Ustekinumab therapy for Crohn's disease during pregnancy: a case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVES: The safety of continued ustekinumab (UST) therapy during pregnancy remains unclear in patients with Crohn's disease (CD). There are no meta-analysis reports of exposure to UST during pregnancy. The objective was to describe a case of a pregnant patient with CD who was successfully treated with UST maintenance therapy throughout the pregnancy and delivered a baby boy without any congenital malformations, neurological abnormalities or birth defects. CASE SUMMARY: A 37-year-old patient with CD treated with UST became pregnant. She had been receiving UST for 8 months at the time. After discussion with the patient and the obstetric team, the UST therapy was continued. The result of treatment was an uneventful pregnancy with delivery, at term, of a healthy boy and the maintenance of clinical, biological and endoscopic remission of CD during and after pregnancy. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first reported use of continued UST therapy for CD throughout a pregnancy. The result of treatment was an uncomplicated pregnancy with the mother giving birth to a healthy boy at term and the maintenance of clinical biological and endoscopic remission of CD during and after pregnancy.

[Adalimumab versus etanercept in the treatment of active rheumatoid arthritis: cost-effectiveness analysis]. / Adalimumab versus etanercept en el tratamiento de la artritis reumatoide: análisis coste-efectividad.

PURPOSE: To assess the effectiveness and efficiency of the two alternatives mainly used in our area, etanercept (ETN) and adalimumab (ADA), for the treatment of rheumatoid arthritis (RA) patients under real clinical practice. MATERIAL AND METHODS: We performed a retrospective observational study, where the time horizon was 12 months referred to the year 2012. We analyzed the characteristics of patients, and the effectiveness and efficiency of ETN and ADA in our study population. INCLUSION CRITERIA: patients over 18 years, diagnosed with RA treated at the outpatient clinic of the Rheumatology Health Sector of Teruel. We determined the mean decrease in DAS28 value (DAS28r) of each drug and we defined as a unit of effectiveness in pharmacoeconomic study, a DAS28 value at baseline (DAS28a) less than 3.2 points and DAS28r greater than 1.2 points. As parameter to determine the cost-effectiveness of both alternatives we used net health benefits (NHB). RESULTS: The average value of DAS28a was 2,25 and 2,72 points for ETN and ADA respectively, with a value of DAS28r 1,01 points higher for ETN, although not statistically significant (p> 0.05). NHB obtained a value of -0.121, 95% CI (-0.951 to 0.709). CONCLUSIONS: Both alternatives are effective in the treatment of RA, although it seems to be a trend in favor of ETN in cost-effectiveness degree.

Objetivo: Valorar el grado de efectividad y eficiencia de las dos alternativas principalmente utilizadas en nuestro ámbito, etanercept (ETN) y adalimumab (ADA), para el tratamiento de pacientes diagnosticados de artritis reumatoide (AR) en condiciones reales de la práctica clínica diaria. Material y método: Se realizó un estudio observacional retrospectivo, cuyo horizonte temporal fue de 12 meses referidos al año 2012, en el que se analizaron las características de los pacientes, así como la efectividad y eficiencia de ETN y ADA en la población de estudio. Se estudiaron todos los pacientes de ambos sexos mayores de 18 años, diagnosticados de AR, atendidos en las consultas externas del Servicio de Reumatología del Sector Sanitario de Teruel. Se determinó el descenso medio del valor de DAS28 (DAS28r) de cada fármaco y se definió como unidad de efectividad en el estudio farmacoeconómico un valor DAS28 al inicio (DAS28a) inferior a 3,2 puntos y DAS28r mayor a 1,2 puntos. Como parámetro del estudio para determinar el coste-efectividad de ambas alternativas se utilizó el beneficio neto sanitario (BNS). Resultados: El valor medio de DAS28a fue 2,25 y 2,72 puntos para ETN y ADA respectivamente, con un valor DAS28r de 1,01 puntos superior para ETN, aunque sin ser estadísticamente significativo (p > 0,05). El cálculo del parámetro BNS obtuvo un valor igual a -0,121; IC95% (-0,951 a 0,709), sin embargo la inclusión del valor 0 en el intervalo de confianza hizo que no se observaran diferencias de coste-efectividad. Conclusiones: Ambas alternativas son efectivas en el tratamiento de la AR, aunque parece existir una tendencia a favor de ETN en el grado coste-efectividad sin ser significativa.

