DESMOPRESSIN ACETATE spray
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Patient Information

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)

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 desmopressin acetate nasal solution 0.01% (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.

1. Highlights Of Prescribing Information
2. Indications And Usage
3. Dosage And Administration
4. Dosage Forms And Strengths
5. Contraindications
6. Warnings And Precautions
7. Adverse Reactions
8. Drug Interactions
9. Use In Specific Populations
10. 1 Indications And Usage
11. 2 Dosage And Administration
12. 3 Dosage Forms And Strengths
13. 4 Contraindications
14. 5 Warnings And Precautions
15. 6 Adverse Reactions
16. 7 Drug Interactions
17. 8 Use In Specific Populations
18. 10 Overdosage
19. 11 Description
20. 12 Clinical Pharmacology
21. 13 Nonclinical Toxicology
22. 16 How Supplied/storage And Handling
23. Spl Unclassified
24. Spl Patient Package Insert
25. Package Label.principal Display Panel
26. Desmopressin Acetate Nasal Spray 10 Mcg Per 0.1 Ml
27. Description
28. Clinical Pharmacology
29. Warnings
30. Precautions
31. Overdosage
32. How Supplied
33. Instructions For Usedesmopressin Acetatenasal Spray, 10 Mcg Per 0.1 Mlfor Intranasal Use Only
34. Principal Display Panel - 5 Ml Bottle Carton

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use DESMOPRESSIN ACETATE NASAL SOLUTION 0.01% (NASAL SPRAY) safely and effectively. See full prescribing information for DESMOPRESSIN ACETATE NASAL SOLUTION 0.01% (NASAL SPRAY).

DESMOPRESSIN ACETATE nasal solution 0.01% (nasal spray)
Initial U.S. Approval: 1978

Indications And Usage ⮝

Desmopressin acetate nasal solution 0.01% (nasal spray) is a vasopressin analog indicated as antidiuretic replacement therapy in the management of central diabetes insipidus for adults and pediatric patients 4 years of age and older (1)

Limitations of Use:

Desmopressin acetate nasal solution 0.01% (nasal spray) is not indicated for:

• Treatment of nephrogenic diabetes insipidus (1)
• Treatment of primary nocturnal enuresis (1, 5.1)
• Use in patients with conditions that compromise intranasal route of administration (1, 5.2)
• Use in patients with an impaired level of consciousness (1)
• Use in patients requiring doses less than 10 mcg or doses that are not multiples of 10 mcg (1,3)

Dosage And Administration ⮝

• For intranasal use only (2.1)
• Instruct patients to prime pump prior to use (2.1)
• Adults : 10 mcg to 40 mcg daily (either as a single dose or divided into two or three daily doses) (2.2)
• Pediatrics: 10 mcg once daily into one nostril up to 30 mcg once daily (or 30 mcg divided as 20 mcg during the morning and 10 mcg at night) (2.2)
• See the Full Prescribing Information for recommendations for switching between desmopressin acetate formulations (2.3)

Dosage Forms And Strengths ⮝

Nasal Spray: 10 mcg per 0.1 mL spray, available in a 5 mL bottle with spray pump delivering 50 sprays (3)

Contraindications ⮝

• Known hypersensitivity to desmopressin acetate or to any of the components of desmopressin acetate nasal solution 0.01% (nasal spray) (4, 6)
• Patients with renal impairment (creatinine clearance below 50 mL/min) (4, 8.6, 12.3)
• Hyponatremia or a history of hyponatremia (4, 5.1)

Warnings And Precautions ⮝

• Hyponatremia: Instruct patients about proper fluid restriction and monitor serum sodium as needed (2.1, 5.1)
• Altered Absorption in Patients with Nasal Mucosa Abnormalities: May occur with chronic administration, and require use of other formulations instead (5.2)

Adverse Reactions ⮝

Adverse reactions that have been identified in patients administered desmopressin acetate nasal solution 0.01% (nasal spray) are headache, nasal congestion, rhinitis, nosebleed, sore throat, cough, upper respiratory infections, nausea, flushing, and mild abdominal cramps (6)

