DESMOPRESSIN ACETATE solution
For Healthcare Providers >

1. Patient Information
2. Hat Is Desmopressin Acetate Nasal Solution 0.01% (nasal Spray)?
3. Are Allergic To Desmopressin Acetate 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). Before Using Desmopressin Acetate Nasal Solution 0.01% (nasal Spray), Tell Your Healthcare Provider About All Your Medical Conditions Including If You:
4. How Should I Use Desmopressin Acetate Nasal Solution 0.01% (nasal Spray)?
5. Desmopressin Acetate Nasal Solution 0.01% (nasal Spray) May Cause Serious Side Effects Including:
6. Hat Are The Ingredients In Desmopressin Acetate Nasal Solution 0.01% (nasal Spray)?
7. Tive Ingredient:
8. Inactive Ingredients:

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.


Distributed by:
Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512

Manufactured by:
Sun Pharmaceutical Industries Ltd.
Halol-Baroda Highway,
Halol-389 350, Gujarat, India.

ISS. 01/2019
PJPI0438C

Hat 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.

W

Are Allergic To Desmopressin Acetate 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). 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 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 theInstructions for Usethat 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.

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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 notdrink 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 nausea, vomiting weight gain
    • restlessness tiredness sleepiness
    • disorientation loss of appetite
    • feeling irritable feeling weak muscle cramps
    • hallucinations confusion
• 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 1-800-818-4555.
W

Hat Are The Ingredients In Desmopressin Acetate Nasal Solution 0.01% (nasal Spray)? ⮝

Ac

Tive Ingredient: ⮝

desmopressin acetate, USP

Inactive Ingredients: ⮝

benzalkonium chloride solution (50%), sodium chloride, citric acid monohydrate, disodium phosphate dihydrate

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

Instructions for Use

Desmopressin Acetate Nasal Solution 0.01% (Nasal Spray)
10 mcg per 0.1 mL for Intranasal Use Only

Read these instructions before using desmopressin acetate nasal solution 0.01% (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 solution 0.01% (nasal spray), to make sure the right amount of medicine is used.

The parts of your desmopressin acetate nasal solution 0.01% (nasal spray) pump
(

Store desmopressin acetate nasal solution 0.01% (nasal spray) at room temperature between 68 F to 77 F (20 C to 25 C).
Store desmopressin acetate nasal solution 0.01% (nasal spray) standing upright.

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

Distributed by:
Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512

Manufactured by:
Sun Pharmaceutical Industries Ltd.
Halol-Baroda Highway,
Halol-389 350, Gujarat, India.

Rev. 01/19

1. No Title 1572547132
2. No Title 1572449107
3. Principal Display Panel - 10 Ml Vial Carton
4. Principal Display Panel - Ten 1 Ml Ampule Carton
5. Desmopressin Acetatenasal Spray Solution, 10 Mcg/0.1 Ml
6. Description
7. Clinical Pharmacology
8. Indications And Usage
9. Contraindications
10. Warnings
11. Precautions
12. Adverse Reactions
13. Overdosage
14. Dosage And Administration
15. How Supplied
16. Patient Instructions
17. Principal Display Panel-desmopressin Acetate Nasal Spray Solution, 10 Mcg/0.1 Ml
18. Highlights Of Prescribing Information
19. Dosage Forms And Strengths
20. Warnings And Precautions
21. Drug Interactions
22. Use In Specific Populations
23. 1 Indications & Usage
24. 2 Dosage & Administration
25. 3 Dosage Forms & Strengths
26. 4 Contraindications
27. 5 Warnings And Precautions
28. 6 Adverse Reactions
29. 7 Drug Interactions
30. 8 Use In Specific Populations
31. 10 Overdosage
32. 11 Description
33. 12 Clinical Pharmacology
34. 13 Nonclinical Toxicology
35. 16 How Supplied/storage And Handling
36. Package Label.principal Display Panel
37. Desmopressin Acetatenasal Solution, 0.01%
38. Description:
39. Clinical Pharmacology:
40. Indications And Usage:
41. Contraindication:
42. Warnings:
43. Precautions:
44. Adverse Reactions:
45. Overdosage:
46. Dosage And Administration:
47. How Supplied:
48. Principal Display Panel
49. Contraindications:
50. Patient Instruction Guide
51. Package Label.principal Display Panel - Label
52. Package Label.principal Display Panel - Carton

