Sublingual desmopressin PBS listed — where does desmopressin fit in primary nocturnal enuresis?

An enuresis alarm is the first choice for primary nocturnal enuresis. Alarms are at least as effective as desmopressin, more likely to have a sustained effect, and do not have the risk of serious hyponatraemia.^2,3 Although alarms require close involvement from a parent or carer in the first few weeks of use, about two-thirds of children with nocturnal enuresis become dry at night when using an enuresis alarm, and about half of children stay dry when the alarm is withdrawn.^2,4 Alarms are usually withdrawn after 14 consecutive dry nights and may be trialled for up to 12–16 weeks.⁵

Several different enuresis alarms are available: pad-and-bell alarms that are placed on the bed, and personal alarms that are worn between pairs of underpants. Choice is determined by the child's preference and by cost — there is insufficient evidence to show any one alarm is more effective than another.²

Desmopressin acts faster than alarms at reducing the number of wet nights in the first week of treatment, but this advantage does not persist.⁶ Relapse rates after stopping desmopressin are similar to those for placebo and higher than for alarms.⁶ Desmopressin may have a role in special circumstances, such as short-term use when sleeping away from home.^3,5

Discuss simple behavioural strategies with the child and their parent or carer. Although there is insufficient evidence to prove effectiveness, some of these may help, are not associated with side effects, and may be preferred by children and parents.^7,8

Desmopressin sublingual wafer can be taken without water, which may make it easier for some children to take.⁹ A single desmopressin 120 micrograms sublingual wafer has an equivalent bioavailability¹⁰ and efficacy to that of a single desmopressin 200 micrograms tablet.⁹ There is no difference in the safety profile for the two formulations at recommended doses.⁹

The nasal formulation of desmopressin is more likely to cause hyponatraemia and seizures than oral formulations (15 cases versus 6 cases per 100,000 years of patient exposure for nasal versus oral formulations).¹¹

Hyponatraemia is a rare but serious adverse effect of desmopressin, which may present as anorexia, nausea and vomiting, difficulty concentration, confusion, lethargy, agitation, headache, and seizures.¹¹

Use the nasal formulation only when oral or sublingual desmopressin use is not feasible for primary nocturnal enuresis.¹² Children taking nasal desmopressin for primary nocturnal enuresis are heavily represented in reports of severe hyponatraemia and seizures with desmopressin. ^11,13

If prescribing desmopressin for primary nocturnal enuresis:

• use cautiously and monitor serum sodium levels in children with conditions that may increase the risk of hyponatraemia or water intoxication (eg, systemic infections, gastroenteritis, syndrome of inappropriate ADH secretion [SIADH])¹⁰
• reserve the nasal formulation for when an oral or sublingual formulation is not feasible^11,12
• avoid concomitant use with medicines known to induce SIADH (eg, tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, carbamazepine)¹⁰
• avoid NSAIDs, as they may induce water retention¹⁰
• advise children and their parents or carers that they can help to minimise the risk of hyponatraemia by:
  • • limiting the child's fluid intake for 1 hour before and 8 hours after taking desmopressin¹⁰ — parents or carers may need to closely watch the ingestion of fluid by their child after dosing
    • avoiding excessive fluid ingestion at all times³
    • stopping the medicine if the child develops symptoms of water retention (eg, headache, nausea, vomiting, weight gain or convulsions) and reporting these promptly to their doctor¹⁴
    • stopping the medicine temporarily if the child develops vomiting or diarrhoea from any cause, to allow recovery of normal fluid balance.^3,10

The benefit of desmopressin is not sustained after stopping, but spontaneous remission of bedwetting does occur. Assess for remission regularly to determine the need for ongoing treatment. The intended duration of desmopressin sublingual wafer for primary nocturnal enuresis is up to 3 months.¹⁰ Consider capping the number of repeats to ensure an assessment takes place within this period. To assess whether bedwetting has resolved, stop desmopressin and wait a week before reviewing the number of dry nights.³

Resources for parents and children on the management of bedwetting are available at www.bladderbowel.gov.au. These include a series of booklets, updated in 2008 (Sleepover, Watertight, and The Dry Night), which provide advice on behavioural therapies, alarms, and the place of medicines.