Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in October 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.


There is limited evidence from 2 small short-term studies that fludrocortisone improves postural blood pressure and orthostatic symptoms. In another slightly larger study fludrocortisone had no effect on supine blood pressure or wellbeing in a population with chronic fatigue syndrome.

Regulatory status: off-label


  • Statistically significant increase in mean tilted and supine systolic blood pressure (~30–40 mmHg) and tilted diastolic blood pressure (~10 mmHg) compared with placebo (1 randomised controlled trial [RCT], 3 weeks, n=6).

  • Statistically significant improvement in orthostatic domain of Composite Autonomic Symptom Scale (1 RCT, 3 weeks, n=17).

  • No effect on wellbeing or mean supine systolic blood pressure or diastolic blood pressure in those with chronic fatigue syndrome (1 RCT, 9 weeks, n=100).


  • Fludrocortisone is a potent mineralocorticoid.

  • Dosage and salt intake should be monitored to avoid development of hypertension, oedema or weight gain. Monitoring of serum electrolyte levels advisable during prolonged therapy.

  • Adverse effects reported include oedema, weight gain, headache and electrolyte disturbances. Limited data on long-term safety. Common adverse effects may be associated with more serious consequences in old age.

Patient factors

  • Patients should carry a steroid treatment card.

  • Tolerance to long-term treatment may be an issue. In an observational study of 64 older adults, 17 stopped treatment because of adverse effects after a mean of 5 months.

  • Needs to be stored in the fridge with bottle tightly closed to protect from moisture.

Resource implications

  • Cost of £5.05 for 100 tablets.

Key points

Use of fludrocortisone acetate (Florinef) for treating postural (orthostatic) hypotension is off label because it does not have a UK marketing authorisation for this indication, but it does have marketing authorisation for other indications. No other drugs currently have a UK marketing authorisation for postural hypotension.

Three small randomised controlled trials (RCTs) were identified for inclusion in this evidence summary. In all of the trials, postural blood pressure was investigated using a head-up tilt-test, in which the body is tilted head-up to at least a 60° angle on a tilt-table.

Campbell et al. (1975) was a double-blind, crossover RCT that included 6 adult males (mean age 52 years) with symptomatic postural hypotension as a result of diabetic autonomic neuropathy. Participants were randomised to 3 weeks of 100 micrograms fludrocortisone twice daily or placebo, followed by a 3‑week washout period, then crossover to 3 weeks of the alternative treatment.

This study found a statistically significant increase in mean tilted position systolic blood pressure (SBP) with fludrocortisone compared with placebo (154 [±29] mmHg versus 110 [±16] mmHg; p<0.005). There was also a statistically significant increase in mean supine SBP with fludrocortisone compared with placebo (180 [±26] mmHg versus 149 [±21] mmHg; p<0.05) and tilted position diastolic blood pressure (DBP) (88 [±11] mmHg versus 76 [±4] mmHg; p<0.05).

A second, small, double-blind, crossover RCT (n=17) in adults (mean age 69 years) with symptomatic postural hypotension and Parkinson's disease (Schoffer et al. 2007) is included in this evidence summary. The active comparator in this crossover trial was domperidone (off-label use); however, no direct comparisons with fludrocortisone were made. Instead, non-pharmacological treatment alone was compared with non-pharmacological treatment plus drug treatment.

This study found a statistically significant improvement in the orthostatic domain score of the Composite Autonomic Symptom Scale (COMPASS\u2011\OD) after taking 100 micrograms fludrocortisone daily for 3 weeks compared with non-pharmacological treatment alone. The clinical significance of this improvement (a decrease in the mean score of 3 points; on a 16‑point scale) is unclear. The authors concluded that there was a trend towards reduced blood pressure drop on tilt-table testing with fludrocortisone and domperidone. However, no statistical analysis for the results of tilt-table testing was provided.

The third RCT included in this evidence summary (Rowe et al. 2001) was a double-blind, placebo-controlled trial (n=100) carried out in a population with chronic fatigue syndrome (see Evidence review: efficacy for details). This RCT found that 9 weeks' treatment with fludrocortisone titrated to 100 micrograms daily had no significant effect on global wellness score, mean supine SBP or DBP compared with placebo.

Safety of fludrocortisone has not been adequately assessed in these 3 RCTs. However, fludrocortisone is a potent mineralocorticoid and its adverse effect profile in its summary of product characteristics (Florinef) reflects this. The incidence of predictable adverse effects is dependent on the dosage, frequency and duration of treatment. Patients should be advised to carry a steroid treatment card.

Because the studies included in this evidence summary are all short term, they provide no information on the long-term safety and efficacy of fludrocortisone for treating postural hypotension.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.