Demeclocycline in the treatment of the syndrome of inappropriate secretion of antidiuretic hormone.

Abstract

Fourteen patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) have been treated with demethylchlortetracycline (demeclocycline) 1200 mg daily. In 12 patients the underlying lesion was malignant. The serum sodium returned to normal (> 135 mmol/l) in all patients after a mean of 8-6 days (SD+5-3 days). Blood urea rose significantly from the pretreatment level of 4-2±2-3 mmol/l to 10-1±5-1 mmol/l at ten days (p<0 001). The average maximum blood urea was 13-4-6-8 mmol/l. In four patients the urea rose above 20 mmol/l, and in two of these demecyocycline was discontinued because of this rise. The azotaemia could be attributed to a combination of increased urea production and a mild specific drug-induced nephrotoxicity. Discontinuation of demeclocycline in six patients led to a fall in serum sodium, in one case precipitously, and return of the urea towards normal levels. Demeclocycline appears therefore to be an effective maintenance treatment of SIADH, and the azotaemia that occurs is reversible and probably dose dependent.

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.…”

“…We found several case series demonstrating an increase in serum sodium concentration after 2-7 days for urea (202,203,204,205,206), demeclocycline (207), loop diuretics in combination with oral NaCl (123,125,208), phenytoin (209) and fluid restriction (210). We also identified case series of patients experiencing an increase in serum sodium over a longer time period of up to 12 months for urea (211,212,213), up to 3 weeks for demeclocycline (214,215,216,217,218,219), up to 20 weeks for lithium (220), up to 150 days for furosemide with oral NaCl (221) and up to 30 days in phenytoin (220).…”

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

“…All four studies reported an increase in mean serum sodium levels during treatment with demeclocycline at doses of up to 1200 mg/day 20, 22, 26, 27.…”

“…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).…”

“…(if the study is retrospective this may not be applicable)NoWhere blinding was not possible, is there some recognition that knowledge of exposure status could have influenced the assessment of outcome?NoIs the method of assessment of exposure is reliable?YesIs evidence from other sources used to demonstrate that the method of outcome assessment is valid and reliable?NoIs the exposure level or prognostic factor assessed more than once?NoAre the main potential confounders identified and taken into account in the design and analysis?NoHave confidence intervals been provided?NoConfidence intervals not provided but standard deviations reported Perks WH et al. 1979 22  Internal validity Does the study address an appropriate and clearly focused question?YesThe authors determined the effect of demeclocycline on patients with SIADH, especially renal functionAre the two groups being studied selected from source populations that are comparable in all respects other than the factor under investigation?NASingle cohort/case series; no controlsDoes the study indicate how many of the people asked to take part did so, in each of the groups being studied?UnclearUnclear if any patients refused to participateIs the likelihood that some eligible subjects might have the outcome at the time of enrolment assessed and taken into account in the analysis?NAAll patients had SIADH based on specific criteriaWhat percentage of the individuals or clusters recruited into each treatment arm of the study dropped out before the study was completed?7/14 patients (50%) discontinued, including one death, however it appears that all patients were taking demeclocycline at the analysis timepoint of 10 days…”