A Case of Esophagogastric Junction Cancer Treated with Pain Control by Administering Methadone Tablets Through a Gastrostomy.

Introduction: Methadone is used to treat intractable cancer pain when other opioid analgesics are ineffective. Methadone tablets may be difficult to administer in cases of gastrointestinal passage obstruction. However, changing the route of methadone tablet administration is possible. Case Description: The patient, diagnosed with esophagogastric junction cancer with multiple metastases, continued to receive methadone tablets even after not being longer able to take oral medication. Method: Methadone tablets were administered using a simple suspension method via gastrostomy. We measured the respiratory rate during sleep daily. We also measured weekly QTc values using a 12-lead electrocardiogram and methadone blood concentration periodically. No side effects were observed. Conclusion: Using a simple suspension method to administer methadone is a safe pain management method when accompanied by careful monitoring. To date, no study has examined the tube administration safety of methadone tablets. Thus, this case report is of important clinical significance.

Evaluation of the Simple Suspension Method for Oral Anticancer Drugs.

The simple suspension method (SSM) involves administering tablets or capsules using a tube after disintegration and suspension in hot water without crushing or opening the capsule. Particularly, for anticancer drugs, it is an excellent method of administration that reduces the risk of exposure during dispensing. In contrast, information on SSM for individual drugs is insufficient. Anticancer drugs present a therapeutic challenge because their information is limited. We investigated whether SSM is possible with 36 anticancer drugs. Furthermore, we examined the pH of the suspension of these drugs, for which no information on SSM is available. We found that suspension was possible for 24 of the 36 drugs. Furthermore, the pH of the suspension was measured, which provided important information when considering dissolution solutions other than hot water. Little changes in the pH were observed before or after passing through the tube. The results of this study may improve medication adherence in patients with cancer experiencing dysphagia.

A study on the chemical stability of cholesterol-lowering drugs in concomitant simple suspensions with magnesium oxide.

BACKGROUND: Difficulty in taking solid medicines is a common issue particularly for the elderly because of a decline in swallowing function, also known as dysphagia. For patients with such a dysfunction, a simple suspension method, in which solid medicines are disintegrated and suspended using warm water, has been developed and widely used in Japanese clinical settings. However, there is little information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. In this study, the chemical stability of typical cholesterol-lowering drugs was investigated in a simple co-suspension with alkaline magnesium oxide (MgO) which is frequently used as a laxative or antacid in Japan. METHODS: A cholesterol-lowering drug (one tablet) was soaked with or without MgO in warm water (55°C), and the vessel was left at room temperature for 10 min or 5 h. The suspensions prepared were then analyzed by high-performance liquid chromatography. Degradation products were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry for the structural elucidation. RESULTS: In the simple co-suspension with MgO, no significant degradation was observed for atorvastatin or pravastatin, while a significant decrease of the recovery from the co-suspension was observed for rosuvastatin after 5 h. On the other hand, simvastatin and ezetimibe co-suspended with MgO were partially degraded to simvastatin acid and a pyran compound, respectively. CONCLUSIONS: A simple co-suspension with MgO is feasible for atorvastatin, pravastatin, and rosuvastatin, although the rosuvastatin tablet should not be left soaking for a long time. Further it is inadvisable to suspend simvastatin or ezetimibe together with MgO because of their partial degradation.

Optimal Administration of Phosphorus Adsorbents When Using Medical Nutritional Supplements for Tube-fed Patients.

