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

Mol. Wt. 1183.34.............................Empirical Formula: C₄₆H₆₄N₁₄O₁₂S₂•C₂H₄O₂•3H₂O

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

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

Each mL contains:
Desmopressin acetate ..... 0.1 mg
Sodium Chloride ..... 7.5 mg
Citric acid monohydrate ..... 1.7 mg
Disodium phosphate dihydrate ..... 3.0 mg
Benzalkonium chloride solution (50%) ..... 0.2 mg

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

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

Central Cranial Diabetes Insipidus: DDAVP Nasal Spray 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 DDAVP. The usual dosage range in adults is 0.1 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 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 DDAVP 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 four times. The bottle will now deliver 10 mcg of drug per spray. Discard DDAVP Nasal Spray after 50 sprays since the amount delivered thereafter per spray may be substantially less than 10 µg 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.)

DDAVP Nasal Spray is available in a 5-mL bottle with spray pump delivering 50 sprays of 10 mcg (NDC 0075-2452-01). Desmopressin acetate is also available as DDAVP Rhinal Tube, a refrigerated product with 2.5 mL per bottle, 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.

Keep out of the reach of children.

Manufactured for: sanofi-aventis U.S. LLC Bridgewater, NJ 08807 Rev. July 2007. FDA Rev date: 10/26/2007

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.

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.

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.

1. For intranasal use only.
2. DDAVP Nasal Spray should only be used in patients where orally administered formulations are not feasible.
3. Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with DDAVP (desmopressin acetate). DDAVP 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 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 (See PRECAUTIONS, Pediatric Use and Geriatric Use.) All patients receiving DDAVP 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. DDAVP 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.

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.

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.

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 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.

DDAVP contains as active substance desmopressin acetate, a synthetic analogue of the natural hormone arginine vasopressin. One mL (0.1 mg) of intranasal DDAVP 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 DDAVP 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 DDAVP provides a prompt onset of antidiuretic action with a long duration after each administration.
2. The change in structure of arginine vasopressin to DDAVP 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. DDAVP administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection.

Human Pharmacokinetics: DDAVP 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 DDAVP 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)

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 5
0-Dose Check-off

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.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DESMOPRESSIN SOLUTION - NASAL

(dess-mow-PRESS-in)

COMMON BRAND NAME(S): DDAVP

USES: This medication is used to reduce urination in certain cases (e.g., diabetes insipidus, surgery). It is a man-made form of a certain natural hormone made by the body (vasopressin). It works by making your kidneys concentrate your urine, so you produce less of it.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using desmopressin and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

This medication is given into the nose. Draw up the proper dose in the marked, flexible tube provided with the medication, and use as directed by your doctor. Your doctor will prescribe the total daily dose and how it should be taken. Follow these instructions exactly. Do not use it more frequently than prescribed without your doctor's approval. Wash the tube with water after use. Shake the tube thoroughly to dry.

A parent or other responsible adult should supervise a child using this medication. If you have any questions, consult your doctor or pharmacist.

Limit drinking of water or other fluids while using this medication. Consult your doctor for details.

Dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time(s) each day.

Tell your doctor if your condition persists or worsens. After taking desmopressin for 6 months or more, some patients may notice that the medicine does not work as well or last as long. Consult your doctor if this medication stops working well.

SIDE EFFECTS: Headache, runny nose, nausea, stomach ache, or flushing of the face may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Desmopressin can infrequently cause serious low levels of sodium. Drinking too much water or other fluids increases the risk of low sodium. Follow your doctor's directions for limiting fluids. Tell your doctor immediately if any of these unlikely symptoms of low sodium occur: loss of appetite, severe headache, muscle weakness/spasms/cramps, stomach cramps, tiredness, sudden weight gain, vomiting.

Seek immediate medical attention if any of these rare but very serious side effects occur: slow/shallow breathing, loss of consciousness, severe drowsiness/difficulty staying awake, mental/mood changes (e.g., confusion, hallucinations, irritability), seizures.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking desmopressin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: kidney disease, low sodium blood levels (hyponatremia or history of hyponatremia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood pressure, breathing problems, congestion in the nose, heart disease, mineral imbalance (low potassium blood levels), unusual/extreme thirst (habitual or psychogenic polydipsia), cystic fibrosis, type 2 or 3 von Willebrand disease.

Caution is advised when using this drug in children because they may be more sensitive to the effects of the drug, especially loss of sodium in the blood (hyponatremia).

Kidney function declines with age. This medication is removed by the kidneys. Therefore, caution is advised when using this drug in the elderly.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: chlorpromazine, chlorpropamide, clofibrate, demeclocycline, drugs that increase blood pressure (e.g., dopamine, epinephrine, ephedrine, norepinephrine), fludrocortisone, heparin, lithium, narcotic pain relievers (e.g., codeine), nonsteroidal anti-inflammatory drugs (e.g., celecoxib, ibuprofen, naproxen), oxybutynin, anti-seizure drugs (e.g., carbamazepine, lamotrigine), SSRI antidepressants (e.g., fluoxetine, sertraline), tricyclic antidepressants (e.g., amitriptyline, imipramine), urea, "water pills" (diuretics such as furosemide, hydrochlorothiazide), alcohol use.

Ask your doctor how much alcohol you may drink, if any. Alcohol interferes with desmopressin by increasing urination.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medicine may be harmful if swallowed. If overdose or swallowing is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., urinalysis, blood tests) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose and use 1 dose daily, use it as soon as you remember, unless you do not remember until the next day. In that case, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

If you use more than 1 dose daily, use it as soon as you remember, unless it is almost time for the next dose. In that case, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the US product in the refrigerator between 36-46 degrees F (2-8 degrees C). Do not freeze. When traveling, the US product may remain at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture for 3 weeks. Discard after 3 weeks out of the refrigerator.

Store the Canadian product in the refrigerator between 36-46 degrees F (2-8 degrees C). Do not freeze.

Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.