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GOT18-0038. COMPOUNDING OF 2% ANPHOTERICIN B OINTMENT FOR TOPICAL TREATMENT OF LONG EVOLUTION LOCALIZED CUTANEOUS LEISHMANIASIS. Background

Cutaneous leishmaniasis is a common problem in our Hospital. Despite the fact that our region is not endemic, we recieve lots of inmigrants from the north of Africa. In this case, Pediatric Service of our hospital requested a topical preparation of amphotericin B to treat a one year of evolution case of cutaneous leishmaniasis localized in the cheeks of a two years old infant.

Purpose

Describe the process of compounding a 2% amphotericin B ointment, answering the request of a Pediatric Service to treat a case of localized cutaneous leishmaniasis of long evolution.

Material and methods

Pediatric Service of our hospital requested a topical preparation of amphotericin B to treat a case of cutaneous leishmaniasis localized in the cheeks, with a year of evolution, in a two years old infant. We performed a search to seek for physicochemical stability of an ointment based in amphotericin B(powder), paraffin wax and liquid paraffin.

Results

A preparation of amphotericin B ointment was designed based on amphotericin B powder, liquid paraffin and paraffin wax.

To preparate 10 g of the ointment, the following steps were followed: 0.2 g of amphotericin B powder were first weighed in a precision balance inside a powder extraction cabinet, then a mortar was tared, the weighed active ingredient was added and 1 ml of liquid petrolatum was added, mixing until an homogeneous paste was obtained, to which paraffin wax was added q.s 10 g. Finally it was packaged in a 10 ml opaque syringe and labeled indicating the need for preservation between 2 ° and 8 ° and protected from light. The expiration date was established in 30 days in the refrigerator.

Conclusion

The preparation of amphotericin B 2% ointment was well tolerated by the patient, with improvement of the cutaneous injuries in subsequent reviews with the specialist. We consider the ointment an alternative for treatment of these injuries while waiting for more results.

References and/or Acknowledgements

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Conflict of Interest No conflict of interest

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GOT18-0040. COMPOUNDING OF BEVACIZUMAB 5 MG/ML EYE DROPS FOR CORNEAL NEOVASCULARIZATION. Background

From the Ophthalmology Service we are requested a formulation of bevacizumab as antiangiogenic agent in two cases of corneal neovascularization.

Purpose

Describe the process of compounding of a bevacizumab eye drops at a concentration of 5 mg/ml in an Hospital Pharmacy Service for two patients with corneal neovascularization.

Material and methods

We performed a search to seek for physicochemical stability and we determined the risks of the preparation and the expiracy date.

Results

A bevacizumab 5 mg/ml eye drops formulation was designed from Bevacizumab 25 mg / ml injectable 4 ml and 0.9% sodium chloride ampoules 10 ml. Working in a Laminar Flow Cabinet in a cleanroom and performing aseptic technique, 2 ml of Bevacizumab 25 mg/ml was loaded into a 10 ml Luer Lock® syringe. Then, the volume was diluted with 0.9% sodium chloride q.s. 10 ml, resulting in a bevacizumab concentration of 5 mg / ml. We homogenized and packaged it in an opaque plastic dropper bottle. Finally, we labeled it indicating that it should be stored between 2 ° and 8 ° C. Given the aqueous nature of the preparation and the absence of preservative, the expiration that was assigned to the eye drops was 14 days in a refrigerator.

Conclusion

Eye drops were well tolerated by patients, requiring a longer duration of treatment to determine its effectiveness. We considered the inclusion of an ophthalmic preservative such as benzalkonium chloride in the preparation to prolong the expiration to 30 days in the refrigerator.

References and/or Acknowledgements

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Conflict of Interest No conflict of interest

GOT18-0046. AUTOMATION OF PARENTERAL NUTRITION ELABORATION IN A HOSPITAL PHARMACY SERVICE Background

As the parenteral nutrition (PN) is a high-risk medication, the quality control must be guarantied. This should be considered in the automation process of its production.

Purpose

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To evaluate the impact of implementing an automated system (Exacta-Mix 2400® Baxa) on the quality of the elaboration of PN (parenteral nutrition).

Material and methods

The gravimetric control is a strategy used for the quality control in the elaboration of PN. It consists of comparing the actual weight with that calculated according to the volume and density of each of its components (theoretical weight). Regulatory agencies establish an acceptable margin of error of 5%, and it is advisable to reduce this to 3%, especially in pediatric nutrition.

Once the equipment was implanted, a comparison was made between the manual procedure and the new one. A comparative gravimetric control was performed between the PNs made the first week of December 2015 (manual procedure) and the same week one year later (automated system), excluding the tricameral ones. The deviations from the theoretical weight and the percentage of preparations that exceeded 3% were analyzed. For the comparison of means of deviation, a K-W test was performed using software R. Results

A total of 144 PNs (77 manuals and 77 automated) were analyzed. The mean variation of the actual weight with respect to the theoretical weight was 3.37% and 0.73%, respectively (significant decrease (p <0.05)). The reduction in the percentage of preparations above the 3% limit was also significant. None of the PNs made with Exacta-Mix 2400® Baxa exceeded the variation limit of 3%, with a maximum variability of 1.95%.

Conclusion

Automation means an increase in accuracy control and a decrease in the risk of exceeding acceptable limits. Despite the difficulties of implementing a new technological process, robotization tends to become an essential in Hospital Pharmacy Services and allows an improvement in the integral quality of care.

References and/or Acknowledgements

Llop Talavera JM et al. Automation of parenteral nutrition elaboration: adaptation to in force legislation.Nutr Hosp. 2006 Mar-Apr;21(2):184-8.

Conflict of Interest No conflict of interest

GOT18-0066. EVALUATION OF THE EFFICIENCY AND SATISFACTION OF ORAL LIQUID MAGISTRAL PREPARATION FOR MUCOSITIS ELABORATED IN A TERTIARY HOSPITAL Background

Mucositis is a complication arising from chemotherapy which reduces the quality of life of a cancer patient. Its prevention and treatment is important.

Purpose

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To evaluate efficiency and satisfaction of the suspension for mucositis elaborated in the Pharmacy Service, destined for patients with mucositis as a consequence of cytostatic treatment, in order to identify where improvement is needed.

Material and methods

Observational descriptive study for one month. Oncohematological day hospital patients who attended for treatment and to pick up the suspension for mucositis were included. A form was designed that was an anonymous questionnaire. It included information about demographics data, pathology, degree of mucositis (according to the World Health Organisation), tolerability, effectiveness and patient satisfaction. The replies referred to qualitative dichotomous or polytomous variables, with nominal or ordinal gradations. The replies were analysed via an Excel® 2010.

Results

69 questionnaires were collected. 26 belonged to men. 4 were excluded from the study for lack of information. The average age of the patients was 63±10,83 years old.

The patients were classified based on the degree of mucositis: 21 patients grade 0, 19 grade 1, 23 grade 2, 1 grade 3 and 1 grade 4.

In no patient was it necessary to suspend the chemotherapy treatment as a consequence of the mucositis which presented.

56 patients (86.15%) indicated a considerable improvement in symptoms after the use of the magistral preparation after 2-4 days of use. In 5(7.69%) patients there was no improvement.

As for the taste, the valuation of the majority (64.68%) was that it was disagreeable.

In general the valuation of the magistral preparation was: 1 (3.07%), 2 (9.23%), 3 (40%), 4 (36.92%), and 5 (10.77%), 1 being nothing, 2 being a little, 3 being quite a bit, 4 being a lot and 5 being totally satisfactory.

Conclusion

The magistral preparation for mucositis elaborated in the Pharmacy Service is efficient in the control of the symptoms of mucositis at all levels.

The patients showed a high degree of satisfaction globally, palatability being the factor that needed improvement. As an opportunity to improve we found the study of flavourings compatible with the preparation and that they did not interfere with the therapeutic effect.

References and/or Acknowledgements

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Conflict of Interest No conflict of interest

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GOT18-0087. EXTEMPORANEOUS PREPARATION OF ORAL VANCOMYCIN SUSPENSION FOR PEDIATRIC PATIENTS Background

Solutions of vancomycin for oral administration are not available commercially in Bosnia and Herzegovina but are needed for pediatric patients who cannot swallow capsules. Child 40 days old diagnosed with Megacolon congenitum, St.post Ileus meconialis, Peritonitis diff., Sepsis, Hepatitis toxica, Convulsiones, Insuff. cardiorespiratoria, ARDS was admitted in Pediatric Clinic. Child was also diagnosed with Clostridium difficile and should receive 25mg/ml of vancomycin suspension as the first-line therapy. The recommended dose was not available on the market and the only solution was that pharmacists prepare the suspension extemporaneously from the injectable form.

Purpose

The aim was to describe the preparation procedure of vancomycin suspension dedicated to child and the standard technology process.

Material and methods

Pediatric Clinic send request for preparation of 25 mg/ml vancomycin oral suspension. After consultation with colleagues in Pharmacy and examined available literature we have created following drug formulation. Vancomycin oral suspension were prepared by reconstituting commercially available vancomycin for injection (Edicin® à 1 g) with sterile water for injection and then diluting with a mixture of equal volumes of Ora- Sweet® and distilled water then placed in glass for 5 to 10 minutes stirring. After that suspension were transferred in dark glass bottle with plastic seal. For 120 ml vancomycin suspension we used 3 Edicin® Injections, 60 ml sterile water for injection and 60 ml Ora-Sweet® vehicle. Stability and storage were determined in published research study from Canada. The recommended stability was for 75 days stored at 4° C or 30 days at room temperature.

Results

The child received vancomycin suspension prepared in our Pharmacy in dosage of 4 times 40 mg per day through nasogastric tube. Unfortunately the result was lethal due to additional very complicated diagnoses and general condition of the child.

