AGRYLIN CAPSULE 0.5 MG [SIN12525P]

Product Info

AGRYLIN CAPSULE 0.5 MG

[SIN12525P]

4.1 Therapeutic indications
Agrylin is indicated for the reduction of elevated platelet counts in patients with essential thrombocythaemia (ET) who are intolerant to their existing therapy or for whom other therapies are not considered appropriate.

4.2 Posology and method of administration
Treatment with Agrylin should be initiated by a clinician with experience in the management of essential thrombocythaemia.

Posology
The recommended starting dosage of anagrelide is 1 mg/day, which should be administered orally in two divided doses (0.5 mg/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 0.5 mg/day in any one week and the recommended maximum single dose should not exceed 2.5 mg (see section 4.9 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). During clinical development dosages of 10 mg/day have been used.

The effects of treatment with anagrelide must be monitored on a regular basis (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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 3 mg/day (for further information on the clinical effects refer to section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Elderly
The observed pharmacokinetic differences between elderly and young patients with ET (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) do not warrant using a different starting regimen or different dose titration step to achieve an individual patient optimised anagrelide regimen.

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).

Renal impairment
There are limited pharmacokinetic data for this patient population. The potential risks and benefits of anagrelide therapy in a patient with impairment of renal function should be assessed before treatment is commenced. Doses are titrated on an individual patient basis. (see sections 4.3).

Hepatic impairment
There are limited 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 sections 4.3 and 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Paediatric population
The safety and efficacy of anagrelide in children has not been established. The experience in children is very limited; anagrelide should be used in this patient group with caution. In the absence of specific paediatric guidelines, WHO diagnostic criteria for adult diagnosis of ET are considered to be of relevance to the paediatric population. Diagnostic guidelines for essential thrombocythemia should be followed carefully and diagnosis reassessed periodically in cases of uncertainty, with effort made to distinguish from hereditary or secondary thrombocytosis, which may include genetic analysis and bone marrow biopsy.

Typically cytoreductive therapy is considered in high risk paediatric patients.

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.

Platelet targets are assigned on an individual patient basis by the treating physician.

Discontinuation of treatment should be considered in paediatric patients who do not have a satisfactory treatment response after approximately 3 months.

Currently available data are described in sections 4.4, 4.8, 5.1 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information, but no recommendation on a posology can be made.

Method of Administration
For oral use. The capsules must be swallowed whole. Do not crush or dilute the contents in a liquid.

4.3 Contraindications
Hypersensitivity to anagrelide or any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.
Patients with moderate or severe hepatic impairment.
Patients with moderate or severe renal impairment (creatinine clearance < 50 ml/min).