Time-Dependent and Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Converted from Tacrolimus to Sirolimus Regimens.

STUDY OBJECTIVE: To evaluate the safety and tolerability of immunosuppressive drugs used in a planned randomized conversion from a calcineurin inhibitor, tacrolimus, to a mammalian target of rapamycin inhibitor, sirolimus, in de novo kidney transplant recipients. DESIGN: Prospective safety analysis of data from a prospective, randomized, open-label, controlled study. PATIENTS: A total of 119 adult kidney transplant recipients who received tacrolimus (TAC), mycophenolate sodium (MPS), and prednisone between February 2008 and May 2010; after 3 months of this regimen, 60 of these patients were randomized to conversion from TAC to sirolimus (SRL/MPS group), and 59 patients continued with the TAC regimen (TAC/MPS group). MEASUREMENTS AND MAIN RESULTS: Both groups were followed for 24 months after transplantation for immunosuppressive regimen-associated and time-dependent occurrences of adverse events (AEs) and serious adverse events (SAEs). Before conversion from TAC to SRL, the cumulative incidence of AEs was 98%; 25% were SAEs. Gastrointestinal AEs (66%) and infections (58%) were the most frequent AEs. The incidences of TAC and MPS dose reductions due to AEs were 1.7% and 12%, respectively. After conversion, no significant differences were noted in the SRL/MPS group versus the TAC/MPS group in the cumulative incidences of AEs (100% vs. 98%) and SAEs (27% vs. 30%). The most common AEs were gastrointestinal (70% vs. 54%, p=0.23) and infection (77% vs. 73%, p=0.79) in the SRL/MPS versus TAC/MPS groups. The incidence of aphthous ulcer (28% vs. 0%, p=< 0.01), sinusitis (10% vs. 0%, p=0.01), dermatitis (15% vs. 3%, p=0.03), and dyslipidemia (35% vs. 14%, p=0.02) were higher in the SRL/MPS group compared with the TAC/MPS group. Cox proportion regression analysis showed a higher relative risk for gastrointestinal (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.2-3.01, p<0.05) and skin and subcutaneous tissue (HR 2.5, 95% CI 1.1-4.1, p<0.05) AEs in the SRL/MPS group compared with the TAC/MPS group. AE-related dose reductions occurred in 18.3% of patients receiving SRL and 3.3% of patients receiving TAC. MPS dose reductions due to AEs occurred in 11.7% of patients receiving SRL and 13.6% of patients receiving TAC. CONCLUSION: SRL/MPS treatment was associated with a time-dependent higher incidence of gastrointestinal and skin and subcutaneous tissue AEs, which occurred mainly during the first 6 months after conversion from TAC/MPS. Although the treatments with SRL or TAC after 3 months of transplantation showed different safety profiles, both regimens demonstrated adequate tolerability, with low rates of early discontinuation related to AEs.

Progression of drug exanthemas to serious drug eruptions: A retrospective review identifying early determinants.

BACKGROUND/OBJECTIVES: Maculo-papular drug exanthema (MPE) is the most common type of cutaneous adverse drug reaction (CAR). Exanthematous macules and papules may also be the initial presentation of severe CAR (SCAR). We aimed to identify characteristics associated with the diagnosis of SCAR in CAR-hospitalised patients. METHODS: This cross-sectional study was performed in a tertiary hospital in Chile. All CAR patients who were initially evaluated for exanthematous macules and papules were assessed for clinical, laboratory and pathological variables and these were contrasted with MPE or SCAR diagnosis at discharge. RESULTS: We enrolled 86 patients, of whom 25 (29%) had an at-discharge diagnosis of SCAR. SCAR patients were younger and the latency (time from starting drug to development of first skin lesions) was longer than in MPE patients: 43.6 ± 18.7 years versus 54.0 ± 21.8 years (P = 0.039) and 14 days; range 1 to 35, versus 7 days; range 1 to 45 (P = 0.001). The presence of cutaneous pain (OR 7.4 95% CI 1.3-41), mucosal involvement (OR 9.5 CI 95% 2.6- 34.5) and anticonvulsant use (OR 6.11 95% CI 1.91-19.53) were significantly associated with SCAR at discharge. Antibiotics use was significantly associated with MPE diagnosis (OR 2.8 95% CI 1.1-7.6). These six variables together explain 45% of the risk of having SCAR (R2 = 0.449). None of the early laboratory or pathological variables was associated with SCAR. CONCLUSIONS: In hospitalised patients assessed for exanthematous macules and papules, the evaluation of these clinical features may aid in the early identification of SCAR cases.

Drug eruptions in the elderly.

Because the older group of the population is becoming more numerous, we see a high prevalence in drug adverse reactions among the elderly. Polypharmacy, which is the use of five or more medications, is one reason why this group has a greater risk of adverse drug reactions. Cutaneous adverse reactions to drugs are not always life threatening, but they can be an important factor for a poor quality of life among older patients. The potential benefits of appropriately prescribed medications are unquestionable, but the possibility of an adverse reaction must be recognized and prevented in older people so they can have a better quality of life.

Risk of skin reactions when using ibuprofen-based medicines.

Adverse reactions to drugs are a frequent cause of morbidity and medical consultation; it is no surprise that nonsteroidal anti-inflammatory drugs (NSAIDs) run second, after antibiotics, mainly of the beta-lactam group (penicillins and cephalosporins). Numerous clinical pictures involving the skin--various morbilliform rashes, urticaria and angioedema as the most common--due to hypersensitivity to a particular NSAID (i.e., ibuprofen) have been described; other clinically defined skin diseases such as vasculitis, Steven-Johnson's syndrome, photosensitivity, fixed drug eruptions, livedo-like dermatitis, linear drug eruption, lichenoid drug eruption, exanthematous pustulosis, eczematous eruption, contact dermatitis and pemphigoid have received the attention of physicians. Extensive use around the world makes it interesting to investigate adverse cutaneous reactions to ibuprofen and other members of the propionic acid derivative group, to ascertain their prevalence, clinical presentation and prevention. This paper presents a review of published literature concerning cutaneous hypersensitivity reactions to ibuprofen and related arylpropionic acids.

Farmacodermias / Drug eruptions

Os autores fazem uma revisão bibliográfica da fisiopatogenia, diagnóstico e principais expressões dermatológicas das erupções cutâneas provocadas por drogas, bem como seu tratamento

Dermatitis livedoide de Nicolau / Livedoid dermatitis of Nicolau

Se presentan dos casos de dermatitis livedoide de Nicolau, necrosis cutánea secundaria a una inyección intrarterial accidental. Las drogas involucradas en estos casos son ampicilina benzatínica y un derivado pirazolónico. Asimismo comentamos las distintas teorías patogénicas y los diferentes diagnósticos diferenciales que podrían plantearse

Dermatitis livedoide de Nicolau / Livedoid dermatitis of Nicolau

Se presentan dos casos de dermatitis livedoide de Nicolau, necrosis cutánea secundaria a una inyección intrarterial accidental. Las drogas involucradas en estos casos son ampicilina benzatínica y un derivado pirazolónico. Asimismo comentamos las distintas teorías patogénicas y los diferentes diagnósticos diferenciales que podrían plantearse (AU)