No Title 1572547132 ⮝

Manufactured for:
AMRING PHARMACEUTICALS INC.
BERWYN, PA 19132
Origin Sweden

1.1 US Patents 5,500,413; 5,763,407

Rev. 07/2015
2009054056

No Title 1572449107 ⮝

Manufactured for:
AMRING PHARMACEUTICALS INC.
BERWYN, PA 19132
Origin Sweden

1.1 US Patents 5,500,413; 5,763,407

Rev. 07/2015
2009054056

Principal Display Panel - 10 Ml Vial Carton ⮝

10 mL vial
4 mcg/mL

NDC 69918-901-10

Desmopressin
Acetate
Injection

AMRING
PHARMACEUTICALS

Principal Display Panel - Ten 1 Ml Ampule Carton ⮝

NDC 69918-899-10

DESMOPRESSIN
ACETATE
Injection

PRESERVATIVE FREE
For Intravenous
and Subcutaneous
Use Only

Ten 1 mL Ampules

AMRING
PHARMACEUTICALS

DESMOPRESSIN ACETATE desmopressin acetate solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:69918-901 Route of Administration INTRAVENOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Desmopressin Acetate (UNII: XB13HYU18U) (desmopressin - UNII:ENR1LLB0FP) Desmopressin Acetate 4 ug in 1 mL

Inactive Ingredients Ingredient Name Strength Sodium Chloride (UNII: 451W47IQ8X) Hydrochloric Acid (UNII: QTT17582CB) Chlorobutanol (UNII: HM4YQM8WRC)

Product Characteristics Color WHITE Score Shape Size Flavor Imprint Code Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:69918-901-10 1 in 1 CARTON 10/26/1999 1 10 mL in 1 VIAL, MULTI-DOSE; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA018938 10/26/1999

DESMOPRESSIN ACETATE desmopressin acetate solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:69918-899 Route of Administration INTRAVENOUS

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Desmopressin Acetate (UNII: XB13HYU18U) (desmopressin - UNII:ENR1LLB0FP) Desmopressin Acetate 4 ug in 1 mL

Inactive Ingredients Ingredient Name Strength Sodium Chloride (UNII: 451W47IQ8X) Hydrochloric Acid (UNII: QTT17582CB)

Product Characteristics Color WHITE Score Shape Size Flavor Imprint Code Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:69918-899-10 10 in 1 CARTON 10/26/1999 1 1 mL in 1 AMPULE; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product) 2 NDC:69918-899-01 1 mL in 1 AMPULE; Type 9: Other Type of Part 3 Combination Product (e.g., Drug/Device/Biological Product) 10/26/1999

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA018938 10/26/1999

Labeler - Amring Pharmaceuticals Inc. (079843051)

Establishment
Name	Address	ID/FEI	Business Operations
Rechon Life Science AB		775207769	MANUFACTURE(69918-899, 69918-901)

Establishment
Name	Address	ID/FEI	Business Operations
Ferring International Center S.A.		481210362	PACK(69918-899, 69918-901)

Revised: 5/2016 Document Id: e9be4ef2-067c-4c01-b1cc-7bb6f464c0ba 34391-3 Set id: 29df0492-f7ef-47bb-aa67-4ef9e5c2846f Version: 2 Effective Time: 20160511 Amring Pharmaceuticals Inc.

Desmopressin Acetatenasal Spray Solution, 10 Mcg/0.1 Ml  ⮝

Rx only
FOR INTRANASAL USE ONLY

Description ⮝

DESMOPRESSIN ACETATE Injection (desmopressin acetate) 4 mcg/mL 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 ACEATE Injection 4 mcg/mL is provided as a sterile, aqueous solution for injection.

Each mL provides:

Desmopressin acetate 4.0 mcg

Sodium chloride 9.0 mg

Hydrochloric acid to adjust pH to 4

The 10 mL vial contains chlorobutanol as a preservative (5.0 mg/mL).

Clinical Pharmacology ⮝

DESMOPRESSIN ACETATE Injection 4 mcg/mL contains as active substance, desmopressin acetate, a synthetic analogue of the natural hormone arginine vasopressin. One mL (4 mcg) of DESMOPRESSIN ACETATE (desmopressin acetate) solution has an antidiuretic activity of about 16 IU; 1 mcg of DESMOPRESSIN ACETATE is equivalent to 4 IU.

DESMOPRESSIN ACETATE has been shown to be more potent than arginine vasopressin in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand's disease Type I.