Conclusion

Recommendations and available research studies are designed to help the preparation of the drugs that are not available on domestic market. Such preparations are essential especially for pediatric patients.

References and/or Acknowledgements

Ensom MHH, Decarie D, Lakhani A. Stability of Vancomycin 25 mg/mL in Ora-Sweet and Water in Unit-Dose Cups and Plastic Bottles at 4°C and 25°C. Can J Hosp Pharm. 2010; 63 (5): 366-372

Conflict of Interest No conflict of interest

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GOT18-0095. EVALUATION OF ECONOMIC SAVINGS COMPOUNDING CEFUROXIME INTRAVITREAL INJECTIONS TO PREVENT ACUTE POSTCATARACT ENDOPHTALMITIS. Background

Acute postcataract endophthalmitis is the most common form of endophthalmitis. Several studies indicate an incidence of 0.05% to 0.2%. Despite its low incidence, it is an important clinical problem due to the high number of cataract operations performed in a year.

Purpose

To analize the savings in acute postcataract endophthalmitis profilaxis with intravitreal injections of cefuroxime 10 mg/ml prepared in a Hospital Pharmacy Service compared to commercial intravitreal cefuroxime.

Material and methods

In this study, we have made a comparison between the costs of 10 mg/ml cefuroxime intravitreal injection prepared under sterile conditions (Laminar Flow Cabinet) in our ISO 5(Grade B) clean room and commercial intravitreal cefuroxime.

Results

We produce in our service 200 cefuroxime intravitreal injections a week which represents 10430 intravitreal injections a year. With a single vial of 750 mg of cefuroxime we can produce 200 intravitreal injections with a cost of 1,06 €. On the other hand we have the commercial intravitreal cefuroxime vial, with only 50 mg to produce 50 intravitreal injections with a cost of 7,5 €.

Conclusion

Compounding cefuroxime intravitreal injections in our Laminar Flow Cabinet in a ISO 5 (Grade B) clean room supposes an economic saving of 1509€ a year. We can ensure a microbiological and physicochemical stability of 120 days at -20ºC for this injections.

References and/or Acknowledgements

.

Conflict of Interest No conflict of interest

GOT18-0096. COMPOUNDING AND USE OF A DOXYCYCLINE FOAM FOR THE TREATMENT OF AN ANEURYSMAL BONE CYST. Background

Aneurysmal bone cysts (ABC) are benign expansile vascular lesions that consist of blood-filled channels and appear generally in adolescents. ABC are often treated with excision, curettage, and bone grafting. Doxycycline has been proposed as an anti-VEGF drug in this type of benign cysts. In our Hospital Pharmacy Service, we were requested

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to compound a 10 mg/ml doxycycline foam in order to reduce an aneurysmal bone cyst in a 7 years old patient's femur.

Purpose

Describe the process of compounding a 10 mg/ml doxycycline foam to treat an ABC and evaluate its effectiveness

Material and methods

Pediatric Service of our hospital requested an sterile preparation of 10 mg/ml doxicicline foam. First of all 240 mg of doxycycline(as doxycycline hyclate 86,7%)were weighed in a precision balance inside a powder extraction cabinet. Doxycycline was then solved in 6 ml of water for injection obtaining a 40 mg/ml solution. In a laminar flow cabinet, the obtained solution was filtered twice with a 0,22 micrometers hydrophilic filter. To compound the foam we mixed 5 ml of sterile 40 mg/ml doxycycline solution with 5 ml of an sterile solution of albumin 20%, obtaining a 20 mg/ml solution. Finally, this 10 ml of solution were mixed with 10 ml of sterile air and shaked to compound the final 10 mg/ml foam. We can ensure an expiration date of 3 days at 2ºC-8ºC given the non sterile nature of the starting drug.

Results

The final doxycycline foam was sent to the quirophan where it was injected in the bone lesion. Four months later patient was evaluated by the pediatric traumatologist. The foam was well tolerated by the patient and a radiologic improvement of the lesion was obtained in the distal part of the lesion.

Conclusion

This foam we prepared appears to be a therapeutic success and it is probable that the patient continue with this treatment given its effectiveness.

References and/or Acknowledgements

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Conflict of Interest No conflict of interest

GOT18-0122. CLEANING OF PHARMACEUTICAL CLEANROOMS AND EQUIPMENT WITH COMPOSITE FIBER CLOTHS AND STERILE WATER Background

Cleaning of pharmaceutical facilities have traditionally included use of chemical disinfectants. A change from cleaning with chemical disinfectants, to cleaning with composite fiber cloths and sterile water have been tested in a hospital pharmacy manufacturing unit.

Purpose

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The goal was to reduce the use of chemical disinfectants, shorten the time used for cleaning, and at the same time maintain an acceptable level of particles, cytotoxic contamination and microbiological cleanliness in the cleanrooms and equipment.

Material and methods

Composite fiber cloths and sterile water were used for all cleaning activities of the cleanrooms and equipment. Sterile 70% ethanol was used for disinfection of grade A between each production, and for surface disinfection of materials to be transferred into grade A, B and C zones.

Monitoring of particles and microorganisms were performed according to standard procedures for hospital pharmacy and EU-GMP limits. Monitoring of cytotoxic contamination was done by a standardized method for environmental control of cyclophosphamide on surfaces.

Results

Cleaning with microfiber and sterile water have eliminated the use of all chemical disinfectants except for 70% ethanol. The time spent cleaning is about 1/3 compared to traditional cleaning with chemical disinfectants.

The monitoring of particles, microorganisms and cytotoxic contamination of the working environment has remained at the same levels as before the change.

Conclusion

A change to cleaning with composite fiber cloths and sterile water gives an environmental benefit with the reduction in chemical disinfectants, and it maintains an acceptable level of cleanliness. It also has a positive effect for the personnel considering exposure of disinfectants, less strain and time used during cleaning.

References and/or Acknowledgements

None

Conflict of Interest No conflict of interest

GOT18-0138. ARE DAY-TO-DAY CHANGES IN THE INDIVIDUALIZED PRESCRIPTIONS OF NEONATAL AND PEDIATRIC PARENTERAL NUTRITIONS CLINICALLY SIGNIFICANT? Background

Individualized parenteral nutritions (PN) for neonates and children are produced daily in our institution. This flexibility offered to clinicians has a high impact on the pharmacy workload (compounding, laboratory quality control), especially on the week-end.

Purpose

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To analyse if individualized PN prescribed each day of the week-end have clinically significant day-to-day formulation changes justifying daily compounding.

Material and methods

Retrospective study of all compounded PN (Friday to Sunday) during two 8-months periods (2015/2016). PN prescription sequences of at least 3 days were defined as: - unplanned (PN prescribed each day of the week-end) - planned (PN prescribed on Friday for 3 days)

Clinically significant day-to-day formulation changes were defined by a neonatologist and a pediatric gastroenterologist as: change in glucose>±2 mg/kg/min and/or amino acids>±1g/kg/24h, sodium>±2.0 mmol/kg/24h, potassium>±1.0 mmol/kg/24h, magnesium>±0.3 mmol/kg/24h, calcium>±0.5 mmol/kg/24h, phosphate>±0.5 mmol/kg/24h.

Outcome: % of at least one clinically significant formulation change on PN sequences and associated factors (year, weight [kg])

Results

A total of 306 PN prescription sequences were analysed (2015:163;2016:143): 226/306 (73.9%) were unplanned, 54/306 (17.6%) planned, 26/306 (8.5%) half-planned (prescribed for 1 day and then 2 days (or inverse)). Unplanned PN were more prescribed in 2015 than in 2016 (57.1% vs 42.9%, p=0.004), mainly for the neonatal and intensive care unit (81.4%) and for smaller patients compared to planned or half-planned PN (median weight 2.4 kg [IQR 1.0 to 8.6] vs 11.7 [4.0 to 16.2] vs 14.5 [7.5 to 25.4], p< 0.001).

Only 42/226 (18.6%) of unplanned PN had at least one clinically significant day-to-day formulation change. A trend to more frequent clinically significant day-to-day formulation changes was observed for smaller patients (1.3 kg [IQR 0.9 to 3.7] vs 2.6 [1.0 to 9.6], p= 0.055). More frequent significant formulation changes were for glucose (23/42 (54.8%)) and phosphate (16/42 (38 %)).

Conclusion

About 75% of PN compounded during the week-end were unplanned and mainly for the neonatal and intensive care unit. Only 18.6% of the unplanned PN had at least one clinically significant formulation change justifying daily compounding. Planned PN prescription during the week-end for all patients- or over a cut-off weight - will be discussed and evaluated economically in the next future.

References and/or Acknowledgements

-

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Conflict of Interest No conflict of interest

GOT18-0139. STABILITY OF MIXTURES OF ONDANSETRON AND HALOPERIDOL STORED IN INFUSORS AT DIFFERENT TEMPERATURES Background

Mixing different drugs for use in continuous infusion systems is a common practice in palliative care, but the analytical study of compatibility and stability is not always available.

Purpose

To evaluate the compatibility and stability of two admixtures of ondansetron and haloperidol at different temperatures (25ºC, 37ºC). The concentrations of the admixtures are: 0.15 mg/ml – 0.25 mg/ml and 0.3 mg/ml – 0.4 mg/ml of haloperidol and ondansetron respectively in NaCl 0.9% stored in elastomeric infusors protected from light.

Material and methods

The samples were prepared and diluted in NaCl 0.9% in elastomeric infusors in triplicate to obtain four different conditions of concentration and/or temperature of storage (concentration: 0.15 mg/ml – 0.25 mg/ml and 0.3 mg/ml – 0.4 mg/ml of haloperidol and ondansetron respectively; temperature of storage 25ºC and 37ºC).