[Analisis of the budget impact of adalimumab and etanercept in rheumatoid arthritis and spondyloarthropathies]. / Análisis del impacto presupuestario de adalimumab y etanercept en artritis reumatoide y espondiloartropatías.

PURPOSE: To assess the economic impact derived from the widening of the administration intervals of adalimumab (ADA) and etanercept (ETN) for the treatment of rheumatoid arthritis (RA) and spondyloarthropathies (SAP) at our working environment. MATERIAL AND METHODS: A budget impact model (BIM) was developed to estimate the economic impact that would have widening the usual administration intervals of ADA, 40 mg every 2 weeks and ETN, 50 mg weekly (scenario A), to ADA, 40 mg every 3 weeks, and ETN, 50 mg every 2 weeks (scenario B) according to the guidelines and recommendations applied to these studies, specifying the target population, the study perspective, the temporal horizon, and analysing the study robustness by a threshold univariate sensitivity analysis. RESULTS: 71 patients were included in the study. The application of the BIM showed yearly savings for ADA and ETN of 19.784 ??and 38.271 ?, respectively. The net cost, that is to say the saving that this would imply within the temporal horizon considered (2 years), was 116.110 ?. The sensitivity analysis showed that the estimated BIM for the study period was very robust since the net result in the different scenarios varied very little, being negative in the new scenarios. CONCLUSIONS: widening the administration intervals of ADA and ETN to every 3 weeks and 2 weeks respectively, would be a strategy that would allow generating savings in the hospital budget close to 116.110 ??for the temporal horizon considered, achieving this way optimization of the treatment with these two drugs.

Objetivo: Evaluar el impacto económico derivado de la ampliación de los intervalos de administración de adalimumab (ADA) y etanercept (ETN), en el tratamiento de la artritis reumatoide (AR) y espondiloartropatias (EAP) en nuestro ámbito de trabajo. Material y método: Se desarrolló un modelo de impacto presupuestario (MIP) para estimar la repercusión económica que tendría la ampliación en los intervalos habituales de administración de ADA 40 mg cada dos semanas y ETN 50 mg semanal (escenario A), por ADA 40 mg cada tres semanas y ETN 50 mg cada dos semanas (escenario B) de acuerdo a las guías y recomendaciones que se aplican a estos estudios, especificando la población diana, la perspectiva del estudio, el horizonte temporal y analizando la robustez del estudio a través de un análisis de sensibilidad univariante de tipo umbral. Resultados: Se incluyeron un total de 71 pacientes en el estudio. La aplicación del MIP mostró unos ahorros anuales para ADA y ETN de 19.784??y 38.271 ??respectivamente. El coste neto, es decir, el ahorro que esto supuso en el horizonte temporal considerado (dos años) ascendió a 116.110 ?. El análisis de sensibilidad realizado mostró que el MIP estimado para el periodo de estudio fue muy robusto ya que el resultado neto en diferentes escenarios apenas variaba, manteniéndose negativo en los nuevos escenarios. Conclusiones: La ampliación de los intervalos de administración de ADA y ETN cada tres semanas y dos semanas respectivamente, sería una estrategia que permitiría generar ahorros en el presupuesto hospitalario cercanos a los 116.110 ??en el horizonte temporal considerado, consiguiendo así una optimización del tratamiento con estos fármacos.

Hyperhidrosis related to nevirapine therapy.

