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BackgroundBlister pack is commonly used as a package of internal medicine in Japan. In addition, emptied blister packs of particular drugs are recovered by pharmacists to check their appropriate use. Pomalidomide is an orally active thalidomide analogue and used for multiple myeloma. Because it has both high efficacy and risk of teratogenicity, the use of Pomalyst capsules is strictly managed through the RevMate procedure. Pharmacists must recover emptied blister packs of Pomalyst capsules from all patients according to guidance from the Celgene Corporation. However, the risk of exposure of pomalidomide via the used blister packs to pharmacists have not been well assessed.PurposeTo prevent pharmacists from unintended exposure to pomalidomide, the contamination level of pomalidomide on the surface of used blister packs in the normal clinical situation was assessed.Material and methodsThe used blister packs of Pomalyst capsules, seven-tablet PTP sheets, were recovered from five patients. Pomalidomide was extracted and its amount was analysed by LC-MS/MS. Separation was performed on an ACQUITY UPLC BEH C18 column (Waters, 1.7 µm, 2.1 mm ×50 mm). The mobile phase consisted of a mixture of phase A (0.1% formic acid in water) and phase B (acetonitrile). Transition channel of the protonated molecular ions was 274.17/201. 12 were used for detection of pomalidomide.ResultsThe amount of pomalidomide was 2.33±4. 60 µg per blister pack (0.1–10 µg per blister pack).ConclusionIn this study, although most used blister packs were contaminated by pomalidomide at a very low level, a sheet was contaminated at a high level of approximately 10 µg of pomalidomide. Because pomalidomide is known for high teratogenicity, our data suggested that the standard protection procedure was recommended to prevent unintended exposure to the drug for pharmacists.No conflict of interest

ObjectivesLenalidomide, a hazardous drug, has strict distribution controls. However, the risk of contamination with lenalidomide when patients take the drug has not been studied and the risk of drug exposure to people in the patient’s living environment is unknown. Thus, we investigated the amount of lenalidomide that could be dispersed during the period between removal of the capsule and returning the used blister packages, and we considered the conditions under which lenalidomide could be dispersed and countermeasures.MethodsThe amount of lenalidomide contamination was measured on the outside of the unused blister packages returned by the patients, on the surface of the capsule, and on the inside of the package immediately after removal of the capsule. In addition, the amount of contamination was measured on the blister packages used by the patients and on the gloves worn by the pharmacists on receipt of the packages. Lenalidomide was analysed by liquid chromatography–tandem mass spectrometry.ResultsLenalidomide amounts on the outside of the unused blister packages returned by the three patients were <10, <10, and 26.8 ng/pack, those on the capsule surface immediately after removal from the packages were 297, 388, and 297 ng/capsule, and those on the inside of packages immediately after removal of all capsules were 143, 184, and 554 ng/pack, respectively. A median of 15.6 ng/pack lenalidomide was detected on the surface of packages used by the patients (n=18). The lenalidomide remaining in the packages immediately after capsule removal (~200 ng/pack), except for the 15.6 ng/pack detected in the packages used by the patients, may have been dispersed in the patient’s living environment (~90% or more). The maximum amount of lenalidomide on the surface of the packages used by the patients was over 2500 ng/pack.ConclusionsThe amount of lenalidomide contamination per package was found to be at least 100 ng less after collection by the pharmacist than immediately after removal of the capsules. Therefore, it is recommended to clean the surrounding area and wash one’s hands after taking the capsules.

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Background Dabigatran, an oral anticoagulant classified as a direct thrombin inhibitor, is used for the prevention of stroke and systemic embolism. However, it has limitations in its method of administration; dabigatran should not be removed from the capsule and administered through a tube because of its unstable bioavailability. Purpose To report a case that required dabigatran to be administered through a tube after removal from the capsule. Materials and MethodsA 79-year-old Japanese male with normal hepatic and renal function was receiving warfarin for the prevention of systemic embolism due to atrial fibrillation. When he started S-1 treatment as an adjuvant treatment for gastric cancer, PT- and INR levels exceeded the scale. Because this elevation was thought to be due to the interaction between warfarin and S-1, warfarin was replaced with dabigatran. After switching anticoagulants, PT-INR and aPTT stabilised. Subsequently, however, the patient fell and experienced paralysis due to medullary damage. We tried to administer dabigatran through a tube after removal from the capsule while carefully monitoring the blood levels. Although the typical daily dose of dabigatran is 220 mg, the daily dose in the present case was set to 150 mg in consideration of elevated blood concentration due to removal from the capsule. The dabigatran concentration 4 h after the first administration (peak) and before the second and third doses (trough) was measured by ultra-performance liquid chromatography/mass spectrometry. ResultsThe dabigatran concentration was 115.8, 62.45, and 80.05 ng/mL 4 h after the first administration and before the second and third doses, respectively, which is similar to data obtained in a clinical study using healthy Japanese volunteers. aPTT was 38–48 s. Conclusions We were able to administer dabigatran after removal from the capsule through a tube at two-thirds the regular dose and maintain a similar dabigatran blood concentration to that obtained in a clinical study through careful monitoring of dabigatran plasma levels. No conflict of interest.