To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions ⮝

• Drugs that Increase Risk of Hyponatremia: Requires more frequent monitoring of serum sodium (7.1)
• Other Vasocontrictors: Concomitant use may elevate blood pressure and require a reduction in desmopressin acetate nasal solution 0.01% (nasal spray)

Use In Specific Populations ⮝

• Pediatric Use: Use requires careful fluid intake restriction to prevent hyponatremia with water intoxication (5.1, 8.4)
• Geriatric Use : Carefully monitor renal function; restrict fluid intake to prevent hyponatremia with water intoxication (5.1, 8.5)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 12/2018

1 Indications And Usage ⮝

Desmopressin acetate nasal solution 0.01% (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 solution 0.01% (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 Dosage And Administration ⮝

2.1 Important Administration Instructions

Administer desmopressin acetate nasal solution 0.01% (nasal spray) by intranasal use only. Instruct patients about appropriate fluid restriction during desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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 solution 0.01% (nasal spray) is not indicated.
• For pediatric patients 4 years of age and older, the recommended starting dosage of desmopressin acetate nasal solution 0.01% (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 solution 0.01% (nasal spray) if patients demonstrate decreased response over a long period of time.

2.3 Switching Between Desmopressin Acetate Formulations

When switching from the desmopressin acetate injection to desmopressin acetate nasal solution 0.01% (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 solution 0.01% (nasal spray) individual dose titration is required because intranasal desmopressin is approximately 10 to 40 fold more potent than oral (tablet) desmopressin.

3 Dosage Forms And Strengths ⮝

Desmopressin acetate nasal solution 0.01% (nasal spray), 10 mcg/ 0.1 mL per spray is available in a 5 mL bottle with spray pump delivering 50 sprays of 10 mcg.

4 Contraindications ⮝

Desmopressin acetate nasal solution 0.01% (nasal spray) is contraindicated in patients with:

• Known hypersensitivity to desmopressin acetate or to any of the components of desmopressin acetate nasal solution 0.01% (nasal spray). Severe allergic reactions and anaphylaxis have been reported [see Adverse Reactions (6)].
• Renal impairment defined as estimated creatinine clearance (CLcr) by Cockcroft-Gault equation less than 50 mL/min [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] .
• Hyponatremia or a history of hyponatremia [see Warnings and Precautions (5.1)] .

5 Warnings And Precautions ⮝

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 desmopressin acetate nasal solution 0.01% (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)].

Desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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 solution 0.01% (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.

6 Adverse Reactions ⮝

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

• Hyponatremia [see Warnings and Precautions (5.1)].
• Altered Absorption in Patients with Changes in Nasal Mucosa [see Warnings and Precautions (5.2)] .

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 [see Drug Interactions (7.1)].

Severe allergic reactions and anaphylaxis [see Contraindications (4)]

7 Drug Interactions ⮝

7.1 Other Drugs that may Increase Risk of Hyponatremia

The concomitant administration of desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (nasal spray) with other vasocontrictors may require a reduction of the desmopressin acetate nasal solution 0.01% (nasal spray) dosage [see Adverse Reactions (6)].

8 Use In Specific Populations ⮝

8.1 Pregnancy

Risk summary

Prolonged experience with desmopressin in pregnant women over several decades, based on the available published data and case reports, did not identify a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In addition, in vitro studies with human placenta demonstrate poor placental transfer of desmopressin. No adverse developmental outcomes were observed in animal reproduction studies with administration of desmopressin during organogenesis to pregnant rats and rabbits at doses approximately < 1 and 38 times, respectively, the maximum recommended human dose based on body surface area (mg/m2) (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Desmopressin acetate at up to 50 ng/kg/day was given by subcutaneous injection to pregnant rats, from gestation day 1 to 20 during the period of early embryonic development and organogenesis without teratogenic effects. Desmopressin acetate at up to 10 mcg/kg/day was given to pregnant rabbits by subcutaneous injection from gestation day 6 to 18 during fetal organogenesis without teratogenic effects. These doses of desmopressin acetate represent approximately < 1 times (rat) and 38 times (rabbit) the maximum recommended human dose based on body surface area (mg/m2).

