Hydroxyurea dosage remains a challenging phenomenon for a drug that has changed how we manage sickle cell disease.

Hydroxyurea dosage. Prescribe it the right way!

Hydroxyurea dosage remains a challenging phenomenon for a drug that has changed how we manage sickle cell disease. We’ve extensively discussed hydroxyurea in sickle cell disease through a series of articles on the website, including its administration and adverse effects. The drug has properties that render it a ‘perfect’ therapeutic agent for use among people living with sickle cell disease. In today’s article, we demystify the nitty-gritty that surrounds its dosage.

Hydroxyurea is a chemotherapeutic agent. It implies that you do not use it unless you fully understand its mechanism of action, desired and adverse effects. It’s imperative that you don’t prescribe it unless you are well acquainted with it, or else you will do more harm than good.

The starting dose is 10-15mg/kg body weight per day – that is, the child has 10kg, the starting dose will be 100-150mg. We should note that currently, hydroxyurea exists in 500mg capsule forms only on the Ugandan market. We haven’t got the liquid formulations yet. It means that it is difficult to approximate any dose below 250mg. We hope it will change sooner than later.

We increase the dose by 5mg/kg body weight per day every four to six weeks until we achieve the maximal toxic dose (MTD). To understand the maximal toxic dose, we should know that the aim of administering hydroxyurea is to increase the amount of foetal haemoglobin (HbF) and reduce that sickle haemoglobin (HbS). Because people living with sickle cell disease have inherently raised neutrophil counts, hydroxyurea targets these cells and; we use their numbers to achieve this dose, usually at 35mg/kg body weight per day. If the patient’s neutrophils are about 2000 to 3000 cells per microlitre of blood, we deduce that we’ve achieved the maximum toxic dose. It is the dose at which hydroxyurea has maxed out its effects without necessarily causing adverse effects. At a neutrophil count of 2000 to 3000 cells per microlitre of blood, people living with sickle cell disease are almost ‘crises’ free.

We neither taper nor load hydroxyurea – say 1000mg once a day for two weeks and then 500mg for the next two weeks. Once we begin hydroxyurea administration, we don’t stop it unless we have documented adverse effects like drug-induced hepatitis – these are very rare.

Related articles:

Hydroxyurea in sickle cell disease: Administration and Adverse Effects: Part 3

It’s imperative to ascertain and acknowledge that hydroxyurea is still an expensive drug. So, as a clinician, you must affluently explain what the drug is such that the patients and their attendants understand. It will help them assess the risk-benefit analysis such that they make informed choices.

We must monitor the drug and advise the patients to report for routine check-ups to promptly observe a positive clinical or haematological effect and inquire about the side effects.

In a nutshell, hydroxyurea dose starts at 10-15mg/kg/day. We escalate it by 5mg/kg/day every 4-6 weeks up to when we achieve a maximal toxic dose that’s approximately 35mg/kg/day. We must not halt the drug once we begin it such that we acquire its desired effects in reducing the neutrophil account and abnormal haemoglobin S levels.

 

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