A 70-year-old white man presented to the internal medicine outpatient clinic with symptoms of significant hyperhidrosis. He had been started on antiretroviral therapy (ART) with tenofovir, lamivudine and nevirapine. The patient complained of excessive sweating following severe asthenia after taking nevirapine. Based on these findings, we suspected that the causative agent was nevirapine and a diagnosis of hyperhidrosis due to nevirapine was made. Nevirapine treatment was stopped and was substituted with efavirenz: the patient continued on therapy with tenofovir and lamivudine. The hyperhidrosis symptoms resolved in 2-3 days. No relapse was observed with the new ART regimen. Drugs that induce hyperhidrosis can cause patient discomfort and embarrassment. In our patient, this adverse drug reaction also caused severe asthenia that decreased the patient's physical and emotional quality of life. There was a temporal relationship between the developments of symptoms and starting nevirapine therapy. Once nevirapine was suspended and switched to efavirenz, excessive sweating resolved. An objective causality assessment revealed that the adverse effect was probable. Until further data are available, clinicians should consider discontinuation of nevirapine therapy in patients who develop severe hyperhidrosis.

Imipenem-induced Clostridium difficile diarrhea in a patient with chronic renal failure.

An 80-year-old man was diagnosed to have pneumonia and advanced chronic kidney disease. He presented with anuria and hemodialysis, by temporary femoral catheter, was initiated. He was empirically treated with imipenem/cilastatin 500 mg/24 h after hemodialysis. After 10 days of antibiotic intake, he developed severe diarrhea. Diagnosis of Clostridium difficile (CD)-associated diarrhea was confirmed by detection of the toxins A and B in his stool. Imipenem therapy was discontinued; Vancomycin 500 mg orally every 6 h and 1000 mg per rectum every day was added. After two weeks of this treatment, the patient reported complete resolution of the diarrhea and stool samples were negative for Clostridium toxin. In this case, the most possible cause of CD colitis was considered to be imipenem because of the temporal relationship between exposure to the drug and onset of symptoms.

Foot ischaemia and toe skin necrosis associated with interleukin-2 infusion in an HIV-infected patient.

A 39-year-old white man developed a severe left toe foot ischaemia and toe skin necrosis following his 12 courses of interleukin (IL)-2 (4.5 MIU twice a day, subcutaneously) for five days every two months. He had no known general risk factors for thrombosis other than HIV infection. An arterial Doppler ultrasound examination of the leg confirmed the permeability of the posterior tibial artery and its digital pulse. A diagnosis of foot ischaemia and toe skin necrosis was made. The suspected causative agent was IL-2 since this was the only drug that the patient was taking before the symptoms appeared. The patient was empirically treated with an aspirin and pentoxifylline in order to improve local microcirculation. We observed a satisfactory response with a quick resolve of skin lesions. The most possible cause of foot ischaemia and toe skin necrosis was considered to be IL-2 because of the temporal relationship between the exposure to the drug and onset of symptoms. Based on the Naranjo probability scale, IL-2 could be considered the probable cause of the foot ischaemia and toe skin necrosis. If clinical evaluation leads to the suspicion of ischaemic process, therapy with IL-2 should be discontinued immediately.

Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection.

HIV-infected patients have a higher risk of developing cutaneous reactions than the general population, which has a significant impact on patients' current and future care options. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. HIV-infected patients just at the beginning of antiretroviral treatment can frequently show a wide variety of adverse drug effects such as drug rashes, hyperpigmentation, hair loss, hypersensitivity reactions, injection site reaction, urticarial reaction, erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome. The early detection and treatment of cutaneous adverse drug reactions, plus identification of the causative agent, are essential to prevent the progression of the reaction, preventing additional exposures and ensuring the appropriate use of medications for the current condition and keeping in mind others, such as patient age. This article emphasizes the most common features of an antiretroviral drug-induced cutaneous reaction from protease inhibitors, non-nucleoside analogue reverse transcriptase inhibitors, fusion inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors and inhibitors of the CCR5 chemokine receptor, paying special attention to the newest drugs approved for the treatment of HIV infection, such as tipranavir, darunavir, etravirine, enfuvirtide, raltegravir and maraviroc.

