Drugs List

Therapeutic Indications

Uses

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.

Unlicensed Uses

Prevention of recurrent vaso-occlusive crises in sickle cell syndrome

Administration

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.

Contraindications

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
Breastfeeding
Galactosaemia
Pregnancy
Severe anaemia
Severe myelosuppression

Precautions and Warnings

Children under 18 years
Elderly
History of radiotherapy
Glucose-galactose malabsorption syndrome
Hepatic impairment
Lactose intolerance
Myelosuppression secondary to chemotherapy
Positive HIV status
Renal impairment
Skin ulcer

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
Contains lactose
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

Pregnancy

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.

Lactation

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.

Side Effects

Abdominal pain
Allergic alveolitis
Alopecia
Alveolitis
Anaemia
Anorexia
Asthenia
Azoospermia
Chills
Constipation
Convulsions
Cough
Cutaneous atrophy
Dermatomyositis
Desquamation
Diarrhoea
Disorientation
Dizziness
Drowsiness
Dyspnoea
Dysuria
Elevation of liver enzymes
Erythema
Fever
Gangrene
Gastro-intestinal discomfort
Hallucinations
Headache
Hepatitis
Hepatotoxicity
Hyperpigmentation
Hypersensitivity reactions
Impaired renal tubular function
Increased risk of skin cancer
Increased uric acid level
Interstitial lung disease
Keratosis
Leg ulcers
Leucopenia
Leukaemia
Malaise
Megaloblastosis
Melaena
Mucositis
Nail disorders
Nausea
Neurological disorders
Oligospermia
Pancreatitis
Peripheral neuropathy
Pneumonitis
Pruritus
Pulmonary fibrosis
Pulmonary infiltrates
Pulmonary oedema
Rash
Renal impairment
Scaling of skin
Secondary leukaemia
Serum bilirubin increased
Serum creatinine increased
Serum urea increased
Skin carcinoma
Skin ulcer
Stomatitis
Thrombocytopenia
Tumour lysis syndrome
Violet papules
Vomiting

Presentation

Oral formulations of hydroxycarbamide.

Drugs List

Therapeutic Indications

Uses

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.

Unlicensed Uses

Prevention of recurrent vaso-occlusive crises in sickle cell syndrome

Dosage

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.

Adults

Patients with Renal Impairment

Additional Dosage Information

Administration

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.

Contraindications

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
Breastfeeding
Galactosaemia
Pregnancy
Severe anaemia
Severe myelosuppression

Precautions and Warnings

Children under 18 years
Elderly
History of radiotherapy
Glucose-galactose malabsorption syndrome
Hepatic impairment
Lactose intolerance
Myelosuppression secondary to chemotherapy
Positive HIV status
Renal impairment
Skin ulcer

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
Contains lactose
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

Pregnancy

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.

Lactation

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.

Side Effects

Abdominal pain
Allergic alveolitis
Alopecia
Alveolitis
Anaemia
Anorexia
Asthenia
Azoospermia
Chills
Constipation
Convulsions
Cough
Cutaneous atrophy
Dermatomyositis
Desquamation
Diarrhoea
Disorientation
Dizziness
Drowsiness
Dyspnoea
Dysuria
Elevation of liver enzymes
Erythema
Fever
Gangrene
Gastro-intestinal discomfort
Hallucinations
Headache
Hepatitis
Hepatotoxicity
Hyperpigmentation
Hypersensitivity reactions
Impaired renal tubular function
Increased risk of skin cancer
Increased uric acid level
Interstitial lung disease
Keratosis
Leg ulcers
Leucopenia
Leukaemia
Malaise
Megaloblastosis
Melaena
Mucositis
Nail disorders
Nausea
Neurological disorders
Oligospermia
Pancreatitis
Peripheral neuropathy
Pneumonitis
Pruritus
Pulmonary fibrosis
Pulmonary infiltrates
Pulmonary oedema
Rash
Renal impairment
Scaling of skin
Secondary leukaemia
Serum bilirubin increased
Serum creatinine increased
Serum urea increased
Skin carcinoma
Skin ulcer
Stomatitis
Thrombocytopenia
Tumour lysis syndrome
Violet papules
Vomiting

Overdosage

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 ).

Further Information

Last Full Review Date: November 2019

Reference Sources

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