Oxaliplatin is a chemotherapy drug that is given as a treatment for some types of cancer. It is most commonly used to treat bowel cancer. This information describes oxaliplatin, how it is given and some of its possible side effects.

What oxaliplatin looks like

Oxaliplatin is a colourless fluid.

How it is given

Oxaliplatin may be given:

• by injection into a vein (intravenously), through a fine tube (cannula) inserted into the vein
• through a central line (Hickman, Portacath), which is inserted under the skin into a vein near the collarbone, or into a PICC, which is inserted into a vein in the crook of the arm.

Oxaliplatin is normally infused over 2 hours.

Chemotherapy is usually given as a course of several sessions (or cycles) of treatment over a few months. The length of your treatment and the number of cycles you have will depend on the type of cancer for which you are being treated.

Possible side effects

Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others experience more. The side effects described in this information will not affect everyone who is given oxaliplatin and may be different if you are having more than one chemotherapy drug.

We have outlined the most common side effects as well as rarer ones, so that you can be aware of them if they occur. However, we have not included those that are very rare and therefore extremely unlikely to affect you. If you notice any effects which you think may be due to the drug, but which are not listed in this information, please discuss them with your doctor or chemotherapy nurse.

Numbness or tingling in hands or feet

Oxaliplatin can have an effect on the nerve endings, which is known as peripheral neuropathy. This may result in feelings of numbness or tingling, especially in the hands, feet, neck or throat.

For some people, these symptoms can be triggered by anything cold, such as iced drinks and cold air. If you notice that your symptoms are related to the cold you should avoid cold drinks and wrap up warmly in the cold weather. It is important to report your symptoms to your doctor as they may be controlled by slightly lowering the dose of the drug. The Vitamin B6 (pyridoxine) tablets can also help the neuropathy and these may be given to you.

Sometimes the tingling or numbness may not happen with the first treatment, but after several treatments. This is known as a ‘cumulative effect’ and should improve after the treatment has finished.

This is the most common side effect of oxaliplatin, and occurs in over 90% of patients. For many patients it is fairly mild and lasts just a few days between each treatment cycle, but for some it is more severe, and you may need a dose reduction, or even the drug stopped altogether.

Some recent evidence suggests that giving infusions of calcium and magnesium salts before and after oxaliplatin can help to protect the nerve endings. A clinical trial showed this decreased the severity of neuropathy by around 50% All my patients receiving oxaliplatin now have these additional infusions given as standard. It does however lengthen the overall treatment time by about an hour but I feel it is worth it.

The neuropathy can persist after chemotherapy has finished and it slowly heals. The healing can take many months – 6 to 12 months, or even longer, is not unusual. If the tingling is troublesome medications such as amitriptyline or gabapentin are sometimes given to calm it down.

Lowered resistance to infection

Oxaliplatin can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin seven days after treatment has been given. Your blood cells will then increase steadily and will usually have returned to normal before your next cycle of chemotherapy is due.

Contact your doctor or the hospital straightaway if:

• your temperature goes above 38ºC (100.5ºF)
• you suddenly feel unwell (even with a normal temperature).

You will have a blood test before having more chemotherapy to make sure that your cells have recovered. Occasionally it may be necessary to delay your treatment if the number of blood cells (the blood count) is still low.

Bruising or bleeding

Oxaliplatin can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, or bleeding gums.

Anaemia (low number of red blood cells)

While having treatment with oxaliplatin you may become anaemic. This may make you feel pale, tired and short of breath on exertion. Let your doctor or nurse know if these symptoms are a problem. You may need a blood transfusion or Iron tablets.

Feeling sick (nausea) and being sick (vomiting)

This is not too common with oxaliplatin. If you do feel sick this may begin a few hours after the treatment is given and last for a few days. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce this feeling. If the sickness is not controlled, or continues, tell your doctor; they can prescribe other anti-sickness drugs which may be more effective.

Diarrhoea

Fairly unusual with oxaliplatin, usually attributed to the fluorouracil or capecitabine that is given with it. This can usually be easily controlled with medicine but tell your doctor if it is severe or if it continues. It is important to drink plenty of fluids if you have diarrhoea.

Tiredness and feeling weak

You may feel very tired. It is important to allow yourself plenty of time to rest.

Less common side effects

Difficulty swallowing and breathing problems

Rarely the area around the voice box (larynx) can be affected by oxaliplatin. This can make you feel as if you can’t swallow and can cause breathing difficulties. This is known as laryngeal spasm. It can be very frightening, but should only be a temporary side effect. This symptom may be triggered by cold and it is advisable to avoid things like cold drinks for a few days after treatment. It is important to let the doctor know if you have this side effect.

A severe reaction is very unusual but around 10% patients can have this in a mild form. Keep calm and keep warm. Slow deep breaths and it will settle. The chance of this happening again can be reduced by increasing the infusion time of oxaliplatin from 2 hours to 4 or even 6 hours, so do let us know.

Allergic reaction

Signs of an allergic reaction include skin rashes and itching, a high temperature, shivering, redness of the face, dizziness, headache, breathlessness and anxiety. You will be monitored for any signs of an allergic reaction during the treatment. Tell your doctor or nurse if you have any of these signs.

