Ipilimumab and nivolumab

Ipilimumab and nivolumab are types of cancer treatment called immunotherapy. They are used together to treat a number of different cancer types.

You pronounce ipilimumab as ih-pih-lih-moo-mab. You pronounce nivolumab ni-vol-you-mab.

How do ipilimumab and nivolumab work?

Ipilimumab and nivolumab work by blocking proteins that stop the immune system from working properly and attacking cancer cells. They help to make your immune system find and kill cancer cells. 

How do you have ipilimumab and nivolumab?

You have ipilimumab and nivolumab through a drip into your bloodstream (intravenously).

You might have treatment through a long plastic tube that goes into a large vein in your chest. The tube stays in place throughout the course of treatment. This can be a:

  • central line
  • PICC line
  • portacath

If you don't have a central line

You might have treatment through a thin short tube (a cannula) that goes into a vein in your arm. You have a new cannula each time you have treatment.

How often do you have ipilimumab and nivolumab?

You have ipilimumab and nivolumab as cycles of treatment. This means that you have the drugs and then a rest to allow your body to recover.

You have ipilimumab and nivolumab every 3 weeks for the first 4 treatments. After this, you only have nivolumab every 2 or 4 weeks.  

You have ipilimumab over 30 or 90 minutes depending on your cancer type. And you have nivolumab over 30 or 60 minutes.

You usually continue treatment for up to 2 years, as long as it is working and the side effects are not too bad.

Tests

You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver, kidneys and thyroid are working.

What are the side effects of ipilimumab and nivolumab?

Side effects can vary from person to person. They also depend on what other treatment you are having. 

This treatment affects the immune system. This may cause inflammation in different parts of the body which can cause serious side effects. They could happen during treatment, or some months after treatment has finished. In some people, these side effects could be life threatening.

When to contact your team

Your doctor, pharmacist or nurse will go through the possible side effects. They will monitor you closely during treatment and check how you are at your appointments. Contact your advice line as soon as possible if:

  • you have severe side effects

  • your side effects aren’t getting any better

  • your side effects are getting worse

Early treatment can help manage side effects better. 

Contact your healthcare team immediately if you have signs of infection, including a temperature above 37.5C or below 36C.

We haven't listed all the side effects here. Remember it is very unlikely that you will have all of these side effects, but you might have some of them at the same time.

Common side effects

These side effects happen in more than 10 in 100 people (more than 10%). You might have one or more of them. They include:

High temperature (fever)

If you get a high temperature, let your healthcare team know straight away. Ask them if you can take paracetamol to help lower your temperature.

Skin problems

Symptoms of skin problems can include a rash and itching.

Less commonly your skin might develop reddening of the skin, pale white patches of the skin (vitiligo), raised red crusty ring-like patches, flaky skin, hives or spots.

In rare cases, some people get severe peeling of the skin (toxic epidermal necrolysis). Your doctor will check your skin regularly throughout your treatment.

Let your doctor or nurse know if you get any skin rash or a rash that gets worse, or you’re worried about any other changes to your skin.

Diarrhoea or constipation

Contact your advice line if you have 4 loose watery poos (diarrhoea) or more in 24 hours. Or if you have diarrhoea for more than 3 days. Or if you can't drink to replace the lost fluid. 

Also, call if you have blood or mucus in your poo, your poo looks darker than usual, or if you develop pain in your tummy (abdomen).

You can help to prevent worsening your diarrhoea by eating less fibre, avoiding raw fruits, fruit juice, cereals and vegetables, and drinking plenty to replace the fluid lost.

Constipation is easier to sort out if you treat it early. Drink plenty of fluids and eat as much fresh fruit and vegetables as you can. Try to take gentle exercise, such as walking. Tell your doctor, nurse or pharmacist if you are constipated for more than 3 days. They can prescribe a laxative.

Inflammation of the bowel

Inflammation of the bowel can cause abdominal pain, bloating or diarrhoea. Speak to your doctor if you have these symptoms.

Headaches and dizziness

Tell your healthcare team if you keep getting headaches. They can give you painkillers to help.

Tiredness and weakness

Tiredness and weakness (fatigue) can happen during and after treatment. Doing gentle exercises each day can keep your energy up. Don't push yourself, rest when you start to feel tired and ask others for help.

