Stability of morphine sulphate and diamorphine hydrochloride in Intrasite gel

***

Stability of morphine sulphate and diamorphine hydrochloride in Intrasite gel

Giovambattista Zeppetella G; Joel SP; Ribeiro MDC.
St. Clare Hospice, Hastingwood, Essex; Medical Oncology Department, St. Bartholomew's Hospital, London; Peace Hospice, Watford

Several studies have reported that opioids applied topically to painful ulcers produce an analgesic effect. It is unknown whether these opioids (usually mixed with hydrogels) are stable and, if so, for how long. We investigated the stability of morphine sulphate and diamorphine hydrochloride, each mixed with intrasite gel at a concentration of 1.25 mg/mL. Samples were prepared in the laboratory and then stored in plastic containers in the dark, at room temperature, in conditions of normal day/night at room temperature, and at 48C. Aliquots were collected from each container over a 28-day period and analysed using HPLC. No known degradation products were measured in the morphine–intrasite gel mixture stored for up to 28 days, irrespective of the temperature and whether or not samples were exposed to light, suggesting that morphine remains stable. Diamorphine, breaks down to morphine and no other degradation products are measurable.

Reference: Palliative Medicine, Vol. 19, No. 2, 131-136 (2005)

Efectividad y seguridad de diltiazem 2 % tópico

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Efectividad y seguridad de diltiazem 2 % tópico en fisura anal

M.I. Fernández García*, R. Albornoz López, I. Pérez Rodrigo y J. Abellón Ruiz

Servicio de Farmacia, Hospital Universitario Reina Sofía, Córdoba, España

Objetivo: Evaluar la efectividad y la seguridad de la pomada de diltiazem al 2 % en el tratamiento de la fi sura anal. Analizar la relación entre la cicatrización de la fi sura y diagnóstico, duración del tratamiento y número de aplicaciones.

Métodos: Estudio prospectivo observacional de todos los pacientes diagnosticados de fi sura anal que comenzaron tratamiento con diltiazem tópico entre enero y junio de 2007. La pomada de diltiazem al 2 % se preparó como fórmula magistral en el servicio de farmacia. La efectividad y la seguridad se evaluó mediante encuesta telefónica a cada paciente tras 8 semanas de tratamiento, completándose con la historia clínica del paciente. Las variables analizadas fueron cicatrización, efectos adversos, diagnóstico, duración del tratamiento y número de aplicaciones, entre otras. Se realizó seguimiento hasta resolución de la fi sura hasta un período de 1 año. El análisis de los datos se realizó mediante estadística descriptiva y frecuencia, tablas de contingencia y  2.

Resultados: Se incluyó a un total de 70 pacientes y se produjo cicatrización en el 48,6 % de éstos. Cicatrizó en el 54,5 % de los pacientes con fi sura anal y en el 33,3 % con fi sura anal y hemorroides. El 30 % experimentó efectos adversos. El 5,7 % abandonó el tratamiento por reacción adversa. La fi sura cicatrizó en el 60 % de los pacientes que estuvieron más de 1 mes en tratamiento. No hubo más cicatrización con más de 2 aplicaciones diarias. En ninguno de estos resultados hubo diferencias estadísticamente signifi cativas.

Conclusiones: A pesar de no encontrarse diferencias signifi cativas entre las variables estudiadas, el tratamiento de la fi sura anal con la pomada de diltiazem al 2 % ha evitado la intervención quirúrgica casi en un 50 % de los pacientes, con efectos adversos poco frecuentes.

Reference: Farm Hosp. 2009;33(2):80-8

Vancomycin: stability in syringes

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Chemical stability and microbiological potency of intravenous
vancomycin hydrochloride in polypropylene syringes for use in
the neonatal intensive care unit

Study objectives : To determine the chemical stability and microbiological potency of “almost” ready-to-use vancomycin solutions in polypropylene syringes at a concentration of 5 mg/mL in both 5% glucose and 0.9% sodium chloride at 4°C and 25°C, for use in the neonatal intensive care unit.

Methods: Ten-millilitre syringes were filled using aseptic techniques with a solution of vancomycin, covering body weights of 500 g to 3 kg at a dosage of 15mg/kg, prepared by reconstitution and dilution of commercially available vancomycin hydrochloride powder (Vancocin) and kept at 4°C and 25°C, respectively. At various storage times, the chemical stability was determined using a high-performance liquid chromatography method and the microbiological potency was assayed according to the European Pharmacopoeia 2002. Arbitrarily, 56 day samples at 4°C were brought to 25°C and analyzed after 48 hours to simulate ward conditions. The standards were the T0 solution kept at -70°C and the International Vancomycin Reference Standard.

Results: The vancomycin was found to be chemically and microbiologically stable at 4°C for 6 months. Losses were important after 14 days at 25°C in both cases. The samples subjected to simulated ward conditions were stable for 48 hours at 25°C. A shelf life of 6 months was proposed.