8.2 Lactation

Risk Summary

Breastfeeding is not expected to result in clinically relevant exposure of the infant to desmopressin following maternal intranasal administration. Desmopressin is poorly transferred into human breastmilk at negligible amounts (see Data). 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 clinical need for desmopressin acetate nasal solution 0.01% (nasal spray) and any potential adverse effects on the breastfed infant from desmopressin acetate nasal solution 0.01% (nasal spray) or from the underlying maternal condition.

Data

A trial was conducted in six healthy lactating women, at greater than 4 months postpartum, to evaluate intranasal administration of 300 mcg single dose of another desmopressin product (7.5 times the recommended adult dose of desmopressin acetate nasal solution 0.01% (nasal spray)). Samples of maternal plasma and breastmilk were obtained at 0, 30, 60, 120, 240, 360 and 480 min after the drug administration. At 8 hours after dose intake, the levels in the milk ranged between 4.16 and 101 pg/ml, and the plasma levels ranged between 40 and 242 pg/ml. The total amount of desmopressin present in the milk over the 8 hours ranged between 491 pg and 16 ng, which corresponds to 0.0001 to 0.005% of the administered dose to the breastfeeding mother.

8.4 Pediatric Use

Desmopressin acetate nasal solution 0.01% (nasal spray) is indicated as antidiuretic replacement therapy in the management of central diabetes insipidus in pediatric patients 4 years of age and older. Desmopressin acetate nasal solution 0.01% (nasal spray) is not indicated in pediatric patients less than 4 years of age.

Use of desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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. desmopressin acetate nasal solution 0.01% (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)].

10 Overdosage ⮝

Signs of desmopressin acetate overdosage may include confusion, drowsiness, continuing headache, problems with passing urine, and rapid weight gain due to fluid retention [see Warnings and Precautions (5.1)]. In case of overdosage, reduce the dosage, decrease the frequency of administration, or discontinue desmopressin acetate nasal solution 0.01% (nasal spray). There is no known specific antidote for desmopressin acetate.

11 Description ⮝

Desmopressin acetate is a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation. It is chemically defined as follows:

Molecular weight: 1183.34

Molecular formula: C46H64N14O12S2 C2H4O2 3H2O

1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate.

Desmopressin acetate nasal solution 0.01% (nasal spray) is provided as an aqueous solution for intranasal use.

Each mL contains:

Desmopressin acetate, USP	0.1 mg
Sodium Chloride	7.5 mg
Citric acid monohydrate	1.7 mg
Disodium phosphate dihydrate	3.0 mg
Benzalkonium chloride solution (50%)	0.2 mg
Purified water to 1 mL

The desmopressin acetate nasal solution 0.01% (nasal spray) compression pump delivers 0.1 mL (10 mcg) of desmopressin acetate per spray.

12 Clinical Pharmacology ⮝

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 desmopressin acetate nasal solution 0.01% (nasal spray) in patients with central diabetes insipidus reduces urinary output, increases urine osmolality, and decreases plasma osmolality.

12.3 Pharmacokinetics

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.

Specific Populations

Renal Impairment

Desmopressin acetate is mainly excreted in the urine. A pharmacokinetic study was conducted in subjects with normal renal function and patients with mild, moderate, and severe renal impairment (n=24, 6 subjects each group) with a single 2 mcg dose of desmopressin acetate injection (this results in approximately 20 times the exposure of 10 mcg of desmopressin acetate nasal solution 0.01% (nasal spray)). The terminal half-life was 2.8 hours in subjects with normal renal function, 4.0 hours in mild renal impairment, 6.6 hours in moderate renal impairment and 8.7 hours in severe renal impairment. In patients with mild, moderate and severe renal impairment, mean desmopressin exposure was 1.5 fold, 2.4 fold and 3.6 fold higher, respectively compared to that of subjects with normal renal function [see Contraindications (4), Use in Specific Populations (8.6)].

