Demeclocycline in the treatment of the syndrome of inappropriate antidiuretic hormone release: with measurement of plasma ADH

Abstract

Summary A patient with the syndrome of inappropriate antidiuretic hormone release (SIADH) following head injury and meningitis was studied during treatment with demeclocycline, a drug known to produce a reversible nephrogenic diabetes insipidus. No changes were observed during six days of demeclocycline 1200 mg/24 hr but urine output increased significantly, with the production of a dilute urine, when the dose was increased to 2400 mg/24 hr. The patient lost weight, and all biochemical features of the syndrome were rapidly corrected despite an unchanged fluid intake and despite the persistence of high plasma levels of ADH. The rise in serum sodium was accompanied by mild sodium retention, as measured by external balance and exchangeable sodium. A complication of treatment was the development of acute renal failure possibly induced by a nephrotoxic effect of high circulating levels of demeclocyline. On stopping demeclocyline renal function returned to normal and, after some delay, SIADH returned, and was still present 9 months after initial presentation. This confirms earlier reports of the efficacy of demeclocycline in SIADH; but the authors advise caution against increasing the dose above 1200 mg/24 hr.

Clinical practice guideline on diagnosis and treatment of hyponatraemia

“…We also found several observational reports of acute kidney injury with demeclocycline (214,215,218,219,222,223,224,225,226,227,228,229,230,231,232); a single case report of confusion and somnolence with lithium (220) and unspecified neurological abnormalities with phenytoin (233). Finally, we identified two reports of adverse events with fluid restriction.…”

Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH : a systematic review

“…In total, 16 non‐RCTs were considered relevant, comprising six cohort studies (four observational studies 20, 22, 26, 27, two retrospective chart analyses 21, 28, and 10 case reports 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 (Tables 2 and 3, respectively); no cost‐effectiveness or HRQoL studies were identified. Quality assessments for all studies other than case reports are presented (Appendix C).…”

“…Ten case reports, detailing 11 patients in total, presented safety data pertaining to demeclocycline 29, 30, 31, 32, 33, 34, 35, 36, 37, 38. Demeclocycline effectiveness and safety data reported in case studies are presented in Table 6.…”

“…Three reports associated deterioration in renal function with demeclocycline in four patients with a diagnosis of SIADH (30,31,35). Distinct but reversible episodes of glomerular filtration rate (GFR) reduction were observed in two patients (31), with acute renal failure reported in a third receiving demeclocycline at up to 2400 mg/day (35).…”

“…Three reports associated deterioration in renal function with demeclocycline in four patients with a diagnosis of SIADH (30,31,35). Distinct but reversible episodes of glomerular filtration rate (GFR) reduction were observed in two patients (31), with acute renal failure reported in a third receiving demeclocycline at up to 2400 mg/day (35). A fourth patient (94-year-old male hospitalised following collapse and subsequent diagnosis of SIADH) died of irreversible acute renal failure that authors attributed to dehydration associated with demeclocycline 1200 mg/day and a compromised fluid intake (30).…”