Promethazine Methylenedisalicylate

A 78-year-old woman visited a local clinic because of cough and fever, and was prescribed levofloxacin, carbocisteine, and cold medicine (salicylamide, acetaminophen, anhydrous caffeine, promethazine methylene disalicylate). The following day, erythema appeared on the trunk, and spread. Multiple pustules independent of hair follicles developed on the erythema mainly in the skin folds. Histopathological examination revealed subcorneal pustular dermatosis. The clinical course and characteristics of the rashes led to a diagnosis of acute generalized exanthematous pustulosis (AGEP). Although the administration on levofloxacin, carbocisteine, and cold medicine were discontinued, the rashes recurred. We reviewed the patient's history, and found that she had a history of taking the over-the-counter drug Kerorin, and had taken a dose of Kerorin on the day before the first examination and before the recurrence. The ingestion of Kerorin was regarded as an incidental oral administration test, which was positive. Thus, oral administration tests with Kerorin and its ingredients acetylsalicylic acid and anhydrous caffeine were positive, leading to a diagnosis of AGEP caused by Kerorin.

A 27-year-old female was admitted to a hospital because of severe anemia (hemoglobin 4.9 g/dl) after taking PL (a drug for common cold consisted of Salicylamide, Acetaminophen, Caffeine and Promethazine methylene di-salicylate) and Cefadroxil (an oral antibiotic) for ten days. History and laboratory data leaded to a diagnosis of drug induced hemolytic anemia. 6 units of concentrated red blood cells were transfused and the suspected drugs were discontinued immediately. Though resolution of anemia and no further hemolysis were observed, progressive leukocytopenia developed since four days after the admission. Bone marrow aspiration revealed marked decrease of granulocytic series. The patient was transferred to our hospital and was isolated under laminar air-flow to prevent her from bacterial and fungal infections. She was treated with prednisolone and granulocyte-colony stimulating factor. She recovered from leukocytopenia in two weeks without suffering from any life-threatening infection. We extensively analyzed the suspected drugs and mechanism of hemolysis and granulocytopenia. Cefadroxil is turned out to be contributed to hemolysis by an immune complex mechanism. Cefadroxil and Salicylamide were suggested to be involved in granulocytopenia by the induction of antibodies against the leukocytes to which these drugs were bound. Thus Cefadroxil was regarded as a causative drug of both hemolysis and granulocytopenia. This case is of interest for analyzing drug-induced blood abnormality because it is very rare that two lineage of blood were injured by one drug at the same time as far as we know.