Exacerbation of psoriatic skin lesions in a patient with psoriatic arthritis receiving adalimumab.

OBJECTIVE: To report a case of a patient with psoriatic arthritis (PsA) receiving adalimumab, who developed an exacerbation of palmoplantaris pustulosa psoriasis. CASE SUMMARY: A 38-year-old woman diagnosed with PsA had received treatment with non-steroidal antiinflammatory drugs. Two months prior to admission, the patient had a Disease Activity Score of 3.8; diclofenac therapy was suspended and physicians considered treatment with adalimumab. Chest X-rays were normal and the tuberculin skin test was negative. Treatment with adalimumab was started. After the third dose of adalimumab, the patient developed an exacerbation of psoriatic skin lesions on palms and soles. The clinical course was consistent with an exacerbation of palmoplantaris pustulosa psoriasis. Adalimumab treatment was suspended. The patient was treated with oral methotrexate 2.5 mg once weekly. One month after methrotexate was started, the patient developed a severe alopecia. Methrotexate therapy was suspended. Three months later, the patient continued with psoriatic skin lesions on palms and soles. Treatment with Psoralen and ultraviolet A therapy was initiated and the patient condition improved without occurrence of psoriatic skin lesions in the next 4 months. DISCUSSION: Cases of worsening or exacerbation of psoriatic skin lesions induced by anti-tumour necrosis factor (TNF) agents in patients diagnosed PsA are infrequently described in the literature. The most likely cause of the exacerbation of palmoplantaris pustulosa psoriasis in this case was considered to be adalimumab because of the close temporal relationship between exposure to the drug and onset of symptoms. Adalimumab was the only identifiable precipitant that the patient encountered before the exacerbation of psoriasis developed. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered probable. CONCLUSIONS: Patients initiated on adalimumab therapy should be closely monitored for the development of exacerbation of psoriasis. Clinicians should be aware of this rare adverse effect of this anti-TNF drug.

Septic shock and community-acquired pneumonia associated with etanercept therapy.

OBJECTIVE: To report a case of septic shock and community-acquired pneumonia in a patient with psoriatic arthritis receiving treatment with etanercept. PATIENT DETAILS: A 65-year-old woman diagnosed as having psoriatic arthritis had received treatment with etanercept. Chest X-ray studies were normal and the tuberculin skin test was negative. Two months after etanercept therapy, the patient presented to our emergency department with fever, cough, chest pain and generalized weakness. Chest radiography revealed a right pulmonary infiltrate. Her condition rapidly deteriorated and she went into shock with a further drop in her blood pressure, tachycardia and tachypnea. She was intubated, mechanically ventilated and was treated with fluids, cardioversion and amiodarone. Empiric therapy with levofloxacin, amikacin and cefepime were initiated. In the urinalysis, the result of a rapid test for Streptococcus pneumoniae was positive. Etanercept treatment was suspended due to a possible adverse reaction associated with this drug. At the start of therapy her clinical condition improved slowly. On Day 28, the patient was afebrile and she was discharged from the intensive care unit. DISCUSSION: Most of the infections associated with etanercept therapy have been reported in patients with rheumatoid arthritis. Based on our observations, etanercept was the possible offender in the development of septic shock and respiratory failure in community-acquired pneumonia. There was a temporal relationship between exposure to the drug and onset of symptoms. Etanercept was the only drug administered before the septic shock developed. Based on the Naranjo algorithm, the adverse reaction could be considered possible. CONCLUSION: Patients initiated on etanercept should be counseled and receive appropriate screening before drug initiation. All febrile and newly occurring concomitant illnesses should be promptly evaluated. General practitioners should discontinue etanercept treatment and institute prompt and aggressive intervention if infection develops.

Successful desensitization protocol for hypersensitivity reactions caused by oxaliplatin.

