Trametinib and dabrafenib induced rhabdomyolysis, renal failure, and visual loss. Report of one case

ABSTRACT MEK- and BRAF-inhibitors trametinib and dabrafenib are successfully used for BRAF-mutated, metastasizing melanoma, but these compounds may induce side effects. We report a 50 years old female with BRAF-mutated metastasizing melanoma who received trametinib (2 mg/d) and dabrafenib (200 mg/d) after using interferon without benefit. Shortly after starting trametinib/dabrafenib, she experienced an inability to abduct the left eye. Eight days after starting this therapy the patient experienced loss of appetite, vomiting, diarrhea, vertigo, and fever of 40°C. Two days later she experienced visual loss, requiring permanent support for her daily activities. Two further days later myoglobinuria appeared in the absence of myalgias or muscle weakness but accompanied by marked tiredness and inactivity. She could not eat or drink during four days prior to admission. The patient suspected an adverse effect of trametinib/dabrafenib and discontinued it 2 days prior to admission. Thereafter, she experienced an almost complete remission of the deficits except for ocular muscle weakness and visual impairment.

Los inhibidores de MEX and BRAF como trametinib y dabrafenib se usan en el melanoma metastásico con mutación BRAF, pero pueden tener efectos secundarios. Informamos una paciente de 50 años con un melanoma metastásico con la mutación BRAF que recibió trametinib (2 mg/día) y dabrafenib (200 mg/día) después de usar interferón sin beneficio. Después de iniciar esta terapia la paciente notó una incapacidad de abducir el ojo izquierdo. Ocho días después de iniciar el tratamiento, tuvo falta de apetito, vómitos, diarrea, vértigo y fiebre de 40°C. Dos días después notó pérdida de su agudeza visual, requiriendo asistencia para efectuar sus actividades de vida diaria. Dos días después apareció coluria, en ausencia de mialgias o debilidad muscular, pero acompañadas de fatiga. Ella no pudo comer o tomar líquidos por cuatro días antes de ingresar al hospital. La paciente sospechó que estaba experimentando efectos secundarios de los medicamentos y los suspendió dos días antes del ingreso, experimentando una casi completa remisión de sus síntomas, con excepción de la debilidad de musculatura ocular y déficit visual.

Combined influence of illness duration and medication type on visual sensitivity in schizophrenia

Objective: Patients with schizophrenia have visual processing impairments. The main findings from the literature indicate that these deficits may be related to differences in paradigms, medications, and illness duration. This study is part of a large-scale study investigating visual sensitivity in schizophrenia. Here we aimed to investigate the combined effects of illness duration and antipsychotic use on contrast sensitivity function. Methods: Data were collected from 50 healthy controls and 50 outpatients with schizophrenia (classified according to illness duration and medication type) aged 20-45 years old. The contrast sensitivity function was measured for spatial frequencies ranging from 0.2 to 20 cycles per degree using linear sine-wave gratings. Results: Patients with an illness duration > 5 years had more pronounced deficits. Differences in the combined effects of illness duration and antipsychotic use were marked in patients on typical antipsychotics who had been ill > 10 years. No significant differences were found between typical and atypical antipsychotics in patients with an illness duration < 5 years. Conclusion: Visual impairment was related to both long illness duration and medication type. These results should be tested in further studies to investigate pharmacological mechanisms.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment

OBJECTIVES: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. METHOD: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients’ outcomes were analyzed. ClinicalTrials.gov: NCT00979290. RESULTS: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. CONCLUSIONS: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used. .

Miopia aguda e hipertensão intraocular após uso de topiramato / Acute miopia and intraocular hypertension after topiramate use

A migrânea acomete cerca de 6% a 7% dos homens e 18% a 20% das mulheres, principalmente entre 25 e 55 anos de idade, e é responsável por enorme impacto na atividade produtiva. O topirama-to é um das drogas antiepilépticas aprovadas pela Food and Drug Administration (FDA), sendo usado para a prevenção da migrânea. É uma droga segura, mas não isenta de efeitos adversos. Embora alterações oftalmológicas causadas pelo uso dessa medicação não sejam comuns, aqui é relatado um caso de uma paciente que, ao procurar profilaxia para as crises de migrânea, apresentou efeito adverso ocular, o qual, se não fosse reconhecido em tempo hábil, causaria efeitos maiores e mais danosos à paciente.

Migraine affects approximately 6% and 7% of men and 18% and 20% of women mainly between 25 and 55 years old, responsible for its enormous impact on productive activity. Topiramate is one of the Food and Drug Administration (FDA) approved antiepileptic drugs used for migraine prevention. It is a safe drug but not without side effects. Although ophthalmologic changes caused by this medication are not common, here is reported a case of a patient looking for pro-phylaxis of migraine attacks exhibited an ocular adverse effect, and if not recognized in due time, larger and more harmful effects could be inflicted to the patient.

Cystoid macular edema and visual loss as sequelae to interferon alpha treatment of systemic hepatitis C.

Hepatitis C virus infection and interferon treatment may be associated with retinopathy but visual function is generally unaffected. This paper reports the rare occurrence of unilateral macular edema with visual loss. We present an interventional case report with fundus photograph and optical coherence tomography (OCT). A 48-year-old white male with hepatitis C, treated with a six-month course of pegylated interferon alpha and ribavirin, complained of gradual reduction in the vision of his left eye. Visual acuities were 20/16 right and 20/400 left with clinical examination and OCT confirming cystoid macular edema.This report shows that cystoid macular edema may rarely occur in association with hepatitis C infection and/or interferon therapy. Physicians and ophthalmologists should be alert to this potential but infrequent association as the resultant visual loss is a significant potential complication that should be discussed when obtaining informed consent for interferon treatment.

Ocular toxicity by latex of Calotropis procera (Sodom apple).

We report the spectrum of ocular toxicity following accidental inoculation of latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and December 2006. All patients presented with sudden painless dimness of vision with photophobia. Twenty-five (86%) patients had initial visual acuity of less than 20/60. All eyes had conjunctival congestion and mild to severe corneal edema with Descemet's folds. Three (10%) eyes had an epithelial defect, nine (31%) had iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic saline and tears supplements, 27 (93%) eyes recovered completely within 3-14 days. After three months, 17 (74%) out of 23 eyes showed a significant low endothelial cell count compared to the normal fellow eye ( P 0.001). The latex of Calotropis procera causes significant ocular morbidity which may be preventable by simple health education. The long-term effect on corneal endothelium has to be studied further.

Vigabatrin and Visual Field Defects in Pediatric Epilepsy Patients

We studied the prevalence, type and severity of vigabatrin (VGB)-attributed visual field defects (VFDs), and used these data to assess the associated risk factors in pediatric patients. Medical records were retrospectively reviewed for 67 pediatric patients who received VGB alone or in combination with other antiepileptic drugs, and who had undergone visual field examinations using a Humphrey visual field analyzer. Of the 67 patients, 15 had VGB-attributed VFDs: 13 had nasal arcuate type, 1 had nasal and temporal constricted type and 1 had nasal constricted type. In terms of severity, 7 patients had Grade I VGB-attributed VFDs, 5 had Grade II, 2 had Grade III, and 1 had Grade IV. Although there were no significant differences between the VFD and non-VFD groups with regards to all tested parameters, there were no cases of VGB-attributed VFDs in patients with total treatment durations <2 yr and cumulative doses <10 g/kg. In conclusion, the prevalence of VGB-attributed VFDs in VGB-treated pediatric epilepsy patients was 22%. The high frequency of VGB-attributed VFDs indicates that physicians should inform all patients of this risk prior to VGB treatment and perform periodic visual field examinations.