The concentration of each constituent drug into different mixtures was periodically determined using a HPLC-UVmethod. The drugs were chromatographed on a C18 reverse phase column; the mobile phase was methanol:KH 2PO 4 0.05 M, adjusted to -1 pH 3 with H 3PO 3 (60:40, v/v) delivered at flow rate of 1.0 mL min . The sample injection volume was 20 μL, and triplicate injections were performed for every sample. The signal was recorded during 8 minutes and the retention times were 3.6 for ondansetron and 6.6 min for haloperidol. Ondansetron and haloperidol concentrations were determined at 254 nm by interpolation from the calibration curves prepared from the standards. Statgraphics centurion XVI program has been used to data treatment.

Results

All solutions were initially clear and colorless but visible particles appear, in all cases, into the infusers after two days since their preparation. Chemical stability of the admixtures diluted in NaCl 0.9% are as follow: haloperidol-ondansetron (0.15 mg/ml – 0.25 mg/ml) is stable (retained >90% of their initial concentration) two days at 25ºC and 37ºC; (0.3 mg/ml -0.4 mg/ml) is stable two days at 25ºC and 37ºC.

Conclusion

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The mixture of haloperidol and ondansetron stored in infusor devices is not stable because visible particles appear in less than 48 hours. Physical pressure by the elastomeric infusor may have a role in the instability, since precipitate is not appreciated when stored in flask

References and/or Acknowledgements

-

Conflict of Interest No conflict of interest

GOT18-0144. STUDY OF STABILITY OF TWO LIQUID FORMULATIONS OF OMEPRAZOLE ELABORATED IN THE PHARMACEUTICAL SERVICE Background

As many medicines are not available for paedriatic use they have to be elaborated in the Pharmacy Service. Generally there are different formulations described in the bibliography.

Purpose

To compare two liquid formulations of omeprazole elaborated in the pharmacy service of a tertiary hospital evaluating physicochemical stability and organoleptic characteristics (OC) with the aim of defining what the most ideal formulation is.

Material and methods

A bibliographic check of the different formulations of omeprazole carried out and two liquid magistral preparation were elaborated in triplicate. Formulation 1 was prepared from omeprazole monohydrate salt, using as excipients: simple syrup, mixture conservans and purified water. Formulation 2 was prepared from omeprazole capsules using bicarbonate 1M as excipient. Conditions of refrigeration and of light protection were established. As an indicator of physicochemical stability the pH was selected. For its determination a pH measurer, Mettler Toledo SevenMulti ™ was used. The data was analyzed using an Excel® 2010 spreadsheet. The results were expressed as average±standart deviation. Also OC (colour, smell and taste) were evaluated, as well as homogeneity of the formulations. 30 days was established as a period of study. The determinations were carried out the days 0,10,17,24 and 30 post elaboration.

Results

The pH was stable with barely any oscillations during the period of study. The data obtained for formulation 1 was: 8.476±0.012(sample 1),8.544±0.01(sample 2),8.547±0.018(sample 3). For formulation 2 it was: 6.777±0.026(sample 1),6.373±0.005(sample 2),6.382±0.003(sample 3). The homogeneity of the formulations remained stable. The OC fluctuated significantly during the period of study. The colour of formulation 1 evolved from amber and opaque to dark brown; the smell evolved from sweet to metallic and the taste (bitter-sweet) remained stable. In formulation 2 the opaque white colour and the disagreeable metallic smell remained unchanged. The taste changed, going from very bitter to salty.

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Conclusion

In both formulations the pH remained stable.

The formulation based on raw material presents significant changes OC mainly in colour.

With regard to the formulation whose elaboration is made from capsules, the OC remain more stable.

As a result of this, it was decided to establish formulation 2 as a preferential magistral preparation in spite of its more disagreeable taste.

References and/or Acknowledgements

.

Conflict of Interest No conflict of interest

GOT18-0152. EFFECTIVENESS OF EMPIRIC TREATMENT WITH INTRAVITREAL AMPHOTERICIN B IN ENDOPHTHALMITIS Background

The empiric treatment with amphotericin B 5 mcg / 0.1 mL intavitreal in endophthalmitis, associated with antifungal systemic therapy in patients with or without infection extension to the vitreous has a degree of evidence IC (specialists opinion and / or small retrospective studies and /or patients records have shown evidence that treatment is beneficial). Therefore there is no much published evidence in this field.

Purpose

To evaluate the effectiveness of intravitreal amphotericin B in the empiric treatment of endophthalmitis.

Material and methods

Description of a clinical case in a patient admitted to the Surgery Department who presented endophthalmitis of unknown origin and who had two Amphotericin B 5 mcg/0.1 mL intravitreal administrations on day 0 (day of vitrectomy) and day 3 of hospitalization, both prepared in the aseptic Pharmacy unit to ensure sterile conditions. Systemic therapy with Voriconazole 200 mg 2x / day and Valganciclovir 900 mg 2x / day was initiated at the same time. The effectiveness of the treatment was assessed by visual acuity (VA) measure in the left eye (LE) and the right eye (RE) during the period of hospitalization and the following month in the ophthalmology specialized clinics.

Results

On day 1 of hospitalization, the VA was 0.01 in the RE and 0.5 in the LE; on day 2 was 0.02 and 0.4, respectively; on day 3 was 0.02 and 0.5; on day 4 was 0.02 and 0.5; on day 7 (discharge date) was 0.05 and 0.6, respectively. On day 3 post-discharge (+3)

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was 0.4 and 0.1; on day +15 was 0.7 and 0.9 and on days +19 and +25 was 0.8 and 1 respectively.

Conclusion

Intravitreal amphotericin B is effective in the empiric treatment of endophthalmitis administered in combination with antifungal systemic therapy. Our results are in line with those from the studies already published

References and/or Acknowledgements

Hospital construction-associated outbreak of ocular aspergillosis after cataract surgery. Tabbara KF, al Jabarti AL. Ophthalmology. 1998; 105: 522.

Conflict of Interest No conflict of interest

GOT18-0173. SMALL SCALE COMPOUNDING USING A POWDER DISPENSING TOOL FOR INDIVIDUALISED SOLID DOSAGE FORM DRUG DELIVERY Background

Pharmacy compounding is a valuable tool for personalised medicine (e.g. dose and excipients). This is an important tool in drug delivery to children where suitable doses/dosage forms are not available from the pharmaceutical industry. In many cases, liquid-based dosage forms are available allowing for a mL-based, individualised therapy, however, there are cases where e.g. capsules are the preferred form. Solid dosage forms allows for a child to easily self administer the medication e.g. during times away from hospital and home such as during school. For many years there have been methods for reformulating tablets by crushing or use active pharmaceutical ingredients to fill batches of capsules (e.g. batch six of 50 or 100 capsules).

Purpose

The purpose of this study was to evaluate powder dispensing equipment as a means for filling of single capsules.

Material and methods

Capsules were filled as part of a master thesis project at the Department of Pharmacy, Uppsala University, Sweden. To dispense powder the microbalance MT5 (Mettler Toledo), "Quantos handheld powder dosing system", model HPD (Mettler Toledo, orifice size 2,5/4 mm) was used. Model substances: Allopurinol Teva 100 mg tablet (Teva, Sweden) and Cellets microcrystalline cellulose pellets (Harke Pharma GmbH). Capsule "Coni-snap" of various sizes (Capsugel) were screened.

Results

HPD Quantos can be part of a method for preparing individual solid dosage forms, the equivalence that of one-fifth of a tablet. Capsules were made with the mean filling weight of 19,0 mg (target dose 20 mg) and a relative standard deviation of 12% for allopurinol.

Conclusion

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We present a method for producing capsules that allows for individualised dosing. An advantage is that single capsules can be produced with the possibility of daily dosage regimen change, tapering schemes etc.

The handheld version of Quantos is not accurate enough for small capsule sizes. There are automated systems with integrated scales on the market that can be used also for potential toxic substances that enable filling of smaller doses. With that in place the method would be well-functioning in a hospital pharmacy setting.

References and/or Acknowledgements

Mettler Toledo are acknowledged for providing the Quantos handheld dispenser free of charge.

Conflict of Interest No conflict of interest

GOT18-0211. AZATHIOPRINE ORAL SUSPENSION - a case-study Background

A 5 year-old-boy underwent a renal transplant and started its immunossupression therapy with azathioprine. As in Portugal this drug is only available as 25 and 50mg tablets, the 13mg dose prescribed must be given as an oral suspension prepared at the hospital pharmacy. A syrup-based and methylcellulose gel was selected(1). After two months of administration the caregivers reported a fungus growth on the bottle cap.

Purpose

Efficacy study of preservatives in a suspension of azathioprine prepared at the hospital pharmacy, which had developed microbial growth.

Material and methods

The azathioprine suspension was prepared with simple syrup, methilcelulose 1% and Imuran® tablets. The antimicrobial activity was assessed with a modification of membrane filtration method (Ph.Eur.,5.1.3.). Briefly, 5 samples were contaminated with P.aeruginosa , S.aureus , C.albicans , A.brasiliensis and E.coli . The antimicrobial activity was evaluated during 28 days and results were expressed as log reduction of the colony-forming units (cfu). The bacteria should be diminished at least by 2log-steps after 2days, by 3log-steps after 7days and on day 28 their number must not increase. With fungi, the cfu should be reduced at least about 2log-steps after 14days and on day 28 the cfu should not increase (A criteria) and 1log-step after 14days and on day 28 the cfu should not increase (B criteria).

Results

A yellow uniform suspension was obtained with pH 6. The efficacy of antimicrobial preservation test showed the suspension did lack adequate antimicrobial activity, which prompted an investigation of the underlying problem. It was hypothesized that the pH might not be at optimal level for the activity of the selected preservative (sodium benzoate), which is more efficient at pH 2-5(3). A second suspension was prepared using a citric acid 25% solution to lower the pH value to 2-3,

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followed by new efficacy of antimicrobial preservation test. This time the results meet criteria A.