OBJECTIVE: To report the successful desensitization of a patient with a hypersensitivity reaction to oxaliplatin. CASE SUMMARY: A 57-year-old woman with metastatic colon cancer was receiving oxaliplatin, fluorouracil and leucovorin every 2 weeks and showed a partial response to therapy. During the fourth cycle, an anaphylactic reaction with palpitations and rash occurred. The patient was hypotensive with mild pulmonary wheezing. Since oxaliplatin was the probable cause of the hypersensitivity reaction, therapy with this drug was discontinued. Therapy in the patient was continued using cetuximab and irinotecan but this resulted in progression of the cancer. In view of the initial satisfactory response to the oxaliplatin-based regimen, it was decided to attempt desensitization to oxaliplatin using a protocol adapted from carboplatin regimens. The desensitization procedure was successful and the patient subsequently tolerated an additional three cycles using this regimen without further symptoms of hypersensitivity. DISCUSSION: In cases with moderate-to-severe reactions to oxaliplatin, reexposure is not usually considered. However, a need to use first-line therapy when there is recurrence of the cancer has encouraged the development of rapid desensitization procedures which allow patients to be treated with medications to which they have previously shown hypersensitivity reactions. A combination of premedication using intravenous dexamethasone and a desensitization regimen was designed which was used successfully to increase concentrations and flow rates of oxaliplatin. CONCLUSIONS: Hypersensitivity reactions to oxaliplatin are not rare and physicians need to be aware of these. When substitution of another antineoplastic drug is not feasible, oxaliplatin desensitization should be considered even when hypersensitivity reactions to oxaliplatin are severe.

Possible delayed onset of osteonecrosis of the jaw in association with zoledronic acid.

OBJECTIVE: To report a case of possible delayed-onset osteonecrosis of the jaw after treatment with zoledronic acid. CASE SUMMARY: A 53-year-old white man with no history of allergic drug reactions had been diagnosed as having bronchial epidermoid carcinoma. He received therapy with docetaxel and zoledronate. Because of metastatic progression of the disease, he started treatment with irinotecan and zoledronate. The patient received 18 monthly cycles of zoledronate. One year after the last cycle of bisphosphonate therapy, the patient had one tooth extracted. Three weeks later, he complained of continuous mandibular pain and swallowing difficulties. A diagnosis of osteonecrosis of the jaw was made. Surgical treatment was chosen, with debridement and a mucosal flap, complemented with antibiotic therapy. Other potential aetiologic risk factors for osteonecrosis were investigated and could not be identified. Accordingly, a diagnosis of possible delayed onset jaw osteonecrosis associated with zoledronate was made. DISCUSSION: Osteonecrosis of the jaws has recently emerged as a potential complication of bisphosphonate therapy in patients with metastatic cancer undergoing dental surgery. This is the first report of possible delayed-onset osteonecrosis of the jaw associated with zoledronate. Patients appear to remain at low risk of developing osteonecrosis even in the absence of zoledronate, especially after a dental extraction or oral surgery. Based on the Naranjo algorithm the adverse reaction was classed as possible.

Possible macular exanthema associated with linezolid therapy.

OBJECTIVE: To report a case of macular exanthema associated with linezolid therapy. CASE SUMMARY: A 54-year-old white man diagnosed as having laryngeal epidermoid carcinoma attended our emergency department because of fatigue, fever, neck pain and a fistulized fixed mass in the right side of the neck with purulent exudation. Treatment with amoxicillin/clavulanic acid 875 mg/125 mg p.o. every 8 hours as empirical therapy was started. Cultures of the exudates from the fistula confirmed the presence of methicillin-resistant Staphylococcus aureus (MRSA). Amoxicillin/clavulanic acid was discontinued and therapy was started with linezolid 600 mg p.o. every 12 hours but 5 days after commencing linezolid the patient came to our emergency room because of generalized erythematous macular eruptions. A diagnosis of severe and generalized macular exanthema induced by linezolid was made. Administration of linezolid was suspended and there was an improvement in the skin lesions and general state of health. The patient was discharged without further symptoms. DISCUSSION: In this case, there was a close temporal correlation between drug exposure and the onset of symptoms. When linezolid was discontinued, the skin lesions resolved quickly and the general condition of the patient improved. Furthermore, linezolid was the only drug added before the cutaneous lesions appeared. It is possible that the adverse reaction was associated with administration of amoxicillin/clavulanic acid. However, the patient had been treated with this antibiotic previously without appearance of any cutaneous reaction. An objective causality assessment revealed that an adverse effect was possible. CONCLUSION: Based on our observations, we conclude that linezolid was the most likely cause of the adverse reaction. Clinicians should be aware of this infrequent but severe reaction.