Tell your team if you feel tired and weak, you may need a blood test to check your hormone levels.

Changes to thyroid levels

Your thyroid hormone level may go up (hyperthyroidism) or there might not be enough (hypothyroidism). Symptoms can include feeling tired or having too much energy, gain or lose weight, sweat more than usual, feel anxious, nervous, irritable, or have mood swings or a fast pounding heartbeat.

Pain

You might feel some pain in your bones, muscles, joints or tummy. Tell your doctor or nurse so they can find the cause and give you medicine to help.

Call 999 or go to A&E if you have chest pain. Call 999 or go to A&E if you have chest pain.

Changes in blood sugar levels

You might get changes to your blood sugar levels. Some of the symptoms for high blood sugar levels (hyperglycaemia) are feeling very thirsty, a dry mouth, passing urine very often, feeling tired, blurred vision, weight loss, feeling or being sick, and fruity smelling breath.

Or you might get low blood sugar levels (hypoglycaemia). These symptoms include: sweating, feeling hungry, shaky or trembling, a fast heartbeat, dizziness, changes to your mood, and feeling tired.

Less commonly you may develop diabetes.

Contact your team or advice line if you have any of these symptoms.

Liver changes

You might have liver changes that are usually mild and unlikely to cause symptoms. They usually go back to normal when treatment finishes. You have regular blood tests to check for any changes in the levels of chemicals produced by the liver.

Kidney changes

You might have some changes in the way your kidneys work. You have regular blood tests to check how well they are working.

In some cases, your kidneys might stop working - symptoms can include high blood pressure, feeling or being sick, not passing enough urine, swelling of your legs, ankles and feet, and confusion.

High levels of pancreatic enzymes in your blood

You might have high levels of substances (enzymes) called amylase and lipase in your blood. It doesn’t usually cause symptoms. You have regular blood tests to check this and they usually return to normal when you stop treatment.

Changes in the levels of minerals and salts in your body

Your blood contains different minerals and salts. This treatment can change the levels of calcium, magnesium, sodium and potassium in your blood.

Rarely, you might get high levels of mineral and salts in your blood due to the breakdown of tumour cells (tumour lysis syndrome). You have regular blood tests during treatment to check this.

Feeling short of breath (breathlessness) or cough

You might feel breathless when doing your normal day to day activities or from climbing a short flight of stairs. There could be different causes for this. Call your advice line if you feel short of breath.

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. It might help to avoid fatty or fried foods, eat small meals and snacks and take regular sips of water. Relaxation techniques might also help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is easier to prevent sickness rather than treat it once it has started.

Loss of appetite

You might lose your appetite for various reasons while having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

Lower than normal level of blood cells in your blood

Your blood tests might show a low number of red blood cells (anaemia), white blood cells (these help fight infection) or platelets (helps your blood clot). 

You have regular blood tests to check your blood cell count levels.

Nose, throat and sinus infection

You might have an infection of your upper respiratory tract. This includes your nose, throat and sinuses.

Lung problems

You might have lung problems such as an infection (pneumonia), inflammation (pneumonitis) or fluid around the lungs (pleural effusion).

Swollen hands and feet

Swelling of hands and feet is due to fluid build up. This is called oedema. Let your doctor or nurse know if you have any swelling.

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (between 1 and 10%). You might have one or more of them. They include:

  • a blood clot in your lung (pulmonary embolism) – call 999 or go to A&E if you have pain in your chest or upper back, difficulty breathing or cough up blood
  • a reaction during the infusion – you might get a rash, shortness of breath, redness or swelling of the face and dizziness – tell your team straight away
  • numbness, tingling in the hands and feet or loss of feeling, or muscle spasms and weakness - call your advice line straight away if you have any of these symptoms
  • changes to hormone levels – symptoms might include fatigue, loss of appetite and weight loss, low blood pressure, feeling or being sick and darkening of your skin
  • eye problems including blurred vision. You might have an infection (conjunctivitis) – the eye may feel gritty, itchy, sticky from pus, watery and look red.
  • high levels of a type of white blood cell called eosinophils in your blood
  • pituitary gland problems that can cause fatigue, vision problems and headaches
  • inflammation of parts of the body such as the thyroid, pituitary gland, liver, eyes, lungs, pancreas, heart and joints
  • fast heart beat
  • lack of fluid in your body (dehydration)
  • mouth sores and ulcers
  • dry mouth
  • shivering or shaking (chills)
  • weight loss

