Nourem

Desmopressin Acetate Nasal Spray is indicated as antidiuretic replacement therapy in the management of central diabetes insipidus in adults and pediatric patients 4 years of age and older.

Limitations Of Use

Desmopressin Acetate Nasal Spray is not indicated for:

• Treatment of nephrogenic diabetes insipidus,
• Treatment of primary nocturnal enuresis ,
• Use in patients with conditions that compromise the intranasal route of administration (e.g., severe nasal congestion and blockage, nasal mucosa atrophy, severe atrophic rhinitis, recent nasal surgery such as transsphenoidal hypophysectomy).
• Use in patients with an impaired level of consciousness,
• Use in patients requiring doses less than 10 mcg or doses that are not multiples of 10 mcg.

Important Administration Instructions

Administer Desmopressin Acetate Nasal Spray by intranasal use only. Instruct patients about appropriate fluid restriction during Desmopressin Acetate Nasal Spray treatment.

Must prime the spray pump prior to the first use. Instruct patients to:

• Prime pump by pressing down on pump four times (if the spray pump is not used for one week, re-prime the pump by pressing down on the pump once).
• Discard Desmopressin Acetate Nasal Spray after 50 sprays since the amount delivered thereafter may be substantially less than the recommended dosage.

Recommended Dosage

The use of Desmopressin Acetate Nasal Spray is not indicated for patients who require less than 10 mcg doses or doses that are not multiples of 10 mcg because the spray pump can only deliver doses of 10 mcg. If other doses are required, use another desmopressin acetate product.

Individualize the dosage of Desmopressin Acetate Nasal Spray for each patient with particular attention in pediatric and elderly patients and adjust according to the diurnal pattern of response to limit nocturia and to ensure fluid intake with respect to urine output is not excessive. Monitor continued response to Desmopressin Acetate Nasal Spray by urine volume and osmolality to ensure adequate diuresis to limit the risk of hyponatremia, and include measurements of serum sodium and plasma osmolality as needed.

Adults

The recommended dosage in adults is 10 mcg once daily into one nostril up to 40 mcg once daily (or 40 mcg divided into two or three daily doses). If administered more than once a day, adjust for an adequate diurnal rhythm of urine output.

Pediatric Patients

• For pediatric patients requiring doses less than 10 mcg, Desmopressin Acetate Nasal Spray is not indicated.
• For pediatric patients 4 years of age and older, the recommended starting dosage of Desmopressin Acetate Nasal Spray is 10 mcg once daily into one nostril. The dose can be titrated up to 30 mcg once daily (or 30 mcg divided into two daily doses, typically with 20 mcg given in the morning and 10 mcg given at nighttime). If administered more than once a day, adjust for an adequate diurnal rhythm of urine output.

Because administration of desmopressin acetate can been associated with decreased responsiveness with prolonged use, consider increasing the dosage of Desmopressin Acetate Nasal Spray if patients demonstrate decreased response over a long period of time.

Switching Between Desmopressin Acetate Formulations

When switching from the desmopressin acetate injection to Desmopressin Acetate Nasal Spray, administer 10 times the amount of desmopressin acetate, rounding down to the nearest 10 mcg.

When switching from the desmopressin acetate tablets to Desmopressin Acetate Nasal Spray individual dose titration is required because intranasal desmopressin is approximately 10 to 40 fold more potent than oral (tablet) desmopressin.

Desmopressin Acetate Nasal Spray is contraindicated in patients with:

• Known hypersensitivity to desmopressin acetate or to any of the components of Desmopressin Acetate Nasal Spray. Severe allergic reactions and anaphylaxis have been reported.
• Renal impairment defined as estimated creatinine clearance (CLcr) by Cockcroft-Gault equation less than 50 mL/min).
• Hyponatremia or a history of hyponatremia.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hyponatremia

Excessive fluid intake when urine output is limited by the antidiuretic effect of desmopressin may lead to water intoxication with hyponatremia. Cases of hyponatremia have been reported from postmarketing experience in patients treated with desmopressin acetate. Unless properly diagnosed and treated, hyponatremia can be fatal.

All patients receiving Desmopressin Acetate Nasal Spray should be observed for the following signs or symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness, and confusion. Severe symptoms due to an extreme decrease in serum sodium and plasma osmolality may include one or a combination of the following: seizure, coma, and/or respiratory arrest.

In order to decrease the risk of water intoxication with hyponatremia, fluid restriction is recommended. Careful fluid intake restriction is particularly important in pediatric and geriatric patients because these patients are at greater risk of developing hyponatremia. More frequent monitoring of serum sodium levels is recommended in the following patients: those with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, heart failure, renal disorders, habitual or psychogenic polydipsia or those taking concomitant drugs that may cause hyponatremia.

Desmopressin Acetate Nasal Spray is not an indicated formulation for the treatment of primary nocturnal enuresis due to a higher risk of hyponatremia and hyponatremic convulsions with the use of the nasal spray formulation compared to desmopressin tablets seen in postmarketing reports.

Altered Absorption In Patients With Nasal Mucosa Abnormalities

Chronic administration of Desmopressin Acetate Nasal Spray may result in changes to nasal mucosa. Nasal mucosa abnormalities (such as scarring and edema) due to chronic administration, or due to other causes (nasal blockage, nasal mucosal atrophy, severe atrophic rhinitis, recent nasal surgery such as transsphenoidal hypophysectomy) may cause erratic, unreliable absorption. Avoid use of Desmopressin Acetate Nasal Spray in such patients.

Geriatric Use

Clinical studies of Desmopressin Acetate Nasal Spray did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at a low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy

Because elderly patients are more likely to have renal impairment, care should be taken in dose selection, and monitoring renal function is recommended.

Use of Desmopressin Acetate Nasal Spray in geriatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia.

Renal Impairment

Desmopressin acetate is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with renal impairment than patients with normal renal function. Desmopressin Acetate Nasal Spray is contraindicated in patients with estimated CLcr by Cockcroft-Gault equation less than 50 mL/min.

The following serious reactions are described below and elsewhere in the labeling:

• Hyponatremia.
• Altered Absorption in Patients with Changes in Nasal Mucosa.

The following adverse reactions have been identified during post-approval use of desmopressin acetate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Increase in blood pressure, headache, nasal congestion, rhinitis, nosebleed, sore throat, cough, upper respiratory infections, nausea, flushing, and abdominal cramps.

Water intoxication with hyponatremia

Hyponatremic convulsions associated with concomitant use of the following medications: oxybutinin and imipramine.

Severe allergic reactions and anaphylaxis

Signs of desmopressin acetate overdosage may include confusion, drowsiness, continuing headache, problems with passing urine, and rapid weight gain due to fluid retention. In case of overdosage, reduce the dosage, decrease the frequency of administration, or discontinue Desmopressin Acetate Nasal Spray. There is no known specific antidote for desmopressin acetate.

The use of Desmopressin Acetate Nasal Spray in patients with central diabetes insipidus reduces urinary output, increases urine osmolality, and decreases plasma osmolality.

Absorption

Desmopressin acetate is absorbed through the nasal mucosa.

Elimination

Desmopressin acetate exhibits a biphasic elimination profile, with half-lives of 7.8 and 75.5 minutes for the initial and terminal phases, respectively.