All medical enteral nutrition products contain phosphorus and when administered to patients with chronic kidney disease (CKD) and on dialysis, they lead to the risk of elevated serum phosphorus levels. Thus, serum phosphorus levels should be monitored, and phosphorus adsorbents should be used in cases of high serum phosphorus levels. In this study, we investigated the effect of phosphorus adsorbents on enteral nutrition, using Ensure Liquid®, a medical nutritional formula, for patients with CKD and those on dialysis. Additionally, we compared the effects of the simple suspension method, in which various phosphorus-adsorbing agents are suspended and mixed directly with the nutritional formula for tube administration (hereafter referred to as the "pre-mix method"), and the conventional method, in which only the phosphorus-adsorbing agents are administered separately from the nutritional formula for tube administration (hereafter referred to as the "normal administration method"). The administration of various phosphorus adsorbents using the pre-mix technique resulted in a phosphorus removal rate of 8-15% (approximately 12% on average). Therefore, through the pre-mix method, maintaining the phosphorus content of Ensure Liquid® below the daily phosphorus intake standard was possible for patients on dialysis. The pre-mix method via the simple suspension method of administering phosphorus adsorbent with Ensure Liquid® resulted in less drug adsorption to the injector and tube and a higher phosphorus removal rate than the normal administration method.

Survey on the Status of Descriptions regarding Reference Information for Dispensing and Medication Support in the Interview Form / 医薬品情報学

Objective: We examined the descriptions of reference information regarding the dispensing process in the interview form (IF). If there was no description, we determined the test data’s availability from the pharmaceutical company.Methods: The survey targeted 78 drugs that complied with the new description IF guidelines, for regular tablets and capsules launched from April 2018 to December 2021. The survey was conducted between March 13th and June 14th, 2022. We investigated the reference information regarding the stability of the medications during the crushing and simple suspension method during dispensing.Results: Regarding the data related to the stability of medications during the crushing process, ten drugs were described as having “data available,” 18 drugs were to be “inquired individually,” 31 drugs had “no applicable data,” and 14 drugs had “no items.” Regarding the status of descriptions on the simple suspension method, ten drugs were described as having “data available,” 18 drugs had data that was to be “inquired individually,” 32 drugs had “no applicable data,” and 14 drugs had “no items.” Regarding the 35 drugs for which both the stability during crushing and the simple suspension method were listed as either “no applicable data” or “no items,” we contacted the pharmaceutical companies to inquire about the test data for the stability during the crushing and simple suspension method. We found that four drugs had “data available” on the stability of medications during the crushing process, while six drugs had “data available” on the simple suspension method.Conclusion: Many IFs that complied with the new description guidelines had items for reference information regarding dispensing. However, the test data’s description was not sufficient. Furthermore, even if there is no description of reference information regarding dispensing in the IF, we confirmed that the pharmaceutical company owns the test data.

Enteral lorlatinib after alectinib as a treatment option in anaplastic lymphoma kinase-positive non-small cell lung cancer with triple problems: carcinomatous meningitis, poor performance status, and dysphagia-a case report.

Alectinib treatment is effective in patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive non-small cell lung cancer (NSCLC; hereafter ALK-positive NSCLC) who exhibit central nervous system (CNS) relapse and poor performance status (PS). Lorlatinib treatment is effective upon failure of other ALK inhibitor-based treatments. However, much remains unknown about the efficacy of lorlatinib in patients with ALK-positive NSCLC, who have triple problems, carcinomatous meningitis, poor PS, and dysphagia, after alectinib treatment. Here, we report the remarkable response of a 73-year-old patient with ALK-positive NSCLC showing carcinomatous meningitis due to CNS metastases, poor PS, and dysphagia to lorlatinib. Lorlatinib administration through a nasogastric tube alleviated complications related to consciousness within three days, and the patient survived for 16 months after CNS relapse. Lorlatinib could be a treatment option for patients with ALK-positive NSCLC showing carcinomatous meningitis, poor PS, and dysphagia upon failure of other ALK inhibitor-based treatments.

Mixture of clopidogrel bisulfate and magnesium oxide tablets reduces clopidogrel dose administered through a feeding tube.