Rare side effects

This side effects happens in fewer than 1 in 100 people (fewer than 1%). You might have one or more of them. They include:

  • inflammation of tissues covering the brain and spinal cord (aseptic meningitis) - symptoms might include fever, headaches, neck pain or stiffness, feeling or being sick or sensitivity to light
  • swelling in the brain
  • clumping of cells to make small lumps in your body, often in the lungs (sarcoidosis)
  • a build up of a substance called ketones in the blood (diabetic ketoacidosis) – symptoms include feeling very thirsty, being sick, passing urine more than usual, and passing out
  • imbalance of substances in your blood (metabolic acidosis) – it can cause confusion, tiredness, shortness of breath and headaches
  • the immune system attacking the nervous system (Guillain-Barre syndrome) - causing numbness, weakness and pain in the body
  • an irregular or abnormal heart beat
  • a tear in the bowel wall (perforation)
  • stiffness in the muscles
  • a problem with the parts of the body that produce fluids, like tears and spit (Sjögren's syndrome)
  • damage to muscle tissue releasing certain substances into the blood
  • urinary tract infection

Other side effects

If you have side effects that aren't listed on this page, you can look at the individual drug pages:

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do I need to know?

Other medicines, foods and drink

Cancer drugs can interact with medicines, herbal products, and some food and drinks. We are unable to list all the possible interactions that may happen. An example is grapefruit or grapefruit juice which can increase the side effects of certain drugs.

Tell your healthcare team about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies. Also let them know about any other medical conditions or allergies you may have.

Pregnancy and contraception

It is unknown whether treatment may or may not harm a baby developing in the womb. It is important not to become pregnant or get someone pregnant while you are having treatment. Let your team know straight away if you or your partner become pregnant while having treatment.

Talk to your doctor or nurse about effective contraception you can use during treatment. Ask how long you should use it before starting treatment and after treatment has finished.

Fertility

It is not known whether this treatment affects fertility in people. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Breastfeeding

It is not known whether these drugs come through into the breast milk. Doctors usually advise that you don’t breastfeed during this treatment.

Treatment for other conditions

If you are having tests or treatment for anything else, always mention your cancer treatment. For example, if you are visiting your dentist.

Immunisations

Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and one of the shingles vaccines called Zostavax.

You can have:

  • other vaccines, but they might not give you as much protection as usual
  • the flu vaccine (as an injection)
  • the coronavirus (COVID-19) vaccine - talk to your doctor or pharmacist about the best time to have it in relation to your cancer treatment

Members of your household who are aged 5 years or over are also able to have the COVID-19 vaccine. This is to help lower your risk of getting COVID-19 while having cancer treatment and until your immune system Open a glossary item recovers from treatment.

Contact with others who have had immunisations - You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine. Sometimes people who have had the live shingles vaccine can get a shingles type rash. If this happens they should keep the area covered.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray as this is a live vaccine. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn't possible, wash your hands well after changing their nappy.

More information about this treatment

For further information about this treatment and possible side effects go to the electronic Medicines Compendium (eMC) website. You can find the patient information leaflet on this website.

You can report any side effect you have to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.

  • Electronic Medicines Compendium
    Accessed March 2023

  • Immunisation against infectious diseases
    UK Health Security Agency
    First published: September 2013 and regularly updated on the Gov.UK website

  • Nivolumab in combination with ipilimumab for treating advanced melanoma

    National Institute for Health and Care Excellence, July 2016

  • Nivolumab with ipilimumab for previously treated metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency

    National Institute for Health and Care Excellence, July 2021

  • Nivolumab with ipilimumab for untreated advanced renal cell carcinoma

    National Institute for Health and Care Excellence, March 2022

  • Nivolumab with ipilimumab for untreated unresectable malignant pleural mesothelioma

    National Institute for Health and Care Excellence, August 2022

Last reviewed: 
10 May 2023
Next review due: 
10 May 2026

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