Dose-response studies were performed in healthy persons, using doses of 0.1 to 0.4 mcg/kg body weight, infused over a 10-minute period. Maximal dose response occurred at 0.3 to 0.4 mcg/kg. The response to DESMOPRESSIN ACETATE of factor VIII activity and plasminogen activator is dose-related, with maximal plasma levels of 300 to 400 percent of initial concentrations obtained after infusion of 0.4 mcg/kg body weight. The increase is rapid and evident within 30 minutes, reaching a maximum at a point ranging from 90 minutes to two hours. The factor VIII related antigen and ristocetin cofactor activity were also increased to a smaller degree, but still are dose-dependent.

1. The biphasic half-lives of DESMOPRESSIN ACETATE were 7.8 and 75.5 minutes for the fast and slow phases, respectively, compared with 2.5 and 14.5 minutes for lysine vasopressin, another form of the hormone. As a result, DESMOPRESSIN ACETATE provides a prompt onset of antidiuretic action with a long duration after each administration.
2. 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 antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle.
3. When administered by injection, DESMOPRESSIN ACETATE has an antidiuretic effect about ten times that of an equivalent dose administered intranasally.
4. The bioavailability of the subcutaneous route of administration was determined qualitatively using urine output data. The exact fraction of drug absorbed by that route of administration has not been quantitatively determined.
5. The percentage increase of factor VIII levels in patients with mild hemophilia A and von Willebrand's disease was not significantly different from that observed in normal healthy individuals when treated with 0.3 mcg/kg of DESMOPRESSIN ACETATE infused over 10 minutes.
6. Plasminogen activator activity increases rapidly after DESMOPRESSIN ACETATE infusion, but there has been no clinically significant fibrinolysis in patients treated with DESMOPRESSIN ACETATE.
7. The effect of repeated DESMOPRESSIN ACETATE administration when doses were given every 12 to 24 hours has generally shown a gradual diminution of the factor VIII activity increase noted with a single dose. The initial response is reproducible in any particular patient if there are 2 or 3 days between administrations.

   
   

Human Pharmacokinetics: 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 in each group) receiving single dose desmopressin acetate (2mcg) injection demonstrated a difference in DESMOPRESSIN ACETATE terminal 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.)

Indications And Usage ⮝

Desmopressin acetate 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) (1)

Limitations of Use:

Desmopressin acetate is not indicated for: (1)

• 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)

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) (4)

Warnings ⮝

1. Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with DESMOPRESSIN ACETATE (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.

2. When DESMOPRESSIN ACETATE Injection is administered to patients who do not have need of antidiuretic hormone for its antidiuretic effect, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia. (See PRECAUTIONS, Pediatric Use and Generic 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 of 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.

3. DESMOPRESSIN ACETATE should not be used to treat patients with Type IIB von Willebrand's disease since platelet aggregation may be induced.

4. 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: For injection use only.

DESMOPRESSIN ACETATE Injection (desmopressin acetate) 4 mcg/mL has infrequently produced changes in blood pressure causing either a slight elevation in blood pressure or a transient fall in blood pressure and a compensatory increase in heart rate. The drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease.

DESMOPRESSIN ACETATE (desmopressin acetate) 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.

There have been rare reports of thrombotic events following DESMOPRESSIN ACETATE Injection 4 mcg/mL in patients predisposed to thrombus formation. No causality has been determined, however, the drug should be used with caution in these patients.

Severe allergic reactions have been reported rarely. Anaphylaxis has been reported rarely with intravenous and intranasal DESMOPRESSIN ACETATE, including isolated cases of fatal anaphylaxis with intravenous DESMOPRESSIN ACETATE. It is not known whether antibodies to DESMOPRESSIN ACETATE Injection 4 mcg/mL are produced after repeated injections.

Hemophilia A: Laboratory tests for assessing patient status include levels of factor VIII coagulant, factor VIII antigen and factor VIII ristocetin cofactor (von Willebrand factor) as well as activated partial thromboplastin time. Factor VIII coagulant activity should be determined before giving DESMOPRESSIN ACETATE for hemostasis. If factor VIII coagulant activity is present at less than 5% of normal, DESMOPRESSIN ACETATE should not be relied on.

von WIllebrand's Disease: Laboratory tests for assessing patient status include levels of factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII von Willebrand factor antigen. The skin bleeding time may be helpful in following these patients.

Diabetes Insipidus: Laboratory tests for monitoring the patient include urine volume and osmolality. In some cases, plasma osmolality may be required.

Drug Interactions: Although the pressor activity of DESMOPRESSIN ACETATE is very low compared with the antidiuretic activity, use of doses as large as 0.3 mcg/kg of DESMOPRESSIN ACETATE with other pressor agents should be done only 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.