13 Nonclinical Toxicology ⮝

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 How Supplied/storage And Handling ⮝

16.1 How Supplied

Desmopressin acetate nasal solution 0.01% (nasal spray), 10 mcg/ 0.1 mL per spray is available in a 5 mL bottle with the spray pump delivering 50 sprays of 10 mcg.

NDC 68382-384-01

16.2 Storage and Handling

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

Spl Unclassified ⮝

Manufactured by:

Cadila Healthcare Limited

Ahmedabad, India.

Distributed by:

Zydus Pharmaceuticals (USA) Inc.

Pennington, NJ 08534

Rev.: 12/18

Spl Patient Package Insert ⮝

Patient Information Desmopressin Acetate Nasal Solution 0.01% (des " moe pres ' in as ' e tate) (Nasal Spray), 10 mcg per 0.1 mL for Intranasal Use Only

What is desmopressin acetate nasal solution 0.01% (nasal spray)? Desmopressin acetate nasal solution 0.01% (nasal spray) is a prescription medicine called a vasopressin analog used as an antidiuretic replacement to manage central diabetes insipidus. Desmopressin acetate nasal solution 0.01% (nasal spray) is not effective in the treatment of nephrogenic diabetes insipidus. Desmopressin acetate nasal solution 0.01% (nasal spray) should not be used in people with nasal problems that may keep them from using a nasal spray.

Who should not use desmopressin acetate nasal solution 0.01% (nasal spray)? Do not use desmopressin acetate nasal solution 0.01% (nasal spray) if you: are allergic to desmopressin acetate nasal solution 0.01% (nasal spray) or any of the ingredients in desmopressin acetate nasal solution 0.01% (nasal spray). Some people have had severe allergic reactions while taking desmopressin acetate nasal solution 0.01% (nasal spray). See the end of this Patient Information for a complete list of ingredients in desmopressin acetate nasal solution 0.01% (nasal spray). have kidney problems have or have had low levels of sodium in your blood (hyponatremia)

What should I tell my healthcare provider before using desmopressin acetate nasal solution 0.01% (nasal spray)? Before using desmopressin acetate nasal solution 0.01% (nasal spray), tell your healthcare provider about all your medical conditions including if you: have or have had nasal sores, nasal surgery, nasal injury, or have problems such as a stuffy nose or trouble breathing through your nose. have or have had any heart, blood circulation, or blood pressure problems have a condition that causes fluid or water imbalance problems such as cystic fibrosis, or heart failure. have or have had a condition that causes you to be very thirsty are pregnant or plan to become pregnant. It is not known if desmopressin acetate nasal solution 0.01% (nasal spray) will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if desmopressin acetate nasal solution 0.01% (nasal spray) passes into your breast milk. You and your healthcare provider should decide if you will use desmopressin acetate nasal solution 0.01% (nasal spray). Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I use desmopressin acetate nasal solution 0.01% (nasal spray)? Read the Instructions for Use that comes with your desmopressin acetate nasal solution 0.01% (nasal spray). Use desmopressin acetate nasal solution 0.01% (nasal spray) exactly as your healthcare provider tells you to use it. Your healthcare provider may change your dose of desmopressin acetate nasal solution 0.01% (nasal spray) if needed.

