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Drug details for : XAGRID Hard Capsule
| Drug class description : | L 01 X (Other Antineoplastic Agents) |
| Generic Name : | Anagrelide |
| Drug description : | Capsule, hard An opaque white hard capsule imprinted with S 063 |
| Presentation : | Xagrid 0.5mg hard capsule - Each capsule contains 0.5 mg anagrelide (as 0.61 mg anagrelide hydrochloride) |
| Indications : | Xagrid is indicated for the reduction of elevated platelet counts in at risk essential thrombocythaemia (ET) patients who are intolerant to their current therapy or whose elevated platelet counts are not reduced to an acceptable level by their current therapy. An at risk patient An at risk essential thrombocythaemia patient is defined by one or more of the following features: >60 years of age or A platelet count>1000 x 109/l or A history of thrombo-haemorrhagic events. |
| Adult Dosage : | Treatment with Xagrid capsules should be initiated by a clinician with experience in the management of essential thrombocythaemia. The recommended starting dosage of anagrelide is 1mg/day, which should be administered orally in two divided doses (0.5mg/dose). The starting dose should be maintained for at least one week. After one week the dosage may be titrated, on an individual basis, to achieve the lowest effective dosage required to reduce and/or maintain a platelet count below 600 x 109/l and ideally at levels between 150 x 109/l and 400 x 109/l. The dosage increment must not exceed more than 0.5mg/day in any one-week and the recommended maximum single dose should not exceed 2.5mg. During clinical development dosages of 10mg/day have been used. The effects of treatment with anagrelide must be monitored on a regular basis (See Special Precautions). If the starting dose is>1mg/day platelet counts should be performed every two days during the first week of treatment and at least weekly thereafter until a stable maintenance dose is reached. Typically, a fall in the platelet count will be observed within 14 to 21 days of starting treatment and in most patients an adequate therapeutic response will be observed and maintained at a dosage of 1 to 3mg/day. Renal impairment Currently, there are no specific pharmacokinetic data for this patient population and the potential risks and benefits of anagrelide therapy in a patient with impairment of renal function should be assessed before treatment is commenced. Hepatic impairment Currently, there are no specific pharmacokinetic data for this patient population. However, hepatic metabolism represents the major route of drug clearance and liver function may therefore be expected to influence this process. Therefore it is recommended that patients with moderate or severe hepatic impairment are not treated with anagrelide. The potential risks and benefits of anagrelide therapy in a patient with mild impairment of hepatic function should be assessed before treatment is commenced (See Contraindications and Special Precautions). |
| Elderly Dosage : | No specific pharmacokinetic studies have been conducted in this patient population. However, during the clinical development approximately 50% of the patients treated with anagrelide were over 60 years of age and no age specific alterations in dosage were required in these patients. However, as expected, patients in this age group had twice the incidence of serious adverse events (mainly cardiac). Doses are titrated on an individual patient basis. |
| Contra Indications : | Hypersensitivity to anagrelide or to any of the excipients of the medicinal product. Patients with moderate or severe hepatic impairment. Patients with moderate or severe renal impairment (creatinine clearance <50ml/min). |
| Special Precautions : | Hepatic impairment: (See Adult Dosage and Contraindications) the potential risks and benefits of anagrelide therapy in a patient with mild impairment of hepatic function should be assessed before treatment is commenced. It is not recommended in patients with elevated transaminases >5 times the upper limit of normal). Renal impairment: (See Adult Dosage and Contraindications) the potential risks and benefits of anagrelide therapy in a patient with impairment of renal function should be assessed before treatment is commenced. General: therapy requires close clinical supervision of the patient which will include a full blood count (haemoglobin and white blood cell and platelet counts), and assessment of liver function (ALT and AST) and renal function (serum creatinine and urea) tests. Platelets: the platelet count will increase within 4 days of stopping treatment with Xagrid capsules and will return to pre-treatment levels within 10 to 14 days. Cardiovascular: Cases of cardiomegaly and congestive heart failure have been reported (see section 4.8). Anagrelide should be used with caution in patients of any age with known or suspected heart disease, and only if the potential benefits of therapy outweigh the potential risks.Anagrelide is an inhibitor of cyclic AMP phosphodiesterase III and because of its positive inotropic effects, a pre-treatment cardiovascular examination (including further investigation such as echocardiography, electrocardiogram) is recommended. Patients should be monitored during treatment for evidence of cardiovascular effects that may require further cardiovascular examination and investigation. Paediatric patients: limited data are available on the use of anagrelide in the paediatric population and anagrelide should be used in this patient group with caution. Clinically relevant interactions: anagrelide is an inhibitor of cyclic AMP phosphodiesterase III (PDE III). Concomitant use of anagrelide with other PDE III inhibitors such as milrinone, amrinone, enoximone, olprinone and cilostazol is not recommended. The potential risks and benefits of the concomitant use of anagrelide with acetylsalicylic acid in patients with a platelet count greater than 1500 x 109/l and/or a history of haemorrhage should be assessed before treatment is commenced. Excipients: This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. |
