Hydroxyurea for treatment of sickle cell disorder : University College London Hospitals NHS Foundation Trust

What is hydroxyurea?

Hydroxyurea is a medicine which has been used to treat various blood disorders for many years. It is also known as hydroxycarbamide. Over the past 30 years, it has helped people with sickle cell disorder (SCD) manage their condition more effectively. Before hydroxyurea, the main treatments for SCD included pain relief, antibiotics, and blood transfusions. Bone marrow transplants were the only way to change the course of the condition, but now hydroxyurea offers a new option.

There is growing evidence for using hydroxyurea in both children and adults with SCD and thalassaemia. The national standards of care listed below recommend hydroxyurea in a variety of situations including:

‘Standards for the Clinical Care of Adults with Sickle Cell Disease in the UK’
‘Sickle Cell Disease in Childhood – Standards and Guidelines for Clinical Care’
British Society for Haematology: ‘Guidelines for the use of hydroxycarbamide in children and adults with sickle cell disease’.

The best evidence comes from two large multi-centre studies carried out in America. In the first study¹, published in 1995, a large group of patients received either hydroxyurea capsules or a placebo. A placebo is an identical looking dummy drug. In the second study², published in 2012, newborns with SCD received either placebo or hydroxyurea liquid. This study was called the BABY HUG trial. In both studies, neither the patients, parents nor the doctors knew which drug they took, so that the benefits and side effects could be monitored objectively. They monitored all patients for nearly two years. In both studies, about eight out of 10 patients who took hydroxyurea found their health improved significantly. The improvements included:

A longer pain-free period after starting treatment
A longer period before the next painful episode
Fewer episodes of chest crises or sickle chest syndrome
Fewer blood transfusions.

Overall, people who took hydroxyurea had fewer and less severe crises. Unfortunately, it is not possible to predict who will benefit from taking hydroxyurea. More recently the BABY HUG study showed benefits in babies treated from birth.

In the United States and the UK, all children with severe forms of SCD (HbSS and HbSBeta zero thalassaemia) are now offered hydroxyurea soon after birth, regardless of their symptoms. Children with other sickling disorders are also offered hydroxyurea if they have symptoms.

It appears to work in at least three ways:

Increases fetal haemoglobin. This can take weeks or months to show results.
Reduces red blood cell stickiness. When red blood cells stick to the blood vessel lining, they may start a sickle cell crisis. This may be why some people notice that they feel better soon after starting treatment.
Decreases white blood cells and platelets. These are often raised in people with SCD. White blood cells produce a substance that causes inflammation which may worsen a sickle cell crisis. Having fewer white cells makes this less likely. Platelets also contribute to stickiness.

Hydroxyurea comes in a liquid for children and capsules for adults. Treatment starts with a low dose, usually at:

20mg/kg in a child
0.5g (one capsule) or 15mg/kg (rounded up to the nearest capsule) in an adult.

We will gradually increase the dose every two to three weeks until we reach the right dose for you or your child. This will be the dose that gives you or your child the most benefits without any side effects. We base the decision on you or your child’s symptoms and the blood test results. It may take several weeks to reach the right dose. After that, you or your child will need blood tests every two to three months.

If you or your child experience side effects or a blood test shows a problem, we may stop the hydroxyurea or restart it at a lower dose.

Pregnancy and contraception. If you are sexually active, you must use contraception while taking hydroxyurea. This is because its effects during pregnancy have not been well-tested. Both the woman and man should stop taking it for three months before trying to get pregnant. Once the woman is pregnant, the man can restart his hydroxyurea. Women must not take hydroxyurea while pregnant and during breastfeeding.

Patients who are not willing to have regular check-ups will not be prescribed hydroxyurea.

You will need to sign a consent form if you agree to take hydroxyurea, or if you agree for your child to take it. If you are under 18 years of age, a parent or guardian may need to sign the consent form, but you can sign it too.

Most people who take hydroxyurea remain well and have very little or no side effects. It is important that you do not stop taking hydroxyurea if you don’t notice any changes straight away. It may take a couple of months before you reach the right dose and notice any benefits.

Hydroxyurea occasionally causes:

Nausea and vomiting
Skin rashes
Hair loss
Diarrhoea
Infection or bleeding (if blood counts drop significantly)
Darkening of the nails.

Some medicines can increase the risk of cancer. This is true of several medicines which work in a similar way to hydroxyurea. But there is no evidence that the risk of cancer is increased in people with SCD who take hydroxyurea.

There is no evidence that hydroxyurea affects fertility. But we advise people to stop taking it before conception. This is because it has not been tested in large trials on pregnant women. If you are worried about fertility or starting a family, talk to your consultant. They can advise you on fertility, sperm bank collection and contraception.

Haematology admin team:

uclh.redcelladminteam@nhs.net

Haematology clinical nurse specialists (CNSs):

uclh.redcell.cnsteam@nhs.net

Haematology advice line (office hours, adults and children):

020 3447 7359

Adult haematology advice line (out of hours):

07852 220 900

Paediatric helpline (out of hours):