What are the possible side effects of desmopressin acetate nasal solution 0.01% (nasal spray)? Desmopressin acetate nasal solution 0.01% (nasal spray) may cause serious side effects including: low levels of sodium in the blood (hyponatremia). People using desmopressin acetate nasal solution 0.01% (nasal spray) are at risk for low sodium levels in the blood, water intoxication, and fluid overload. Follow your healthcare provider's instructions on limiting the amount of fluid you can drink when using desmopressin acetate nasal solution 0.01% (nasal spray). Do not drink more than you need to satisfy your thirst. You can have serious side effects such as seizures, coma, and death from drinking too much fluid. Children and the elderly are at higher risk for these problems and should follow their healthcare provider's limits on drinking fluids. Call your healthcare provider right away if you have any of the following symptoms while using desmopressin acetate nasal solution 0.01% (nasal spray). They may mean that your blood sodium level is too low. headache restlessness disorientation feeling irritable hallucinations nausea, vomiting tiredness loss of appetite feeling weak confusion weight gain sleepiness muscle cramps nasal scarring or swelling. Some people using desmopressin acetate nasal solution 0.01% (nasal spray) for long periods of time may have nasal problems such as scarring or swelling. This may affect how well desmopressin acetate nasal solution 0.01% (nasal spray) works for you. The most common side effects of desmopressin acetate nasal solution 0.01% (nasal spray) include: headache, stuffy nose, runny nose, nosebleed, sore throat, cough, upper respiratory infections, nausea, flushing, and stomach cramps. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of desmopressin acetate nasal solution 0.01% (nasal spray). Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use desmopressin acetate nasal solution 0.01% (nasal spray) for a condition for which it was not prescribed. Do not give desmopressin acetate nasal solution 0.01% (nasal spray) to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about desmopressin acetate nasal solution 0.01% (nasal spray) that is written for health professionals. For more information call 1-877-993-8779

What are the ingredients in desmopressin acetate nasal solution 0.01% (nasal spray)? Active ingredient: desmopressin acetate, USP Inactive ingredients: benzalkonium chloride solution (50%), sodium chloride, citric acid monohydrate, disodium phosphate dihydrate, purified water

This Patient Information has been approved by the Food and Drug Administration

Manufactured by: Cadila Healthcare Limited Ahmedabad, India. Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 Rev.: 12/18

Package Label.principal Display Panel ⮝

NDC 68382-384-01

Desmopressin Acetate Nasal Solution 0.01% (Nasal Spray), 10 mcg/ 0.1 mL per spray

5 mL

Rx only

Zydus

DESMOPRESSIN ACETATE desmopressin acetate spray

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68382-384 Route of Administration NASAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DESMOPRESSIN ACETATE (UNII: XB13HYU18U) (DESMOPRESSIN - UNII:ENR1LLB0FP) DESMOPRESSIN ACETATE 0.1 mg in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE (UNII: 451W47IQ8X) CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP) SODIUM PHOSPHATE, DIBASIC, DIHYDRATE (UNII: 94255I6E2T) BENZALKONIUM CHLORIDE (UNII: F5UM2KM3W7) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68382-384-01 5 mL in 1 BOTTLE, SPRAY; Type 0: Not a Combination Product 02/01/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA091345 02/01/2018

Labeler - Zydus Pharmaceuticals (USA) Inc. (156861945)

Registrant - Zydus Pharmaceuticals (USA) Inc. (156861945)

Establishment
Name	Address	ID/FEI	Business Operations
Cadila Healthcare Limited		918596198	ANALYSIS(68382-384) , MANUFACTURE(68382-384)

Revised: 12/2018 Document Id: 01586ba1-31a5-4949-982a-fdd308c0fa5a 34391-3 Set id: 509693b1-5627-4440-83fa-79bc032a8034 Version: 4 Effective Time: 20181207 Zydus Pharmaceuticals (USA) Inc.

Desmopressin Acetate Nasal Spray 10 Mcg Per 0.1 Ml ⮝

Rx only

Description ⮝

Desmopressin Acetate Nasal Spray is a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation. It is chemically defined as follows:

Mol. wt. 1183.34

Empirical formula: C46H64N14O12S2 C2H4O2 3H2O

1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate.

Desmopressin Acetate Nasal Spray is provided as an aqueous solution for intranasal use.

Each mL contains:
Desmopressin acetate	0.1 mg
Sodium chloride	7.5 mg
Citric acid monohydrate	1.7 mg
Disodium phosphate dihydrate	3 mg
Benzalkonium chloride solution (50%)	0.2 mg

The Desmopressin Acetate Nasal Spray compression pump delivers 0.1 mL (10 mcg) of desmopressin acetate per spray.