DESMOPRESSIN ACETATE has been used with epsilon aminocaproic acid without adverse effects.

Carcinogenicity, Mutagenicity, 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: Use in infants and pediatric patients will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication. Fluid restriction should be discussed with the patient and/or guardian. (See WARNINGS .) DESMOPRESSIN ACETATE Injection 4 mcg/mL should not be used in infants less than three months of age in the treatment of hemophilia A or von Willebrand's disease; safety and effectiveness in pediatric patients under 12 years of age with diabetes insipidus have not been established.

Geriatric Use: Clinical studies of DESMOPRESSIN ACETATE Injection 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 patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other 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 50ml/min). (See CLINICAL PHARMACOLOGY, Human Pharmacokinetics, and CONTRAINDICATIONS.)

Use of DESMOPRESSIN ACETATE injection in geriatric patients will require careful fluid intake restrictions to prevent possible hyponatremia and water intoxication. Fluid restriction should be discussed with the patient. (See WARNINGS.)

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 Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. (6)

Overdosage ⮝

Signs of overdose 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 dosage 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 Injection 4 mcg/mL.

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

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)

How Supplied ⮝

DESMOPRESSIN ACETATE Injection 4 mcg/mL is available as a sterile solution in cartons of ten 1 mL single-dose ampules (NDC 69918-899-10) and in 10 mL multiple-dose vials (NDC 69918-901-10), each containing 4.0 mcg DESMOPRESSIN ACETATE per mL.

Store refrigerated 2 to 8 C (36 to 46 F).

Keep out of the reach of children.

Patient Instructions ⮝

Desmopressin Acetate
Nasal Solution, 0.01%

A BETTER WAY TO DELIVER DESMOPRESSIN ACETATE NASAL SOLUTION

DELIVERING DESMOPRESSIN ACETATE MORE EFFICIENTLY

Your doctor has prescribed desmopressin acetate nasal solution as antidiuretic hormone replacement therapy. Follow the dosage schedule that is specified. The convenient nasal spray pump provides an efficient, reliable way to administer your medication. It is important, however, to adhere completely to the following instructions so that you will always receive a consistent dose of your medication.

CAUTION: The nasal spray pump accurately delivers 50 sprays of 10 micrograms each. Any solution remaining after 50 sprays should be discarded since the amount delivered in each spray thereafter may be substantially less than 10 micrograms of the drug. Do not transfer any remaining solution to another bottle. Please read the following instructions carefully before using the spray pump.

Ensure that in children administration is under adult supervision in order to control the dose intake.

If you accidentally deliver/administer too much of a dose, immediately telephone your doctor or a certified Regional Poison Center for advice. Possible signs of overdose may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention.

USING YOUR DESMOPRESSIN ACETATE NASAL SPRAY PUMP

1. Remove protective cap.
2. The spray pump must be primed prior to the first use. To prime the pump, hold the bottle as shown in Figure A and press down with a quick and firm motion a total of five (5) times. This initial priming is very important to assure you receive the correct amount of the solution when you begin to administer the product. The bottle is filled with extra solution to accommodate for this priming activity.
3. Once primed, the spray pump will deliver the correct amount of solution each time it is pressed. To administer, hold bottle upright as shown in Figure A and place the spray nozzle in nostril. Then press the spray pump once with a quick and firm motion. To ensure dosing accuracy, it is very important to hold the bottle upright while administering the solution; it may be necessary to lean your head slightly forward so as to not tilt the bottle. Tilting the bottle, especially when less than half of the solution is left, may cause the pump to not dispense correctly. NOTE - If necessary, clear nasal passages before administering.
   
4. If a higher dose (or more than one spray) is prescribed, spray half the dose in each nostril. For example, if 4 sprays are prescribed, administer two sprays into each nostril. Please note that the spray pump cannot be used for doses less than 10 micrograms or doses other than multiples of 10 micrograms.
5. Replace the protective cap on bottle after use and store in the refrigerator in an upright position. The pump will stay primed for up to one week under refrigeration. If the product has not been used for a period of one week, re-prime the pump by pressing once.
6. We have included a convenient check-off chart to assist you in keeping track of the number of sprays (doses) used. This will help assure that you receive the labeled 50 sprays (doses) after the initial priming activity. As mentioned above, please discard any remaining solution after administering the 50 sprays as the correct dosage cannot be assured past this point.

