- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of hydroxycarbamide.
Cervical cancer: in conjunction with radiotherapy
Leukaemia - chronic myeloid
Management of thrombocythemia
Treatment of polycythemia vera
Chronic myeloid leukaemia (CML): Pre-TKI treatment phase before confirmation of BCR-ABL fusion with an immediate need for therapy due to high leukocyte and thrombocyte counts or palliative care in patients in blastic phase with leucocytosis and thrombocytosis.
Cervical cancer, in conjunction with radiotherapy.
Essential thrombocythemia in patients with a high risk for thromboembolic events.
Polycythemia vera in patients with a high risk for thromboembolic events.
Prevention of recurrent vaso-occlusive crises in sickle cell syndrome
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Doses should be based on the real or ideal weight of the patient, whichever is less.
Hydroxycarbamide should be started 7 days before concurrent irradiation therapy. When hydroxycarbamide is used concurrently with radiotherapy, adjustment of radiation dosage is not usually necessary.Concurrent use of hydroxycarbamide with other myelosuppressive agents may require adjustments of dosages.
A trail period of 6 weeks is sufficient to determine the antineoplastic effect.
Other formulations with different indications and strengths are available.
Chronic myeloid leukaemia (also referred to as continuous therapy)
Initial dose: 40mg/kg/day
Maintenance dose: 20 to 30mg/kg/day
One manufacturer recommends that the dose is reduced to 20mg/kg when the white cell count falls below 20 x 10 the power of 9/L and then titrated individually to maintain the white cell count between 5 and 10x 10 to the power of 9/L.
Cervical cancer (also referred to as intermittent therapy)
80mg/kg as a single dose given every third day.
Using this intermittent regime, the likelihood of white blood cell depression is diminished, but if white cell counts are low, 1 or more doses should be omitted.
Initial dose: 15mg/kg/day
Dosage adjust to maintain a platelet count below 600 x 10 to the power of 9/L, without lowering the white blood cell count below 4 x 10 to the power of 9/L.
Initial dose: 15 to 20mg/kg/day
Dosage adjust to maintain the haematocrit below 45% and a platelet count below 400 x 10 to the power of 9/L
In most patients this can be achieved with a daily dose of 500 to 1000mg. If haematocrit and platelet counts can be controlled, treatment should be maintained indefinitely.
Patients with Renal Impairment
Manufacturers advise caution but give no specific dosing recommendations.
The Renal Drug Handbook suggests the following dose adjustments:
Glomerular filtration rate greater than 60ml/minute: 85% of normal dose and titrate to response.
Glomerular filtration rate 45 to 60ml/minute: 80% of normal dose and titrate to response.
Glomerular filtration rate 30 to 45ml/minute: 75% of normal dose and titrate to response.
Glomerular filtration rate 10 to 30ml/minute: 50% of normal dose and titrate to response.
Glomerular filtration rate less than 10ml/minute: 20% or normal dose and titrate to response.
Additional Dosage Information
CML, cervical cancer, essential thrombocythemia and polycythemia vera in patients at high risk of thromboembolism
An adequate trial period for determining the antineoplastic effect of hydroxycarbamide is 6 weeks. If there is a significant clinical response, therapy may be maintained indefinitely.
For oral administration. The capsules should swallowed whole and not be allowed to disintegrate in the mouth. Some manufacturers suggest that capsule contents may be dispersed in water immediately before administration. Care should be taken not to allow inhalation or contact with the skin or mucous membranes of the contents and to ensure any spillages are dealt with immediately.
Leucocyte count below 2.5 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Precautions and Warnings
Children under 18 years
History of radiotherapy
Glucose-galactose malabsorption syndrome
Myelosuppression secondary to chemotherapy
Positive HIV status
Live virus vaccine should not be given for 6 months after treatment
May exacerbate previously existing erythema
Talimogene laherparepvec should not be given for 6 months after treatment
Advise patient ability to drive or operate machinery may be impaired
Give pre-treatment counselling and consideration of sperm cryopreservation
May be increased risk of skin cancer
Not all available brands are licensed for all indications
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
Ensure patient has adequate fluid intake
Staff: Not to be handled by pregnant staff
Correct anaemia with transfusions before and during treatment
Monitor renal and hepatic function before and during treatment
Monitor for signs and symptoms of interstitial lung disease
Monitor for signs of bone marrow depression
Monitor full blood counts weekly
Monitor patients for development of second primary malignancies
Monitor serum folic acid levels regularly
Monitor skin changes
Monitor uric acid levels
Consider discontinuing if pulmonary adverse events suspected/confirmed
Discontinue if evidence of significant bone marrow depression
Suspend treatment if leukocyte count less than 2.5 x 10 to the power 9/L
Suspend treatment if platelets fall below 100,000/cubic mm
Discontinue/review treatment if cutaneous vasculitic ulcers develop
Female: Ensure adequate contraception during treatment
Male: Contraception required during and for 3 months after treatment
Advise patient on appropriate sun protection methods
Erythrocytic abnormalities are often seen early in the course of hydroxycarbamide. The morphological change resembles pernicious anaemia, but is not related to vitamin B12 or folic acid deficiency. The macrocytosis may mask the incidental development of folic acid deficiency. Hydroxycarbamide may delay plasma iron clearance and reduce the rate of iron utilisation by erythrocytes. It does not appear to alter the red blood cell survival time
Secondary leukaemia has been reported in patients receiving long term treatment for myeloproliferative disorders such as polycythemia vera, thrombocythemia and vaso-occlusive crises in sickle cell syndrome. It is unknown whether this leukaemogenic effect is related to hydroxycarbamide or associated with the patients underlying disease. Cases of squamous cell carcinomas have been reported during long term treatment, therefore it is advisable to monitor any skin changes.
Cutaneous vasculitic toxicities including vasculitic ulcerations and gangrene have occurred in patients with myeloproliferative disorders during therapy. The risk is increased in patients who have received prior or concomitant interferon therapy. Due to the potentially severe clinical outcomes hydroxycarbamide should be reviewed and the dose reduced or discontinued if cutaneous vasculitic ulcerations develop. Discontinuation of hydroxycarbamide usually leads to a slow resolution of the ulcers.
Erythema caused by previous irradiation may be exacerbated by hydroxycarbamide therapy.
Pregnancy and Lactation
Hydroxycarbamide is contraindicated during pregnancy.
The manufacturer does not recommend using hydroxycarbamide during pregnancy, unless the potential benefits outweigh the risks. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Hydroxycarbamide is contraindicated during breastfeeding.
Use of hydroxycarbamide when breastfeeding is contraindicated by the manufacturer. Hydroxycarbamide is present in human breast milk, a decision should be made to discontinue hydroxycarbamide or discontinue breastfeeding.
Elevation of liver enzymes
Impaired renal tubular function
Increased risk of skin cancer
Increased uric acid level
Interstitial lung disease
Scaling of skin
Serum bilirubin increased
Serum creatinine increased
Serum urea increased
Tumour lysis syndrome
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: November 2019
The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
Summary of Product Characteristics: Hydrea Capsules 500mg. E.R. Squibb & Sons Ltd. Revised July 2019.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 16 October 2019
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.