Repeated daily dosing of weekly methotrexate therapy causing multiorgan toxicity: a case report

Figures & data

Figure 1. Plots of white cell count and neutrophils (A), platelets (B), haemoglobin (C) and alanine transaminase (ALT) versus time.

Table 1. Cases of accidental daily dosing of methotrexate in the existing literature.

Study	Patient	MTX concentration	Dosing regime	Folinic acid	Other treatments	Fatal	Comorbidities	Toxic effects
Bookstaver et al.	59yo F	<0.02 µmol/L on D3 (nil on admission)	2.5 mg OD for 6 mo (360 mg total)	15 mg IV 6hrly (2 d), then 15 mg IV (4 d) then 15 mg po OD on discharge (7 d)	Antimicrobials (IV cefazolin)	N	Psoriasis, DM, HTN, CAD, morbid obesity	Oral ulceration Pancytopenia ARF
Kalyanpad et al. Case 1	62yo M	Not reported	2.5 mg OD for 10 d, then 5 mg BD for 4 d (45 mg total)	Inj. 150 mg 6hrly until death (unclear duration)	Blood products - G-CSF 300 mg OD Antimicrobials - vancomycin, fluconazole and metronidazole Enhanced elimination - urinary alkalinisation	Y	Psoriasis, nil other reported	Oral ulceration Neutropenia + thrombocytopenia Mild hepatitis ARF Septic shock (COD)
Kalyanpad et al. Case 2	45yo F	Not reported	15 mg OD for 10 d (150 mg total)	Inj. 150 mg 6hrly until death	Antimicrobials - vancomycin, fluconazole and metronidazole Enhanced elimination - urinary alkalinisation	Y	Psoriasis, nil other reported	Oral ulceration Pancytopenia Mild hepatitis + coagulopathy Severe ARF Septic shock (COD)
Moisa et al. Case 1	72yo F	Not reported	15 mg OD for 7 d (105 mg total)	2 d (details not reported)	Blood products – erythrocyte and thrombocyte conc	Y	RA, CCF	Oral ulceration Pancytopenia Septic shock (COD)
Moisa et al. Case 2	76yo M	Not reported	10 mg OD for 9-16 d (90-160 mg total)	Nil reported	Nil reported	Y	CAD, DM, dyslipidaemia, RA, BPH	Oral ulceration + erosive dermatitis Pancytopenia Septic shock (COD)
Moisa et al. Case 3	85yo F	Not reported	20 mg OD for 8 d (160 mg total)	9 d (details not reported)	Blood products – erythrocyte and thrombocyte conc, G-CSF OD for 7 d (dosage unclear)	Y	COPD, CCF, RA	Oral ulceration + erythroderma Pancytopenia Septic shock + respiratory failure (COD)
Moisa et al. Case 4	78yo F	Not reported	10 mg OD for 8 d	Administered (details not reported)	Blood products – G-CSF for 6d (dosage unclear)	Y	RA, nil other reported	Pancytopenia Oral ulceration + erythroderma Sepsis (likely COD but not stated)
Singh et al.	57yo M	Not reported	5 mg OD for 4 d (20 mg total)	15 mg IV 6hrly (4 days)	Blood products – G-CSF 300 mg OD for 4d Antimicrobials – meropenem, teicoplanin and amphotericin B	N	DM, CAD, ESRF (on dialysis)	Oral ulceration Mild hepatitis Pancytopenia
Sinicina et al. Case 1	65yo M	0.25 µmol/L	?10 mg OD for 23 d (230 mg total)	‘Folinic acid rescue therapy’ (details unclear)	Nil reported	Y	RA, nil other reported	Oral ulceration Septic shock (COD)
Sinicina et al. Case 4	74yo F	undetectable	10 mg OD for 9 d (90 mg total)	Nil given as MTX level undetectable	Initially managed for presumed medication allergy Nil other described	Y	Nil reported	Pancytopenia Exanthema (not further clarified) Pneumonia (COD)
Sinicina et al. Case 5	26yo F	undetectable	15 mg OD for 6 d (90 mg total)	Nil given as MTX level undetectable	Nil reported	Y	Down syndrome, RA	Oral ulceration Pancytopenia Multiorgan failure (COD)
Sweet et al.	81yo F	0.12 µmol/L	2.5 mg OD for 22 d (55 mg total)	100 mg IV 4hrly until death	Blood Products – G-CSF and platelet transfusions Antimicrobials – ‘broad spectrum antibiotics’	Y	HTN, dyslipidaemia, osteoporosis	Oral ulceration Pancytopenia Dehydration, ARF and elevated CK Septic shock and AMI (COD)

Abbreviations: AMI – acute myocardial infarction, ARF – acute renal failure, BD – twice daily, BPH – benign prostatic hyperplasia, CAD – coronary artery disease, CCF – congestive cardiac disease, CK – creatinine kinase, COD – cause of death, COPD – chronic obstructive pulmonary disease, d – day(s), DM – diabetes mellitus, ESRF – end stage renal failure, F – female, freq. – frequency, G-CSF – granulocyte colony-stimulating factor, HTN – hypertension, inj. – injected, IV – intravenous, M – male, mo – month(s), MTX – methotrexate, N – no, OD – once daily, RA – rheumatoid arthritis, Y – yes, yo – years old.