[Stevens-Johnson syndrome, toxic epidermal necrolysis and phenytoin. Factors linked to a higher risk]. / Síndrome de Stevens-Johnson, necrólisis epidérmica tóxica y fenitoína. Factores asociados a un aumento del riesgo.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, although not very common, clinical skin pictures that are usually related to the use of medication. Several antiepileptic drugs, including phenytoin, have been linked to SJS/TEN. Some authors have described an increased risk for SJS/TEN when phenytoin is associated to radiotherapy, while others report the possibility of an increased risk when it is associated to corticoids. DEVELOPMENT: This work includes a review of the spontaneous reports of suspected cases of phenytoin-linked SJS/TEN recorded in the database of the Pharmacovigilance Department at Pfizer-España between October 2000 and December 2003. Nine cases compatible with SJS/TEN were found; four occurred in cancer patients that had received radiotherapy, three of whom were also treated with corticoids. DISCUSSION AND CONCLUSIONS: After reviewing the spontaneously reported cases in the database of the Pharmacovigilance Department at Pfizer-España as well as the cases in the literature, it can be concluded that when it comes to indicating a prophylactic antiepileptic treatment for cancer patients with cerebral metastasis, the clinician must take into account the existence of a greater risk of SJS/TEN if the patient is going to receive radiotherapy. If the patient already presents a history of skin rashes following administration of an antiepileptic drug, care must be taken in choosing another because phenytoin together with carbamazepine, phenobarbital and lamotrigine have all been linked to SJS/TEN. Cross-sensitivity of carbamazepine and barbiturates with phenytoin has been observed. Gabapentin and valproic acid could be considered as therapeutic options in such cases.

Síndrome de Stevens-Johnson, necrólisis epidérmica tóxica y fenitoína. Factores asociados a un aumento del riesgo / Stevens-Johnson syndrome, toxic epidermal necrolysis and phenytoin. Factors linked to a higher risk

Introducción. El síndrome de Stevens-Johnson (SSJ) y la necrólisis epidérmica tóxica (NET) son cuadros cutáneos graves, aunque poco frecuentes, que en la mayoría de los casos se relacionan con el consumo de fármacos. Varios antiepilépticos se han asociado a SSJ/NET, entre ellos la fenitoína. Algunos autores han descrito un aumento del riesgo de SSJ/NET cuando la fenitoína se asocia a radioterapia, y otros han informado de la posibilidad de un mayor riesgo cuando se asocia al empleo de corticoides. Desarrollo. En este trabajo se realiza una revisión de las notificaciones espontáneas de sospecha de SSJ/NET asociados a fenitoína registradas en la base de datos del Departamento de Farmacovigilancia de Pfizer-España, desde octubre de 2000 hasta diciembre de 2003.Se han recogido nueve casos compatibles con SSJ/NET; cuatro ocurrieron en pacientes oncológicos que habían recibido radioterapia y, además, tres de ellos se trataron también con corticoides.Discusión y conclusiones. Tras revisar los casos de notificación espontánea de la base de datos del Departamento de Farmacovigilancia de Pfizer-España, y tras revisar los casos de la literatura, se concluye que a la hora de indicar un tratamiento antiepiléptico profiláctico en pacientes oncológicos con metástasis cerebrales, debería valorarse la existencia de un mayor riesgo de presentar SSJ/NET si el paciente va a recibir radioterapia. Si el paciente ya presenta antecedentes de reacción cutánea con un antiepiléptico, la elección de otro debe realizarse con precaución, ya que tanto la fenitoína, como la carbamacepina, el fenobarbital y la lamotrigina se han asociado a SSJ/NET, y se ha observado sensibilidad cruzada de la carbamacepina y los barbitúricos con la fenitoína. La gabapentina y el ácido valproico podrían considerarse como opciones terapéuticas en estos casos (AU)

Introduction. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe, although not very common, clinical skin pictures that are usually related to the use of medication. Several antiepileptic drugs, including phenytoin, have been linked to SJS/TEN. Some authors have described an increased risk for SJS/TEN when phenytoin is associated to radiotherapy, while others report the possibility of an increased risk when it is associated to corticoids. Development. This work includes a review of the spontaneous reports of suspected cases of phenytoin-linked SJS/TEN recorded in the database of the Pharmacovigilance Department at Pfizer-España between October 2000 and December 2003. Nine cases compatible with SJS/TEN were found; four occurred in cancer patients that had received radiotherapy, three of whom were also treated with corticoids. Discussion and conclusions. After reviewing the spontaneously reported cases in the database of the Pharmacovigilance Department at Pfizer-España as well as the cases in the literature, it can be concluded that when it comes to indicating a prophylactic antiepileptic treatment for cancer patients with cerebral metastasis, the clinician must take into account the existence of a greater risk of SJS/TEN if the patient is going to receive radiotherapy. If the patient already presents a history of skin rashes following administration of an antiepileptic drug, care must be taken in choosing another because phenytoin together with carbamazepine, phenobarbital and lamotrigine have all been linked to SJS/TEN. Cross-sensitivity of carbamazepine and barbiturates with phenytoin has been observed. Gabapentin and valproic acid could be considered as therapeutic options in such cases (AU)

[Safety of meningococcal A and C vaccine. Data from the Spanish drug surveillance system. Meningococcal Vaccine Research Group of the Spanish System of Drug Surveillance]. / Seguridad de la vacuna antimeningocócica A+C. Datos recogidos por el Sistema Español de Farmacovigilancia. Grupo de Investigación sobre la vacuna antimeningocócica del Sistema Español de Farmacogigilancia.

