Abstract
Although anagrelide is widely used for the treatment of essential thrombocythemia (ET) in the USA and Europe, it is not licensed in Japan. Existing literature has reported differences in polymorphism and activity of CYP1A2 in Japanese and non-Japanese ethnic groups, which may alter anagrelide metabolism. We intended to identify the optimum dosage of anagrelide in treatmentnai ̈ve Japanese patients with ET and assess its long-term safety and efficacy. Twelve patients with ET and a platelet count of ≤80 × 104/μL were enrolled. Anagrelide was administered at an initial dose of 0.5 mg/day (weeks 1-4), then increased to 1.0 mg/day (weeks 5-8). During the following maintenance (weeks 9-52) and continuation periods (weeks 53-104), the dose was adjusted according to patient safety data and to maintain target platelet counts (<60 × 104/lL). Increasing the dose led to a decrease in mean platelet count, and target platelet counts were maintained in 11 patients. Adverse events were mild or moderate, and none led to discontinuation. This cohort of Japanese patients exhibited higher pharmacokinetic exposures of anagrelide and its active metabolite than those previously documented in non-Japanese patients. These differences were modest, suggesting specific dosing regimens for Japanese patients are not required.
| Original language | English |
|---|---|
| Pages (from-to) | 360-368 |
| Number of pages | 9 |
| Journal | International Journal of Hematology |
| Volume | 97 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2013 Mar |
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Keywords
- Anagrelide
- Elevated platelet count
- Essential thrombocythemia
- Japanese patients
- Pharmacokinetic profiles
ASJC Scopus subject areas
- Hematology
Cite this
Open-label, dose-titration and continuation study to assess efficacy, safety, and pharmacokinetics of anagrelide in treatment-naïve Japanese patients with essential thrombocythemia. / Okamoto, Shinichiro; Miyakawa, Yoshitaka; Smith, Jonathan; Hodgson, Ian; Abhyankar, Brihad; Troy, Steven; Kanakura, Yuzuru.
In: International Journal of Hematology, Vol. 97, No. 3, 03.2013, p. 360-368.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Open-label, dose-titration and continuation study to assess efficacy, safety, and pharmacokinetics of anagrelide in treatment-naïve Japanese patients with essential thrombocythemia
AU - Okamoto, Shinichiro
AU - Miyakawa, Yoshitaka
AU - Smith, Jonathan
AU - Hodgson, Ian
AU - Abhyankar, Brihad
AU - Troy, Steven
AU - Kanakura, Yuzuru
PY - 2013/3
Y1 - 2013/3
N2 - Although anagrelide is widely used for the treatment of essential thrombocythemia (ET) in the USA and Europe, it is not licensed in Japan. Existing literature has reported differences in polymorphism and activity of CYP1A2 in Japanese and non-Japanese ethnic groups, which may alter anagrelide metabolism. We intended to identify the optimum dosage of anagrelide in treatmentnai ̈ve Japanese patients with ET and assess its long-term safety and efficacy. Twelve patients with ET and a platelet count of ≤80 × 104/μL were enrolled. Anagrelide was administered at an initial dose of 0.5 mg/day (weeks 1-4), then increased to 1.0 mg/day (weeks 5-8). During the following maintenance (weeks 9-52) and continuation periods (weeks 53-104), the dose was adjusted according to patient safety data and to maintain target platelet counts (<60 × 104/lL). Increasing the dose led to a decrease in mean platelet count, and target platelet counts were maintained in 11 patients. Adverse events were mild or moderate, and none led to discontinuation. This cohort of Japanese patients exhibited higher pharmacokinetic exposures of anagrelide and its active metabolite than those previously documented in non-Japanese patients. These differences were modest, suggesting specific dosing regimens for Japanese patients are not required.
AB - Although anagrelide is widely used for the treatment of essential thrombocythemia (ET) in the USA and Europe, it is not licensed in Japan. Existing literature has reported differences in polymorphism and activity of CYP1A2 in Japanese and non-Japanese ethnic groups, which may alter anagrelide metabolism. We intended to identify the optimum dosage of anagrelide in treatmentnai ̈ve Japanese patients with ET and assess its long-term safety and efficacy. Twelve patients with ET and a platelet count of ≤80 × 104/μL were enrolled. Anagrelide was administered at an initial dose of 0.5 mg/day (weeks 1-4), then increased to 1.0 mg/day (weeks 5-8). During the following maintenance (weeks 9-52) and continuation periods (weeks 53-104), the dose was adjusted according to patient safety data and to maintain target platelet counts (<60 × 104/lL). Increasing the dose led to a decrease in mean platelet count, and target platelet counts were maintained in 11 patients. Adverse events were mild or moderate, and none led to discontinuation. This cohort of Japanese patients exhibited higher pharmacokinetic exposures of anagrelide and its active metabolite than those previously documented in non-Japanese patients. These differences were modest, suggesting specific dosing regimens for Japanese patients are not required.
KW - Anagrelide
KW - Elevated platelet count
KW - Essential thrombocythemia
KW - Japanese patients
KW - Pharmacokinetic profiles
UR - http://www.scopus.com/inward/record.url?scp=84887573442&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84887573442&partnerID=8YFLogxK
U2 - 10.1007/s12185-013-1265-4
DO - 10.1007/s12185-013-1265-4
M3 - Article
C2 - 23378182
AN - SCOPUS:84887573442
VL - 97
SP - 360
EP - 368
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 3
ER -