5 mg/ ml
Netherlands	Oxaliplatin Hikma 5 mg/ ml concentrate for solution for infusion
Portugal	Oxaliplatin Hikma
United Kingdom/ Northern Ireland	Oxaliplatin 5 mg/ml Concentrate for Solution for infusion

Date of last review of this leaflet: March 2022

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.es/

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This information is intended for healthcare professionals only:

Special precautions for handling and disposal

As with other potentially toxic compounds, extreme caution must be exercised during handling and preparation of solutions containing oxaliplatin.

Instructions for drug handling

Handling of this cytotoxic agent by healthcare personnel requires taking precautions to ensure protection of the handler and the working environment.

Preparation of injectable solutions of cytotoxic agents should be carried out by appropriately trained and qualified personnel, under conditions that guarantee drug integrity, environmental protection, and particularly the protection of personnel handling the drugs, in accordance with hospital regulations. A dedicated preparation area is required for this purpose. Smoking, eating, or drinking in this area is prohibited.

Personnel must use appropriate protective equipment when handling the drug, such as sleeves, protective mask, cap, protective goggles, sterile disposable gloves, protective gown for the work area, and containers and bags for waste collection.

Faeces and vomit must be handled with care.

Pregnant women should avoid handling cytotoxic agents.

Any broken container must be treated with the same precautions and considerations as contaminated waste. Contaminated waste must be incinerated in rigid, properly labelled containers. See the section Disposal below for further information.

If the concentrate or infusion solution of oxaliplatin comes into contact with the skin, immediately wash the affected area thoroughly with plenty of water.

If the concentrate or infusion solution of oxaliplatin comes into contact with mucous membranes, immediately wash the affected area thoroughly with plenty of water.

Special administration precautions

• DO NOT use injection materials containing aluminium.
• DO NOT administer undiluted.
• Only 5% glucose solution for infusion should be used as diluent. DO NOT dilute with sodium chloride-containing or chloride-containing infusion solutions.
• DO NOT mix with other drugs in the same infusion bag or administer simultaneously via the same infusion line.
• DO NOT mix with alkaline solutions or drugs, particularly 5-fluorouracil or folinic acid preparations containing tromethamine as excipient, or tromethamine salts of other drugs. Alkaline solutions or drugs may adversely affect the stability of oxaliplatin.

Instructions for use with folinic acid (as calcium folinate or disodium folinate)

The intravenous infusion of 85 mg/m² of oxaliplatin in 250–500 ml of 5% glucose solution is administered simultaneously with folinic acid (FA) diluted in a 5% glucose solution over 2–6 hours, using a Y-line placed immediately before the infusion site. These two drugs must not be combined in the same infusion bag. Folinic acid must not contain tromethamine as an excipient and should only be diluted in an isotonic 5% glucose solution, never in alkaline solutions or in sodium chloride or chloride-containing solutions.

Instructions for use with 5-fluorouracil

Oxaliplatin must always be administered before fluoropyrimidines, e.g., 5-fluorouracil

After administration of oxaliplatin, flush the line and then administer 5-fluorouracil.

For detailed information on combined drug administration, refer to the corresponding Summary of Product Characteristics.

Concentrate for infusion solution

Visually inspect the vial before use. Only clear solutions free of suspended particles should be used.

This medicine is for single use only. Any unused concentrate must be discarded.

Dilution for intravenous infusion

Withdraw the required volume of concentrate from the vials and dilute it in 250–500 ml of 5% glucose solution to achieve an oxaliplatin concentration of not less than 0.25 mg/ml.

Administer by intravenous infusion.

From a microbiological standpoint, the infusion preparation should be used immediately.

If not used immediately, the storage time and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 2–8 °C, unless dilution has been performed under controlled and validated aseptic conditions.

Chemical and physical in-use stability has been demonstrated when diluted to a concentration of 0.25 mg/ml with 5% glucose for 24 hours at 2–8 °C, and for 6 hours at 20–25 °C at a concentration of 0.25 mg/ml with 5% glucose.

Visually inspect the vial before use. Only clear solutions free of suspended particles should be used.

This medicine is for single use only. Any unused infusion solution must be discarded (see Disposal section below).

NEVER use sodium chloride or chloride-containing solutions for dilution.

Infusion

Administration of oxaliplatin does not require prehydration.

Diluted oxaliplatin in 250–500 ml of 5% glucose solution to achieve a concentration of not less than 0.25 mg/ml should be administered via central or peripheral venous route over 2–6 hours. When oxaliplatin is administered with 5-fluorouracil (5-FU), the oxaliplatin infusion must precede the 5-fluorouracil (5-FU) infusion.

Disposal

Disposal of unused medicinal product and all materials that have come into contact with it during dilution and administration must be carried out in accordance with local regulations for cytotoxic agents and in compliance with local legal requirements for disposal of hazardous waste.

Dosage

For adults only

The recommended dose of oxaliplatin for adjuvant treatment is 85 mg/m² administered intravenously, repeated every two weeks for 12 cycles (6 months).

The recommended dose of oxaliplatin in the treatment of metastatic colorectal cancer is 85 mg/m² administered intravenously, repeated every two weeks until disease progression or unacceptable toxicity occurs.

The administered dose should be adjusted according to tolerance (see section 4.4 Warnings and special precautions for use in the corresponding Summary of Product Characteristics).

Oxaliplatin must always be administered before fluoropyrimidines, i.e., 5-fluorouracil (5-FU).

Oxaliplatin is administered as an intravenous infusion lasting 2–6 hours, diluted in 250–500 ml of 5% glucose solution (50 mg/ml) to achieve a concentration of 0.2–0.7 mg/ml; in clinical practice, 0.7 mg/ml is the maximum concentration for an oxaliplatin dose of 85 mg/m².

Shelf life

Packaged medicine for sale: 24 months.

In-use stability after dilution

From a microbiological standpoint, the infusion solution should be used immediately.

If not used immediately, the storage time and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 2–8 °C, unless dilution has been performed under controlled and validated sterile conditions.

Chemical and physical in-use stability has been demonstrated when diluted to a concentration of 0.25 mg/ml with 5% glucose for 24 hours at 2–8 °C, and for 6 hours at 20–25 °C when diluted to a concentration of 0.25 mg/ml with 5% glucose.

Special storage precautions

Store the vial in the outer packaging to protect it from light. Do not freeze.

Store below 25°C.