Conclusions: Syringes of low dose vancomycin manufactured and supplied by the pharmacy can be stored in the neonatal intensive care unit refrigerator for use in emergency situations thus avoiding calculation and dilution errors and reducing the risk of bacterial contamination. The solution brought to 25°C must be used within 48 hours.

References: This work was presented as a poster at the 8th congress of the European
Association of Hospital Pharmacists, Florence, Italy, 2003.

Dr Pascal Bonnabry, Head of pharmacy, Pharmacy Department University Hospitals of Geneva (HUG). William Griffiths, PharmD, Jocelyne Favet, PhD, Ho Ing, PharmD, Farshid Sadeghipour, PhD, Pascal Bonnabry, PhD

Elaboración de mezclas intravenosas individualizadas

***

Elaboración de mezclas intravenosas individualizadas
como mejora de la seguridad del paciente

Gimeno MJ, Fernández J, Pinto C, Acosta P

Servicio de Farmacia. Hospital de Poniente. Almeria

Objetivo: Los errores relacionados con medicamentos constituyen la principal causa de eventos adversos en los hospitales. La elaboración de mezclas intravenosas individualizadas por parte del Área de Farmacia permite evitar errores de dosifi cación que puedan producirse durante la preparación de éstas en el área de hospitalización. El objetivo del presente trabajo es describir la actividad asistencial que se ha llevado a cabo desde la unidad de mezclas intravenosas durante el 2006.

Material y métodos: A partir de los datos de dispensación en dosis unitarias la unidad de mezclas intravenosas elabora de forma individualizada aquellos antibióticos cuya estabilidad sea mayor de 48 h. Se consideran mezclas intravenosas individualizadas aquellas cuya dosifi cación es diferente a la de las mezclas protocolizadas que se elaboran a modo de reposición de stock.

Resultados: En el 2006 se han elaborado 230868 mezclas intravenosas de las que 2217 fueron individualizadas (0,96% total). De éstas el 87,1% (1931) pertenecen al Área de Pediatría.

Conclusiones: La elaboración centralizada en el Área de Farmacia de los antibióticos descritos evita que el personal de enfermería de hospitalización tenga que realizar cálculos de dosifi cación a los que puede no estar habituado (p.e. no tener en
cuenta el aumento de volumen que se produce al reconstituir algunos antibióticos); facilita la administración del tratamiento ya que va correctamente identifi cado; y se asegura una elaboración en condiciones estériles al ser preparados en cabina
de fl ujo laminar horizontal.

Referência: IV Congreso de la Sociedad Andaluza de Farmacéuticos de Hospitales. Spaña. 2007

Aripiprazol, eficaz a largo plazo en el tratamiento del trastorno bipolar

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El trastorno bipolar es una enfermedad mental grave que provoca cambios extremos en el estado de ánimo, la energía y las habilidades de los afectados (se calcula que aproximadamente 2,4 millones de ciudadanos europeos padecen este tratorno).

Por ello, es especialmente importante que los tratamientos "sean eficaces y bien tolerados a largo plazo", según señala a CF Eduard Vieta, profesor de Psiquiatría de la Universidad de Barcelona y director del Programa de Trastornos Bipolares del Hospital Clínico de Barcelona.

Este experto ha dirigido un ensayo clínico presentado en el último congreso de la World Psychiatric Association (WPA), celebrado en Florencia, que ha demostrado que aripiprazol, un moderno antipsicótico, en combinación con los estabilizadores del ánimo (litio o valproato) es un tratamiento bien tolerado a largo plazo en pacientes con trastorno bipolar de tipo I y con respuesta inadecuada a la monoterapia con litio o valproato, terapias habituales en esta patología.

Según comenta Vieta, "ya se tenían datos previos positivos de aripiprazol en monoterapia, pero el nuevo estudio aporta valor añadido, al describir el comportamiento del fármaco en condiciones clínicas mucho más habituales en la clínica, como es el caso de la terapia combinada".

En este trastorno, explica, el fármaco proporciona un control rápido de los episodios maníacos, evita que aparezcan nuevos episodios y aporta un control continuado de la manía.

La eficacia y seguridad de aripiprazol, en combinación con litio o valproato, fueron investigadas en un estudio multicéntrico, doble ciego, randomizado y controlado con placebo de 6 semanas de duración, en el que participaron 348 pacientes.

Una vez finalizado, se ofreció a los participantes la posibilidad de continuar en una fase de extensión abierta de 46 semanas.

Referência: Correo Farmaceutico. Madrid: Apr 13, 2009.

Ketamina: estabilidade em seringas

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Development of ready-to-use ketamine hydrochloride syringes for safe use in post-operative pain

M Cyril Stucki, PharmD; Sandrine Fleury-Souverain, PhD; Anna-Maria Sautter, PhD; Farshid Sadeghipour, PhD; Pascal Bonnabry, PhD

ABSTRACT: Study objectives: To increase safety in use of ketamine. This would be achieved by introducing a ready-to-use (RTU) intravenous syringe of ketamine hydrochloride, which would be prepared under aseptic conditions in the hospital pharmacy, for post-operative pain.