Conclusion

The preservative in the oral suspension of azathioprine was effective at pH 2-3. This study emphasizes the importance of evaluating the microbiological stability of compounded non-sterile formulations (often not investigated) and also reports potential problems in the clinical practice.

References and/or Acknowledgements

1- Azathioprine Oral Suspension, Hospital of Sick Children, Canada, 2000 2 - European Pharmacopoeia 9.0.2017.

Conflict of Interest No conflict of interest

GOT18-0246. Compounding drug: 5% acetylcysteine eye drops Background

Acetylcysteine has been used for the treatment of various eye conditions such as dry eye or keratoconjunctivitis sicca, and alkali burns, but it has not yet been possible to develop a standard formulation that is well tolerated and meets pH and Osmolarity levels.

Purpose

Develop a 5% acetylcysteine ophthalmic formulation and optimize patient tolerance.

Material and methods

Three compounding drugs of acetylcysteine 5% were elaborated by aseptic technique, they were used as starting products Acetylcysteine 10% (Flumil® 10%) and Acetylcysteine 20% (Hidonac antidote®) both diluted with Liquifilm® tears (Allergan) and in the third with powder Acetylcysteine diluted in sterile distilled water and sodic hydroxide like a pH stabilizer. They were packed in topaz glass eye drops.

The pH and osmolarity of the samples were subsequently checked. The determination of pH was made with Futech pH510® and the osmolarity with Autoosmostat Daiichi OH- 620®

Stability was determined by calculating the risk matrix and based on the preparation and quality criteria of the preparation.

Results

The organoleptic properties of the three compounds were acceptable, as well as their sterility. The pH and osmolarity results were; Formulation from Flumil®: pH 6,97 and 772 mOsm/L, from Hidonac® pH 9,94 and 862 mOsm/L and from powder: pH 8,9 and 479 mOsm/L.

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Conclusion

Because the commercial preparations are hypertonic, this high osmolarity can reduce the concentration of active ingredient in the ocular surface, thus diminishing the effectiveness of eye drops, so we can conclude that the formula that best fits the physiology of natural teardrop and therefore will be more effective and better tolerated is acetylcysteine drops 5% from acetylcysteine powder.

References and/or Acknowledgements

Anaizi, N. H., C. F. Swenson and P. J. Dentinger. "Stability of Acetylcysteine in an Extemporaneously Compounded Ophthalmic Solution." Am J Health Syst Pharm 54, no. 5 (1997): 549-53.

Conflict of Interest No conflict of interest

GOT18-0249. MEDIA-FILL SIMULATION TESTS OF INFUSION BAGS PREPARED IN SERIES BY THE COMPOUNDING ROBOT APOTECACHEMO Background

The implementation of dose banding in centralized cytotoxic preparation units allows the preparation of standardised doses in series. Based on this concept, dose-banded ready- to-administer ganciclovir infusion bags are prepared in series in the pharmacy department by using the APOTECAchemo robot. Expiration dates are to be determined based on physicochemical and microbiological stability studies.

Purpose

The aim of the study was to evaluate the microbiological stability of dose-banded, automatically prepared ready-to-administer infusion bags (10 per series) by media fill simulation tests.

Material and methods

The aseptic preparation of a series of 10 infusion bags was simulated with purchased double strength growth medium TSB (BD TM , Germany) and prefilled 250 mL 0.9% NaCl polyolefin infusion bags (Freeflex®, Fresenius Germany). After withdrawal of superfluous vehicle solution, 125 ml of TSB were added and a final volume of 250 mL achieved. The simulation process was performed with the APOTECAchemo robot on five consecutive days. In total, 50 infusion bags were filled, incubated, and stored for 12 weeks (maximum intended storage interval) at room temperature. The media-filled bags were visually inspected for turbidity after 2, 4, 8, 10, and 12 weeks. After 4 weeks, 10 bags were randomly sampled and growth promotion tests performed by inoculation of S.epidermidis KH6 or S.aureus ATCC6538 suspensions in order to achieve a concentration of 10 CFU/mL, i.e. 2500 CFU/bag. During the simulation tests, airborne contamination was monitored with settle plates and microbial surface contamination with contact plates.

Results

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None of the 50 media-filled bags showed turbidity after an incubation period of 2 weeks and storage period up to 8 weeks indicating the absence of microorganisms. Positive growth promotion tests proved the process reliability, since both bacteria species caused turbidity in all samples after 5 days of incubation. The environmental monitoring with settle/contact plates matched the recommended limits set for cleanroom Grade A zones, except in the loading area of the robot.

Conclusion

Media-fill simulation tests and supplemental environmental monitoring of aseptic preparation of infusion bags in series by the APOTECAchemo revealed an adequate sterility level and a well-controlled aseptic procedure. The sterility was maintained over extended incubation and storage periods, thereby encouraging extended expiration dating.

References and/or Acknowledgements

-

Conflict of Interest No conflict of interest

GOT18-0254. MANAGEMENT OF HAND-FOOT SYNDROME INDUCED BY CAPECITABINE WITH VITAMIN E-ALLANTOIN CREAM Background

Hand-foot syndrome (HFS) is the most frequent adverse reaction derived from antineoplastic treatment with capecitabine. Clinical manifestations include painful erythema in the palms and soles, sometimes preceded by paresthesia, whose appearance is related to dose and peak concentration of the cytostatic, as well as its accumulation. Its pathophysiology is unknown. Treatment interruption or dose reduction are the most frequently methods used to manage HFS.

Purpose

The main objective is to present a new topic formulation made with Vitamin E - Allantoin to manage the HFS in a patient treated with capecitabine.

Material and methods

Initially, bibliographic research on active ingredients and compatible excipients potentially likely to be used as topic compounded formulation was made (Martindale, Pubmed, Micromedex).

Results

To prepare the formulation, weigh 3 g of Vitamin E Acetate, and then incorporate the Cold-Cream until reach 50 g and homogenize. Weigh 1 g of Allantoin and dissolve it in 2 ml of distilled water previously heated to 60° C. Later incorporate the Allantoin into the initial mixture, completing and homogenizing with Cold-Cream to a final weight of 100 g. Vitamin E-Allantoin cream (VEAC) was applied twice a day during seven days on a patient who had HFS derived from capecitabine treatment. VEAC acts on cell

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proliferation in the corneum stratum, accelerating the healing of wounds, while cleaning and eliminating necrotic tissues. Seven days later, the level of desquamation, erythema, inflammation and pain in the affected areas were reduced considerably. An increase in the comfort and patient’s quality of life were shown.

Conclusion

The use of VEAC both in prophylaxis and treatment may be recommended in all grades of HFS and especially in those patients in whom suspension/ dose reduction is not recommended. The increase in the quality of life derived from the treatment with this formulation will reinforce the acceptance and adherence to the chemotherapy treatment.

References and/or Acknowledgements

N/A

Conflict of Interest No conflict of interest

GOT18-0261. IMPLEMENTATION OF NEW RECOMMENDATIONS FOR HANDLING HAZARDOUS DRUGS Background

Some drugs can be considered hazardous because of their potential to cause irreversible effects.

Purpose

To describe the actions carried out in a Pharmacy service after the publication of Spanish National Institute of Occupational Health and Safety (INSHT) recommendations about Hazardous Drugs (HD).

Material and methods

A list with the HD included in the pharmacotherapeutic guide was drawn up. HD were classified according to the requirements when handling them and actions about their storage, repackaging, preparation and dispensation needed. The pharmacotherapeutic guide and the guidelines for nasogastric drug administration were updated. The actions carried out were communicated to the Hospital’s Management team and nursing staff.

Results

Of the 321 pharmaceutical forms included in the INSHT list, 134 were excluded (not included in the pharmacotherapeutic guide) and 4 were withdrawn from the guide because of the low level of consumption. The 183 drugs included were classified as: 101 from group 1, 44 from group 2 and 28 from group 3. The HD were classified according to the actions carried out into 6 groups: -64 parenteral antineoplastic drugs which are prepared in a class IIb Biological Safety Cabinet (IIb-BSC).

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-40 oral antineoplastic drugs for which the pharmacotherapeutic guide and the guidelines for nasogastric drug administration were modified to avoid splitting or crushing.Nursing staff should contact with Pharmacy service to assess it the treatment is temporally stopped, administered via another route or split in a IIb-BSC. -15 drugs that not require any manipulation to compound them (pre-filled syringes, ointments, vaginal tablets and oral solutions). -47 oral drugs (groups 2 and 3) for which the pharmacotherapeutic guide and the guidelines for nasogastric drug administration were modified to avoid splitting or crushing. -10 drugs that must be reconstituted in a IIb-BSC. -7 parenteral drugs with recommendations only if the handler is at reproductive risk. Furthermore, the repackaging process of 5 drugs and the Standard Operating Procedures of 5 compounded medications were modified to be carried out inside the IIb- BSC.

Conclusion

The actions adopted have supposed a decrease in the risk of occupational exposure in nursing staff, minimizing the handling of HD with a consequent increase in safety. These modifications have led to an increase in the Pharmacy service workload.

References and/or Acknowledgements

INSHT recommendations about Hazardous Drugs.2017

Conflict of Interest No conflict of interest

GOT18-0267. PHYSICOCHEMICAL STABILITY OF RECONSTITUTED DECITABINE (DACOGEN®) SOLUTIONS AND READY-TO-ADMINISTER INFUSION BAGS WHEN STORED REFRIGERATED OR FROZEN Background

Profound knowledge about the physicochemical stability is necessary in order to determine the ‘beyond-use-dates’ of reconstituted and diluted ready-to-administer preparations of decitabine (Dacogen ® ).

Purpose

The stability of Dacogen ® powder reconstituted with cold sterile water for injections (SWFI) (5 mg/mL) and further diluted with prechilled 0.9% NaCl solution in polyolefine (PO) infusion bags (0.5 mg/mL) has been determined after storage under refrigeration for a maximum period of 48 hours. Furthermore the stability of reconstituted solutions in 1mL single-use syringes stored at –25 °C should be investigated.