Storage: Store in refrigerator at 2 -8 C (36 -46 F). When traveling, product will maintain stability for up to 3 weeks when stored at room temperature, 22 C (72 F).

Principal Display Panel-desmopressin Acetate Nasal Spray Solution, 10 Mcg/0.1 Ml ⮝

NDC 24208-342-05

Desmopressin

Acetate

Nasal Spray

Solution,

10 mcg/0.1 mL

FOR INTRANASAL
USE ONLY

50 sprays

10 mcg per spray

Rx only 5 mL

BAUSCH + LOMB

DESMOPRESSIN ACETATE desmopressin acetate solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:24208-342 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) WATER (UNII: 059QF0KO0R) HYDROCHLORIC ACID (UNII: QTT17582CB) CHLOROBUTANOL (UNII: HM4YQM8WRC)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:24208-342-05 1 in 1 CARTON 01/25/1999 1 5 mL in 1 BOTTLE, PUMP; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074830 01/25/1999

Labeler - Bauch & Lomb Incorporated (196603781)

Establishment
Name	Address	ID/FEI	Business Operations
Bauch & Lomb Incorporated		079587625	MANUFACTURE(24208-342) , PACK(24208-342) , LABEL(24208-342)

Establishment
Name	Address	ID/FEI	Business Operations
Quality Packaging Specialists International, LLC		078440982	LABEL(24208-342) , PACK(24208-342)

Revised: 10/2018 Document Id: 340a8d9d-4114-42a6-9a07-4436ddfee2fd 34391-3 Set id: 8ca799f1-7029-4527-9ab4-7512504bb8e2 Version: 10 Effective Time: 20181008 Bauch & Lomb Incorporated

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use DESMOPRESSIN ACETATE NASAL SOLUTION safely and effectively. See full prescribing information for DESMOPRESSIN ACETATE NASAL SOLUTION.
DESMOPRESSIN ACETATE nasal solution
Initial U.S. Approval: 1978

Dosage Forms And Strengths ⮝

Desmopressin acetate nasal solution (nasal spray): 10 mcg per 0.1 mL spray, available in a 5 mL bottle with spray pump delivering 50 sprays (3) (3)

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) (5)

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) dosage (7.2) (7)

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) (8)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 1/2019

1 Indications & 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 & 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 & Strengths ⮝

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

Desmopressin acetate nasal solution 0.01% (nasal spray) is available as a 5 mL bottle with spray pump delivering 50 sprays.

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 2-4% and 15-20%, 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 - 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, USP is a vasopressin 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 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 mg
Benzalkonium chloride solution (50%) 0.2 mg

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) is available as a 5mL bottle containing an aqueous solution with the spray pump delivering 50 sprays of 10 mcg (0.1 mL) (NDC 47335-788-91).

16.2 Storage and Handling

Store at Controlled Room Temperature 20 to 25 C (68 to 77 F); excursion permitted to 15 C to 30 C (59 to 86 F) [see USP Controlled Room Temperature]. STORE BOTTLE IN UPRIGHT POSITION.

Package Label.principal Display Panel ⮝

Desmopressin Acetate Nasal Solution 0.01% - Bottle Label
NDC 47335-788-91
Desmopressin Acetate Nasal Solution 0.01% (Nasal Spray)
10 mcg/0.1 mL per spray
50 doses in a 5 mL bottle
Rx only
Needs no refrigeration

Desmopressin Acetate Nasal Solution 0.01% - Carton

NDC 47335-788-91
Desmopressin Acetate Nasal Solution 0.01% (Nasal Spray)
10 mcg/0.1 mL per spray
(0.01 mg/Spray)
FOR INTRANASAL USE ONLY
Needs no refrigeration
50 doses in a 5 mL bottle
Rx only
SUN PHARMA

DESMOPRESSIN ACETATE desmopressin acetate solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:47335-788 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)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:47335-788-91 1 in 1 CARTON 12/24/2013 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 ANDA ANDA078271 12/24/2013

Labeler - Sun Pharmaceutical Industries, Inc. (146974886)

Establishment
Name	Address	ID/FEI	Business Operations
Sun Pharmaceutical Industries Limited		725959238	ANALYSIS(47335-788) , MANUFACTURE(47335-788)

Revised: 1/2019 Document Id: df0d31d9-48f9-408d-9a97-58d8f9f97a0a 34391-3 Set id: b47d691e-28a9-4e10-92b8-310aecc2f953 Version: 5 Effective Time: 20190110 Sun Pharmaceutical Industries, Inc.

