OXALIPLATIN HIKMA 5 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Oxaliplatin Hikma 5 mg/ml Concentrate for Solution for Infusion EFG

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. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Oxaliplatin Hikma is and what it is used for
2. What you need to know before you use Oxaliplatin Hikma
3. How to use Oxaliplatin Hikma
4. Possible side effects
5. Storage of 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 anti-cancer medicine and contains the active substance oxaliplatin.

Oxaliplatin is used to treat colon cancer after it has been removed by surgery or when it has spread.

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

2. What you need to know before you use Oxaliplatin Hikma

Do not use Oxaliplatin Hikma:

1. if you are allergicto oxaliplatin or any of the other ingredients of this medicine (listed in section 6).
2. if you are breast-feeding.
3. if you already have a low number of blood cells.
4. if you already have tingling or numbness of the fingers and toesand have difficulty performing delicate tasks, such as buttoning your clothes.
5. if you have severe kidney disease.

Warnings and precautions

Tell your doctor or pharmacist before you start receiving Oxaliplatin Hikma: If you have ever had an allergic reaction to platinum-based medicines, such as carboplatin and cisplatin. Allergic reactions can occur during the infusion of oxaliplatin.

• If you have moderate or mild kidney problems.
• If you have liver problems or abnormal liver function test results during treatment.
• If you have or have had heart problems, such as an abnormal electrical signal called QT interval prolongation, an irregular heartbeat, or a family history of heart problems.
• If you have been given or are planned to be given any vaccine. During treatment with oxaliplatin, you should not be vaccinated with live or attenuated live vaccines, such as the yellow fever vaccine.

Other medicines and Oxaliplatin Hikma

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

Pregnancy, breast-feeding, and fertility

Pregnancy

• It is not recommended that you become pregnant during treatment with oxaliplatin and you must use an effective contraceptive method. Patients must take adequate contraceptive measures during treatment and for 4 months after the end of treatment.
• If you are pregnant or are thinking of becoming pregnant, it is very important that you talk to your doctor beforereceiving any treatment.
• If you become pregnant during treatment, you must inform your doctor immediately.

Breast-feeding

• Breast-feeding must be stopped during treatment with oxaliplatin

Fertility

• Oxaliplatin may affect fertility irreversibly. Male patients should seek advice on sperm preservation before treatment.
• Male patients are advised not to father children during treatment and up to 6 months after treatment and to take appropriate contraceptive measures during this time.

Ask your doctor or pharmacist for advice 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 can affect walking and balance. If you are affected by any of these symptoms, do not drive or operate machinery. If you have vision problems while being treated with oxaliplatin, do not drive, operate heavy machinery, or engage in hazardous activities.

3. How to use Oxaliplatin Hikma

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

Oxaliplatin is only indicated in adults.

Dose

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 will also depend on the results of your blood tests and whether you have previously experienced side effects with this medicine.

Form and route of administration

• Oxaliplatin will be prescribed by a specialist doctor in the treatment of cancer.
• You will be treated by a healthcare professional, and they will have calculated the dose of medicine you need.
• Oxaliplatin is administered by 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 the 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

Generally, 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 removal of the tumor.

If you use more Oxaliplatin Hikma than you should

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

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

If you miss a dose of Oxaliplatin Hikma

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

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

• Symptoms of an allergic reaction or anaphylaxis, 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 fatigue (you may feel like you are going to faint). These symptoms usually occur during the infusion or shortly after it, 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 (very common), difficulty breathing, and wheezing, as they can be indicators of a serious lung disease that can be fatal.
• Stomatitis/mucositis (sores on the lips and ulcers in the mouth) (very common).
• Blood or dark brown particles in the vomit (common)
• A set of symptoms such as headache, altered mental status, seizures, and abnormal vision (from blurred vision to loss of vision) (symptoms of posterior reversible leukoencephalopathy syndrome, a rare neurological disorder) (rare).
• Symptoms of stroke (including sudden severe headache, confusion, difficulty seeing with one or both eyes, numbness or weakness of the face, arm, or leg, usually on one side, drooping face, difficulty walking, dizziness, loss of balance, and difficulty speaking).
• Extreme fatigue, accompanied by a decrease in the number of red blood cells and shortness of breath (hemolytic anemia) (rare), alone or accompanied by a decrease in the number of platelets, and kidney problems that cause little or no urine production (symptoms of hemolytic uremic syndrome), which can be fatal.
• Tingling and/or numbness in the fingers and toes, around the mouth, or in the throat, which can sometimes occur in association with cramps and can also lead to difficulty performing delicate tasks, such as buttoning clothes (symptoms of peripheral neuropathy) (very common).