Clinical Pharmacology ⮝

Desmopressin acetate contains as active substance 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin, which is a synthetic analogue of the natural hormone arginine vasopressin. One mL (0.1 mg) of intranasal desmopressin acetate has an antidiuretic activity of about 400 International Units (IU); 10 mcg of desmopressin acetate is equivalent to 40 IU. The change in structure of arginine vasopressin to desmopressin acetate has resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antiduretic activity, so that clinically effective antiduretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle.

Desmopressin acetate administered intranasally has an antiduretic effect about one-tenth that of an equivalent dose administered by injection.

Pharmacokinetics

Intranasal Desmopressin Acetate is absorbed from the nasal mucosa. Desmopressin Acetate exhibits a biphasic elimination profile, with half-lives of 7.8 and 75.5 minutes for the initial and terminal phases, respectively, in contrast to lysine vasopressin, which has initial and terminal phase half-lives of 2.5 and 14.5 minutes, respectively. Desmopressin Acetate is mainly excreted in the urine. A pharmacokinetic study conducted in healthy volunteers and patients with mild, moderate, and severe renal impairment (n=24, 6 subjects each group) receiving single dose Desmopressin Acetate (2 mcg) injection demonstrated a difference in Desmopressin Acetate half-life. Terminal half-life significantly increased from 3 hours in normal healthy patients to 9 hours in patients with severe renal impairment [see CONTRAINDICATIONS].

Warnings ⮝

1. For intranasal use only.

2. Desmopressin Acetate Nasal Spray should only be used in patients where orally administered formulations are not feasible.

3. Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with Desmopressin Acetate. Desmopressin Acetate is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required.

4. When Desmopressin Acetate Nasal Spray is administered, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward in order to decrease the potential occurrence of water intoxication and hyponatremia [see PRECAUTIONS, Pediatric Use and Geriatric Use]. All patients receiving Desmopressin Acetate therapy 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 may include one or a combination of the following: seizure, coma and/or respiratory arrest. Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma.

5. Desmopressin Acetate should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.

Precautions ⮝

General

Desmopressin Acetate Nasal Spray at high dosage has infrequently produced a slight elevation of blood pressure, which disappeared with a reduction in dosage. The drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease because of possible rise in blood pressure.

Desmopressin Acetate Nasal Spray should be used with caution in patients with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, heart failure and renal disorders because these patients are prone to hyponatremia.

Rare severe allergic reactions have been reported with desmopressin acetate. Anaphylaxis has been reported rarely with intravenous administration and intranasal administration of desmopressin acetate.

Central Cranial Diabetes Insipidus

Since Desmopressin Acetate is used intranasally, changes in the nasal mucosa such as scarring, edema, or other disease may cause erratic, unreliable absorption in which case intranasal Desmopressin Acetate should not be used. For such situations, desmopressin acetate injection should be considered.

Information for Patients

Ensure that in children administration is under adult supervision in order to control the dose intake. Patients should be informed that the Desmopressin Acetate Nasal Spray bottle accurately delivers 50 sprays of 10 mcg each. Any solution remaining after 50 sprays should be discarded since the amount delivered thereafter may be substantially less than 10 mcg of drug. No attempt should be made to transfer remaining solution to another bottle. Patients should be instructed to read accompanying directions on use of the spray pump carefully before use.

Fluid intake should be adjusted downward based upon discussion with the physician.

Laboratory Tests

Laboratory tests for following the patient with central cranial diabetes insipidus or post-surgical or head trauma-related polyuria and polydipsia include urine volume and osmolality. In some cases plasma osmolality measurements may be required.