Methods: The chemical stability of ketamine hydrochloride solution (1 mg/mL) in 0.9% sodium chloride was determined at 4°C, 25°C and 40°C by means of a stability-indicating capillary electrophoresis method. Changes in pH and the presence
of non-visible particulate matter were measured throughout the study. Sterility testing was performed to check the integrity of the syringes.

Results: The loss in potency was less than 8% after 12 months at the three temperatures, and no degradation products were detected. The pH values did not change appreciably and the syringe contents remained sterile throughout the study. Each syringe fulfilled all US Pharmacopeia criteria in terms of non-visible particles.

Conclusion: RTU syringes of ketamine hydrochloride with a shelf life of one year can be manufactured and supplied by the hospital pharmacy for use in post-operative pain. This product will help reduce the risk of dilution errors and lead to
significant economic advantages.

M Cyril Stucki, PharmD
Pharmacy Department
University Hospitals of Geneva
24 Rue Micheli du Crest
CH-1211 Geneva 14, Switzerland
Tel: +41 22 382 39 74
Fax: +41 22 382 39 40
cyril.stucki@hcuge.ch
www.hcuge.ch/Pharmacie

Reference: EJHP Science • Volume 14 • 2008 • Issue 1 • P. 14-18

Bupivacaína + sufentanila: estabilidade em seringas

***

Chemical stability of a solution of bupivacaine hydrochloride 0.125% and sufentanil citrate 0.5 μg/mL for filling syringes using a repeater pump.

Karin Janssen, PharmD; René Wisselo, B App Sci; Charles Geerlings, PharmD; Jan Pieter Schouten, PharmD, MBM

ABSTRACT: Study objective: In Sint Franciscus Gasthuis, Rotterdam, The Netherlands, syringes filled with bupivacaine hydrochloride 0.125% and sufentanil citrate 0.5 μg/mL are administered epidurally during post-operative analgesia. These syringes are filled in the pharmacy using a Baxa Repeater pump. The suitability of the filling method and the shelf-life of the solution in the syringes were investigated.

Methods: During the filling process six samples were taken. Three syringes were stored at room temperature and three in the refrigerator. Samples were taken on days 4, 7, 14 and 28. High performance liquid chromatographic (HPLC) methods were used to measure the concentrations of both drugs in the samples.

Results: No loss of drugs was observed during the filling process. After 28 days at room temperature and in the refrigerator, the concentration of bupivacaine hydrochloride was 97.4 ± 0.9% and 97.9 ± 1.0% respectively, and that of sufentanil
citrate was 95.6 ± 4.2% and 99.2 ± 1.4%.

Conclusion: The filling method used with a Baxa Repeater pump is acceptable. Bupivacaine/sufentanil solution in syringes is chemically stable for at least 28 days in the refrigerator.

Contact: Karin Janssen, PharmD
Apotheek Zuwe Hofpoort Ziekenhuis
2 Polanerbaan
3447 GN Woerden, The Netherlands
Tel: +31 348 427385
Fax: +31 348 427489
kjanssen@zuwe.nl

Reference: EJHP Science • Volume 15 • 2009 • Issue 1 • P. 11-14

Osmolalidade e pH: metotrexato, citarabina e tiotepa.

Evaluation of osmolality and pH of various concentrations of methotrexate, cytarabine, and thiotepa prepared in normal saline, sterile water for injection, and lactated Ringer's solution for intrathecal administration.

Background: Neurotoxicity of intrathecal (IT) chemotherapy has been variously attributed to the preservatives, volume, osmolality, and pH of the preparations. There has been little evaluation of how different drug concentrations or diluents can affect the osmolality and pH of the final solution. We conducted a three-part study: survey of cancer centers regarding the drug concentrations and diluent used in preparing IT chemotherapy; review of the literature on common practice of preparing IT chemotherapy; evaluation of the pH and osmolality of commonly used chemotherapy preparations for IT.

Method: We surveyed selected cancer centers to provide information on their standard volume, drug concentrations, and choice of diluents. MEDLINE was searched for clinical reports using the MeSH terms of 'cytarabine,' 'methotrexate,' or 'thiotepa' with the subheading 'Cerebrospinal fluid' and combined with 'intrathecal' in all database fields. Data retrieved included the choice of diluent, volume, and/or drug concentration. We evaluated the pH and osmolality of methotrexate (1, 2, 5, and 10 mg/mL), cytarabine (2, 5, 10, and 25 mg/mL), and thiotepa (1, 2, and 5 mg/mL) in normal saline, sterile water for injection (SWFI), and lactated Ringer's solution.

