IMPORTANT SAFETY INFORMATION FOR NOCDURNA

NOCDURNA (desmopressin acetate) sublingual tablets

WARNING: HYPONATREMIA

• NOCDURNA can cause hyponatremia. Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death.
• 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 the serum sodium concentration is normal before starting or resuming NOCDURNA. Measure serum sodium within 7 days and approximately 1 month after initiating therapy, and periodically during treatment. More frequently monitor serum sodium 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.

NOCDURNA INDICATIONS AND USAGE

NOCDURNA is indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void.

In the NOCDURNA clinical trials nocturnal polyuria was defined as night-time urine production exceeding one-third of the 24-hour urine production.

Before starting NOCDURNA:

• Evaluate the patient for possible causes for the nocturia, including excessive fluid intake prior to bedtime, and address other treatable causes of nocturia.
• Confirm the diagnosis of nocturnal polyuria with a 24-hour urine collection, if one has not been obtained previously.

CONTRAINDICATIONS

NOCDURNA is contraindicated in patients with the following conditions due to an increased risk of hyponatremia:

• Hyponatremia or a history of hyponatremia
• Polydipsia
• Concomitant use with loop diuretics
• Concomitant use with systemic or inhaled glucocorticoids
• Renal impairment with estimated glomerular filtration rate (eGFR) below 50 mL/min/1.73 m²
• Known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion
• During illnesses that can cause fluid or electrolyte imbalance, such as gastroenteritis, salt-wasting nephropathies, or systemic infection

NOCDURNA is contraindicated in patients with the following conditions because fluid retention increases the risk of worsening the underlying condition:

• Heart failure
• Uncontrolled hypertension

WARNINGS AND PRECAUTIONS

Hyponatremia

Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of NOCDURNA without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia. Advise patients to avoid drinks containing caffeine or alcohol before bedtime. The frequency of serum sodium monitoring should be based on the patient’s risk for hyponatremia. The incidence of hyponatremia was higher in patients 65 years of age or older compared to younger patients. More frequent monitoring is recommended for patients 65 years of age or older or those on concomitant medications that can increase the risk of hyponatremia, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide. If hyponatremia occurs, NOCDURNA may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia. Women are more sensitive to the effects of NOCDURNA compared to men. The recommended dose for women is lower than for men because women had a higher risk of hyponatremia with the 55.3 mcg dose in clinical trials.

Fluid Retention

NOCDURNA can cause fluid retention, which can worsen underlying conditions that are susceptible to volume status. Therefore, NOCDURNA is contraindicated in patients with heart failure or uncontrolled hypertension. In addition, NOCDURNA is not recommended in patients at risk for increased intracranial pressure or those with a history of urinary retention.

ADVERSE REACTIONS

The safety database includes three double-blind, placebo-controlled, multicenter, randomized trials of NOCDURNA and one open-label extension trial. The most common adverse reactions reported with both the 27.7 mcg/day and 55.3 mcg/day dosages included dry mouth, hyponatremia or blood sodium decreased, and dizziness.

Serious adverse reactions included 2 reports of hyponatremia in men treated with NOCDURNA 55.3 mcg. These 2 reports occurred in a trial in which all cases of serum sodium ≤125 mmol/L were reported as serious adverse reactions.

DRUG INTERACTIONS

Drugs That May Increase the Risk of Hyponatremia

Concomitant use of NOCDURNA and loop diuretics or systemic or inhaled glucocorticoids is contraindicated because of the risk of severe hyponatremia. NOCDURNA can be started or resumed three days or five half-lives after the glucocorticoid is discontinued, whichever is longer.

Drugs such as tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, opiate analgesics, thiazide diuretics, carbamazepine, lamotrigine, sulfonylureas, particularly chlorpropamide, and NSAIDs may increase the risk of hyponatremia. Monitor serum sodium more frequently in patients taking NOCDURNA concomitantly with these drugs and when doses of these drugs are increased.

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

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.

There are no data with NOCDURNA use in pregnant women to inform any drug-associated risks. No adverse developmental outcomes were observed in animal reproductive and developmental studies following administration of desmopressin acetate during organogenesis to pregnant rats and rabbits, at exposures 92- and 8- times, respectively, the maximum recommended dose in women, based on body surface area (mg/m²).

Lactation

Risk Summary

Desmopressin is present in small amounts in human milk. There is no information on the effects of desmopressin on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s need for NOCDURNA and any potential adverse effects on the breastfed child from NOCDURNA or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of NOCDURNA have not been established in pediatric patients.

Geriatric Use

A total of 562 subjects 65 years or older were enrolled in the clinical trials, about 48% of the study population. Clinical studies of desmopressin have shown an increased risk of hyponatremia in patients 65 years of age or older compared to those younger than 65 years of age.

Renal Impairment

No dose adjustment of NOCDURNA is required for patients with an eGFR at or above 50 mL/min/1.73 m². NOCDURNA is contraindicated in patients with an eGFR below 50 mL/min/1.73 m².

OVERDOSAGE

Overdosage of desmopressin leads to an increased risk of prolonged fluid retention and hyponatremia. Signs of overdosage may include nausea, headache, drowsiness, confusion, and rapid weight gain due to fluid retention.

In case of overdosage, NOCDURNA must be discontinued, serum sodium assessed, and hyponatremia treated appropriately.

See the full NOCDURNA prescribing information for additional safety information.

 

1. NOCDURNA [package insert). Parsippany, NJ: Ferring Pharmacueticals Inc. Ewing, NJ: Antares Pharma, Inc.