Drug Interactions

Although the pressor activity of Desmopressin Acetate is very low compared to the antidiuretic activity, use of large doses of intranasal Desmopressin Acetate with other pressor agents should only be done with careful patient monitoring. The concomitant administration of 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 and carbamazepine) should be performed with caution.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Pregnancy Category B

Fertility studies have not been done. Teratology studies in rats and rabbits at doses from 0.05 to 10 mcg/kg/day (approximately 0.1 times the maximum systemic human exposure in rats and up to 38 times the maximum systemic human exposure in rabbits based on surface area, mg/m2) revealed no harm to the fetus due to desmopressin acetate. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Several publications of desmopressin acetate's use in the management of diabetes insipidus during pregnancy are available; these include a few anecdotal reports of congenital anomalies and low birth weight babies. However, no causal connection between these events and desmopressin acetate has been established. A fifteen year Swedish epidemiologic study of the use of desmopressin acetate in pregnant women with diabetes insipidus found the rate of birth defects to be no greater than that in the general population. However, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action and the physician will have to weigh the therapeutic advantages against the possible risks in each case.

Nursing Mothers

There have been no controlled studies in nursing mothers. A single study in postpartum women demonstrated a marked change in plasma, but little if any change in assayable desmopressin acetate in breast milk following an intranasal dose of 10 mcg. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when desmopressin acetate is administered to a nursing woman.

Pediatric Use

Central Cranial Diabetes Insipidus

Desmopressin Acetate Nasal Spray has been used in children with diabetes insipidus. Use in infants and children will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication (see WARNINGS). The dose must be individually adjusted to the patient with attention in the very young to the danger of an extreme decrease in plasma osmolality with resulting convulsions. Dose should start at 0.05 mL or less. Since the spray cannot deliver less than 0.1 mL (10 mcg), smaller doses should be administered using the rhinal tube delivery system. Do not use the nasal spray in pediatric patients requiring less than 0.1 mL (10 mcg) per dose.

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. Other reported clinical experience has not identified differences in responses between the elderly and 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.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Desmopressin Acetate is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min) [see CLINICAL PHARMACOLOGY, Human Pharmacokinetics and CONTRAINDICATIONS].

Use of Desmopressin Acetate Nasal Spray in geriatric patients will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication [see WARNINGS].

There are reports of an occasional change in response with time, usually greater than 6 months. Some patients may show a decreased responsiveness, others a shortened duration of effect. There is no evidence this is due to the development of binding antibodies but may be due to a local inactivation of the peptide.

Overdosage ⮝

Signs of overdosage may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention [see WARNINGS]. In case of overdosage, the dose should be reduced, frequency of administration decreased, or the drug withdrawn according to the severity of the condition. There is no known specific antidote for desmopressin acetate or Desmopressin Acetate Nasal Spray.

An oral LD50 has not been established. An intravenous dose of 2 mg/kg in mice demonstrated no effect.

How Supplied ⮝

Desmopressin Acetate Nasal Spray is available as a 5 mL bottle with spray pump delivering 50 sprays of 10 mcg (NDC 69918-501-05).

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

Keep out of the reach of children.
U.S. Pat. Nos. 5,500,413, 5,596,078, and 5,674,850

Toll free number for providers and patients to call with questions:
1-844-Amring1 (1-844-267-4641)

Manufactured for:
Amring Pharmaceuticals Inc.
Berwyn, PA 19312

Origin Germany

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Instructions For Usedesmopressin Acetatenasal Spray, 10 Mcg Per 0.1 Mlfor Intranasal Use Only ⮝

Read these instructions before using Desmopressin Acetate nasal spray, and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

Children should be helped by an adult when using Desmopressin Acetate nasal spray, to make sure the right amount of medicine is used.

The parts of your Desmopressin Acetate nasal spray pump (See Figure A):

Figure A

Priming your Desmopressin Acetate nasal spray:

Your Desmopressin Acetate nasal spray pump must be primed before you use it for the first time.

• Remove the protective cap (See Figure B).

Figure B

• Press down on the shoulders at the top of your Desmopressin Acetate nasal spray pump 4 times. Hold the spray tip away from your face and eyes (See Figure C).

