Label: DESMOPRESSIN ACETATE solution

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.

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.)

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.

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.

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.

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.

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.

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).

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

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

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