[Assessment of quality as perceived by users of an outpatient pharmaceutical care unit]. / Evaluación de la calidad percibida por los usuarios de una unidad de atención farmacéutica a pacientes externos.

OBJECTIVE: To assess quality of care by an Outpatient Pharmaceutical Care Unit (OPCU) from patient satisfaction regarding the unit s premises and activities. METHOD: A transversal study performed at the OPCU using a patient survey. Patient opinions were obtained regarding structural aspects, pharmaceutical care, patient information, overall satisfaction, and preference for care in the OPCU or pharmacy office. The response variable was the presumed choice for the OPCU or traditional pharmacy office. A multivariate analysis using logistic regression was used to evaluate the independent effect of variables. RESULTS: In all, 256 surveys were administered, of which 195 were assessable. Response rate was 76%. Responses with highest scores included communication and interaction with professionals (4.8 points on average) and care received (4.5 points). Worst assessments included OPCU s timetable (3.8 points) and location (3.9 points); 98.4% of patients were satisfied or very satisfied with care received, and only 18.4% would switch to the pharmacy office if allowed to. The multivariate analysis suggested that variables associated with the pharmacy office choice included a negative rating of OPCU s location (OR 9.8, CI 1.3-76.8) and a negative rating of information delivered (OR 4.1, CI 1.7-9.8); p < 0.05. CONCLUSIONS: Information received and OPCU s location had the greatest impact on patient satisfaction. Patient remarks and suggestions were very useful to identify areas of improvement, and to introduce modification suiting their views.

Acute renal failure associated with an accidental overdose of colchicine.

CASE SUMMARY: A 47-year-old man with a history of polyarticular gout was admitted to the nephrology service because of severe renal insufficiency (creatinine 6.25 mg/dl). Three days before admission he had a pain crisis in his knees and ankles and self-administered 20 x 1 mg granules of colchicine p.o. over a period of 4 - 5 hours together with six suppositories each containing 100 mg of indomethacin. The patient began vomiting within 24 hours, experienced diarrhea which persisted for three days and then came to the hospital. The patient reported oliguria during the preceding 24 hours. In hospital, attempts to correct water and electrolyte balance were initiated. The patient became stabilized hemo-dynamically, the diarrhea disappeared within 24 hours, diuresis resumed and the renal function progressively improved. Leukopenia and thrombopenia were diagnosed, the transaminases increased: AST = 79 U/l, ALT = 132 U/l on the eighth day after taking the colchicine. The serology for hepatitis A, B, C and HIV viruses was negative; the serology for CMV and VEB revealed a previous infection. After being discharged from hospital 11 days after admission, the patient presented with the following parameters: hematocrit 39%, leukocytes 5,920/microl (3 470 neutrophils), prothrombin time 13 seconds, urea 44 mg/dl, creatinine 1.29 mg/dl, AST 16 U/l and ALT 35 U/l. DISCUSSION: The patient mistakenly ingested 20 mg ofcolchicine p.o. (0.22 mg/kg). The intoxication was associated with gastroenterocolitis, dehydration and renal failure during the first three days after ingestion. The patient also developed leukopenia, thrombopenia and mild hepatocellular injury. Renal failure due to colchicine intoxication is due to various factors such as depletion of volume/hypotension, rhabdomyolysis and multiorgan failure. In this case, the hypovolemia was probably the fundamental cause of the acute renal insufficiency as demonstrated by the quick recovery after administering fluids. It is possible that indomethacin may have enhanced the toxic effect of colchicine on the kidneys and bone marrow. Some colchicine intoxications, as in this case, are caused by an error in interpreting the dose for treating an acute attack of gout. A way to prevent these errors would be to use a low-dose treatment protocol.

