Effective Date

Date of Origin 

10/1/2022              

Nocdurna^®

(desmopressin acetate)

Tablet

Treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void

1

Nocturia

The International Continence Society (ICS) defines nocturia as the complaint that the individual wakes at night one or more times to void. Nocturnal polyuria occurs when an increased proportion of the 24-hour urine output occurs at night.(2) Evidence suggests nocturia becomes bothersome to patients at two or more voids per night.(3) The prevalence of nocturia is equal in both genders, however age distribution differs between genders. One-third of young women (18-29 years old) in a study reported nocturia at least once per night, compared to 1 in 9 of young men. Moreover, the prevalence of nocturia increases with age twice as rapidly in men compared to women. By the sixth decade of life, the percentage of nocturia reported in both genders is the same. Population studies have confirmed that nocturia increases with age and is common in the elderly. It was found that the majority of elderly men and women experience clinically significant nocturia: 29% to 59.3% in men and 28.3 to 61.5% in women aged greater than or equal to 70 years experienced 2 or more voids per night.(3)

Evaluation for nocturia should focus on patterns of fluid intake, other urinary symptoms, symptoms of possible underlying causes, and a focused physical examination. Nocturnal polyuria is defined as the excretion of greater than or equal to 35% of the 24-hour urine output during the hours of sleep. Management of nocturia may require multifaceted approach. Treatment of underlying medical conditions should be optimized and may reduce nocturia symptoms. Nocturia has been associated with many comorbidities including hypertension, diabetes, obstructive sleep apnea, and major depressive disorder.(3) First line management of nocturia involves behavior modifications such as reduction in alcoholic or caffeinated beverages, afternoon naps, compression stockings, and restriction of evening fluid intake.(3,4) Several pharmacologic options are used for nocturia. 5-alpha reductase inhibitors (i.e., dutasteride, finasteride) are commonly used in men for treatment of prostatic obstruction and lower urinary tract symptoms. Alpha-blockers (i.e., alfuzosin, doxazosin, tamsulosin, terazosin) have shown modest effects on nocturia. Anticholinergic agents (i.e., oxybutynin, tolterodine) are useful in treatment of overactive bladder and also used in the treatment of nocturia.(3,4) Loop diuretics (i.e., furosemide, bumetanide) are also used to regulate urine production in the daytime in order to decrease urine production during sleep.(4)

Desmopressin use aims to increase vasopressin in patients with nocturia, which results in reduced urine production by the kidneys.(3,4) Desmopressin therapy is not recommended for use in patients with baseline hyponatremia or impaired renal function (eGFR less than 60mL/min).(3)

Efficacy

One hundred and twenty-seven people, with greater than or equal to 2 voids nightly, were randomized to receive either an escalating dose of desmopressin or placebo. After 3 weeks, a clinically significant reduction (greater than 50% reduction in mean number of voids) was found in 33% of the treatment arm, compared to 11% of the placebo arm (P = 0.0014).(4) A study examined the efficacy of desmopressin, which was maintained for the duration of long-term treatment. Patients taking varying doses (25, 50, or 100 micrograms) of desmopressin sublingual “melt” tablets for 52 weeks had a mean decrease in the number of nocturnal voids of 1.4, 1.8, and 2.1 voids, respectively.(4) For Nocdurna, two studies were completed, one for women and one for men. In Study 1, 237 women with nocturia were randomized to receive Nocdurna 27.7mcg (n=121) or placebo (n=116) every night one hour before bedtime for 3 months. In Study 2, 230 men with nocturia were randomized to receive Nocdurna 55.3 mcg (n=102) or placebo (n=128) every night one hour before bedtime for 3 months. In both studies, endpoints were 1) the change in number of nocturia episodes per night from baseline and 2) a “33% responder status”, which was defined as a subject with a decrease of at least 33% in the mean number of nocturnal voids compared to baseline. In Study 1, Nocdurna patients had a -1.5 change from a baseline of 2.9 versus -1.2 for placebo. This equated to a -0.3 difference from placebo with a 95% CI of -0.5, -0.1. Probability of 33% responder status was 0.78 for Nocdurna compared to 0.62 with placebo, leading to a 2.15 odds ratio with a 95% CI of 1.36, 3.41. In Study 2, Nocdurna patients had a -1.3 reduction from a baseline of 3.0. Placebo patients had a reduction of -0.9, leading to a -0.4 difference from placebo (95% CI=-0.6 to -0.2). Probability of 33% responder status was 0.67 on Nocdurna versus 0.50 on placebo, leading to an odds ratio of 2.02 (95% CI=1.30, 3.14).(1) 

