By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first treatment for nocturnal polyuria. Desmopressin is a 9-amino synthetic analog of the pituitary hormone, vasopressin. Other formulations are approved for diabetes insipidus, primary nocturnal enuresis, hemophilia A, and von Willebrand disease (type 1). It is marketed as Noctiva nasal spray.
INDICATION
Desmopressin nasal spray is indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least twice per night to void.1
DOSAGE
For patient < 65 years of age who are not at risk for hyponatremia, the dose is one spray (1.66 mcg) in either nostril nightly approximately 30 minutes before going to bed.1 For those ≥ 65 years age or younger patients at risk for hyponatremia, the dose is 0.83 mcg nightly. Clinicians may increase the dose to 1.66 mcg after at least seven days if needed, provided serum sodium has remained normal. The nasal spray must be primed before initial use and if not used for more than three days. Desmopressin acetate is available as 1.66 mcg per spray and 0.83 mcg per spray.
POTENTIAL ADVANTAGES
Desmopressin acetate nasal spray is currently the only FDA-approved agent for this indication.
POTENTIAL DISADVANTAGES
Desmopressin can cause hyponatremia, which, in severe cases, may be life-threatening.1 It is contraindicated in patients at risk for severe hyponatremia (e.g., history of hyponatremia, primary nocturnal enuresis, use of loop diuretics, use of corticosteroid, renal impairment, known or suspected syndrome of inappropriate antidiuretic hormone secretion).1 The FDA states that it is not approved for all causes of night-time urination, and clinicians should conduct an appropriate workup before considering administration.2
COMMENTS
The efficacy and safety of desmopressin were evaluated in two 12-week randomized, double-blind, placebo-controlled trials in adults (at 50 years of age) with nocturia due to nocturnal polyuria.1,3 This is defined as having a six-month history of at least an average of two nocturic episodes per night. In addition, they had at least 13 documented nocturia episodes over six nights during screening. In both studies nocturnal polyuria was defined as a night-time urine production exceeding one-third of the 24-hour production. In the first trial, subjects were randomized to desmopressin 1.66 mg (n = 199), 0.88 mcg (n = 209), or placebo (n = 145). In the second trial, subject distributions were 143, 145, and 145, respectively. Studies had a two-week screening period, a two-week lead-in period, and a 12-week treatment period. The two co-primary efficacy endpoints were change in the mean number of nocturic episodes per night from baseline during the 12-week period and the percentage of subjects who achieved at least a 50% reduction from baseline. In the first trial, the 0.88 mcg dose did not achieve statistical significance with both co-primary endpoints. In the second trial, the lower dose was better than placebo in terms of mean reduction of episodes, but it did not achieve statistical significance with at least 50% reduction from baseline.3 From a baseline of a mean of 3.2-3.4 episodes per night, desmopressin 1.66 mg showed a reduction of 0.3-0.4 compared to placebo (9-12% reduction). For the co-primary endpoint, 47% achieved a 50% reduction, compared to 27% in the first trial, and 49% and 29%, respectively, for the second trial (absolute difference of 21% and 20%). In the first trial, the data suggest that some subjects responded to the lower dose similarly to those treated with the higher dose.2 This may be related to large inter-individual variation in systemic exposure to desmopressin. Because of this variation and greater risk of hyponatremia with the higher dose, both doses were approved.
CLINICAL IMPLICATIONS
Desmopressin is the first drug approved for nocturia due to nocturnal polyuria, defined as overproduction of urine at night. The cause may be idiopathic or due to other conditions such as edema-associated states.2 Desmopressin acetate appears to provide clinically meaningful but modest benefit.2 The price was not available at the time of this review.
REFERENCES
- Noctiva Prescribing Information. Serenity Pharmaceuticals. March 2017.
- U.S. Food and Drug Administration. FDA approves first treatment for frequent urination at night due to overproduction of urine. Available at: http://bit.ly/2n2X2LX. Accessed March 12, 2017.
- U.S. Food and Drug Administration. Summary Review for Regulatory Action, Noctiva. Available at: http://bit.ly/2mZdDiF. Accessed March 12, 2017.
Desmopressin nasal spray is indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least twice per night to void.
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