Results: Nine centers were surveyed (seven in Canada, one in Australia, one in United Kingdom). Most centers used 5mL of preservative-free normal saline, irrespective of the drug or drug concentration used. Forty-four reports in the literature were reviewed. Most reported 5mL of preservative-free normal saline. Most information on drug concentrations was provided for methotrexate, with an average concentration of about 1-2.5 mg/ mL. Cytarabine 0.4-20 mg/mL and thiotepa 1 mg/mL were also reported. In our in vitro evaluation, there was a trend of increased pH associated with increasing concentration of methotrexate and cytarabine. There was no apparent impact of thiotepa concentration on the pH values of the final preparations, irrespective of the diluent used. Except for cytarabine 10 and 25 mg/mL, all the tested solutions have pH within 10% of the physiologic range of CSF. There was a concentration-dependent change in osmolality with methotrexate and cytarabine preparations. Osmolality was increased with increased concentrations in all except methotrexate mixed in SWFI and thiotepa mixed in normal saline and lactated Ringer's solution. Except for some thiotepa solutions, all the tested solutions have osmolality within 10% of the physiologic range of CSF.

Conclusions: There is limited published literature on the potential impact of diluent and drug concentration on the pH and osmolality of IT chemotherapy preparation. Most cancer centers conventionally prepare IT chemotherapy with 5mL of preservative diluent normal saline, irrespective of the specific drug or dose used. The conventional practice means that most methotrexate preparations are likely to have comparable pH and osmolality to CSF. In contrast, cytarabine preparations may show significantly higher pH than the CSF, while thiotepa preparations generally have lower osmolality than the CSF.

Reference: Lemos et al. Evaluation of osmolality and pH of various concentrations of methotrexate, cytarabine, and thiotepa prepared in normal saline, sterile water for injection, and lactated Ringer's solution for intrathecal administration. Journal of Oncology Pharmacy Practice; Mar 2009, Vol. 15 Issue 1, p 45-52

Chemical stability of a solution of bupivacaine hydrochloride 0.125% and sufentanil citrate 0.5 μg/mL

***

Chemical stability of a solution of bupivacaine hydrochloride 0.125% and sufentanil citrate 0.5 μg/mL for filling syringes using a repeater pump

Karin Janssen, PharmD; René Wisselo, B App Sci; Charles Geerlings, PharmD; Jan Pieter Schouten, PharmD, MBM

ABSTRACT: Study objective: In Sint Franciscus Gasthuis, Rotterdam, The Netherlands, syringes filled with bupivacaine hydrochloride 0.125% and sufentanil citrate 0.5 μg/mL are administered epidurally during post-operative analgesia. These syringes are filled in the pharmacy using a Baxa Repeater pump. The suitability of the filling method and the shelf-life of the solution in the syringes were investigated.

Methods: During the filling process six samples were taken. Three syringes were stored at room temperature and three in the refrigerator. Samples were taken on days 4, 7, 14 and 28. High performance liquid chromatographic (HPLC) methods were used to measure the concentrations of both drugs in the samples.

Results: No loss of drugs was observed during the filling process. After 28 days at room temperature and in the refrigerator, the concentration of bupivacaine hydrochloride was 97.4 ± 0.9% and 97.9 ± 1.0% respectively, and that of sufentanil
citrate was 95.6 ± 4.2% and 99.2 ± 1.4%.

Conclusion: The filling method used with a Baxa Repeater pump is acceptable. Bupivacaine/sufentanil solution in syringes is chemically stable for at least 28 days in the refrigerator.

References: EJHP Science • Volume 15 • 2009 • Issue 1 • P. 11-14

Jarabe de Paracetamol

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Jarabe de Paracetamol

Fórmula:
Paracetamol ............................................................. 1 % p/v
Propilenglicol ......................................................... 25 % v/v
Agua purificada..........................................................35 % v/v
Esencia de fresa.................................................................c.s.
Colorante hidrosoluble........................................................c.s.
Conservante......................................................................c.s.
Jarabe simple c.s.p........................................................ 100 mL

Tecnica: En un vaso de precipitado, se disuelve el paracetamol en el agua. Se añade el propilenglicol y se homogeneiza. Esta mezcla se vierte en una probeta graduada y se completa hasta la cantidad a elaborar, con jarabe simple. Finalmente, se vierte el contenido de la probeta al vaso de precipitado, se añaden la esencia, el conservante y el colorante y se mezcla todo bien hasta obtener un sistema
homogéneo.

Envasado: El jarabe se envasa en un frasco de cristal topacio, de capacidad adecuada a la cantidad de fórmula a dispensar; acompañado de jeringa.

Usos y Aplicaciones: Se utiliza como analgésico y antipirético

Conservación y Estabilidad: Se conserva a temperatura ambiente y protegido de la luz.

Referência: UNIVERSIDAD DE SEVILLA, FACULTAD DE FARMACIA, DEPARTAMENTO DE FARMACIA Y
TECNOLOGÍA FARMACÉUTICA

Stability of high dose melphalan in saline solution.