Safety

Nocdurna has a boxed warning for hyponatremia. Nocdurna is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids. Ensure serum sodium concentration is normal before starting or resuming Nocdurna. Measure serum sodium within 1 week and approximately 1 month after initiating therapy, and periodically during treatment (and more frequently in patients 65 years of age and older and in patients at increased risk of hyponatremia). If hyponatremia occurs, Nocdurna may need to be temporarily or permanently discontinued.¹ A normal serum sodium level is between 135 and 145 mEq/L or mmol/L.

Nocdurna is contraindicated in patients with the following conditions due to an increased risk of severe hyponatremia:(1)

• Hyponatremia or a history of hyponatremia
• Polydipsia
• Concomitant use with loop diuretics or systemic or inhaled glucocorticoids
• Renal impairment with an estimated glomerular filtration rate (eGFR) below 50 mL/min/1.73 m^2
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• During illnesses that can cause fluid or electrolyte imbalance

Nocdurna is contraindicated in patients with the following conditions because of fluid retention increases the risk of worsening the underlying condition:(1)

• Congestive heart failure
• Uncontrolled hypertension

Nocdurna is not recommended for the treatment of nocturia in pregnant women. Nocturia is usually related to normal, physiologic changes during pregnancy that do not require treatment with Nocdurna.(1)

1

Nocdurna prescribing information. Ferring Pharmaceuticals. November 2020.   

2

Abrams P, Cardozo L, Fall M, et al. The Standardisation of Terminology in Lower Urinary Tract Function: Report from the Standardisation Sub-Committee of the International Continence Society. Urology. 2003;61(1):37-49.

3

Weiss JP, Everaert K. Management of Nocturia and Nocturnal Polyuria. Urology. 2019 Nov;133:24-33.

4

Johnson TM, et al. Nocturia: Clinical Presentation, Evaluation, and Management in Adults. UpToDate. Literature review current through February 2022. Last updated January 2021.

NOCDURNA*desmopressin acetate sublingual tab

27.7 MCG ; 55.3 MCG

M ; N ; O ; Y

N

302010101007

NOCDURNA*desmopressin acetate sublingual tab

27.7 MCG ; 55.3 MCG

30.0

TABS

30

Days

NOCDURNA*desmopressin acetate sublingual tab

27.7 MCG ; 55.3 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

NOCDURNA*desmopressin acetate sublingual tab

27.7 MCG ; 55.3 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has a diagnosis of nocturnal polyuria confirmed by a 24-hour urine collection AND
2. The requested agent will be used to treat nocturia due to nocturnal polyuria AND
3. The patient’s serum sodium concentration is within normal range [between 135 to 145 mEq/L (mmol/L) or within testing laboratory’s normal range] AND
4. The patient has tried and had an inadequate response to behavior modifications for nocturia (e.g., physician monitored restriction of fluids, afternoon naps, elevation of legs, compression stockings) AND
5. ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication AND
6. ONE of the following:
   1. The patient has tried and had an inadequate response to generic oral desmopressin OR
   2. The patient has an intolerance or hypersensitivity to oral desmopressin that is not expected to occur with the requested agent OR
   3. The patient has an FDA labeled contraindication to oral desmopressin that is not expected to occur with the requested agent AND
7. The patient will NOT be using the requested agent in combination with a loop diuretic AND
8. The patient will NOT be using the requested agent in combination with systemic or inhaled glucocorticoids AND
9. The patient is NOT pregnant AND
10. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND
2. The patient has had clinical benefit with the requested agent AND
3. The patient’s serum sodium concentration is within normal range [between 135 to 145 mEq/L (mmol/L) or within testing laboratory’s normal range] AND
4. The patient will NOT be using the requested agent in combination with a loop diuretic AND
5. The patient will NOT be using the requested agent in combination with systemic or inhaled glucocorticoids AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

Quantity Limits for the Target Agent will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
   1. The requested quantity (dose) is greater than the program quantity limit AND
   2. The requested quantity (dose) does not exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR
3. ALL of the following:
   1. The requested quantity (dose) is greater than the program quantity limit AND
   2. The requested quantity (dose) is greater than the maximum FDA labeled dose for the requested indication AND
   3. The prescriber has provided information in support of therapy with a higher dose for the requested indication

Length of Approval:  12 months