BACKGROUND: In clinical practice, a mixed suspension of clopidogrel bisulfate and magnesium oxide (MgO) tablets is administered frequently via a feeding tube. However, there is no report on the changes occurring when suspensions of these two drugs are combined, including the effects or potential decrease in dose following tube administration. Thus, the purpose of our study was to investigate the (i) changes caused by mixing clopidogrel bisulfate (ion form) and MgO tablets and (ii) effects on the administered clopidogrel dose after passing through a feeding tube. METHODS: The molecular structure of clopidogrel generated in a mixture of clopidogrel bisulfate and a basic compound, such as sodium bicarbonate or MgO tablet, was determined by 1H-NMR after extraction and purification. The suspension of clopidogrel bisulfate tablet alone and the mixed suspension of clopidogrel bisulfate tablet and MgO tablet were passed through a feeding tube. We compared the yield of the molecular form of clopidogrel from each passed fraction. RESULTS: The substance obtained from the mixture of clopidogrel bisulfate tablet and sodium bicarbonate or MgO tablet was identified as the molecular form of clopidogrel, and chemical degradation did not occur under these conditions. In the tube passage test, the yield of clopidogrel (molecular form) from the mixture of clopidogrel bisulfate and MgO tablets was lower than that from the suspension of clopidogrel bisulfate tablet alone. CONCLUSIONS: The mixture of clopidogrel bisulfate and MgO tablets caused a considerable reduction in the administered dose passed through the feeding tube. Therefore, it is recommended to administer the suspensions of clopidogrel bisulfate and MgO tablets separately for safe and effective pharmacotherapy.

Analysis of Awareness and Perception Alteration of Simple Suspension Method by a Workshop for Hospital Pharmacists / 社会薬学

The conventional crushing method for administration of drugs to patients with feeding tubes has been commonly used at the Hyogo College of Medicine College Hospital. Compared with this conventional method, the simple suspension method can reduce drug degradation due to light and moisture absorption as well as avoid drug loss and contamination. We conducted a workshop to introduce this method to pharmacists. We asked the participants to fill a questionnaire-based survey both before and after the workshop to determine the effects of the workshop on the change in the degree of awareness among participants about these methods. The awareness of participants about the simple suspension method was approximately 80% before the workshop. Approximately 60% of participants answered that they had questions about simple suspension method from individuals from other occupations, suggesting a high awareness of this method. After the workshop, approximately 98% of participants answered that they were “satisfied” or “slightly satisfied,” suggesting that they were in favor of introducing the suspension method. The results of text mining indicated a requirement for participants to consider incompatibilities and to educate the nursing department. Participants who actively considered the proposal of simple suspension method had an altered perception toward the introduction and utilization of this method. Therefore, this survey suggested that workshops could alter the perception and behavior of pharmacists about the methods of drug administration via feeding tube.

Development of an appropriate simple suspension method for valganciclovir medication.

BACKGROUND: Valganciclovir (VGC) is essential for preventing cytomegalovirus infections after transplants in adult and pediatric patients. In pediatric patients, VGC tablets have to be pulverized so that they can be delivered via nasogastric tubes. The "simple suspension method" is usually used to suspend tablets in hot water in Japan. However, the optimal suspension conditions and metering methods for preparing VGC suspensions using the simple suspension method are unclear. The purpose of this study was to clarify these issues. METHODS: VGC tablets were suspended in water (initial water temperature: 25 °C or 55 °C) using the simple suspension method. The residual rate of VGC after it had been suspended in hot water was determined using HPLC. In addition, the suspended solution was passed through 6, 8, and 12 Fr. gavage tubes. The VGC concentrations of suspensions produced using different preparation methods were also determined using HPLC. RESULTS: Cracking the surfaces of VGC tablets and suspending them in water at an initial temperature of 55 °C was effective at dissolving the tablets. The VGC concentration of the suspension remained stable for at least 80 min. Furthermore, the VGC concentration remained stable for 48 h during cold dark storage. Cracking the surfaces of VGC tablets could be a more effective metering method than preparing powder from VGC tablets. In addition, little VGC remained in 6, 8, or 12 Fr. gavage tubes after VGC solution was passed through them. CONCLUSION: The amount of VGC should be measured carefully when preparing VGC solutions using the simple suspension method.

Evaluation of Measures against Exposure during Administration of Hazardous Drugs through a Feeding Tube.

