DDAVP Nasal Spray

DDAVP Nasal Spray is contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of DDAVP Nasal Spray.

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

DDAVP is contraindicated in patients with hyponatremia or a history of hyponatremia.

General

Intranasal DDAVP 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.

DDAVP 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 DDAVP. Anaphylaxis has been reported rarely with intravenous and intranasal administration of DDAVP.

Central Cranial Diabetes Insipidus

Since DDAVP is used intranasally, changes in the nasal mucosa such as scarring, edema, or other disease may cause erratic, unreliable absorption in which case intranasal DDAVP should not be used. For such situations, DDAVP 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 DDAVP Nasal Spray 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 DDAVP is very low compared to the antidiuretic activity, use of large doses of intranasal DDAVP 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 DDAVP 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 DDAVP (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 DDAVP 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 DDAVP is administered to a nursing woman.

Pediatric Use

Central Cranial Diabetes Insipidus

DDAVP Nasal Spray has been used in children with diabetes insipidus. Use in infants and children will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication. (See WARNINGS.) The dose must be individually adjusted to the patient with attention in the very young to the danger of an extreme decrease in plasma osmolality with resulting convulsions. Dose should start at 0.05 mL or less.

Since the spray cannot deliver less than 0.1 mL (10 mcg), smaller doses should be administered using the rhinal tube delivery system. Do not use the nasal spray in pediatric patients requiring less than 0.1 mL (10 mcg) per dose.

Geriatric Use

Clinical studies of DDAVP Nasal Spray did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at 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. DDAVP 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 DDAVP Nasal Spray in geriatric patients will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication. (See WARNINGS).

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

Infrequently, high dosages of intranasal DDAVP 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.

ADVERSE REACTION	PLACEBO (N=59)	DDAVP 20 mcg (N=60)	DDAVP 40 mcg (N=61)
	%	%	%
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.

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 DDAVP Nasal Spray.

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

DDAVP® Nasal Spray
(desmopressin acetate)

A better way to deliver DDAVP

Delivering DDAVP more efficiently

Your doctor has prescribed DDAVP 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 DDAVP Nasal Spray Pump

1. Remove protective cap. 2. The spray pump must be primed prior to the first use. To prime pump, press down 4 times. 3. Once primed, the spray pump delivers 10 micrograms of medication each time it is pressed. To ensure dosing accuracy, tilt bottle so that dip tube inside the bottle draws from the deepest portion of the medication.

To administer a 10-microgram 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. The pump will stay primed for up to one week. 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. DDAVP Nasal Spray 50-Dose Check-off

1	2	3	4	5
6	7	8	9	10
11	12	13	14	15
16	17	18	19	20
21	22	23	24	25
26	27	28	29	30
31	32	33	34	35
36	37	38	39	40
41	42	43	44	45
46	47	48	49	50

1. Retain with medication or affix in convenient location. 2. Starting with dose #1, check off after each administration. 3. Discard medication after 50 doses.

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

STORE BOTTLE IN UPRIGHT POSITION.

Manufactured for:
Ferring Pharmaceuticals Inc.
Parsippany, NJ 07054 USA

Origin Sweden

Rev. 04/2015

2009054172

Primary Nocturnal Enuresis:  DDAVP Nasal Spray is indicated for the management of primary nocturnal enuresis. It may be used alone or adjunctive to behavioral conditioning or other nonpharmacological intervention. It has been shown to be effective in some cases that are refractory to conventional therapies.

Central Cranial Diabetes Insipidus:  DDAVP Nasal Spray 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 DDAVP Nasal Spray 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 DDAVP can be monitored by urine volume and osmolality.

DDAVP 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 transphenoidal hypophysectomy create situations where an alternative route of administration is needed as in cases of nasal packing or recovery from surgery.

1. For intranasal use only.
2. When DDAVP Nasal Spray is administered, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward in order to decrease the potential occurrence of water intoxication and hyponatremia with accompanying signs and symptoms (headache, nausea/vomiting, decreased serum sodium and weight gain). 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.

DDAVP Nasal Spray is available in a 5-mL bottle with spray pump delivering 50 sprays of 10 µg (NDC 0075-2452-01). Desmopressin acetate is also available as DDAVP Rhinal Tube, a refrigerated product with 2.5 mL per vial, packaged with two rhinal tube applicators per carton (NDC 0075-2450-01).

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

STORE BOTTLE IN UPRIGHT POSITION.

Rx Only.

Keep out of the reach of children.

Manufactured for:

Aventis Pharmaceuticals Inc.

Bridgewater, NJ 08807

By Ferring AB, Soldattorpsvägen 5

SE-200 G1 Limhamn, Sweden

Rev. December 2002

©2002 Aventis Pharmaceuticals Inc.

PRODUCT PHOTO(S):

NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug's identity should be verified by chemical analysis.