Material and methods

Reconstituted Dacogen ® powder in original glass vials and diluted test solutions in infusion bags were stored under refrigeration. Aliquots were transferred to syringes and immediately frozen at predetermined intervals over a maximum period of 48 hours. Each frozen sample was thawed at room temperature and immediately analysed. pH-values

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were measured at predetermined intervals. Aliquots of reconstituted solutions were transferred into syringes and stored at – 25 ° C over a period of 28 days. Decitabine concentrations were determined on day 0, 22 and 28 immediately after thawing. In parallel, pH-values were determined. Samples were assayed by a validated stability-indicating RP-HPLC assay with PDA detection based on the method published by Yuan et al. 1

Results

In reconstituted and diluted test solutions stored under refrigeration decitabine concentrations remained above 90% of the initial concentration for 12 hours and 24 hours, respectively. Several peaks of degradation products were observed which explicitly increased over time. When reconstituted test solutions were stored at -25 °C, decitabine concentrations decreased less than 2% and no degradation products were detected over the storage period. In all test solutions the pH-values remained unchanged (pH=7). No particulate matter or color changes were observed over the test period.

Conclusion

Refrigerated decitabine (Dacogen ® ) solutions stored in the original glass vials after reconstitution with cold SWFI and in PO infusion bags after dilution with prechilled 0.9% NaCl solution are physicochemically stable for 12 hours and 24 hours, respectively. Reconstituted Dacogen ® solutions in 1mL single-use syringes stored frozen are physicochemically stable for at least 28 days.

References and/or Acknowledgements

1 Yuan et al. Determination of Decitabine for Injection by HPLC. Northwest Pharmaceutical Journal. 2012 Jul. http://en.cnki.com.cn/Article_en/CJFDTOTAL- XBYZ201206015.htm.

Conflict of Interest No conflict of interest

GOT18-0276. COMPARISON OF CHEMOTHERAPY PROCESSES: EVALUATING PREPARATION TIMES UNDER DOUBLE-CHECKING AND COMPUTER-ASSISTED GRAVIMETRIC CONTROL Background

In a centralized preparation of cytotoxic drugs unit, the organization of production lines can be complex. In our hospital, gravimetric control in process (GC) was set up in order to improve performance, quality and security.

Purpose

To check whether this implementation of GC allowed or not an optimization of production, we compared the manufacturing times of each preparation under GC with times under double-checking.

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Material and methods

For double-checking, preparations were timed manually while times under GC were obtained by extracting the GC software. Preparations have been classified according to their characteristics. For each group, an average time of preparation (ATP) was calculated. To compare these ATP, standard normal distribution test and Student's t-test were used. For small samples, Fisher's test demonstrated the equality of the variances.

Results

256 preparations and 5 pharmacy technicians (PT) were timed under GC against 244 preparations and 5 PT under double-checking. 7 groups of preparations have been defined. Across all categories of preparation, ATP differ significantly with a longer time for GC (5,9min versus 6,91min). ATP is 9.06min (±2.36min) for syringe with vial reconstitution, 5,84min (± 2.05min) for chemotherapy with one volume of ready-to-use cytotoxic drug and 9,54min (± 2.71min) for chemotherapy with reconstitution of one vial. Under double-checking, for these categories, ATP are respectively 6,1min (±1,8min), 4,6 min (± 1,6min) and 7,4min (± 1,9min). Concerning these 3 groups, we note a significant difference with a superiority of manufacturing time under GC. ATP from other categories of preparation don’t differ significantly. The step of taking drug from the vial is usually the most time consuming. Human factors and problems with GC software can also lead to a lengthening of preparation time.

Conclusion

Besides to improving security and quality of preparations, GC is accompanied by an increase of ATP for certain types of preparation. Although this increase appears relative compared to organizational benefits that GC offers, production remains perfectible. This study opens up some interesting prospects for improvement such as the development of a more appropriate training of PT and a change in the vision of organization production by working on key stages of the manufacturing process.

References and/or Acknowledgements

Thanks to pharmaceutical team

Conflict of Interest No conflict of interest

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GOT18-0297. STANOZOLOL CAPSULES FOR THE TREATMENT OF ULCERS ASSOCIATED WITH DERMATOLOGICAL PATHOLOGIES Background

Stanozolol is an anabolic derivative of testosterone which is associated with certain fibrinolytic properties that are interesting for the treatment of some severe and chronic ulcers associated with dermatological pathologies such as livedo reticularis or lipodermatosclerosis . These types of ulcers are usually located in the lower limbs, known for being painful and not being good responders to conventional treatments.

Purpose

With the end of commercialization of the brand name drug of stanozolol capsules the need to be prepared as a pharmaceutical compounding has emerged .

Material and methods

A bibliographic research was conducted to find the appropriate excipients (Martindale, European Pharmacopeia, etc.). The capsules were formulated from the stanozolol powder form mixed with microcrystalline cellulose and homogenized in a mixing blender. Finally, they were encapsulated. The dose per capsule was 2mg. Two patients restarted their systemic treatment of their ulcers with stanozolol. One with the diagnosis of livedo reticularis with summer ulcerations and the other with lipodermatosclerosis . Both patients had previously taken the brand name drug.

Results

The lots were dispensed monthly for an initial follow-up of 5 months, the ulcers improved progressively and more rapidly than when they were untreated. On the other hand, the patient's quality of life was improved by the relief and cessation of pain caused by ulcers. Both patients reported no difference in efficacy between the pharmaceutical compounding formula and the brand name capsules. They have been perfectly tolerated and no adverse reactions have been reported so far.

Conclusion

The formulation of stanozolol capsules as a pharmaceutical compounding is an alternative for those patients who require a systemic treatment of certain ulcers associated with dermatological pathologies and who can no longer access the commercial preparation.

References and/or Acknowledgements

NA

Conflict of Interest No conflict of interest

GOT18-0298. CLEANING VALIDATION OF SOLUTION PRODUCTION IN A HOSPITAL PHARMACY Background

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Cleaning of technical equipment should remove residues of products and cleaning agents, as well as avoid microbial contamination 1. In hospital pharmacies multipurpose equipment is used for manufacture of different pharmaceutical preparations. Suitable well documented cleaning procedures are necessary to guarantee patient safety by avoiding cross-contamination of drugs.

Purpose

Effective cleaning procedures should be developed and validated for multipurpose and drug-contaminated equipment used in the solution production e.g. stirrers, tanks, tubes and filling systems. As a final result the contamination risk of all possible production lines could be assessed.

Material and methods

Focussing on direct product contact our multipurpose equipment was grouped into 9 critical and 11 uncritical systems. For 7 of 9 critical systems a validated cleaning process did not exist and had to be developed. The validation covered the cleaning status immediately at the end of production (t 0) and after a 24 hours dirty-hold time (t 24 ). Naphazoline nitrate was defined as worst case active component of our solutions portfolio. The analytical (1/1000 dose criteria) and microbiological residue limits were calculated 1. The HPLC method for the quantitative analysis of naphazoline nitrate was validated 2. Based on a risk assessment evaluating the potential of contamination the number of validation runs for each unit of equipment was defined. The analytical and microbiological results were quantified for each system. To assess the whole process the residues of all production lines at t 0 and t 24 were summarized.

Results

An effective cleaning procedure was evaluated for each system and validated at t 0 and t24 . Each unit of equipment and all possible production lines met the analytical residue limits at t 0, and at t 24 with exception of the tubes. The microbiological requirements were fulfilled for the clean-room zones D and C.

Conclusion

The tube surface consists of polytetrafluoroethylene and has to be cleaned immediately after the end of the production (t 0). All other systems are almost completely made of stainless steel and can be cleaned until t 24 . The cleaning validation of the solution production was the first process in our hospital pharmacy which was completely validated including a dirty-hold time.

References and/or Acknowledgements

1GMP-Guideline, Annex 15: Qualification and Validation 2ICH-Guideline, Topic Q2(R1): Validation of Analytical Procedures

Conflict of Interest No conflict of interest

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GOT18-0303. STABILITY STUDY OF GENTAMICIN LOCK THERAPY WITH HEPARIN OR CITRATE AS ANTICOAGULANT. Background

The antibiotic lock Therapy (ALT), technique that involves the instillation of a highly concentrated antimicrobial solution with additives such as anticoagulants into the catheter lumen, is an option for treatment of catheter-related blood-stream infections when the central venous catheter is retained. An important limitation is the frequent incompatibility between the components, causing great controversy in the literaure. The ALT with gentamicin is one of the most requested ALT for treating bacteriemias by Gram (-).The anticoagulant more studied is the unfractioned heparin. It can be used in hemodialysis pacients, however, other anticoagulant as citrate whose data are limited regarding compatibily should be used for patient with history of heparin-induced trombocytopenua (HIT) or active HIT.

Purpose

To study the stability of catheter lock solution that combine gentamicin 2,5mg/ml and heparin 2500UI/mL or citrate 2% as anticoagulant.

Material and methods

Eight solutions of catheter lock were prepared at fixed concentrations: 4 solutions of gentamicin 2.5mg/ml+heparin 2500UI/ml(A1,B1,C1,D1) and 4 of gentamicin 2.5mg/ml+citrate 2%(A2,B2,C2,D2). Physical and chemical stability were measured on days 0(A1,A2), 2(B1,B2), 3(C1,C2) and 7(D1,D2) after the preparation. Two aliquots were prepared from solutions B1,B2 and C1,C2. One aliquot of each one (B1a,B2a,C1a,C2a) were stored in the refrigerator(2-8ºC) to test stability of the preparation of ALT extemporaneously prior to its use and another(B1b,B2b,C1b,C2b) in the oven(35-37ºC) to simulate the temperatures that reach once installed in the catheter. Chemical stability was defined as concentrations of gentamicin at least 90% measured by colorimetric technique. For the analysis the samples were diluted to gentamycin concentration of 5mcg/ml. Physical stability was considered as the absence of precipitate or appearance of particles.

