Syndrome of Inappropriate Antidiuretic Hormone Secretion Induced by a Single Dose of Oral Cyclophosphamide

Abstract

To our knowledge, our report represents the first case of SIADH due to a single oral dose of cyclophosphamide. Clinicians should be aware of this rare adverse event, as it can have life-threatening consequences.

Cyclophosphamide Administration Routine in Autoimmune Rheumatic Diseases: A Review

“…55,60 Thus, the administration of dexamethasone should be started in the morning, 30 min before the administration of cyclophosphamide, preferably at 7:30 a.m. 58 After the emesis caused by cyclophosphamide was classified as a delayed-type, 56 and in view of the decrease of cyclophosphamide efficacy when ondansetron is administered prior to this chemotherapeutic agent, ondansetron (8 mg PO 31,61 administered at 6 and 14 or 8 and 16 h post-ChT, and with a maximum dose of 16 mg after chemotherapy, not exceeding 32 mg per day) was the last drug used for the prophylaxis of emesis caused by cyclophosphamide. 31 Other important adverse effects of cyclophosphamide include hematologic toxicity, 18 kidney failure, 20 hyponatremia, 45,62 neurological impairment, 45 amenorrhea, 18 early menopause, 46 hair loss, 3 hepatotoxicity (rare), 3 and late-onset cancer. 18 The dose of cyclophosphamide for the treatment of systemic lupus erythematosus, including those patients with neuropsychiatric and/or hematologic disorders, with class IV lupus nephritis, and with other serious manifestations of systemic lupus erythematosus, is 0.5-1 g/m 2 IV monthly, 5,62 with dosage adjustment in patients with hematological toxicity and kidney failure.…”

“…31 Other important adverse effects of cyclophosphamide include hematologic toxicity, 18 kidney failure, 20 hyponatremia, 45,62 neurological impairment, 45 amenorrhea, 18 early menopause, 46 hair loss, 3 hepatotoxicity (rare), 3 and late-onset cancer. 18 The dose of cyclophosphamide for the treatment of systemic lupus erythematosus, including those patients with neuropsychiatric and/or hematologic disorders, with class IV lupus nephritis, and with other serious manifestations of systemic lupus erythematosus, is 0.5-1 g/m 2 IV monthly, 5,62 with dosage adjustment in patients with hematological toxicity and kidney failure. 20,63 Adverse hematologic reactions caused by cyclophosphamide are classified as serious, as they cause high morbidity.…”

“…66 Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was described in a case report in which this syndrome was associated with the use of IV cyclophosphamide in a dose of 500-1000 mg/m 2 , with a serum sodium level <120 mmol/L in a patient presenting neurological complications. 62 Cyclophosphamide may also cause cardiotoxicity. Routinely, echocardiography, a noninvasive method, is used to monitor cardiovascular function in patients treated with immunosuppressants.…”

Hyponatraemia in patients with multiple myeloma

“…Other drugs, including cyclophosphamide, have very rarely been reported to cause severe hyponatraemia, although the mechanism is unknown. To the best of our knowledge, our third patient's is only the third reported case of cyclophosphamide-induced SIADH in a patient with MM 13 14…”

Considering renal risk while managing cancer

“…Owing to differences in metabolism, cyclophosphamide treatment produces much less chloracetaldehyde and is therefore substantially less nephrotoxic than ifosfamide, although another metabolite, acrolein, can lead to urotoxicity with hemorrhagic cystitis 62. Beyond those issues, cyclophosphamide has also been rarely associated with the syndrome of inappropriate antidiuresis hormone secretion (SIADH) 62,68. The mechanism of action of cyclophosphamide-related SIADH has not been determined, but it may be caused by a direct toxic effect of cyclophosphamide or its metabolites on renal collecting tubules, or an antidiuretic hormone-like activity of cyclophosphamide metabolites 68…”