No drug is safe to administer to any patient, not even vitamin supplements. And because hydroxyurea is an anticancer per se, documentation that includes, but not limited to informed consent with the patient or the parents or guardians in cases of minor is of paramount importance. Before administering the drug, hold discussions about the monitoring requirements, potential toxicity, as well as teratogenicity and conception requirements.
Several baseline investigations should be done before starting any patient on hydroxyurea as they will act as the reference for monitoring and therapeutic response. These are;
- Documented complete physical exam (all vital signs without excluding the weight, height, and pulse oximetry);
- Haemoglobin electrophoresis with the quantitative percentage of fetal haemoglobin;
- Complete blood count with differential and reticulocyte count;
- Chemistry profile that includes electrolytes, LDH, total protein, albumin, and total bilirubin;
- Liver function tests, especially AST and ALT;
- Renal function tests that include blood urea nitrogen and creatinine;
- Serum B12 and folate;
- Serum iron, total iron-binding capacity (TIBC) and ferritin; hepatitis B, C, Parvovirus B19, and HIV serology; and
- A pregnancy test.
Hydroxyurea cause macrocytosis. It may mask iron, folate or vitamin B12 deficiency. We avoid this by knowing the baseline values for these three nutrients.
The starting dose is typically 10-15mg/kg/day given as a single daily dose. It can be escalated by 5mg/kg/day every 4 – 6 weeks. We increase it until there’s either evidence of haematological toxicity. It occurs when we have reached the maximal toxic dose (MTD) or an absolute neutrophil count of 2000- 3000 cells/ վL or a 35mg/kg/day.
You can, however, stop dosing escalation if there is a positive clinical +/- haematological effect before MTD. Evidence supports achieving the maximal toxic dose for further clinical efficacy. Evaluate the dosing on every monitoring visit.
Hydroxyurea comes in 500mg capsules. Liquid formulations are available in selected markets.
During the monitoring visit, perform laboratory evaluation every 2-4 weeks as well as to inquire about the side effects, sexual activity, and birth control. Do the quantitative fetal haemoglobin every 3-6 months. Perform a detailed clinical examination every four weeks, focusing on any evidence of toxicity, and these should continue the patient is stable, MTD has bed attained for eight weeks.
Once the patient is stable, you have achieved the MTD, conduct clinical and laboratory evaluations every 4 -8 weeks. Do quantitative HbF every 6 – 12 months, CBC with differential and reticulocyte count every 4 – 8 weeks, ALT, AST, BUN, Cr every six months. Inquiry into the side effects, sexual activity and birth control, haematological toxicity should be an on-going process.
Few reports about the adverse effects exist to date. They are, however, mild and patients can tolerate them. These include headache, abdominal discomfort, and nausea. Skin hyperpigmentation is sporadic and is independent of the dosing. Transient neutropenia that is reversible is not uncommon, as well as reticulocytopenia in younger patients. Severe cytopenias are extremely rare. There are no documented increased risks of malignancy or teratogenicity. It, however, DOES NOT improve its safety in pregnancy.
By this time, you’ve had whatever you need to have the drug administered to the right patient. Lastly, the next article will summarise the recommendations on the use of hydroxyurea in sickle cell disease as put forth by the expert panel on evidence-based management of sickle cell disease.