Figure C

• After your Desmopressin Acetate nasal spray pump is primed, it will spray 10 micrograms (1 dose) of medicine each time it is pressed.

Using your Desmopressin Acetate nasal spray:

Step 1. Remove the protective cap.

Step 2. To make sure you get the right dose of medicine tilt your Desmopressin Acetate nasal spray pump so the dip tube inside the bottle draws the medicine up from the deepest part of the medicine inside the bottle (See Figures D and E).

Figure D	Figure E

Step 3. Put the spray nozzle tip of your Desmopressin Acetate nasal spray into your nostril and press the spray pump 1 time for 1 dose. (See Figure F). If 2 doses are prescribed, spray each nostril 1 time.

Figure F

Step 4. Put the protective cap back on the spray nozzle tip when you finish using your Desmopressin Acetate nasal spray.

Keeping track of your nasal sprays:

• Use the check-off chart to help you keep track of your Desmopressin Acetate nasal sprays used (See Figure G).

Desmopressin Acetate nasal spray 50-Spray Check-off Chart

Figure G

• Keep this chart with your Desmopressin Acetate nasal spray or put it someplace where you can easily get it.
• Check off number 1 on the chart with your first dose of Desmopressin Acetate nasal spray. Check off the numbers after each use of your Desmopressin Acetate nasal spray. If your healthcare provider prescribed a 2-spray dose, then 2 numbers should be checked off.
• Your Desmopressin Acetate nasal spray holds 50 sprays with the right amount of medicine in each spray.
• If any medicine is left in your Desmopressin Acetate nasal spray after 50 sprays, do not use it. You may not get the right amount of medicine.
• Throw away your Desmopressin Acetate nasal spray after 50 sprays.
• Do not count the priming sprays. Your Desmopressin Acetate nasal spray has been filled with extra medicine for your priming sprays.
• Do not try to remove any medicine from your Desmopressin Acetate nasal spray pump and place it in another bottle.

How should I store Desmopressin Acetate nasal spray?

• Store Desmopressin Acetate nasal spray at room temperature between 68 F to 77 F (20 C to 25 C).
• Store Desmopressin Acetate nasal spray standing upright.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured for:
Amring Pharmaceuticals Inc.
Berwyn, PA 19312

Origin Germany

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Principal Display Panel - 5 Ml Bottle Carton ⮝

NDC 69918-501-05

Desmopressin
Acetate

Nasal Spray

10 mcg per 0.1 mL

Rx Only

5 mL
(50 sprays)

Attention Pharmacist-
detach patient's
instructions from
package insert and
dispense with spray pump.

AMRING
PHARMACEUTICALS

DESMOPRESSIN ACETATE desmopressin acetate spray

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:69918-501 Route of Administration NASAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Desmopressin Acetate (UNII: XB13HYU18U) (desmopressin - UNII:ENR1LLB0FP) Desmopressin Acetate 10 ug in 0.1 mL

Inactive Ingredients Ingredient Name Strength Sodium Chloride (UNII: 451W47IQ8X) Citric Acid Monohydrate (UNII: 2968PHW8QP) Sodium Phosphate, Dibasic Dihydrate (UNII: 94255I6E2T) Benzalkonium Chloride (UNII: F5UM2KM3W7)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:69918-501-05 1 in 1 CARTON 1 5 mL in 1 BOTTLE, SPRAY; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA AUTHORIZED GENERIC NDA017922 03/01/2016

Labeler - Amring Pharmaceuticals, Inc. (079843051)

Registrant - Ferring International Center S.A. (481210362)

Establishment
Name	Address	ID/FEI	Business Operations
Ferring International Center S.A.		481210362	MANUFACTURE(69918-501)

Revised: 2/2016 Document Id: e904b7bc-16c7-4597-91b6-c25ad890cfe1 34391-3 Set id: f22be3d4-53f7-451b-87a9-23e2948bbca0 Version: 1 Effective Time: 20160222 Amring Pharmaceuticals, Inc.