Desmopressin Acetatenasal Solution, 0.01% ⮝

Rx only
FOR INTRANASAL USE ONLY.

Description: ⮝

Desmopressin nasal spray solution, USP 0.01% 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
Molecular formula: C46H64N14O12S2 C2H4O2 3H2O

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

Desmopressin nasal spray solution, USP 0.01% is provided as an aqueous solution for intranasal use.

Each mL Contains:
Desmopressin Acetate, USP 0.1 mg
Sodium Chloride 9 mg
Hydrochloric Acid may be added to adjust pH (4.5 to 6)
Chlorobutanol (0.5%) 5.25 mg
Water for Injection q.s. to 1 mL
The desmopressin nasal spray solution, USP 0.01% compression pump delivers 0.1 mL (10 mcg) of desmopressin nasal spray solution, USP 0.01% per spray.

Clinical Pharmacology: ⮝

Desmopressin acetate 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 IU; 10 mcg of desmopressin acetate is equivalent to 40 IU.

1. The biphasic half-lives for intranasal desmopressin acetate were 7.8 and 75.5 minutes for the fast and slow phases, compared with 2.5 and 14.5 minutes for lysine vasopressin, another form of the hormone used in this condition. As a result, intranasal desmopressin acetate provides a prompt onset of antidiuretic action with a long duration after each administration.
2. 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 antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle.
3. Desmopressin acetate administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection.

Human Pharmacokinetics: 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 in each group) receiving single dose desmopressin acetate (2 mcg) injection demonstrated a difference in desmopressin acetate terminal 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.)

Indications And Usage: ⮝

Central Cranial Diabetes Insipidus: Desmopressin nasal spray solution, USP 0.01% is indicated as antidiuretic replacement therapy in the management of central cranial diabetes insipidus and for management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. It is ineffective for the treatment of nephrogenic diabetes insipidus.

The use of desmopressin nasal spray solution, USP 0.01% in patients with an established diagnosis will result in a reduction in urinary output with increase in urine osmolality and a decrease in plasma osmolality. This will allow the resumption of a more normal life-style with a decrease in urinary frequency and nocturia.

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 effect is due to the development of binding antibodies but may be due to a local inactivation of the peptide.

Patients are selected for therapy by establishing the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or the response to antidiuretic hormone. Continued response to intranasal desmopressin acetate can be monitored by urine volume and osmolality.

Desmopressin acetate is also available as a solution for injection when the intranasal route may be compromised. These situations include nasal congestion and blockage, nasal discharge, atrophy of nasal mucosa, and severe atrophic rhinitis. Intranasal delivery may also be inappropriate where there is an impaired level of consciousness. In addition, cranial surgical procedures, such as transsphenoidal hypophysectomy create situations where an alternative route of administration is needed as in cases of nasal packing or recovery from surgery.

Contraindication: ⮝

Desmopressin acetate nasal solution is contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of desmopressin acetate nasal solution.

Desmopressin acetate nasal solution is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min).

Desmopressin acetate nasal solution is contraindicated in patients with hyponatremia or a history of hyponatremia.

Warnings: ⮝

1. For intranasal use only.
2. Desmopressin nasal spray solution 0.01% 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 nasal spray solution 0.01% 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 nasal spray solution 0.01% 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 of 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 nasal spray solution 0.01% 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:

Intranasal desmopressin acetate 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 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 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 nasal spray solution 0.01% bottle accurately delivers 50 doses of 10 mcg each. Any solution remaining after 50 doses 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 a post-partum woman 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 nasal spray solution 0.01% 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 nasal spray solution 0.01% 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 the 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 nasal spray solution 0.01% 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 nasal spray solution 0.01% 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 effect is due to the development of binding antibodies but may be due to a local inactivation of the peptide.

Adverse Reactions: ⮝

Infrequently, high dosages of intranasal desmopressin acetate have produced transient headache and nausea. Nasal congestion, rhinitis and flushing have also been reported occasionally along with mild abdominal cramps. These symptoms disappeared with reduction in dosage. Nosebleed, sore throat, cough and upper respiratory infections have also been reported.

The following table lists the percentage of patients having adverse experiences without regard to relationship to study drug from the pooled pivotal study data for nocturnal enuresis.

