Alternative formulations of sorafenib for use in children

Background Sorafenib is an oral multikinase inhibitor with antiangiogenic and antitumor activity. In most cases, the commercially available 200 mg tablet is not suitable for administration to children. We studied the chemical and physical stability of extemporaneously prepared formulations and evalu...

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Published in:	Pediatric blood & cancer Vol. 60; no. 10; pp. 1642 - 1646
Main Authors:	Navid, Fariba, Christensen, Robbin, Inaba, Hiroto, Li, Lie, Chen, Zhaoyuan, Cai, Xiangjun, Regel, Joshua, Baker, Sharyn D.
Format:	Journal Article
Language:	English
Published:	United States Blackwell Publishing Ltd 01-10-2013 Wiley Subscription Services, Inc
Subjects:	Administration, Oral Adolescent Adult Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacokinetics Child Child, Preschool compounded capsule Female formulation Hematology Humans Infant Male Neoplasms - drug therapy Niacinamide - administration & dosage Niacinamide - adverse effects Niacinamide - analogs & derivatives Niacinamide - pharmacokinetics Oncology Pediatrics Phenylurea Compounds - administration & dosage Phenylurea Compounds - adverse effects Phenylurea Compounds - pharmacokinetics sorafenib suspension formulation compounded capsule sorafenib suspension
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Summary:	Background Sorafenib is an oral multikinase inhibitor with antiangiogenic and antitumor activity. In most cases, the commercially available 200 mg tablet is not suitable for administration to children. We studied the chemical and physical stability of extemporaneously prepared formulations and evaluated the pharmacokinetic profile of cut tablets and smaller‐dosage capsules of sorafenib in children. Procedure Commercially available 200 mg tablets of sorafenib tosylate were used to prepare liquid suspensions of sorafenib in oil and Ora‐Plus®:Ora‐Sweet® solution, and to prepare 5, 10, 20, 50, and 100 mg capsules. Plasma concentrations of sorafenib were measured in patients receiving capsules and cut tablets, using a validated HPLC‐based method with tandem mass spectrometric detection. Results At room temperature and under refrigeration, sorafenib concentrations in Ora Plus®:Ora Sweet® were highly variable (means ranging from 75% to 131% of the intended concentration of 50 mg/ml). In oil suspension, sorafenib concentrations were inconsistent during compounding. In contrast, all smaller‐dosage capsules, except the 5 mg capsule, were within 91–99% of the intended content and were stable at room temperature for at least 8 months. Sorafenib pharmacokinetic parameters in patients receiving capsules or cut tablets were consistent with those reported previously in adults and children receiving intact tablets. Conclusions Sorafenib is not stable in an oral suspension prepared from commercially available tablets, but compounded capsules in smaller‐dosage forms that can be sprinkled on food or cut tablets are alternatives for administration to children who need smaller doses based on body surface area or cannot swallow tablets. Pediatr Blood Cancer 2013;60:1642–1646. © 2013 Wiley Periodicals, Inc.
Bibliography:	Cancer Center Support CORE Grant - No. P30 CA21765; No. R01 CA138744 istex:36CEDA40D85BA3009F52455721810582CA4BA875 ark:/67375/WNG-GLK30G9Z-N American Lebanese Syrian Associated Charities National Cancer Institute, Cancer Center Grant - No. CA23099 Bayer/Onyx Pharmaceuticals ArticleID:PBC24619
ISSN:	1545-5009 1545-5017
DOI:	10.1002/pbc.24619