Hazardous drugs (HD), which need to be handled with care, may be administered through a feeding tube using the simple suspension method. However, instrument contamination during HD administration with the simple suspension method remains unclear. Therefore, to minimize such contamination during the simple suspension method using an injector, we propose the following exposure countermeasures method: (1) Wear two layers of gloves. (2) Prepare injectors for administration and flushing. (3) Use caps. (4) Replace outer gloves after the removal of tablets from the press-through package (PTP) sheet. (5) Handle drugs on a tray. (6) Inject while wrapping the connection site between the injector for administration and the tube with gauze. (7) Wrap the connection site between the injector and tube with gauze. (8) Do not point the injector downward. To establish whether these countermeasures method are effective, 16 ward nurses who routinely administer drugs via a feeding tube were enrolled as subjects. By visual evaluation, we compared differences in instrument contamination between a suspension using a medicine cup and administration via a feeding tube (the conventional method) and the exposure countermeasures method. Exposure with the countermeasures method under our instruction was markedly lower than that with the conventional method. Furthermore, after implementing the exposure countermeasures method, most nurses noted that caution and awareness of exposure countermeasures increased. Thus, to minimize exposure, we recommend the implementation of the exposure countermeasures method and increasing knowledge and awareness of measures against exposure.

Stability of probiotics with antibiotics via gastric tube by simple suspension method: An in vitro study.

Data on the stability of probiotics with antibiotics delivered via gastric tube using the simple suspension method (SSM) are limited. Therefore, we investigated bacterial survivability in probiotics treated with antibiotics prepared by the SSM in vitro. Probiotics and antibiotics were suspended in 20 mL of sterilized hot water (55 °C) and then 1-mL of the suspensions were taken each at 10, 60, 120, 180 and 360 min. Thereafter, the samples were inoculated on 3 media and cultured at 37 °C for 24 h. Survival of probiotic strains was measured in colony-forming units. The growth of Clostridium butyricum did not change without antibiotics at all experimental times, but in the case of Enterococcus faecium tended to increase. On the other hand, the viable bacterial number of C. butyricum was decreased significantly by treatment with cefdinir, tosufloxacin, clarithromycin, or azithromycin, but was not altered by levofloxacin, minocycline, or vancomycin. The viable bacterial number of E. faecium was significantly decreased by treatment with tosufloxacin, levofloxacin, minocycline, vancomycin, or azithromycin, and was significantly increased by clarithromycin. In conclusion, our results suggest that the efficacy of probiotic therapies might be reduced by the SSM when specific antibiotics are used. Moreover, antibiotics might inhibit probiotic growth, although some probiotics are spore-forming and have high minimum inhibitory concentrations. Additionally, early administration of non-spore-forming bacteria might be desirable. Therefore, when patients are administered therapy combining probiotics and antibiotics by the SSM, we should consider the characteristics of the probiotics and the administration times.

Survey on Accumulated Drug Information by Pharmaceutical Companies about Crushed or Simply Suspended Internal Medicines / 医薬品情報学

Objective: We conducted a survey on drug information accumulated by pharmaceutical companies about the adequacy of administration of crushed or simply suspended internal medicines through enteral feeding tube, examination methods to confirm adequacy and inquiries from medical institutions to pharmaceutical companies about the adequacy of these methods.Methods: We sent a questionnaire to 162 pharmaceutical companies that sell internal medicines to collect information. The survey was conducted from May 1, 2016 to March 31, 2017.Results: The questionnaire response rate was 61% (99 companies responded). Eighty and 90 percent of the companies possessed information about the drug crushing methods and simple suspension methods used for administration of internal medicines,respectively. The type of information and examination methods used varied among the companies, was very limited, and was often limited to new drugs. The information acquisition rate about crushing methods was 69.3% in original examination methods of pharmaceutical companies. On the other hand, 90.3% of the information about simple suspension methods was obtained by the unified method of Hand Book of Simple Suspension Method.Conclusions: In the future, medical practice and patients will benefit if examination methods to confirm the adequacy of crushing and administration through feeding tubes are commonly and consistently obtained by pharmaceutical companies. Furthermore, it would be very useful for information of crushing methods and simple suspension methods to be included in package inserts and interview forms.