Other side effects of Oxaliplatin Hikma are:

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 in the throat, which can sometimes be accompanied by cramps.

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

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, specifically when swallowing, which can give the sensation of shortness of breath. This sensation, if it occurs, usually happens during the infusion or in the hours following and can be triggered by exposure to cold.

Although it is unpleasant, it does not last long and disappears without the need for treatment. Your doctor may decide to modify your treatment as a result of this.

• Oxaliplatin may cause diarrhea, mild nausea (feeling of dizziness), and vomiting. However, your doctor will give you treatment to prevent this discomfort before starting treatment and will continue it after treatment.
• Oxaliplatin may cause a temporary decrease in the number of blood cells. A decrease in red blood cells can cause anemia (decrease in the number of red blood cells), unusual bleeding, or bruising (due to a decrease in the number of platelets). A decrease in the number of white blood cells can facilitate the appearance of infections.

Before starting treatment and before each treatment cycle, your doctor will perform a blood test to check that you have a sufficient number of cells in the blood.

• Discomfort around or at the injection site during the infusion.
• Fever, chills (shivering), mild or extreme fatigue, body aches.
• Weight changes, loss of appetite, taste alterations, constipation.
• Headache, back pain.
• Inflammation of the nerve muscles, stiffness of the neck, abnormal sensation in the tongue that can make speaking difficult.
• Stomach pain
• Unusual bleeding, including nosebleeds.
• Cough, difficulty breathing.
• Allergic reactions, skin rash that can be red and itchy, moderate hair loss (alopecia).
• Alterations in blood tests, including changes in liver function.

Common(may affect up to 1 in 10 people)

• Infection due to a decrease in the number of white blood cells.
• Severe blood infection, in addition to a decrease in the number of white blood cells (febrile neutropenia), which can be fatal.
• Decrease in the number of white blood cells, accompanied by fever >38.3°C or prolonged fever

>38°C for more than one hour (febrile neutropenia).

• Indigestion and heartburn, belching, hiccup, dizziness.
• Increased sweating and nail changes, skin peeling.
• Chest pain.
• Lung changes and sputum production.
• Joint pain and bone pain.
• Pain when urinating and changes in kidney function, changes in the frequency of urination, dehydration.
• Blood in the urine/stool, vein inflammation, blood clots in the lung.
• High blood pressure.
• Depression and insomnia.
• Conjunctivitis and vision problems.
• Decreased calcium levels in the blood.
• Falls.

Uncommon(may affect up to 1 in 100 people)

• Severe blood infection (sepsis) that can be fatal.
• Blockage or inflammation of the intestine.
• Nervousness.

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

• Hearing loss.
• Scarring and thickening of the lungs, accompanied by difficulty breathing, which can sometimes be fatal (interstitial lung disease).
• Reversible and temporary loss of vision.
• Unexpected bleeding or bruising due to the spread of blood clots in the small blood vessels of the body (disseminated intravascular coagulation), which can be fatal.

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

• Kidney problems that cause little or no urine production (symptoms of acute kidney failure).
• Vascular disorders of the liver.

Frequency not known(cannot be estimated from the available data)

• Allergic vasculitis (inflammation of the blood vessels).
• Autoimmune reaction that causes a decrease in all blood cell lines (autoimmune pancytopenia), pancytopenia.
• Severe blood infection or low blood pressure (septic shock), which can be fatal.
• Seizures (uncontrolled body agitation).
• Throat spasm that can cause difficulty breathing.
• Extreme fatigue, accompanied by a decrease in the number of red blood cells and shortness of breath (hemolytic anemia), alone or accompanied by a decrease in the number of platelets, and kidney problems that cause little or no urine production (symptoms of hemolytic uremic syndrome), which can be fatal.
• Abnormal heart rhythm (QT interval prolongation), which can be seen on the electrocardiogram (ECG) and can be fatal.
• Heart attack (heart attack), angina pectoris (chest pain or discomfort)
• Muscle pain and swelling, accompanied by weakness, fever, or brownish-red urine (symptoms of muscle damage called rhabdomyolysis), which can be fatal.
• Esophageal inflammation (inflammation of the inner lining of the esophagus - the tube that connects the mouth to the stomach - which causes pain and difficulty swallowing).
• Abdominal pain, nausea, vomiting with blood or vomiting like "coffee grounds", dark/black stools with blood (symptoms of gastrointestinal ulcer, with possible bleeding or perforation), which can be fatal.
• Decreased blood flow to the intestine (intestinal ischemia), which can 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 risk of this type of cancer when taking oxaliplatin and certain other medicines.
• Abnormal liver nodules, non-cancerous (focal nodular hyperplasia).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines www.notificaram.es. By reporting side 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 an accidental spill, immediately inform the doctor or nurse.

