Anagrelide oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of anagrelide (as anagrelide hydrochloride).
Drugs List
Therapeutic Indications
Uses
Management of thrombocythemia
Reduction of elevated platelet counts in at risk essential thrombocythaemia patients (intolerant to or inadequately controlled by their current therapy).
At risk essential thrombocythaemia patients are defined as having one or more of the following: More than 60 years of age Platelet count greater than 1000 x 10 to the power of 9 per litre History of thrombo-haemorrhagic events.
Dosage
Adults
Initial dose: 500micrograms twice daily for at least 1 week.
Subsequent doses: After one week, the dose may be titrated to achieve the lowest effective dose for the individual. The aim is to reduce and maintain a platelet count below 600 x 10 to the power of 9 per litre and ideally at levels between 150 x 10 to the power of 9 per litre and 400 x 10 to the power of 9 per litre.
Dose increments must not exceed 500micrograms per day in any one week.
Maximum single dose must not exceed five 500microgram capsules (2.5mg).
Maximum daily doses of 10mg have been used.
A drop in platelet count should be observed around 14 to 21 days after initiating therapy. In most patients, an effective maintenance dose is 1mg to 3mg per day.
If the starting dose exceeds 1mg per day, platelet counts should be performed every 2 days for the first week of treatment and at least weekly thereafter until a stable maintenance dose is reached.
Children
Not licensed for use in children.
Anagrelide treatment should only be initiated when the patient shows signs of disease progression or suffers from thrombosis. If treatment is initiated, the benefits and risks of treatment with anagrelide must be monitored regularly and the need for ongoing treatment evaluated periodically.
Discontinuation of treatment should be considered in paediatric patients who do not have a satisfactory treatment response after approximately 3 months. Essential thrombocythaemia in at-risk children who have not responded adequately to other therapy or who are intolerant of it (unlicensed dose):
Children aged 7 to 18 years: Initially 500micrograms daily adjusted according to response in steps of 500 micrograms daily at weekly intervals to maximum 10mg daily (maximum single dose 2.5mg); usual dose range 1mg to 3mg daily in divided doses.
Contraindications
Children under 7 years
Elevated serum transaminases - greater than 5 times upper limit of normal
Breastfeeding
Galactosaemia
Long QT syndrome
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic disorder
Torsade de pointes
Precautions and Warnings
Cardiopulmonary disorder
Children aged 7 to 18 years
Elderly
Family history of long QT syndrome
Suspected cardiac disorder
Cardiac disorder
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Lactose intolerance
Mild hepatic impairment
Mild renal impairment
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Evaluate patients for cardiovascular disease prior to treatment
Treatment to be initiated and supervised by a specialist
Contains lactose
Monitor renal function prior to initiating treatment
Perform ECG before and during treatment
Concurrent aspirin- assess risk/benefit in pts with history of haemorrhage
Monitor cardio-respiratory function
Monitor cardiovascular function
Monitor full blood count regularly
Monitor hepatic function regularly
Monitor platelets
Monitor renal function regularly
Monitor serum electrolytes
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Female: Ensure adequate contraception during treatment
Female: Oral contraception may not be adequate during treatment
Monitor platelet count frequently as it will increase within 4 days after discontinuation of anagrelide and return to pre-treatment levels within 10 to 14 days, potentially above baseline values.
Pregnancy and Lactation
Pregnancy
Anagrelide is contraindicated during pregnancy.
At the time of writing there is limited published information regarding the use of anagrelide during pregnancy.
Studies in animals have shown reproductive toxicity although this was at a dose much higher than the dose used in humans.
Briggs (2015) suggests that although it is unknown whether anagrelide crosses human placenta, the molecular weight of the drug (about 275 for the base) is low enough that transfer to the foetus is expected.
Lactation
Anagrelide is contraindicated during breastfeeding.
At the time of writing there is limited published information regarding the use of anagrelide during breastfeeding. The manufacturer states that there is published data of excretion of anagrelide or metabolites in milk in animals. It is not known if anagrelide is excreted into human breast milk, however, the molecular weight of the compound is low enough that passage into milk should be expected. The potential effects of this exposure on a nursing infant are unknown (Briggs, 2015). Since anagrelide is used for prolonged periods of time, there is a possibility of untoward effects such as reduction of blood platelets (thrombocytopenia) and cardiovascular disorders in the infant (Hale, 2014).
Side Effects
Abdominal pain
Abnormal vision
Allergic alveolitis
Alopecia
Amnesia
Anaemia
Angina
Anorexia
Arrhythmias
Arthralgia
Asthenia
Atrial fibrillation
Back pain
Cardiomegaly
Cardiomyopathy
Chest pain
Chills
Colitis
Confusion
Congestive cardiac failure
Constipation
Depression
Diarrhoea
Diplopia
Dizziness
Dry mouth
Dry skin
Dysarthria
Dyspepsia
Dyspnoea
Ecchymosis
Epistaxis
Fatigue
Fever
Flatulence
Fluid retention
Gastritis
Gastro-intestinal haemorrhage
Gastrointestinal disorder
Gingival bleeding
Haemorrhage
Headache
Hepatitis
Hypertension
Hypoaesthesia
Impaired co-ordination
Impotence
Increases in hepatic enzymes
Influenza-like syndrome
Insomnia
Interstitial lung disease
Interstitial nephritis
Malaise
Migraine
Myalgia
Myocardial infarction
Nausea
Nervousness
Nocturia
Oedema
Pain
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Pericardial effusion
Pleural effusion
Pneumonia
Pneumonitis
Postural hypotension
Prolongation of QT interval
Pruritus
Pulmonary hypertension
Pulmonary infiltrates
Rash
Renal failure
Serum creatinine increased
Skin discolouration
Sleep disturbances
Somnolence
Supraventricular tachycardia
Syncope
Tachycardia
Thrombocytopenia
Tinnitus
Torsades de pointes
Vasodilatation
Ventricular tachycardia
Vomiting
Weakness
Weight gain
Weight loss
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: March 2019
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Xagrid 0.5mg hard capsule. Shire Pharmaceuticals Ltd. Revised August 2018.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 March 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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