Administration of Kampo medicine through a tube at an advanced critical care center.

n emergency and critical care medical centers, tube administration is employed for patients who have difficulty swallowing oral drugs owing to decreased consciousness or mechanical ventilation. However, tube clogging due to drug injection is a concern. We compared the crushing method with the simple suspension method for the passage of amlodipine, an antihypertensive drug, in combination with rikkunshito, which has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux in emergency and critical care medical centers, to ascertain the effect of Kampo products on the passage of other drugs during tube administration. When the crushing method was employed, poorly water-soluble solid products were formed, while a uniformly dispersed suspension was obtained using the simple suspension method. In addition, the passage rate of amlodipine through the tube was 64% and 93% in the crushing and simple suspension methods, respectively, thereby indicating that the simple suspension method provided more favorable than the crushing method. The results of this study suggested that the passage rate of amlodipine for patients who received Kampo products concurrently was higher when the simple suspension method was used, and an appropriate drug amount might well be able to administered to patients using this method. J. Med. Invest. 65:32-36, February, 2018.

Stability of lenalidomide suspension after preparation by a simple suspension method for enteral tube administration.

PURPOSE: A simple suspension method has been developed for tube administration, in which tablets (and capsules) are disintegrated in hot water (55℃) without grinding (or opening) them. In the present study, we evaluated the feasibility of this simple suspension method for the preparation of lenalidomide (Celgene, Summit, New Jersey and USA) suspension by testing the stability of this drug at 55℃ and its adsorbability on the tube. METHODS: We examined, by high-performance liquid chromatography, the time-dependent changes in the concentration of lenalidomide in suspensions of the drug prepared by the simple suspension method. The high-performance liquid chromatography analyses of lenalidomide were performed on Prominence LC-20AB/SPD-20 A (Shimadzu, Kyoto, Japan) with a ZORBAX SB-C18 RR analytical column (Agilent Technologies, Santa Clara, California, USA; particle size: 2.1 × 100 mm, 3.5 µm) at a flow rate of 0.4 mL/min. A solvent system consisting of 10 mM ammonium acetate (pH 7.0)/acetonitrile was used as the eluent and the eluate was detected by UV at 254 nm. RESULTS: Lenalidomide was confirmed to remain stable in hot water at 55℃ for 24 h in the prepared suspension by the simple suspension method, and more than 99% of the drug could be recovered from the suspension. In addition, 94.5-98.0% of the drug amount could pass through a percutaneous endoscopic gastrostomy tube. Lenalidomide was scarcely adsorbed on to the percutaneous endoscopic gastrostomy tube made of polyurethane or polyvinyl chloride. CONCLUSION: Lenalidomide was found to be stable even in hot water and was not adsorbed on to the percutaneous endoscopic gastrostomy tube.

Examination Regarding the Simple Suspension Method using Oral Anticancer Drugs / 社会薬学

To administer oral anticancer drugs safely, the simple suspension method has been introduced in many hospitals. Therefore, concerning drugs for which it is unclear whether or not this method is applicable, testing must be able to be conducted at any time. In this study, we investigated 20 oral anticancer drugs to expand information on the application of the simple suspension method. Disintegration/suspension and permeability tests were conducted, as described in the 3rd version of the Tube Administration Handbook for Oral Drugs. All products were disintegrated/suspended after 10 minutes. On permeability tests, there was no residue in any tube for tubal feeding. On the final evaluation, the products were regarded as suitable (grade 1). Bicalutamide tablets (80 mg, TCK and KN), which were analyzed in this study, were regarded as suitable (grade 1) on the final evaluation. On the other hand, the simple suspension method is not applicable for a brand-name drug, Casodex^® tablets (80 mg). This may be related to the different additives. Furthermore, the results suggest that, even when the simple suspension method is not applicable for a brand-name drug, it may become applicable for generic drugs. This may provide a new merit for promoting the use of generic drugs.