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Stability of high dose melphalan in saline solution

M.T. Baylatry, D. Geay, C. Guntz, J.L. Prugnaud, A.C. Joly
Saint-Antoine Hospital, Pharmacy, Paris Cedex 12, France

Background: Melphalan is an effective anticancer drug used in high doses as preparative regimen for haematopoietic stem cell transplantation (off-label indication). In Saint-Antoine hospital, melphalan concentration for chemotherapy infusion bag, in this indication, is between 0.8 mg/mL and 1.6 mg/mL. In melphalan
summary of product characteristics, the recommended maximum concentration is 0.45 mg/mL and the stability at this concentration in infusion bag is reported to be 90 min at room temperature. A chemical stability assay of high dose melphalan has been developed firstly to validate the safety of this unlicensed preparation and then to make possible melphalan centralized preparation and storage.

Methods: A liquid chromatographic UV method was used. The evaluation of stability (International Conference on Harmonization guidelines) and the accelerated degradation (temperature) were performed. The stability was established as the 95% of initial concentration. Melphalan solution in saline (0.9% NaCl) infusion bags were assessed at room temperature (average: 28°C) for 0.3 mg/mL (n=3) and 1.6 mg/mL (n=3) concentrations and at + 4°C for 0.8 mg/mL (n=3) and 1.6 mg/mL (n=3). Samples were collected at different times from 0h to 24h. Visible particulate formation or colour change were also evaluated.

Results: Melphalan solutions were degraded at room temperature within 2 hours (76% and 78% of initial concentration respectively for 0.3 mg/mL and 1.6 mg/mL). At + 4°C, melphalan concentrations (0.8 mg/mL and 1.6 mg/mL) remained above 95% for 3 hours. No color change or visible particulate formation were observed.

Conclusions: High dose melphalan is not degraded rapidly in saline solution. This study allows to prepare high dose melphalan infusion bags without recurring to high volumes of saline solution which may expose patients to hydric overload. The 3 hour stability of melphalan at + 4°C is compatible with an anticancer drug centralized preparation in Pharmacy department in order to avoid an extemporaneous preparation by nurses in Haematology department and improve their safety.

References: 14th Congress of EAHP. Barcelona. 2009

Tamiflu (oseltamivir): preparation and stability of extemporaneous oral liquid formulations of oseltamivir using commercially available capsules.

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Preparation and stability of extemporaneous oral liquid formulations of oseltamivir using commercially available capsules.

Winiarski AP, Infeld MH, Tscherne R, Bachynsky M, Rucki R, Nagano-Mate K.

Professional Product Information, Roche Laboratories, Nutley, NJ 07110-1199, USA. aleksander.winiarski@roche.com

OBJECTIVES: To develop a simple, standardized method for the extemporaneous compounding of an oral liquid form of oseltamivir from commercially available Tamiflu 75 mg capsules (Roche Pharmaceuticals) and to determine the stability of oseltamivir in this preparation.

***

INTERVENTION: Extemporaneous oral liquid formulations of oseltamivir (15 mg/mL) were prepared in Cherry Syrup (Humco) and Ora-Sweet SF (Paddock Laboratories) using methods consistent with current compounding practice in a pharmacy setting. Preparations were stored in amber glass and amber polyethyleneterephthalate bottles at 5 degrees C +/- 2 degrees C (41 degrees F +/- 4 degrees F) and 25 degrees C +/- 2 degrees C (77 degrees F +/- 4 degrees F) at 60% +/- 5% relative humidity (RH) for 35 days and 30 degrees C +/- 2 degrees C (86 degrees F +/- 4 degrees F) at 65% +/- 5% RH for 13 days.

***

RESULTS: The Cherry Syrup preparation, in either bottle type, was stable for up to 35 days under refrigeration (5 degrees C) and up to 5 days at room temperature (25 degrees C). It was not stable when stored at 30 degrees C for 5 days. The Ora-Sweet SF preparation was stable for up to 35 days at 5 degrees C or 25 degrees C and for up to 13 days at 30 degrees C in either bottle type. Both preparations maintained microbiologic stability for 35 days.

***

CONCLUSION: Both preparations are stable under the described conditions and may provide an option in situations where the marketed suspension is unavailable.

Reference: J Am Pharm Assoc (2003). 2007 Nov-Dec;47(6):747-55.

Formulation and stability evaluation of bromhexine hydrochloride for veterinary use

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Formulation and stability evaluation of 1% w/v oral solution of Bromhexine hydrochloride for veterinary use

Purpose: The aim of this study is to develop bromhexine hydrochloride 1 %w/v oral solution for veterinary use and to evaluate its stability.

Methods: Solutions of Bromhexine hydrochloride (1%w/v) were prepared by dissolving bromhexine hydrochloride in benzyl alcohol at 50 °C then alcohol 96 % v/v; Tween 80 and purified water were added. The obtained solution was filled in amber glass bottles, and the solution was stored at 25 °C/60 % relative humidity (RH) and at 40 °C /75% RH. The strengths of bromhexine hydrochloride were determined by High performance liquid chromatographic assay at 0, 2, 4, 6, 8, 10, 12, 16, 20 and 24 months. The concentrations of the drug were directly related to the peak area. pH, odor, color and crystal formation was also monitored.