		Desmopressin Acetate
	PLACEBO (N=59)	20 mcg (N=60)	40 mcg (N=61)
ADVERSE REACTION	%	%	%
BODY AS A WHOLE
Abdominal Pain	0	2	2
Asthenia	0	0	2
Chills	0	0	2
Headache	0	2	5
NERVOUS SYSTEM
Dizziness	0	0	3
RESPIRATORY SYSTEM
Epistaxis	2	3	0
Nostril Pain	0	2	0
Rhinitis	2	8	3
DIGESTIVE SYSTEM
Gastrointestinal Disorder	0	2	0
Nausea	0	0	2
SPECIAL SENSES
Conjunctivitis	0	2	0
Edema Eyes	0	2	0
Lachrymation Disorder	0	0	2

Post Marketing:

There have been rare reports of hyponatremic convulsions associated with concomitant use with the following medications: oxybutinin and imipramine.

See WARNINGS for the possibility of water intoxication and hyponatremia.

Overdosage: ⮝

Signs of overdose 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 nasal spray solution 0.01%.

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

Dosage And Administration: ⮝

Central Cranial Diabetes Insipidus:

Desmopressin nasal spray solution 0.01% dosage must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients with nasal congestion and blockage have often responded well to intranasal desmopressin acetate. The usual dosage range in adults is 0.1 mL to 0.4 mL daily, either as a single dose or divided into two or three doses. Most adults require 0.2 mL daily in two divided doses. The morning and evening doses should be separately adjusted for an adequate diurnal rhythm of water turnover. For children aged 3 months to 12 years, the usual dosage range is 0.05 mL to 0.3 mL daily, either as a single dose or divided into two doses. About 1/4 to 1/3 of patients can be controlled by a single daily dose of desmopressin acetate administered intranasally. Fluid restriction should be observed. (See WARNINGS, PRECAUTIONS, Pediatric Use and Geriatric Use.)

The nasal spray pump can only deliver doses of 0.1 mL (10 mcg) or multiples of 0.1 mL. If doses other than these are required, the rhinal tube delivery system may be used.

The spray pump must be primed prior to the first use. To prime pump, press down five (5) times. The bottle will now deliver 10 mcg of drug per spray. Discard desmopressin nasal spray solution 0.01%

after 50 sprays since the amount delivered thereafter per spray may be substantially less than 10 mcg of drug.

Geriatric Use:

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. (See CLINICAL PHARMACOLOGY, Human Pharmacokinetics, CONTRAINDICATIONS, and PRECAUTIONS, Geriatric Use.)

How Supplied: ⮝

Desmopressin nasal spray solution, USP 0.01% is available in a 5 mL bottle with spray pump delivering 50 sprays of 10 mcg (NDC 62756-161-91).

Storage:

Store in refrigerator at 2 -8 C (36 -46 F).

When traveling, product will maintain stability for up to 3 weeks when stored at room temperature, 22 C (72 F).

STORE BOTTLE IN UPRIGHT POSITION.

Keep out of reach of children


Distributed by:
Caraco Pharmaceutical Laboratories, Ltd.
1150 Elijah McCoy Drive, Detroit, MI 48202

Manufactured by:
Sun Pharmaceutical Industries Ltd.
Acme Plaza, Andheri-Kurla Road,
Andheri (East), Mumbai-400 059, India.

ISS

04/2012
PJPI0203A

Principal Display Panel ⮝

NDC 54868-5602-0

Desmopressin Acetate Nasal Solution, 0.01%

50 doses of 10 mcg

Rx only

[icon- nose] [icon- spray] [icon- 0.01%] [icon- 5 mL]

DESMOPRESSIN ACETATE desmopressin acetate solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-5602(NDC:24208-342) 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 CHLOROBUTANOL (UNII: HM4YQM8WRC) HYDROCHLORIC ACID (UNII: QTT17582CB) WATER (UNII: 059QF0KO0R) SODIUM CHLORIDE (UNII: 451W47IQ8X)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-5602-0 1 in 1 CARTON 1 5 mL in 1 BOTTLE, PUMP

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA074830 05/22/2006

Labeler - Physicians Total Care, Inc. (194123980)

Establishment
Name	Address	ID/FEI	Business Operations
Physicians Total Care, Inc.		194123980	relabel

Revised: 2/2011 Document Id: 983a15fb-e0d8-4e75-aa92-ade42e5e625a 34391-3 Set id: b3b68b3a-aa82-4464-8146-51d27861023d Version: 1 Effective Time: 20110218 Physicians Total Care, Inc.

Contraindications: ⮝

Desmopressin nasal spray solution 0.01% is contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of desmopressin nasal spray solution 0.01%.

Desmopressin acetate is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min).