Development of a Novel Database That Rapidly Provides Valuable Information Efficiently Aimed at Improving the Safety of the Simple Suspension Method / 医薬品情報学

<b>Objective: </b>Many patients in Kagawa University Hospital are administered medicines prepared by the simple suspension method.  Pharmacists in charge of these patients receive inquiries from doctors and nurses regarding the suitability of medicines for the simple suspension method.  Answering these inquiries is complicated and time-consuming as multiple data sources need to be searched.  In order to simplify these complicated procedures, we herein attempted to develop a novel database to provide valuable information that could contribute to the safe performance of the simple suspension method, and evaluated its usefulness.<br><b>Method: </b>The specifications of the database were determined by analyzing previously answered inquiries.  To evaluate the usefulness of the database, we used test prescriptions and compared the amount of time required to gather information using the database and the conventional method, i.e., using books alone.  We also analyzed previous prescriptions with the database in order to determine what kinds of problems could be detected.<br><b>Results: </b>The investigation of previous prescriptions indicated that some medicines needed to be examined not only for their suitability for the simple suspension method, but also their incompatibility.  Therefore, we added a feature regarding the incompatibility of medicines to the database.  The time required to gather the information needed to answer the test prescription was shorter with our database than with the conventional method.  Furthermore, the database improved the detection of medicines that require particular attention for their properties including incompatibility.  An analysis of previous prescriptions using our database indicated the possibility of incompatibility in half of the previous prescriptions examined.<br><b>Conclusion: </b>Our database could rapidly provide information related to the simple suspension method, including the incompatibility of medicines.

Creating a List of Oral Anticancer Drugs using the Simple Suspension Method for Appropriate Therapy / 社会薬学

In cancer chemotherapy, it is very important to take into account the patient’s background. In recent years, a simple suspension method has attracted increased attention as a method that prevents changes in the stability and safety of various drugs. However, of 135 oral anticancer drugs, only 28 have been examined using this method, as of April 2013. In this study, we carefully investigated whether 53 oral anticancer drugs could be adapted to the simple suspension method, except for the 28 drugs that had already been previously reported. The results showed that most of these oral anticancer drugs could be adapted to the simple suspension method. Of seven drugs that were not adapted, six were generic drugs. In addition, it was clear that the evaluation of bicalutamide tablets was significantly different from our expected results. In conclusion, we were able to qualitatively assess all 53 oral anticancer drugs. This is equivalent to half of 107 untested drugs. These results provide useful information to cancer patients using oral anticancer drugs prepared using the simple suspension method.

The role of the pharmacist in determining the method of administration of medicines in suspension through a feeding tube / 医薬品情報学

<b>Objectives</b>: To optimize the treatment of patients on tube feeding, it is important to ascertain whether medicines are appropriate for administration by gastrostomy and nasogastric tubes.  In this study, we evaluated the drug information services provided to medical staff by clinical pharmacists related to 109 patients administered medication via a feeding tube in a neurological ward.<br><b>Design and Methods</b>: We analyzed the records of drug information services provided to medical staff from January 2006 to December 2007 at the Higashi Nagoya Hospital.  We classified drug information services for avoiding obstruction of the feeding tube and chemical changes into four categories: ‘formulation changes’, ‘medication changes’, ‘incompatibilities’ and ‘administration method’, and evaluated the acceptance rate of the pharmacists’ recommendations for drug therapy via feeding tube.<br><b>Results</b>: Drug information related to formulation and medication changes accounted for 130 and 88 cases, respectively.  Information related to incompatibilities accounted for 19 cases, involving anticipated chemical changes related to concurrent administration of drugs.  Information related to administration methods accounted for 24 cases.  The acceptance rate for information by medical staff was 92.0%.<br><b>Conclusions</b>: Drug information to medical staff by pharmacists contributes to improved safety for patients administered medication via feeding tubes.  The acceptance rate for drug information was high, and the provision of drug information by pharmacists in the neurological ward was considered useful.