Results: The degradation of bromhexine hydrochloride 1% w/v oral solution was faster at 40 °C/75% RH than at 25 °C /60% RH. No significant differences were found between the initial and final pH value for the solution at the studied conditions. No detectable changes in color, odor or precipitations were observed for the solutions stored at the upper conditions.

Conclusions: Bromhexine hydrochloride 1% w/v oral solution could be formulated and remains stable for at least 2 years when is stored at 25°C /60% RH and for 16 months when stored at 40 °C /75% RH.

Reference: The Islamic University Journal (Series of Natural Studies and Engineering), Vol.15, No. 1, pp 13 -22 , 2007

GEL DE CLORIDRATO DE DILTIAZEM

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ESTABILIDADE QUÍMICA, FÍSICA E MICROBIOLÓGICA DE UM GEL DE CLORIDRATO DE DILTIAZEM

Ana C. Salgado, Marina Lobo Alves, Fátima Falcão, João F. Pinto.

Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade de Lisboa; Serviços Farmacêuticos Hospital São Francisco Xavier

***

Resumo: A fissura anal é um problema comum que afecta ambos os sexos. A hipertonia do esfíncter anal é o principal factor fisiopatológico que condiciona a cicatrização. É mais frequente em doentes com obstipação crónica. É caracterizada por dor e hematoquezias. O índice de cicatrização não ultrapassa os 65 a 70%, independentemente da utilização dos tratamentos médicos disponíveis, obrigando frequentemente ao recurso a procedimento cirúrgico. A utilização do cloridrato de diltiazem por via tópica constitui uma nova abordagem terapêutica das fissuras anais. O objectivo deste trabalho é o desenvolvimento de um gel de cloridrato de diltiazem a 2% e o estudo da sua estabilidade química, física e microbiológica. O protocolo de estabilidade adoptado obedeceu, nos aspectos relevantes, às normas em vigor para estudos de estabilidade de especialidades farmacêuticas.Para o efeito, foram produzidos três lotes de gel de composição idêntica que foram armazenados durante 93 dias, em frascos de vidro incolor, a 22±3ºC e protegidos da luz. A intervalos de tempo apropriados foram colhidas amostras e analisados os seguintes parâmetros: aspecto, viscosidade, doseamento do cloridrato de diltiazem (HPLC) com pesquisa de produtos de degradação e controlo microbiológico (realizado segundo a FP VII para preparações líquidas para uso oral). O método de doseamento da substância activa foi devidamente validado quanto à sensibilidade, linearidade, exactidão e precisão. A estabilidade do gel foi definida como a retenção de um teor em cloridrato de diltiazem ³95% sem alterações significativas nos restantes parâmetros analisados. Os resultados indicam que o gel de cloridrato de diltiazem a 2% armazenado à temperatura ambiente (22±3ºC) é estável química, física e microbiologicamente durante todo o tempo do estudo (93 dias).

Referência: 5º Congresso Nacional da APFH. Lisboa. 2007

Creme de metadona 0,1%, lidocaína 2% e metronidazol 5% para el tratamiento de úlceras tumorales dolorosas.

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Crema de metadona 0,1%, lidocaína 2% y metronidazol 5% para el tratamiento de úlceras tumorales dolorosas

M.C. Dávila Pousa, L. Herrero Poch y G. Piñeiro Corrales
Complexo Hospitalario de Pontevedra. Pontevedra.

***

Introducción: El alivio del dolor y la eliminación del mal olor causado por microorganismos anaeróbios, es uno de los objetivos principales del tratamiento de las úlceras tumorales dolorosas en una unidad de cuidados paliativos. La asociación de metadona a formulaciones tópicas con metronidazol y lidocaína podría estar valada por la existencia de receptores opiodes periféricos y por sus propiedades de liposolubilidad y elevada vida media.

***

Objetivo: Protocolización de una fórmula magistral con metronidazol lidocaina y metadona para el tratamiento tópico de ulceras tumorales dolorosas.

***

Material y método: Se realizó una busqueda bibliografica en PubMed y google sobre la utilización y dosificación de metadona, lidocaína y metronidazol por vía tópica en el tratamiento de ulceras tumorales. Se analizaron las características físico-químicas de los tres principios activos en Index merck y en el proveedor de materias primas: www.acofarma.com y las características farmacocinéticas en la base de datos de Micromedex. Se revisaron las fórmulas por vía tópica del formulario nacional, formularios de reconocido prestigio y la base de datos del Consejo General de Colegios farmacéuticos que incluyesen alguno de los tres componentes , para seleccionar les excipientes mas adecuados. También se revisaron las concentraciones y composición de los preparados comerciales con metronidazol y/o lidocaína.

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Resultados: Según los datos recogidos, para los principios activos se establecieron las siguientes concentraciones: metadona Cl H 0,1%, lidocaína ClH 2% y metronidazol 5%. Como base se utilizó una crema emoliente O/W compuesta por los siguientes excipientes: Tween 80 2,5%, Alcohol cetílico 15%, vaselina filante 10%, propilenglicol c.s, solución concentrada de hidroxibenzoatos 1% y agua purificada como vehículo. La experiencia de uso por parte del personal médico y de enfermería de la unidad de cuidados paliativos ha resultado muy satisfactoria.