| Interactions : | Limited pharmacokinetic and/or pharmacodynamic studies investigating possible interactions between anagrelide and other medicinal products have been conducted. Drug interactions: effects of other substances on anagrelide Anagrelide is primarily metabolised by CYP1A2. It is known that CYP1A2 is inhibited by several medicinal products, including fluvoxamine and omeprazole, and such medicinal products could theoretically adversely influence the clearance of anagrelide.In vivo interaction studies in humans have demonstrated that digoxin and warfarin do not affect the pharmacokinetic properties of anagrelide. Drug interactions: effects of anagrelide on other substances Anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction with other co-administered medicinal products sharing that clearance mechanism e.g. theophylline. Anagrelide is an inhibitor of PDE III. The effects of medicinal products with similar properties such as the inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide. An in vitro study in human whole blood demonstrated that the anti-aggregatory effects of acetylsalicylic acid were additively, but not synergistically increased by the presence of anagrelide. In vivo interaction studies in humans have demonstrated that anagrelide does not affect the pharmacokinetic properties of digoxin or warfarin.At the doses recommended for use in the treatment of essential thrombocythaemia, anagrelide may theoretically potentiate the effects of other medicinal products that inhibit or modify platelet function e.g. acetylsalicylic acid. However, during clinical development, no such effects have been observed with acetylsalicylic acid. Anagrelide may cause intestinal disturbance in some patients and compromise the absorption of hormonal oral contraceptives. A preclinical in vivo pharmacokinetic interaction study in the dog investigating the potential effects of anagrelide and hydroxyurea when given in combination demonstrated no adverse effects on the kinetics of either medicinal product. Food interactions: Food delays the absorption of anagrelide but does not significantly alter systemic exposure. The effects of food on bioavailability are not considered clinically relevant to the use of anagrelide. Grapefruit juice has been shown to inhibit CYP1A2 and therefore could also reduce the clearance of anagrelide. Pregnancy: There are no adequate data from the use of anagrelide in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Use of Xagrid during pregnancy is not recommended. If Xagrid is used during pregnancy, or if the patient becomes pregnant while using the drug, she should be advised of the potential risk to the foetus. Women of child-bearing potential should use adequate birth-control measures during treatment with anagrelide. Lactation: It is not known whether anagrelide hydrochloride is excreted in milk. Since many medicinal products are excreted in human milk and because of the potential for adverse reactions in breast-feeding infants, mothers should discontinue breast-feeding when taking Xagrid. |
| Adverse Reactions : | The safety of anagrelide has been examined in 4 open label clinical studies. In 3 of the studies 942 patients who received anagrelide at a mean dose of approximately 2mg/day were assessed for safety. In these studies 22 patients received anagrelide for up to 4 years. In the later study 3660 patients who received anagrelide at a mean dose of approximately 2mg/day were assessed for safety. In this study 34 patients received anagrelide for up to 5 years. The most commonly reported drug related adverse reactions were headache occurring at approximately 14%, palpitations occurring at approximately 9%, fluid retention and nausea both occurring at approximately 6%, and diarrhoea occurring at 5%. These adverse drug reactions are expected based on the pharmacology of anagrelide (inhibition of PDE III). Gradual dose titration may help diminish these effects (See Adult Dosage). The following convention was used for frequency of adverse drug reactions: very common >1/10); common >1/100, <1/10); uncommon >1/1,000, <1/100); rare >1/10,000, <1/1,000); not known (cannot be estimated from the available data). Blood and lymphatic system disorders Common: Anaemia Uncommon: Thrombocytopenia, pancytopenia, ecchymosis, haemorrhage Metabolism and nutrition disorders Common: Fluid retention Uncommon: Oedema, weight loss Rare: Weight gain Nervous system disorders Very common: Headache Common: Dizziness Uncommon: Paraesthesia, insomnia, depression, confusion, hypoaesthesia, nervousness, dry mouth, amnesia Rare: Somnolence, abnormal coordination, dysarthria, migraine Special senses Rare: Vision abnormal, tinnitus, diplopia Cardiac disorders Common: Palpitations, tachycardia Uncommon: Congestive heart failure, hypertension, arrhythmia, atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, syncope Rare: Angina pectoris, myocardial infarction, cardiomegaly, cardiomyopathy, pericardial effusion, vasodilatation, postural hypotension Respiratory and thoracic disorders Uncommon: Dyspnoea, epistaxis, pleural effusion, pneumonia Rare: Pulmonary hypertension, pulmonary infiltrates Not known: Allergic alveolitis Gastrointestinal disorders Common: Nausea, diarrhoea, abdominal pain, flatulence, vomiting Uncommon: Dyspepsia, anorexia, pancreatitis, constipation, gastrointestinal haemorrhage, gastrointestinal disorder Rare: Colitis, gastritis, gingival bleeding Hepatobiliary disorders Uncommon: Hepatic enzymes increased Skin and subcutaneous tissue Common: Rash Uncommon: Alopecia, skin discoloration, pruritus Rare: Dry skin Musculoskeletal and connective tissue disorders Uncommon: Myalgia, arthralgia, back pain Urogenital Uncommon: Impotence Rare: Nocturia, renal failure Investigations Rare: Blood creatinine increased General disorders and administration site conditions Common: Fatigue Uncommon: Chest pain, weakness, chills, malaise, fever Rare: Asthenia, pain, flu-like syndrome |
| Manufacturer : | Shire Pharmaceuticals |
| Drug Availability : | (POM) |
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