Sore mouth and ulcers

This is unusual with oxaliplatin. Your mouth may become sore, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Tell your nurse or doctor if you have any of these problems, as special mouthwashes and medicines to prevent or clear any mouth infection can be prescribed.

Taste changes

You may notice that your food tastes different. Normal taste will usually come back after the treatment finishes.

Additional information

Injection site

When oxaliplatin is given it may cause pain along the vein, especially if it is given through a cannula. This can persist for weeks. Let the nurse or doctor know if you experience any pain. Also if a bit of oxaliplatin leaks out of the vein it can cause a patch of numbness and tingling on the skin. This too will also settle over weeks.

Risk of blood clots

Cancer can increase your risk of developing a blood clot (thrombosis), and having chemotherapy may increase this risk further. A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it is important to tell your doctor straightaway if you have any of these symptoms. However, most clots can usually be successfully treated with drugs to thin the blood.

Other medicines

Some medicines can be harmful to take when you are having chemotherapy. Let your doctor know about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

Fertility

Your ability to become pregnant or father a child may be affected by taking this drug. You may wish to discuss fertility with your doctor before starting treatment.

Contraception

It is not advisable to become pregnant or father a child while taking oxaliplatin, as the developing foetus may be harmed. It is important to use effective contraception while taking this drug, and for at least a few months afterwards. Again, if appropriate, discuss this with your doctor.

---

ADDITIONAL INFORMATION FOR HEALTHCARE PROFESSIONALS

ADVERSE REACTIONS SIGNIFICANT — Percentages reported with monotherapy.

>10%:

• Central nervous system: Fatigue (61%), fever (25%), pain (14%), headache (13%), insomnia (11%)
• Gastrointestinal: Nausea (64%), diarrhea (46%), vomiting (37%), abdominal pain (31%), constipation (31%), anorexia (20%), stomatitis (14%)
• Hematologic: Anemia (64%; grades 3/4: 1%), thrombocytopenia (30%; grades 3/4: 3%), leukopenia (13%)
• Hepatic: AST increased (54%; grades 3/4: 4%), ALT increased (36%; grades 3/4: 1%), total bilirubin increased (13%; grades 3/4: 5%)
• Neuromuscular & skeletal: Peripheral neuropathy (may be dose limiting; 76%; acute 65%; grades 3/4: 5%; persistent 43%; grades 3/4: 3%), back pain (11%)
• Respiratory: Dyspnea (13%), cough (11%)

1% to 10%:

• Cardiovascular: Edema (10%), chest pain (5%), peripheral edema (5%), flushing (3%), thromboembolism (2%)
• Central nervous system: Dizziness (7%)
• Dermatologic: Rash (5%), alopecia (3%), hand-foot syndrome (1%)
• Endocrine & metabolic: Dehydration (5%), hypokalemia (3%)
• Gastrointestinal: Dyspepsia (7%), taste perversion (5%), flatulence (3%), mucositis (2%), gastroesophageal reflux (1%), dysphagia (acute 1% to 2%)
• Genitourinary: Dysuria (1%)
• Hematologic: Neutropenia (7%)
• Local: Injection site reaction (9%; redness/swelling/pain)
• Neuromuscular & skeletal: Rigors (9%), arthralgia (7%)
• Ocular: Abnormal lacrimation (1%)
• Renal: Serum creatinine increased (5% to 10%)
• Respiratory: URI (7%), rhinitis (6%), epistaxis (2%), pharyngitis (2%), pharyngolaryngeal dysesthesia (grades 3/4: 1% to 2%)
• Miscellaneous: Allergic reactions (3%); hypersensitivity (includes urticaria, pruritus, facial flushing, shortness of breath, bronchospasm, diaphoresis, hypotension, syncope: grades 3/4: 2% to 3%); hiccup (2%)

<1% (Limited to important or life-threatening; reported with mono- and combination therapy):

Acute renal failure, alkaline phosphatase increased, anaphylactic/anaphylactoid reactions, anaphylactic shock, angioedema, colitis, cranial nerve palsies, deep tendon reflex loss, deafness, dysarthria, eosinophilic pneumonia, extravasation (including necrosis), fasciculations, hemolytic anemia (immuno-allergic), hemolytic uremia syndrome, hepatotoxicity, hypokalemia (due to severe diarrhea, vomiting), ileus, INR increased, interstitial lung diseases, interstitial nephritis (acute), intestinal obstruction, Lhermittes’ sign, metabolic acidosis, necrosis (following extravasation), neutropenic fever, optic neuritis, pancreatitis, perisinusoidal fibrosis, prothrombin time increased, pulmonary fibrosis, seizure, thrombocytopenia (immuno-allergic), tubular necrosis (acute), veno-occlusive liver disease (sinusoidal obstruction syndrome and perisinusoidal fibrosis), visual acuity decreased, visual field disturbance

---

PHARMACODYNAMICS / KINETICS

• Distribution: Vd: 440 L
• Protein binding: >90% primarily albumin and gamma globulin (irreversible binding to platinum)
• Metabolism: Nonenzymatic (rapid and extensive), forms active and inactive derivatives
• Half-life elimination: Terminal: 391 hours; Distribution: Alpha phase: 0.4 hours, Beta phase: 16.8 hours
• Excretion: Primarily urine (~54%); feces (~2%)