Hydroxycarbamide

Oral
Chronic myeloid leukaemia, Solid tumours

Oral
Sickle-cell disease

Chronic myeloid leukaemia; Solid tumours:

CrCl (mL/min)	Dosage
<60	Initially, 7.5 mg/kg daily, titrate according to response.

Sickle-cell disease:

CrCl (mL/min)	Dosage
<30	Contraindicated.
30-60	Initially, 7.5 mg/kg daily, titrate according to response.

Sickle-cell disease: Severe (Child-Pugh class C): Contraindicated.

Severe bone marrow depression. Severe hepatic (Child-Pugh class C) and renal (CrCl <30 mL/min) impairment, when used in the treatment of sickle-cell disease. Lactation. Concomitant use w/ didanosine and stavudine.

Patient w/ severe GI intolerance, history of prior cytotoxic or radiation therapy. Renal and hepatic impairment. Childn. Pregnancy.

Significant: Bone marrow suppression (e.g leucopenia, thrombocytopenia, anaemia), cutaneous vasculitic toxicities (e.g. vasculitic ulcerations or gangrene), erythrocyte abnormalities (e.g. self-limiting macrocytosis/megaloblastic erythropoiesis), secondary neoplasms, tumour lysis syndrome.
Nervous: Peripheral neuropathy, acute delirium, headache, dizziness, disorientation, malaise, asthenia, hallucination, seizure.
CV: Peripheral oedema, hypersentisitivity angiitis.
GI: Acute mucocutaneous toxicity, diarrhoea, gastric distress, nausea, oral mucosa ulcer, anorexia, constipation, GI irritation, mucositis, stomatitis, vomiting.
Resp: Diffuse pulmonary infiltrates, dyspnoea, pulmonary fibrosis, asthma.
Hepatic: Elevated liver enzyme, hepatic failure.
Genitourinary: Dysuria, increased BUN and creatinine, renal tubular disease.
Endocrine: Hyperuricaemia.
Haematologic: Leukaemia, abnormal erythropoiesis, macrocytosis, reticulocytopenia, cytopenia, myeloproliferative disorder (e.g. polycythemia, secondary leukaemia).
Musculoskeletal: Panniculitis, weakness.
Dermatologic: Maculopapular rash, skin ulceration, dermatomyositis-like skin changes, facial oedema, rash, pruritus, alopecia, hyperpigmentation, skin and nails atrophy, violet papules, cutaneous leg ulcers and skin carcinoma, eczema, desquamation, peripheral and facial erythema.
Others: Fever, chills.
Potentially Fatal: Severe myelosuppression.

PO: D

This drug may cause dizziness and drowsiness, if affected, do not drive or operate machinery. Avoid sun exposure.

Monitor CBC w/ differential and platelet (once wkly for antineoplastic indication, every 2 wk initially for sickle cell anaemia), hepatic and renal function, LFT, serum uric, cutaneous toxicities and onset of secondary malignancies. Correct anaemia prior and during therapy.

Symptoms: Acute mucocutaneous toxicity, soreness, violet erythema, oedema on palms and foot soles followed by scaling of hands and feet, intense generalised hyperpigmentation of skin and severe acute stomatitis. Management: Perform gastric lavage immediately, followed by symptomatic and supportive treatment. Monitor haematologic toxicity, if necessary, blood should be transfused.

Increased risk of cutaneous vasculitic ulcerations w/ prior or concomitant use of interferon. Admin of live vaccine may cause severe infection due to the decreased patient’s antibody response.
Potentially Fatal: Increased risk of pancreatitis and hepatotoxicity when used in combination w/ didanosine and stavudine.

False negative triglyceride measurement using glycerol oxidase method. May result in false elevation of lactic acid, urea and uric acid due to analytical interference between hydroxycarbamide and enzymes (e.g. lactate dehydrogenase, urease and uricase).

Description:
Mechanism of Action: Hydroxycarbamide is an S-phase specific DNA synthesis inhibitor. It acts as a ribonucleoside diphosphate reductase inhibitor, thus preventing conversion of ribonucleotides to deoxyribonucleotides causing cell death. In sickle cell anaemia, it can stimulate the production and increase of the concentration of foetal Hb.
Onset: 4-12 wk (foetal Hb production).
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract. Time to peak plasma concentration: W/in 1-4 hr.
Distribution: Well distributed throughout the body. Crosses blood-brain barrier and placenta; enters breast milk. Volume of distribution: Approx 20 L/m². Plasma protein binding: 75-80%.
Metabolism: Metabolised in the liver by urease to acetohydroxamic acid.
Excretion: Mainly via urine (approx 80%, as metabolites and unchanged drug); via lungs (as carbon dioxide). Elimination half-life: 1.9-3.9 hr.

Source: National Center for Biotechnology Information. PubChem Database. Hydroxyurea, CID=3657, https://pubchem.ncbi.nlm.nih.gov/compound/Hydroxyurea (accessed on Jan. 23, 2020)

Store between 25-30°C.
Avoid inhalation and contact w/ skin or mucous membranes by wearing gloves and protective equipment. Wash hands before and after handling.

Cytotoxic Chemotherapy

L01XX05 - hydroxycarbamide ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.

Anon. Hydroxyurea. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/06/2017.

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Droxia (E.R. Squibb & Sons LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 20/06/2017.

Joint Formulary Committee. Hydroxycarbamide (Hydroxyurea). British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/06/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Hydroxyurea. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 20/06/2017.