Results

None of the ALT precipitated during the study nor they showed variations in color. The concentrations of gentamicin were stable in the different selected storage conditions: A1:5,31mcg/mL; A2:5,46mcg/mL; B1a:5,88mcg/mL; B1b:5,8mcg/mL; B2a:5,1mcg/mL; B2b:4,97mcg/mL; C1a:5,9mcg/mL; C1b:5,47mcg/mL; C2a:5,08mcg/mL; C2b:5,21mcg/mL; D1:5,46mcg/mL and D2:5,04mcg/mL. The mean was 5.39+/-0,32mcg/mL.

Conclusion

The ALT with gentamicin 2,5mg/ml and heparin 2500UI/ml or Citrate 2% are chemical and phisical stable. More studies are needed to address areas of uncertainty of great clinical relevance, such as the stability of ALT with other concentration of gentamicin and ALT that combine other antibiotic with citrate.

References and/or Acknowledgements

.

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Conflict of Interest No conflict of interest

GOT18-0325. ASSESSMENT OF DOSING ACCURACY DETERMINED USING GRAVIMETRIC CONTROL IN KIRO ONCOLOGY Background

An automated system for the preparation of intravenous chemotherapy drugs (KIRO Oncology, KIRO GRIFOLS, Spain) was installed in our hospital pharmacy. This system performs an “in process†gravimetric control associated with an identification of the drug to check the quality of final product before automatic release of the preparations.

Purpose

Assess if KIRO Oncology´s automatic release decisions based on gravimetric control agree with the dosing accuracy determined by means of analytical control with HPLC.

Material and methods

A 25 mg/mL phenylephrine standard solution was prepared by weighing phenylephrine powder which was then diluted with water for injection. Forty nine preparations of six different standard solution volumes (9 for 0.6mL; and 8 for 1; 5; 10; 20 and 48 mL) were prepared into 100 mL saline bags using KIRO Oncology, and released automatically when within the 90-110% dosing accuracy range. For each preparation a sample was taken after bag homogenization to determine phenylephrine concentration using HPLC- UV, method that was validated according to ICH guidelines, and calculate dosing accuracy of the preparations. Finally, percentage of preparations for which KIRO Oncology´s release decision corresponded to HPLC-UV dosing accuracies within 90- 110% was calculated.

Results

The release decision made by KIRO Oncology was confirmed by HPLC-UV for 84% of the preparations: 80% were released and 4% were rejected (two 0.6 mL preparations) by both methods. There was a discrepancy on the release decisions for 8 bags (16%): gravimetric control released the preparations whereas the HPLC control rejected them. These were two 0.6 mL (22%), four 1 mL (50%) and two 5 mL (25%) preparations within 85-90% dosing accuracy based on HPLC-UV. All 10 mL, 20 mL and 48 mL preparations were released by both control methods.

Conclusion

Gravimetric control used by KIRO Oncology is an acceptable method to determine dosing accuracy for the automatic release of preparations. However, variations up to 5% away from the acceptable dosing accuracy limits may appear between gravimetric control and HPLC-UV results for volumes 5 mL and lower. These variations may be related to methodological differences and were considered to be clinically acceptable.

References and/or Acknowledgements

The authors are grateful to Kiro Grifols especially Naiara Telleria and Eider Bergareche.

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Conflict of Interest No conflict of interest

GOT18-0337. IMPACT OF ROBOTIC CHEMOTHERAPY COMPOUNDING ON PATIENT SAFETY Background

Purpose

Evaluate the impact on patient safety of the chemotherapy compounding process with Kiro® Oncology robot.

Material and methods

Patient safety was assessed through three different approaches:

1. Failure Mode, Effect and Criticality Analysis (FMECA ): a multidisciplinary team involved in the area identified all risks related to the manual and robotic compounding processes. Criticality Index (CI) was calculated for all of them, by multiplying the frequency, effect and detection scores, using a 1-4 scale. 2. Evaluation of Medication Errors (ME) related to Chemotherapy : errors reported in the database TPSCCloud® during 1 year were analyzed to find out those related to chemotherapy, and especially, those whose origin was the preparation process, in order to reveal the role of the preparation system. 3. Dosing accuracy of compounded preparations : percentage of preparations within the ±5% accuracy range was evaluated by gravimetric control for 9 common drugs prepared manually and using the robotic system.

Results

1. FMECA

23 failure modes were identified in the manual system, with a global CI of 265. Risks with the highest scores were related to labeling errors. In the robotic process 14 failure modes were identified (CI=180). Those errors related to incorrect dose or incorrect reconstitution disappeared completely, while organizational/logistical errors remained unchanged.

2. ME related to Chemotherapy Compounding

56 ME related with chemotherapy were notified in 2016 (31691 preparations) through the voluntary reporting program TPSCCloud® (incidence rate: 0.18%); 13 of these ME were caused by a preparation mistake (incidence rate:0.045%). 8/13 were caused by organizational issues, and had no relation to the compounding system used.

3. Dosing accuracy

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Dosing accuracy was compared for 1031 manual preparations and 756 robotic preparations, including the following drugs: carboplatin, cyclophosphamide, doxorubicin, epirrubicin, 5-fluorouracil, gemcitabine, irinotecan, oxaliplatin and paclitaxel. No statistically significant difference was observed between manual and robotic preparations (Percentage within ±5%: 99.8% manual vs 96.9% robot; χ 2=1.11, p=0.29)

Conclusion

Robotic compounding with Kiro® Oncology is a safe process, with the ability to decrease or eliminate some risks related to human intervention, and with comparable accuracy rates of those achieved in manual compounding.

References and/or Acknowledgements

Acknowledgements: to Pharmacy technicians and KiroOncology staff who kindly collaborated in this study

Conflict of Interest No conflict of interest

GOT18-0340. Screening Methods for Leachables in Syringes used in Hospital Pharmacy Production Background

Knowledge on leachables has become an important issue for hospital pharmacies due to the fact that a growing number of injectables is compounded for long term storage. To estimate the potential risk emerging from these substances, information on extractables is required at first. Such data, however, are hard to obtain from the manufacturers of the containers. The pharmaceutical industry on the other hand is confronted with an increasing variety of regulations pertaining leachables. Specific requirements for plastic immediate packaging materials have been included into the Pharmacopoeias. Little is known on the impact of leachables with respect to injectables produced in hospital pharmacies.

Purpose

Since leachable/extractable studies may be not economical this can result in ineconomic hospital pharmacy production. Therefore we wanted to investigate the capabilities of cheaper screening methods that can be performed in the hospital pharmacy lab or at cooperating labs such as the Pharmaceutical Institute of the University

Material and methods

We used UV-Spectrometry, HPLC/DAD, LC-MS, GC-MS and developed-fingerprints for comparing extractables from different types of syringes used for hospital pharmacy production in Denmark, Germany, Spain and Switzerland.

Results

Even with UV-Spectrometry big differences between different types of syringes are visible. A fingerprint with HPLC-DAD gives further information and allows also analysis

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in presence of the active substances. With help of LC-MS and GC-MS we also could confirm structures of three extractables AO425, BHT and Dichlorobenzamide. In addition to this we could also perform quantitative determination of these substances by HPLC- UV.

Conclusion

Screening methods can be a first step to obtain knowledge on extractables. They can be used to compare different syringes and also to control different lots of the same product. Hospital pharmacists from different countries should share their knowledge about identified extractables in primary package material. Without identification no quantification and without quantification no risk assessment is possible. Therefore the European L/E Group for Hospital Pharmacists was founded and can be contacted to find cooperation partners.

References and/or Acknowledgements

No conflict of interest

Conflict of Interest No conflict of interest

GOT18-0341. MIDAZOLAM 2.5MG/ML ORAL SYRUP: IMPROVING PREOPERATIVE SEDATION IN PAEDIATRIC PATIENTS Background

More than 60% of children experience anxiety during the preoperative period. Therefore, the use of preanaesthetic medication may be beneficial. Midazolam, a short-acting benzodiazepine, is a central nervous system depressant available as a solution for injection ampoule and oral tablets. The intranasal administration of the ampoules is widely used with this purpose in our hospital. However, it has several disadvantages: burning sensation, lacrimation and severe irritation of nasal mucosa. Oral solution is an appropriate alternative, although not available in Spain

Purpose

To create a standard operational procedure (SOP) where is described the prescription, compounding, dispensing and administration of extemporaneous oral midazolam syrup for paediatric patients (age>6months and weight<30kg) as preanaesthetic medication.

Material and methods

The Pharmacy Department in collaboration with Paediatric Anesthesia Department was responsible for creating the SOP. Literature review was done, searching for compounding SOPs to make midazolam oral solution and its dosing in children.

Results

Prescription guidelines were created in the electronic prescribing system with appropriate dosing directions (0.25-0.5mg/kg) and requirements for an informed consent, as it is an off-label indication.

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It was chosen the most simple and concentrated compounding formula, and adjusted to our needs. A non-sterile midazolam 2.5mg/ml oral solution was elaborated as follows: firstly, withdraw 50mL of midazolam hydrochloride injection solution from 50mg/10mL ampoule into a syringe. Then, add to a graduated cylinder using a 5micron filter and qs to 100mL with simple syrup (with preservative - nipagin 0.1%). Transfer to an amber glass prescription bottle and add a drop of orange flavour. pH of the preparation must be acid (<4.2). Mix well. An expiry date of a month was given, stored refrigerated (2ºC to 8ºC). The ward staff can order the midazolam oral syrup via stock orders. The formula is dispensed with purple bottle adapters, exclusive for oral administration syringes and is administered 30-45min prior to surgery, according to the established guideline.

