Hydroxycarbamide

Registered South African indications:

• Malignant neoplastic disease
• Metastatic disease
• Chronic myeloid leukaemia 
• Tumours of the head and neck
• Sarcomas

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Marked leucopenia (<2.5wbcx10⁹/L)
• Marked thrombocytopenia  (< 100x10⁹/L)
• Severe anaemia

Cautions

• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Previous irradiation therapy
• Prolonged use
• Exposure to sunlight
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery
• Live vaccines
• Use of antiretroviral agents
• Respiratory disorders
• Cutaneous vasculitic toxicities
• Thrombocytopenia
• Anaemia
• Leukopenia

Forms avail. in SA and covered in this monograph: cap

Used for the treatment of

Malignant neoplastic disease
Recurrent or metastatic disease
Resistant chronic myeloid leukaemia 
Tumours of the head and neck
Some sarcomas

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy 

• Contraindicated
• Hydroxycarbamide can cause foetal harm when administered to a pregnant woman
• Drugs that affect DNA synthesis, such as hydroxycarbamide, may be potent mutagenic agents
• Hydroxycarbamide should not normally be administered to patients who are pregnant, or to mothers who are breastfeeding unless the potential benefits outweigh the possible hazards

Breastfeeding

• Caution; not recommended
• Hydroxycarbamide is excreted in human breast milk
• Because of the potential for serious adverse reactions in nursing infants from hyrdoxycarbamide, a decision should be made whether to discontinue breastfeeding or to discontinue hydroxycarbamide, taking into account the importance of the drug to the mother

Fertility 

• When appropriate, both male and female patients should be counselled concerning the use of contraceptive measures before and during treatment with hydroxycarbamide
• The physician should carefully consider the possibility before administering this drug to male or female patients who may contemplate conception
• Since hydroxycarbamide is a cytotoxic agent, it has produced a teratogenic effect in some animal species
• In rats and dogs, high doses of hydroxycarbamide reduced sperm production

Renal Impairment

• Caution; dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly            

• Caution; dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Hallucination
• Disorientation
• Convulsion
• Dizziness
• Peripheral neuropathy
• Somnolence
• Headache
• Asthenia

Respiratory Disorders

• Pulmonary fibrosis
• Pulmonary oedema
• Lung infiltration
• Dyspnoea

Gastrointestinal Disorders

• Pancreatitis
• Nausea and vomiting
• Diarrhoea
• Stomatitis
• Constipation
• Mucositis
• Stomach discomfort
• Dyspepsia
• Abdominal pain
• Melaena

Hepatobiliary Disorders

• Hepatotoxicity
• Increased hepatic enzyme 
• Cholestasis
• Hepatitis
• Fatal and non-fatal pancreatitis
• Hepatotoxicity

Genitourinary Disorders

• Dysuria
• Increased blood creatinine 
• Increased blood urea 
• Increased blood uric acid 
• Azoospermia
• Oligospermia

Endocrine and Metabolic Disorders

• Anorexia
• Tumour lysis syndrome

Skin and Subcutaneous Tissue Disorders

• Gangrene
• Skin cancer
• Cutaneous vasculitis
• Dermatomyositis
• Alopecia
• Maculo-papular rash
• Papular rash 
• Skin exfoliation
• Skin atrophy
• Skin ulcer
• Erythema
• Skin hyperpigmentation
• Nail pigmentation
• Nail disorder

Immune, Blood and Lymphatic System Disorders

• Bone marrow failure
• Decreased CD4 lymphocytes
• Leukopenia
• Thrombocytopenia
• Decreased platelet count
• Anaemia
• Pyrexia
• Chills

• Previous or concomitant radiotherapy
• Antineoplastic agents
• Antiretroviral agents
• Didanosine
• Stavudine
• Live vaccines

• Bone marrow examination
• Hepatic function
• Renal function
• Full blood count with differential and platelets
• Uric acid levels
• Haemoglobin F levels

Specific cases may require

• Pregnancy status

Additional observations

• Evaluate lactate dehydrogenase, haptoglobin, reticulocyte, unconjugated bilirubin, urinalysis, and direct and indirect antiglobulin (Coombs') test
• Hemolytic anaemia (eg, acute jaundice or hematuria with persistent or worsening anaemia)
• Cutaneous toxicities
• Respiratory symptoms
• Secondary malignancies

Hydroxycarbamide is an orally active antineoplastic agent. Although the mechanism of action has not yet been clearly defined, hydroxycarbamide appears to be blocking the ribonucleotide reductase system, which results in the inhibition of DNA synthesis. Cellular resistance is normally caused by increased ribonucleotide reductase levels as a result of gene amplification.

Capsule 500mg

• Hydrea (Bristol-Myers Squibb) originator