Limitations of Use:

DDAVP Nasal Spray is not indicated for:

• Treatment of nephrogenic diabetes insipidus,
• Treatment of primary nocturnal enuresis [see Warnings and Precautions (5.1)],
• 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) [see Warnings and Precautions (5.2)].
• 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 [see Dosage Forms and Strengths (3)].

2.1 Important Administration Instructions

Administer DDAVP Nasal Spray by intranasal use only. Instruct patients about appropriate fluid restriction during DDAVP Nasal Spray treatment [see Warnings and Precautions (5.1)].

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 DDAVP Nasal Spray after 50 sprays since the amount delivered thereafter may be substantially less than the recommended dosage.

2.2 Recommended Dosage

The use of DDAVP 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 [see Indications and Usage (1)]. If other doses are required, use another desmopressin acetate product.

Individualize the dosage of DDAVP 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 [see Warnings and Precautions (5.1)]. Monitor continued response to DDAVP 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.

2.3 Switching Between Desmopressin Acetate Formulations

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

5.1 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 DDAVP 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 [see Use in Specific Populations (8.4, 8.5)]. 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 [see Drug Interactions (7.1)].

DDAVP 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 [see Indications and Usage (1)].

5.2 Altered Absorption in Patients with Nasal Mucosa Abnormalities

Chronic administration of DDAVP 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 DDAVP Nasal Spray in such patients [see Indications and Usage (1)] and consider use of other formulations of desmopressin acetate given by other routes of administration.

7.1 Other Drugs that may Increase Risk of Hyponatremia

The concomitant administration of DDAVP Nasal Spray with other drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine, oxybutynin and carbamazepine) requires more frequent serum sodium monitoring [see Warnings and Precautions (5.1) and Adverse Reactions (6)].

7.2 Other Vasoconstrictors

Desmopressin acetate can elevate blood pressure. Use of large doses of DDAVP Nasal Spray with other vasocontrictors may require a reduction of the DDAVP dosage [see Adverse Reactions (6)].

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

DDAVP Nasal Spray is indicated as antidiuretic replacement therapy in the management of central diabetes insipidus in pediatric patients 4 years of age and older. DDAVP Nasal Spray is not indicated in pediatric patients less than 4 years of age.

Use of DDAVP Nasal Spray in pediatric patients 4 years of age and older is supported by evidence from adults and pediatric patients with central diabetes insipidus. Use in pediatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia [see Warnings and Precautions (5.1)].

8.5 Geriatric Use

Clinical studies of DDAVP 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 [see Contraindications (4), Use in Specific Populations (8.6)].

Use of DDAVP Nasal Spray in geriatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia [see Warnings and Precautions (5.1)].

8.6 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. DDAVP Nasal Spray is contraindicated in patients with estimated CLcr by Cockcroft-Gault equation less than 50 mL/min [see Clinical Pharmacology (12.1, 12.3), Contraindications (4)].

12.1 Mechanism of Action

The antidiuretic effects of desmopressin are mediated by stimulation of vasopressin 2 (V2) receptors, thereby increasing water re-absorption in the kidney, and hence reducing urine production. Desmopressin is a replacement hormone for antidiuretic hormone in the treatment of central diabetes insipidus. The change in structure of arginine vasopressin to desmopressin acetate resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses were usually below threshold levels for effects on vascular or visceral smooth muscle.

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with desmopressin acetate have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

16.1 How Supplied

DDAVP Nasal Spray is available as a 5 mL bottle containing an aqueous solution with the spray pump delivering 50 sprays of 10 mcg (0.1 mL) (NDC 55566-2500-0).

16.2 Storage and Handling

Store at Controlled Room Temperature 20 to 25°C (68 to 77°F) [see USP Controlled Room Temperature]. STORE BOTTLE IN UPRIGHT POSITION.

Administration

• Inform caregivers for pediatric patients that administration should be supervised to ensure the patient receives the prescribed dose.
• Inform patients that the pump must be primed prior to first use and again if not used for greater than one week. Inform patients that the DDAVP Nasal Spray bottle delivers 50 sprays of 10 mcg each following the initial 4 priming pumps.
• Inform patients to discard any solution remaining after 50 sprays since the amount delivered thereafter may be substantially less than 10 mcg of drug.

Monitoring

• Educate patients about the signs and symptoms of hyponatremia and advise them to contact a healthcare provider if such symptoms occur.
• Discuss downward adjustment of fluid intake and monitoring of urine output with patients.