Conclusion

The Pharmacy Department in collaboration with Paediatric Anesthesia Department has set up a SOP to achieve a non-invasive sedation by improving the adherence and tolerance of pre-anaesthesia medication in children.

References and/or Acknowledgements

Trissel L. Trissel's stability of compounded formulations. 5th ed. Washington, D.C.: American Pharmacists Association; 2012.

Conflict of Interest No conflict of interest

GOT18-0376. DETERMINATION OF THE PHYSICOCHEMICAL STABILITY OF AMIODARONE HYDROCHLORIDE IN SYRINGES FOR INTENSIVE CARE UNIT. Background

The intensive Care Unit (ICU) use drug solutions within higher concentration to avoid fluid overload

Purpose

To determine the physicochemical stability of concentrated solution of amiodarone in polypropylene syringe during 28 days at 5 ± 3°C with protection from light.

Material and methods

Five syringes of 50 ml, containing 25 mg/ml of amiodarone in 0.9 % NaCl were prepared and stored at 5 ± 3°C with protection from light during 28 days. Immediately after preparation and periodically during the storage, amiodarone concentrations were measured by an ultra performance liquid chromatography (UPLC). Spectrophotometric absorbance at different wavelengths, pH measurement, visual and microscopic observations were also performed.

Results

All solutions were physico-chemically stable during the whole period storage at 5 ± 3° C: no color change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable as the lower limit of the 95 %

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unilateral confidence interval on the mean remained above 90 % of the initial concentration for at least 28 days.

Conclusion

Solutions of amiodarone 25 mg/ml in syringe of 0.9 % NaCl are physically and chemically stable for at least 28 days when stored in syringes at 5 ± 3°C with protection from light and may be prepared in advanced by a Centralized IntraVenous Admixture Service (CIVA).

References and/or Acknowledgements

Simar J, Delcave C, Godet M, Decoster C, Gillet P, Bihin B, Jamart J, Galanti LM, Hecq JD. Stabilité physique du chlorhydrate d’amiodarone dans des seringues de glucose 5 % pour perfusion. Journal de Pharmacie de Belgique 2016 ;98 (1) : 24-25

Conflict of Interest No conflict of interest

GOT18-0377. STABILITY OF CONCENTRATED SOLUTIONS OF ISOSORBIDE DINITRATE IN SYRINGES FOR ADMINISTRATION IN THE INTENSIVE CARE UNIT. Background

In order to avoid fluid overload, the use of more concentrated drug solutions in intensive care units is common.

Purpose

Quantifying the physicochemical stability of concentrated solution of isosorbide dinitrate in polypropylene syringe during 28 days at 5 ± 3°C with protection from light.

Material and methods

Five syringes of 50 ml, containing 0.60 mg/ml of isosorbide dinitrate in 0.9 % NaCl were prepared and stored at 5 ± 3°C with protection from light during 28 days. Immediately after preparation and periodically during the storage, isosorbide dinitrate concentrations were measured by an ultra performance liquid chromatography (UPLC). Spectrophotometric absorbance at different wavelengths, pH measurement, visual and microscopic observations were also performed.

Results

All solutions were physicochemically stable during the whole period storage at 5 ± 3° C: no color change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable as the lower limit of the 95 % unilateral confidence interval on the mean remained above 90 % of the initial concentration for at least 28 days.

Conclusion

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Solutions of isosorbide dinitrate 0.60 mg/ml in syringe of 0.9 % NaCl are physically and chemically stable for at least 28 days when stored in syringes at 5 ± 3°C with protection from light and may be prepared in advanced by a Centralized IntraVenous Admixture Service (CIVA).

References and/or Acknowledgements

Closset M, Hecq JD, Soumoy L, Simar J, Gonzalez E, Charlet L, Declave C, Gillet P, Galanti L. Physical stability of highly concentrated injectable drugs solutions used in intensive care units. Ann Pharm Fr. 2017 Feb 13. pii: S0003-4509(16)30055-4. doi: 10.1016/j.pharma.2016.12.004

Conflict of Interest No conflict of interest

GOT18-0387. STABILITY OF AUTOMATELY RECONSTITUTED CEFUROXIME 1,5G/18,5ML SOLUTIONS IN READY-TO-ADMINISTER SYRINGES Background

Handling of injectable antimicrobials is not without risk to health-care workers. Automated production of ready-to-administer prefilled injections may reduce not only exposure to antimicrobial agents and ergonomical challenges but also the possibility of medication errors. Centrally pre-prepared solutions increase standardization and ensure that items are prepared in controlled clean rooms.

According to product´s marketing authorisation cefuroxime may be administered either by injection or infusion. Cefuroxime sodium powder responding 1,5g cefuroxime is reconstituted by adding at minimum 15ml of suitable solvent. Published stability data of such high concentrations is limited and thus a new study is required to determine shelf life.

Purpose

The purpose of our study was to investigate chemical stability of cefuroxime 80mg/ml solution in ready-to-administer prefilled syringes.

Material and methods

Drug concentration, concentration of degradation products, appearance and pH of the cefuroxime 1,5g reconstituted with 18ml of water for injection and stored in polypropylene syringes was studied over 45 days to determine self life of the product. A stability indicating HPLC method for quantitative analysis of cefuroxime was developed and validated. The samples were stored in two different temperatures (4°C and 23° C). Test for Uniformity of Dosage Units was carried out for automately compounded syringes according to European Pharmacopoeia.

Results

The concentration of cefuroxime remained over 90% (confidence limit of 95%) during 11 days when stored at 4°C and 2 days at 23°C. No color change was detected in samples that were stored at 4°C, but slight change in color appeared after 24 hours at 23°C. The pH rose from 7,4 to 7,6 during the storage. Amount of degradation products

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stayed under the limit of 3% during two weeks. Acceptance value was calculated to be within acceptance limits of European Pharmacopoeia.

Conclusion

We came to a conclusion that the degradation of cefuroxime depends on concentration. The self life of 11 days in refrigerator limits the storage but it, however, enables automated preparation of cefuroxime injections. Pre-loaded syringes seems to be a convenient, closed, simple and safe presentation for ready-to-administer cefuroxime solution.

References and/or Acknowledgements

Mustonen Juho: Stability Studies of Compounded Preparations in Hospital Pharmacies. Master's thesis. University of Eastern Finland, Faculty of Health Sciences, 2016

Conflict of Interest No conflict of interest

GOT18-0388. STABILITY OF CONCENTRATED SOLUTIONS OF SALBUTAMOL HYDROCHLORIDE IN SYRINGES FOR ADMINISTRATION IN THE INTENSIVE CARE UNIT Background

In order to avoid fluid overload, the use of more concentrated drug solutions in intensive care units is common.

Purpose

Quantifying the physicochemical stability of concentrated solution of salbutamol in polypropylene syringe during 30 days at 5 ± 3°C with protection from light.

Material and methods

Five syringes of 50 ml, containing 0.060 mg/ml of salbutamol in 0.9 % NaCl were prepared and stored at 5 ± 3°C with protection from light during 30 days. Immediately after preparation and periodically during the storage, salbutamol concentrations were measured by an ultra performance liquid chromatography (UPLC). Spectrophotometric absorbance at different wavelengths, pH measurement, visual and microscopic observations were also performed

Results

All solutions were physicochemically stable during the whole period storage at 5 ± 3° C: no color change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable as the lower limit of the 95 % unilateral confidence interval on the mean remained above 90 % of the initial concentration for at least 30 days.

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Conclusion

Solutions of salbutamol 0.060 mg/ml in syringe of 0.9 % NaCl are physically and chemically stable for at least 30 days when stored in syringes at 5 ± 3°C with protection from light and may be prepared in advanced by a Centralized IntraVenous Admixture Service (CIVA).

References and/or Acknowledgements

Closset M, Hecq JD, Soumoy L, Simar J, Gonzalez E, Charlet L, Declave C, Gillet P, Galanti L. Physical stability of highly concentrated injectable drugs solutions used in intensive care units. Ann Pharm Fr. 2017 Feb 13. pii: S0003-4509(16)30055-4. doi: 10.1016/j.pharma.2016.12.004

Conflict of Interest No conflict of interest

GOT18-0398. NEW DEVICES AND MANUFACTURING PROCESS FOR AN SAFE, STANDARDIZED, AND READY-TO-USE FECAL MICROBIOTA TRANSFER (FMT) Background

Fecal Microbiota Transfer (FMT) is the administration of fecal dilution from healthy donor into the intestinal tract of a recipient to restore microbial diversity and confer a health benefit. FMT has been demonstrated to successfully treat recurrent Clostridium difficile infection but may also have therapeutic potential for other diseases. FMT is considered as a drug (FDA) and thereby must be prepared under the responsibility of hospital pharmacists.

Preparation, storage and rectal administration of an efficient FMT is a big challenge for health care professional, especially hospital pharmacists. MaaT Pharma has developed patented devices (collection device, storage bag and administration system), and a manufacturing process, to produce from raw fecal material an active and stable therapeutic inoculum. Purpose

The aim of the study was to assess the efficiency of our FMT manufacturing process, to compare to hospital standard practice, and to assess in-use stability of the product (cryo-conservation and thawing).

Material and methods

Phylotranscriptomic and Metabolomic analyses were performed to evaluate the potency of our process to maintain the microbiota composition of our product as closed as the original feces.

Flow cytometry was used to measure microbiota viability in the FMT.

Results

Pearson’s correlation showed that our manufacturing process of the FMT inoculum is well designed as we obtain a very good correlation for the phylotranscriptomic profiles (>80%) and the metabolomic composition (>90%), between the raw feces and our thawed drug product.

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Microbiota viability in the inoculum using our process is much higher (50.15%) than using a standard NaCl/Glycerol solution (32.85%). Stability at -80°C is also much better as microbiota viability in our inoculum is still at 40.1% after 20 days compared to 24.1% when using a standard solution.