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

Do not use this medicine after the expiry date that appears on the carton and on the label of the vial after EXP. The expiry date is the last day of the month indicated.

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

6. Contents of the pack and other information

Composition of Oxaliplatin Hikma

• The active ingredient is oxaliplatin.
• The other components are water for injectable preparations.

Appearance of the product and packaging content

The solution is transparent, colorless, and free of visible particles in suspension.

Each milliliter of solution contains 5 mg of the active ingredient 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.

Package sizes:

50mg/10ml: 1 vial

100mg/20ml: 1 vial

200mg/40ml: 1 vial

With or without protective plastic wrapping.

Only some package sizes may be marketed.

Marketing authorization holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n.º 8, 8A e 8B, Fervença

2705-906 Terrugem SNT

Portugal

Manufacturer

Thymoorgan Pharmazie GmbH

Schiffgraben 23

38690 Goslar

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

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

Date of last revision of this prospectus:March 2022

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

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This information is intended only for healthcare professionals:

Special precautions for handling and disposal

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

Instructions for handling the drug

Handling of this cytotoxic agent by healthcare personnel requires precautions to ensure the protection of the handler and the work area.

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

Personnel should be equipped with appropriate materials for handling the medicine, such as sleeves, protective mask, cap, protective glasses, sterile disposable gloves, protective suit for the work area, containers, and waste collection bags.

Feces and vomit should be handled with care.

Pregnant women should avoid handling cytotoxic agents.

Any broken container should be treated with the same precautions and considerations as contaminated waste. Contaminated waste should be incinerated in properly labeled rigid containers. See the Disposalsection below.

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

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

Special administration precautions

• DO NOT use injection material containing aluminum.
• DO NOT administer undiluted.
• ONLY use a 5% glucose solution for infusion as a diluent. DO NOT dilute with infusion solutions containing sodium chloride or chloride.
• DO NOT mix with other drugs in the same infusion bag or administer simultaneously through the same infusion line.
• DO NOT mix with alkaline solutions or medications, specifically 5-fluorouracil or folinic acid preparations containing tromethamine as an excipient and tromethamine salts of other medications. Alkaline solutions or medications will negatively affect the stability of oxaliplatin.

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

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

Instructions for use with 5-fluorouracil

Oxaliplatin should 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 the administration of concomitant medications, see the corresponding summary of product characteristics.

Concentrate for solution for infusion

Inspect the vial visually before use. Only transparent solutions without visible particles in suspension should be used.

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

Dilution for intravenous infusion

Extract the necessary volume of concentrate from the vials and then dilute it with 250-500 ml of a 5% glucose solution to administer a concentration of oxaliplatin not less than 0.25 mg/ml.

Administer by intravenous infusion.

From a microbiological point of view, the infusion preparation should be used immediately.

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

Chemical and physical stability has been demonstrated when diluted to concentrations 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.

Inspect the vial visually before use. Only transparent solutions without visible particles in suspension should be used.

This medicine is for single use. Any unused infusion solution should be discarded (see the Disposalsection below).

NEVER use sodium chloride or solutions containing chloride for dilution.

Infusion

Administration of oxaliplatin does not require prehydration.

Oxaliplatin diluted in 250-500 ml of a 5% glucose solution to obtain a concentration not less than 0.25 mg/ml should be infused through a central or peripheral venous line over 2-6 hours. When oxaliplatin is administered with 5-fluorouracil (5-FU), the infusion of oxaliplatin should precede that of 5-fluorouracil (5-FU).

Disposal

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

Dosage

Only for adults

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

The recommended dose of oxaliplatin for the treatment of metastatic colorectal cancer is 85 mg/m2 intravenously, repeated every 2 weeks, until disease progression or unacceptable toxicity.

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

Oxaliplatin should always be administeredbefore fluoropyrimidines,i.e., 5-fluorouracil(5FU).

Oxaliplatin is administered as a 2-6 hour intravenous infusion, diluted in 250-500 ml of a 5% glucose solution (50 mg/ml) to obtain 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

Medicinal product packaged for sale: 24 months.

Stability in use, after dilution

From a microbiological point of view, the infusion solution should be used immediately.

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

Chemical and physical stability has been demonstrated when diluted to concentrations 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.