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Conclusiones: La fórmula establecida se ha mostrado eficaz en el tratamiento del dolor y reducción del mal olor de úlceras tumorales. La utilización de metadona por vía tópica ha permitido en algunos pacientes una reducción de la dosis de opioide administrado por vía sistémica. La elaboración de formulas magistrales en una unidad de cuidados paliativos es una buena alternativa para cubrir aquellas lagunas terapéuticas que no proporciona la industria farmacéutica.

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Referência: 53º Congreso Nacional de la Sociedad Española de Farmacia Hospitalaria. Valencia. 21-24 de octubre de 2008

Errores de prescripción de antineoplásicos en pacientes oncohematológicos

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Errores de prescripción de antineoplásicos en pacientes oncohematológicos

Garzás-Martín de Almagro MC, López-Malo de Molina MD, Abellón Ruiz J, Fernández García I, Isla Tejera B.

Servicio de Farmacia. Hospital Universitario Reina Sofía. Córdoba (España)

Objetivo: Detectar los distintos tipos de error de prescripción de citostáticos en pacientes hematológicos y de Oncohematología pediátrica de nuestro hospital, identificar las posibles causas que los originan y proponer medidas de mejora.

Métodos: Estudio observacional longitudinal prospectivo en el que se validaron todas las prescripciones de antineoplásicos procedentes de los servicios de Hematología y Oncohematología pediátrica durante un período de 15 meses (en los años 2006-2007). Se clasificaron los tipos de error atendiendo a la terminología y taxonomía publicadas por Otero y cols en el documento “Errores de medicación: estandarización de la terminología y clasificación,”recogiéndose 11 variables. Entre otros parámetros se determinaron: %error global, % error por tipo de prescripción, % error por servicios, % intervención farmacéutica y su grado de aceptación.

Resultados: Se detectaron un total de 92 errores correspondientes al 1.4% del total de prescripciones, siendo los de mayor relevancia: dosificación incorrecta(28.2%), duración incorrecta (21.7%), volumen y/ó vehículo inadecuado (16.3%) y omisión (13.0%). Además se detectó una órden de tratamiento de un paciente pediátrico alérgico al citostático prescrito. El 81.8% de órdenes con error se prescribieron de forma manual. Para Hematología se obtuvo un 0.9% de error y un 3.5% para Oncohematología pediátrica. Tanto el índice de intervención farmacéutica como su grado aceptación fue del 100%.

Referência: Revista de la OFIL 2007,17;4:29-34

Perfil de consumo de antineoplásicos injetáveis em um Hospital Universitário

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Perfil de consumo de antineoplásicos injetáveis em um Hospital Universitário

Márcia Dias (1,2); Natalia Bousquet (1,2); Manuela Pedroza (3); Araken Caldas (2)

(1) Curso de Especialização Treinamento em Serviços para Farmacêuticos Hospitalares, nos moldes de Residência. Rua Mário Viana, 523 – CEP 24241-000 – Niterói (RJ)
e-mail: marciadias_35@yahoo.com.br, nataliabousquet@gmail.com

(2) Hospital Universitário Antônio Pedro (HUAP)
Rua Marquês de Paraná, 303 - CEP 24030-210 – Niterói (RJ)
e-mail: apcaldas@gmail.com

(3) Centro Universitário Plínio Leite (UNIPLI)
Av. Visconde do Rio Branco, 123 - CEP 24020-000 - Niterói (RJ)
e-mail: manu_pedroza@yahoo.com.br

Introdução: A Política Nacional da Assistência Farmacêutica juntamente com a Política Nacional de Medicamentos constituem um dos elementos fundamentais para a implementação de ações de melhoria das condições de assistência à saúde da população. A atenção farmacêutica envolve vários componentes inclusive o registro sistemático das atividades e avaliação de resultados.

Objetivo: Estimar o perfil de consumo de medicamentos antineoplásicos na central de quimioterapia do HUAP.

Método: As prescrições médicas de serviços ambulatoriais e de internação foram analisadas entre o período de abril a julho de 2008, considerando os antineoplásicos injetáveis padronizados e o número de manipulações deste período.

Resultados: Os medicamentos 5-fluorouracil (5-FU), citarabina (ARA-C), doxorrubicina (DOXO) e etoposido (VP16) apresentaram maior perfil de consumo nos meses estudados, acima de 100 frascos. O número de manipulações feitas no hospital no período foi em média aproximadamente 1140 por mês.

Discussão e Conclusão: Apesar de não ser um hospital especializado em oncologia, a crescente demanda de serviços em quimioterapia vem levando o staff farmacêutico hospitalar a determinar o perfil de consumo destes medicamentos para programar de forma correta a aquisição destes e assim, evitar tanto a demanda reprimida quanto a interrupção do tratamento.