Rapid thawing at 37°C (10’) of our inoculum is the most favourable condition for reconstruction of the microbiota compared to longer exposure at 37°C or 4°C overnight thawing.

Conclusion

MaaT Pharma proposes first to hospital pharmacists and patients a safe, standardized, ready-to-use, solution of FMT manufactured in GMP conditions. Our next short-term objective is to propose an oral form product as an alternative to rectal administration for appropriate patients.

References and/or Acknowledgements

We thank the SFR-Biosciences for the access to their technological platform

Conflict of Interest No conflict of interest

GOT18-0400. PEDIATRIC PARENTERAL NUTRITION ON WEEKENDS, WHO PREPARES? SURVEY OF COUNTRY'S HOSPITALS. Background

Since country's health institution published on March 2015 a directive, parenteral nutrition (PN) must be produced by hospital pharmacists, under pharmaceutical responsibility.How to manage closing periods of the hospital pharmacy unit (HPU) to manufacture individualized formulation of pediatric PN (IFPN) for newborns.

Purpose

Summarize the state of management of the closure of HPU for IFPN through a survey of hospitals in the country on 2017.

Material and methods

A survey with oriented questions according to answers was developed with Google Forms. The first part are general questions (HE type, maternity level,...).Following items raise alternatives solutions if there is no production when HPU is closed. While, in case of IFPN production, questionnaire allows answering to different questions on formulation validation, production and controls.

Results

On 24 asked HE, 19 responses were studied. For HE type: 89.5% of University Hospital Center and 10.5% of General Hospital Center, all had maternity (95% with level 3 maternity). Most of them (65%, n=12) report no IFPN during pharmacy closing period. Major alternative solution is IFPN production, which were produced before closure period (e.g. on Friday). Although 16% of HE reported using only IFPN, 83.3% use IFPN

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and standardized PN (SPN) solution for weekend PN requirement, while 25% associated IFPN, SPN, and industrial PN (with or without supplementation). For other HE (35%, n=7) which report a PN activity on weekend, 57.1% (n=4) producing IFPN at HPU and 42.9% (n=3) in the pediatric care unit. Only IFPN which were produced at HPU are formulation checked by pharmacist. Then, for controls: 100% declare a double visual controls during production, 71% realize analytics assays (mainly Na and K), 40% perform microbiologic assay and 60% labeling checks and mirage. Pharmaceutical liberation is report on 80%.

Conclusion

These results based on statements remain to be analyzed cautiously but trend is no production of IFPN on weekend. In case of preparations, controls on final product allows to provide a quality product for newborns. Compliance with the directive remains difficult, perhaps consensus around SPN with pediatric physicians will make it possible to avoid PN production activity outside the opening period of HPU.

References and/or Acknowledgements

All pharmacist who fill this Survey.

Conflict of Interest No conflict of interest

GOT18-0415. FORMULATION AND STABILITY STUDY OF THE EXTEMPORANEOUS ORAL SOLUTIONS OF CARDIOLOGIC DRUGS FOR PERSONALIZED THERAPY OF NEWBORNS Background

If the commercially available medicinal products lack on the market, the pharmacist needs to compound a preparation extemporaneously attending to the stability of the active pharmaceutical substance for a labelled time period. This typically occurs when the preparation is targeted to paediatric patients, particularly neonates.

Purpose

The aim of study was to test stability of sterile aqueous solutions of cardiologic drugs directed to neonates.

Material and methods

The aqueous solutions of propranolol hydrochloride 2 mg/ml (PCL) and sotalol hydrochloride 5 mg/ml (SCL), respectively, were prepared by dissolution od substance in water for injection, for furosemide 2 mg/ml (FSM), disodium hydrogen phosphate dodecahydrate was used to reach the alkaline pH necessary to dissolve. The preparations were prepared under aseptic conditions and sterilized by membrane filtration or in an autoclave at 121°C for 15 minutes. The concentration of a drug was evaluated using a developed, fully validated HPLC method at the time of compounding, after the autoclaving, and thereafter at time intervals of 7 – 30 days of storage at room temperature.

Results

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At least 95 % of the initial drug concentration was detected throughout whole time period for aseptically prepared solutions and the autoclaved SCL solution. For the autoclaved PCL and FSM solutions, respectively, the concentration of drug ≥ 90% was detected only for 2 weeks.

Conclusion

Aseptic preparation following membrane filtration is recommended for aqueous solutions of PCL 2 mg/ml, SCL 5 mg/ml and FSM 2 mg/ml, respectively, targeted for neonates. Solutions could be prepared in advance in the pharmacy and stored for 1-month until needed.

References and/or Acknowledgements

Supported by the project of Ministry of Health the Czech Republic 00064203 (University Hospital Motol, Prague, Czech Republic) and Student grant SVV 260 412

Conflict of Interest No conflict of interest

GOT18-0435. PHARMACEUTICAL COMPOUNDING OF 0.1 MG/ML DEXAMETHASONE MOUTHWASH AS A SUITABLE ALTERNATIVE TO SWISH: EFFECTIVENESS AND SAFETY Background

Stomatitis is a class adverse effect of mTOR inhibitors which can lead to dose reduction or treatment discontinuation, potentially affecting progression-free survival. Recently, the prophylactic use of an alcohol-free dexamethasone mouthwash reported a reduction of the incidence and severity of stomatitis in patients with HR+, HER2-advanced breast cancer receiving everolimus and exemestane therapy.

Outside US, there is a generally lack of commercially available dexamethasone mouthwash. Moreover, there is no compounding standard to overcome this situation.

Purpose

To present a new dexamethasone mouthwash formulation and determine the effectiveness and safety in patients on everolimus (Afinitor®).

Material and methods Dexamethasone mouthwash 0.1 mg/ml Dexamethasone sodium phosphate 50mg Sodium carboxymethylcellulose 1% 5g Glycerin 15% 75ml Polysorbate 20 (Tween 20®) 2 drops Aqua conservans q.s.500 ml Aqua conservans Methyl 4-hydroxybenzoate (Nipagin®) 0.25g Propyl 4-hydroxybenzoate (Nipasol®) 0.11g Purified water q.s.500

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Dexamethasone sodium phosphate salt was employed because of poor water-solubility of dexamethasone. To ensure dispersion stability of the corticoid formulation, humectants like glycerin and Tween20® were added. Carboxymethylcellulose was also included increasing its persistence on oral mucosa. Aqua conservans was employed to extend expire date up to 3 months stored at room temperature.

Patients were instructed to rinse and hold 2 minutes and then expectorate 10mL of dexamethasone-based mouthwash formula, twice daily.

Results

Dexamethasone mouthwash formulation was prescribed in five patients, four women and one man. Three patients were diagnosed with breast cancer and two patients with neuroendocrine carcinoma. Four patients started with 10 mg/day everolimus and one started with 5mg/day due to hepatic impairment.

Three patients are still on treatment with dexamethasone-mouthwash (follow-up: 28 weeks, 4 weeks and 1 week) and two have reduced the dose at week 2 and 8. No dose reduction or discontinuation was required because of stomatitis.

Adverse effects vary from asthenia, dysgeusia, gastrointestinal and oral pain, peripheral oedema, pruritus and pneumonitis.

Patients reported a well-tolerated mouthwash with favorable organoleptic properties.

Conclusion

Dexamethasone-mouthwash formulation could be considered as a suitable alternative to commercial product if absent to prevent the occurrence of everolimus-induced stomatitis not only for breast cancer patients.

References and/or Acknowledgements

Conflict of Interest No conflict of interest

GOT18-0438. QUANTIFICATION OF WAITING TIME REDUCTION IN OUTPATIENT SETTING USING ASSISTED SYSTEMS IN AN AUTOMATED ONCOLOGY PHARMACY. Background

In outpatient setting, waiting time (WT) between medical visits and administration is strongly conditioned by time needed for preparation. Since WT is one of the most important aspects impacting on patients perception of quality, we decided to switch part of preparations (previously prepared by an automated system) to an assisted system.

Purpose

The aim of the study was to evaluate the real impact of a different strategy in preparing chemotherapy on patients WT.

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Material and methods

Time needed for preparation was monitored in the first trimester of 2016 and compared to the first trimester in 2017. In 2016 period, infusion bags were prepared using an automated system (APOTECA® Loccioni) or manually, in 2017 period we introduced an assisted preparation system (PS1®Loccioni). In the first period we used a “WT optimization†criteria in selecting the preparing technology, while in 2017 we used a “risk based†criteria to optimize quality and safety. Risk based criteria consists of selecting the automated system for high exposure risk drugs, assisted system for antibodies and low risk drugs and manual procedure when no other options are available. To evaluate bias introduced by the risk based selection criteria, we performed a contest comparing preparation times of a defined sequence of preparations representative of all different typologies. We performed three series by three different technicians to reduce human factor impact.

Results

Average WT (AWT) in the first period was 1h36m and median WT (MWT) was 1h22m (2365 preparations in 3 months). AWT in the second period (3437 preparations in 3 months) was 1h17m (-19,79%) and MWT 1h1m (-25,61%). The percentage of therapies dispensed after the internal WT limit (T<2h) decreased by 55,69%. WT was stratified by preparation technology (assisted system: AWT =50m; MWT=44m / automated system: AWT=1h26m; MWT=1h07m).The contest results were (average of three series) : manual preparation 15m19s; assisted 26m42s; automated 1h14m3s.

Conclusion

Assisted systems are able to guarantee quality standards for patients similar to automated ones, but with a reduction in WT and an improvement in traceability compared to the manual procedure. Automated systems could be preferably used in high risk preparation because of a possible reduction in exposure risk.

References and/or Acknowledgements

Sarah Liptrott

Conflict of Interest No conflict of interest

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