OBJECTIVE: Data on meningococcal vaccines safety are scanty. In 1997 several vaccination campaign took place in Spain. Thus, this situation was used to improve our knowledge about the safety profile of this vaccine. METHODS: An inquiry was carried out to the Regional Centers of the Spanish Pharmacovigilance System to know the number of vaccinated people and the type and number of suspected cases of adverse reactions. RESULTS: There were 133 identified cases of suspected adverse reactions associated with meningococcal A and C vaccine until June 1st, 1998. Most of them affected the skin (25,3%) or nervous system (similar proportion). Those of allergic reactions accounted for 35,2%. Two cases were considered as severe, although they were resolved without secuelae. CONCLUSIONS: Serious risks were not detected. The Spanish Pharmacosurveillance System as an epidemiological surveillance resource has been useful to know the safety problems associated with antimeningococcal vaccine in the community.

A cost-analysis of suspected adverse drug reactions in a hospital emergency ward.

The main objective of this study was to analyse the minimum direct cost to the Public Health System (PHS) of diagnosing and treating those patients attended to in the emergency ward (EW) for suspected adverse drug reaction (ADR). The cases were collected during March 1995 in the emergency ward of a 900-bed tertiary teaching hospital that covers 900,000 inhabitants. ADR was considered according to the WHO definition. The following EW costs were used: EW physician visit 78.5 ecus (1 ecu=156 pesetas), thorax or abdomen radiograph 21.5 ecus, computerized tomography 112.7 ecus, endoscopy 48 ecus, specialist physician visit 62 ecus. Three types of laboratory costs were considered: block of biochemical tests 16 ecus, biochemical tests with blood count 22.5 ecus, and biochemical tests with blood count and coagulation study 41.6 ecus. Pharmacotherapy of the ADR and changes in patient's usual drug therapy due to ADR were estimated. For patients admitted in the hospital, a per day cost of 391 ecus was considered. A mean ADR cost per organ or system affected (cutaneous, metabolic, gastrointestinal, nervous) was computed. The main conclusion of this study is that ADR, apart from inflicting damage on the patients, also incur PHS costs. The quantity of 42,732 ecus during the month of March, in a single hospital, can seem small when compared with the cost of some diseases such as AIDS or ischemic heart disease. But remembering that about 40% of all ADR attended to in hospitals is avoidable, a decrease of 40% could produce an annual saving of 205,216 ecus to the hospital, which is twice the annual budget of the Pharmacovigilance Centre of the Basque Country. Pharmacovigilance centres should include cost analysis of ADR among their objectives, to provide health systems managers with enough information to implement those measures that will result in a better utilization of the scarce resources of the Public Health System.

[Adverse drug reaction surveillance in pediatric and adult patients in an emergency room]. / Monitorización en un servicio de urgencias de reacciones adversas causadas por medicamentos en niños y adultos.

BACKGROUND: Adverse drug reactions (ADR) in the pediatric emergency room of a tertiary care hospital in Spain are described and compared with the adult ward. METHODS: Identification of cases was carried out through review of admission diagnoses and selection of those included in a previous list of diagnoses considered as possible ADR, that were thereafter verified. RESULTS: During 25 months, in 47.107 pediatric consultations were detected 451 cases as suspicious of ADR (0.96%). The ADR was moderate in 29 and serious in 1, being hospitalized 4. In adults, there were 68,431 consultations, and 704 cases detected (1.03%); moderate 218, serious 34 and mortal 1, being hospitalized 101. The most common reactions were dermatological (43.9% in children, 19.5% in adults) and of digestive nature (28.5 and 36.6%, respectively). The drugs most frequently involved in children were antimicrobials (49.5%), drugs used in respiratory illnesses (19.9%), non-steroid anti-inflammatory drugs (NSAID) (10.4%) and vaccines (9.2%); only two recently marketed products were involved. In adults, drugs involved were NSAID (28.2%), cardiovascular drugs (15.9%), antimicrobials (14.5%) and drugs active in digestive system (11.1%). There were 10 cases of hypoglycemia in diabetic adults, probably by interaction of hypoglycemic agents with angiotensin-converting enzyme inhibitors, and 7 cases of gastrointestinal hemorrhage associated with ketorolac, that generated an alert; 12 recently marketed products were involved. CONCLUSIONS: Intensive monitoring in emergency ward measures ADR problem, estimates underreporting, but it has a moderate value to generate alert or to survey new products.

Intravesical BCG therapy of superficial bladder cancer: study of adverse effects.

Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) has proved to be more effective than most chemotherapeutic agents in the prophylaxis and treatment of superficial bladder tumours. Side-effects, both local and systemic, are the main limitations against its use. With the aim of lowering the incidence and severity of side-effects, we started to use two vials of BCG, Connaught type, per instillation, instead of three vials, as recommended by the manufacturer. We prospectively reviewed adverse effects of BCG treatment at the lower dosage in 92 patients. Compared with other series, we found a similar incidence of adverse effects except for some local effects as haematuria which showed a higher incidence, but we also found a lower rate of tumour relapse. Four primary tumours were recorded during the study period. In our open study, a lower BCG intravesical dosage is not followed by a reduction in side-effects.

[Multifocal motor neuropathy after administration of gangliosides]. / Neuropatía motora multifocal tras la administración de gangliósidos.

A case of a 38 years-old male with motor neuropathy with multifocal conduction blocks following the administration of ganglioside therapy is reported. There was generalized weakness without areflexia and normal parameters of the spinal fluid, including protein values. Electrophysiological data showed multiple conduction blocks with normal nerve conduction velocities. Antibodies against asialo-GM1 gangliosides were present in the cerebrospinal fluid. There could be a relationship between the ganglioside administration and the development of an immune-mediated neuropathy. Several cases of demyelinating polyradiculoneuritis after ganglioside treatment have been reported. If this association is confirmed, the apparent lack of toxicity of gangliosides should be reconsidered.