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A partir da média mensal de manipulações de um período de quatro meses, foi possível determinar os antineoplásicos de maior consumo médio dentre os padronizados, cujo consumo em conjunto gira em torno de 63% do total de manipulações do período estudado. Nosso trabalho demonstra a importância do ciclo da atenção farmacêutica, em especial a programação, para a correta alocação de recursos públicos hospitalares.

Referência: 1º Congresso de Farmácia Hospitalar em Oncologia do INCA. Rio de Janeiro. 2008

Analysis of pharmaceutical interventions: Hospital Garcia de Orta

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Santos A, Rodrigues C, Alcobia A. Pharmacy Department, Hospital Garcia de Orta, EPE, Almada, Portugal. farmaceuticos@hgo.min-saude.pt

Background: A systematic record is made by the pharmacist of interventions to medical prescriptions in a unit dose drug distribution system. This is a practical method that enables communication between health professionals and allows the detection and resolution of drug-related problems, so enhancing clinical activity. The main objective of this study was to quantify and characterise the pharmaceutical interventions made in some wards of the hospital.

Methods: Prospective observational study of the pharmaceutical interventions that were made during review of the drugs prescribed from January to June 2006 in the gastroenterology, infectious diseases, rheumatology, neurology and vascular surgery departments.

Results: During the study period, 510 interventions were made in the following categories: 259 (51%) nonhospital formulary drugs, 58 (11%) drug substitution, 55 (11%) therapeutic drug monitoring, 54 (11%) antibiotic justifications, 34 (7%) wrong dosage, 16 (3%) drug stability, 9 (2%) drug information, 8 (2%) duplicate therapeutics, 8 (2%) drug interactions, 7 (1%) change from intravenous to oral administration and 2 (<0.5%) wrong indication. Of the 76 drugs studied, those that generated most interventions were: bisoprolol, valsartan, piperacillin–tazobactam, meropenem and vancomycin. All interventions mentioned previously were accepted by the medical staff, as were the suggested courses of action related to interventions.

Conclusions: Adjustment of dosage, drug monitoring and drug stability are just some of the interventions that result in improvements to the care provided to patients, as well as a better management of the available resources. The prevention of these problems must be a priority for the pharmacy department, whose main goal is to ensure the safety and efficacy of the drugs administered in the hospital environment. The next step will be to create a computerized record to classify these interventions and determine the clinical and economic impact of drug-related problems.

Reference: 13th Congress of the European Association of Hospital Pharmacists. 2008

Stability of Oral Liquid Dosage Forms of Glycopyrrolate Prepared With the Use of Powder.

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Vishnu D. Gupta, PhD. Pharmaceutics Division. University of Houston, Houston,Texas

Abstract: A previously developed stability-indicating high-performance liquid chromatographic assay method was used to investigate the stability of glycopyrrolate in oral liquid dosage forms (0.5 mg/mL)that contained a 0.05-M phosphate buffer of pH 5.6 and either 10% sorbitol or 10% sucrose as the sweetening agent.The decomposition product and sorbitol or sucrose did not interfere with the assay procedure.The liquid dosage forms were prepared using com mercially available powder.After 129 days of storage at 25 °C, the loss in potency was less than 6%.The physical appearance of the dosage forms did not change during the study period.The pH value of the dosage forms in sorbitol did not change from the original value of 5.6.The pH value of the dosage forms in sucrose decreased from 5.6 to 4.8 after 129 days of storage at 25 °C.

Reference: Gupta VD. Stability of Oral Liquid Dosage Forms of Glycopyrrolate Prepared With the Use of Powder. IJPC 2003;7(5):386-388

The impact of computerized prescribing on error rate in a department of Oncology

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Small MDC, Barrett B, Price GM. The impact of computerized prescribing on error rate in a department of Oncology. Journal of Oncology Pharmacy Practice 2008;14(4):181-187

Department of Pharmacy, Norfolk and Norwich University Hospital, Norwich, United Kingdom

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Purpose: A comparison of prescribing errors detected for computerized and spreadsheet prescriptions in the Department of Hematology and Oncology of the Norfolk and Norwich University hospital.

Methods: A prospective audit of 1941 prescriptions for chemotherapy was made from January to September 2005. Each new cycle of chemotherapy ordered was monitored for prescribing errors, which were analyzed by method of prescription (computerized or spreadsheet), prescriber, type, and severity.

Results: Computerized prescribing reduced errors by 42%. Errors occurred in 20% of spreadsheet prescriptions compared with 12% of the computerized prescriptions. There was a significant difference in error rates of three different prescribers whichever prescribing system was used. The proportion of errors that were minor was reduced and serious was increased with little change in the proportion of significant or life-threatening errors.

Conclusions: The impact of computerized prescribing on adverse drug events requires further evaluation. Prescriber training may be important in further reducing errors. The implementation of all the existing functions of the electronic system should lead to further reduction in errors.

References: Small MDC, Barrett B, Price GM. The impact of computerized prescribing on error rate in a department of Oncology/Hematology. Journal of Oncology Pharmacy Practice 2008;14(4): 181-187