Unsuspected rhabdomyolysis associated with phenytoin.

CASE SUMMARY: A case of rhabdomyolysis, in which the etiology could be associated with phenytoin administration is presented and guidelines are described which may assist the early recognition, treatment and prevention of renal failure when such patients are treated in intensive care units. A 46-year-old white man experienced a generalized tonic-clonic seizure at home lasting approximately two minutes. The patient presented with similar crises when seen by the emergency services and had a neurological status of seven points on the Glasgow scale. He was intubated orotracheally and mechanically ventilated. Administration of a 1,250 mg loading dose of phenytoin in 250 ml 0.9% sodium chloride injection were administered intravenously according to guidelines approved by the hospital. These require administration of the loading dose over 30 - 60 minutes followed by phenytoin 150 mg/8 h i.v. administered as a drip diluted in 0.9% NaCl 50 ml over 30 - 60 minutes. Obtained plasma levels were within the therapeutic range but on Day 3 the level of creatine kinase (CK) increased. We initiated treatment to prevent renal failure but the level doubled daily reaching a peak of 54,000 U/I on the fifth day. It was suspected that the increase in CK was due to the treatment with phenytoin which was stopped and replaced by valproic acid 500 mg/8 h orally. The cumulative total dose of phenytoin was 3,050 mg. The subsequent serial determinations of CK showed a decrease beginning on the day phenytoin was stopped and levels falling to 14,229 U/l on the day the patient left the ICU. The patient had no recurrence of the convulsive episodes after the day of admission. In the neurology ward, the patient recovered satisfactorily and the CK value gradually returned to normal. The patient was asymptomatic when released on the ninth day. DISCUSSION: The most likely cause of the rhabdomyolysis was phenytoin treatment because of the close temporal relationship between exposure to the drug and onset of symptoms and the rapid resolution of the symptoms and signs after phenytoin was discontinued. An objective causality assessment concluded that a possible adverse drug reaction had occurred.

[Drug therapy for corneo-conjunctival neoplasm]. / Tratamiento farmacológico de la neoplasia corneal y conjuntival.

BACKGROUND: The goal of therapy for corneo-conjunctival neoplasm is lesion removal, with the most widespread procedure being complete tumor resection with or without associated chemotherapy lines. As this sort of procedure entails a high relapse rate (9-52%) the use of adjuvant therapies to reduce the occurence of relapse becomes a need. The administration of a number of topically administered drugs has been used for adjuvant therapy, including mitomycin C, 5-fluorouracil and interferon a 2b. OBJECTIVE: To determine the clinical experience published regarding the effectiveness of the various drug therapies for cor-neo-conjunctival neoplasm. SEARCH STRATEGY: Information reported on this topic in the Medline database (1966-2004) was searched using corneo-conjunctival neoplasm, 5-fluorouracil, mitomycin C, and interferon ca2b as key words. SELECTION CRITERIA: All papers quoting dosage for drugs used,treatment length, adverse effect development, and clinical response obtained were included. PRIMARY RESULTS: Papers reporting the use of 5-fluorouracil re few when compared to those quoting other drugs, with a response rate of 88% and a relapse rate of 20%. The use of mitomycin C is widely described in the medical literature with a response rate of 90% and a relapse rate of 13%, but in association with the development of adverse effects in a high percentage of patients. Interferon ca 2b is the last drug to be incorporated in the treatment of these ocular lesions, with a response rate of 100% and a low incidence of adverse effects, with a relapse rate of 4%. CONCLUSIONS: Mitomycin C is an effective drug, but its use is associated with a high number of adverse events, some of which may lead to therapy discontinuation. Interferon ct 2b has efficacy outcomes comparable to mitomycin C and a lower incidence of adverse effects, which are mostly mild in nature. The use of 5-fluorouracil is relegated to a second-tier status.