Desmopressin acetate is contraindicated in patients with hyponatremia or a history of hyponatremia.

Patient Instruction Guide ⮝

Desmopressin Nasal Spray Solution, USP 0.01%

A better way to deliver desmopressin nasal spray solution, USP 0.01%

Delivering desmopressin nasal spray solution, USP 0.01% more efficiently

Your doctor has prescribed desmopressin nasal spray solution 0.01% as antidiuretic hormone replacement therapy. Follow the dosage schedule that is specified. The convenient nasal spray pump provides an efficient, reliable way to administer your medication. It is important, however, to adhere completely to the following instructions so that you will always receive a consistent dose of your medication.

CAUTION: The nasal spray pump accurately delivers 50 doses of 10 micrograms each. Any

solution remaining after 50 doses should be discarded since the amount delivered thereafter per actuation may be substantially less than 10 micrograms of drug. Do not transfer any remaining solution to another bottle. Please read the following instructions carefully before using the spray pump.

Ensure that in children administration is under adult supervision in order to control the dose intake.

If you accidentally deliver/administer too much of a dose, immediately telephone your doctor or a certified Regional Poison Center for advice. Possible signs of overdose may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention.

Using your Desmopressin Nasal Spray Solution 0.01% Pump

1. Remove protective cap.

2. The spray pump must be primed prior to the first use. To prime pump, press down five (5) times.

3. Once primed, the spray pump delivers 10 micrograms of medication each time it is pressed. To ensure dosing accuracy, hold bottle upright.

To administer a 10 micrograms dose, place the spray nozzle in nostril and press the spray pump once. If a higher dose has been prescribed, spray half the dose in each nostril. The spray pump cannot be used for doses less than 10 micrograms or doses other than multiples of 10 micrograms.

4. Replace the protective cap on bottle after use, and store in refrigerator. The pump will stay primed for up to one week under refrigeration. If the product has not been used for a period of one week, re-prime the pump by pressing once.

5. We have included a convenient check-off chart to assist you in keeping track of medication doses used. This will help assure that you receive 50 full doses of medication. Please note that the bottle has been filled with extra solution to accommodate the initial priming activity.

Storage: Store in refrigerator at 2 -8 C (36 -46 F). When traveling, product will maintain stability for up to 3 weeks when stored at room temperature, 22 C (72 F).

STORE BOTTLE IN UPRIGHT POSITION.

Distributed by:
Caraco Pharmaceutical Laboratories, Ltd.
1150 Elijah McCoy Drive Detroit, MI 48202

Manufactured by:
Sun Pharmaceutical Industries Ltd.
Acme Plaza, Andheri-Kurla Road,
Andheri (East), Mumbai-400 059. India. ISS. 04/2012
PJPI0203A

Package Label.principal Display Panel - Label ⮝

NDC 62756-161-91
Desmopressin Nasal Spray Solution, USP 0.01%
0.1 mg/mL
5 mL
REFRIGERATE
Rx only
FOR INTRANASAL USE ONLY.
50 doses of 10 mcg

Package Label.principal Display Panel - Carton ⮝

NDC 62756-161-91
Desmopressin Nasal Spray Solution, USP 0.01%
0.1 mg/mL
(0.01 mg/Spray)
FOR INTRANASAL USE ONLY.
Rx only
5 mL
50 doses of 10 mcg
SUN PHARMA

DESMOPRESSIN ACETATE desmopressin acetate solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:62756-161 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 CHLOROBUTANOL HEMIHYDRATE (UNII: 3X4P6271OX) 5.250 mg in 1 mL SODIUM CHLORIDE (UNII: 451W47IQ8X) 9 mg in 1 mL HYDROCHLORIC ACID (UNII: QTT17582CB) WATER (UNII: 059QF0KO0R)

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:62756-161-91 1 in 1 CARTON 04/14/2012 1 5 mL in 1 BOTTLE, PUMP; Type 0: Not a Combination Product

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA077212 04/14/2012

Labeler - Sun Pharmaceutical Industries, Inc. (146974886)

Establishment
Name	Address	ID/FEI	Business Operations
Sun Pharmaceutical Industries Limited		725959238	ANALYSIS(62756-161) , MANUFACTURE(62756-161)

Revised: 10/2018 Document Id: 670b5d06-9692-4b0b-999c-b7caf351830e 34391-3 Set id: ceee4883-6c49-4538-a747-354d0743b221 Version: 3 Effective Time: 20181025 Sun Pharmaceutical Industries, Inc.