Etoricoxib/methotrexate interaction

Abstract

Various toxicities: case report A 48-year-old man developed acute methotrexate toxicity in the form of pancytopenia, ulcerations, nausea, vomiting, diarrhoea, worsening of chronic plaque psoriasis and worsening of renal function following concomitant administration of methotrexate for chronic plaque psoriasis and etoricoxib for arthralgia [routes not stated]. The man was admitted to the emergency department with chief complaints of extensive oral and genital erosions, intermittent fever and ulcerations (both type 1 and 2) over the red, scaly lesions on palm and soles for duration of 5 days. His medical history was significant for arthralgia involving the lower back, bilateral shoulder and knee joints for the last 5 years, for which he had been receiving treatment with etoricoxib 90mg daily for the same duration. He also had hypertension, diabetes and hypertensive nephropathy, and he was not compliant to his treatment. He also had chronic plaque psoriasis for 4 years. He had been receiving unspecified steroids and emollients for skin lesions. Eight days prior to his admission, he received a single dose of methotrexate 15mg as advised by a private practitioner. Three days after the methotrexate therapy, he developed fissures and erosions over existing plaques as well as oral and genital erosions along with fever. On admission, clinical examination revealed body temperature of 100.5°C, BP 190/100mm Hg and pulse rate of 112 /minute. The mucocutaneous examination showed multiple well-defined, scaly, erythematous plaques with surface showing erosions and fissures over scalp, palms, legs, thighs, soles, dorsum of toes and posterior aspect of left forearm involving a body surface area of approximately 8%. Additionally, he also developed erosions and ulcers on the penile shaft, scrotum and perineal area. Oral mucosa had multiple discrete erosions present on the lips, buccal and gingival mucosa and over the tongue with reduced mouth opening, pain and crusting. Additionally, nail changes including onychomadesis, distal onycholysis, leukonychia, pitting, oil drop sign, subungual hyperkeratosis, loss of nail folds and eroded cuticles were present in multiple nails, and these were more pronounced in toenails. Based on the clinical presentation, a diagnosis of acute methotrexate toxicity in the form of pancytopenia, ulceration and worsening of chronic plaque psoriasis was made. The routine laboratory testing revealed the following: total RBC count 2.45 x 105 /mm3, haemoglobin 5.7 g/dL, total leukocyte count (TLC) 0.7 x 103 /mm3, platelet count 1.12 lac /mm3, absolute neutrophil count 420 /mm3, serum urea 119 mg/dL, serum uric acid 6.5 mg/dL and serum creatinine 4.81 mg/dL. The man was treated with filgrastim, folinic acid and cilnidipine [clinidipine]. He also received IV fluids for decreased oral intake. Due to the development of neutropenic fever, he was treated with cefoperazone/sulbactam and linezolid. On the next day, his haemoglobin and leukocyte count level further dropped. Therefore, he received one unit of whole blood. Subsequently, his creatinine levels worsened to 5.19 mg/dL. As a result, worsening of renal function was considered. Therefore, he was treated with sodium chloride [normal saline] along with urine alkaliser. On admission day 3, he developed multiple episodes of diarrhoea, nausea and vomiting. Therefore, he was treated with ondansetron in addition to the prior treatment. A single unit whole blood transfusion was also performed due to persistent low blood counts. On admission day 5, an improvement in TLC count and renal functions were noted; however, platelet count further dropped. Therefore, he received one unit of platelet concentrate. Additionally, he had significantly low albumin levels, which required treatment with albumins. Subsequently, his general condition, blood counts and mucocutaneous erosions started improving along with increased oral intake. Therefore, filgrastim and folinic acid were stopped after 5 days of administration. On admission day 8, he was transfused with one more unit of whole blood due to low haemoglobin count. After 12 days of hospital stay, he was discharged with significant improvement in mucocutaneous lesions along with renal functions and normal blood counts. On follow-up 2 weeks later, he was clinically stable with almost all the erosions healed. His renal function and blood count tests were found to be within normal range. It was considered that he developed acute methotrexate toxicity in the form of pancytopenia, ulcerations, nausea, vomiting, diarrhoea, worsening of chronic plaque psoriasis and worsening of renal function following pharmacokinetic interaction between methotrexate and etoricoxib.