DDAVP- desmopressin acetate spray
Ferring Pharmaceuticals Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use DDAVP NASAL SPRAY safely and effectively. See full prescribing information for DDAVP NASAL SPRAY.
DDAVP (desmopressin acetate) nasal spray
Initial U.S. Approval: 1978
INDICATIONS AND USAGE
DDAVP Nasal Spray is a vasopressin analog indicated as antidiuretic replacement therapy in the management of central diabetes insipidus for adults and pediatric patients 4 years of age and older (1)
Limitations of Use:
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
Nasal Spray: 10 mcg per 0.1 mL spray, available in a 5 mL bottle with spray pump delivering 50 sprays (3)
WARNINGS AND PRECAUTIONS
Adverse reactions that have been identified in patients administered DDAVP 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 Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
DDAVP 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:
DDAVP Nasal Spray is not indicated for:
Administer DDAVP Nasal Spray by intranasal use only. Instruct patients about appropriate fluid restriction during DDAVP Nasal Spray treatment [see Warnings and Precautions (5.1)].
Must prime the spray pump prior to the first use. Instruct patients to:
The use of DDAVP 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 DDAVP 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 DDAVP 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.
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.
Because administration of desmopressin acetate can been associated with decreased responsiveness with prolonged use, consider increasing the dosage of DDAVP Nasal Spray if patients demonstrate decreased response over a long period of time.
When switching from the desmopressin acetate injection to DDAVP 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 DDAVP Nasal Spray individual dose titration is required because intranasal desmopressin is approximately 10 to 40 fold more potent than oral (tablet) desmopressin.
DDAVP Nasal Spray pump delivers 10 mcg (0.1 mL) of desmopressin acetate per spray.
DDAVP Nasal Spray is available as a 5 mL bottle with spray pump delivering 50 sprays.
DDAVP Nasal Spray is contraindicated in patients with:
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 DDAVP 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)].
DDAVP 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)].
Chronic administration of DDAVP 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 DDAVP 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.
The following serious reactions are described below and elsewhere in the labeling:
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)]
The concomitant administration of DDAVP 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)].
Desmopressin acetate can elevate blood pressure. Use of large doses of DDAVP Nasal Spray with other vasocontrictors may require a reduction of the DDAVP dosage [see Adverse Reactions (6)].
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.
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).
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 DDAVP Nasal Spray and any potential adverse effects on the breastfed infant from DDAVP Nasal Spray or from the underlying maternal condition.
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 DDAVP 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.
DDAVP Nasal Spray is indicated as antidiuretic replacement therapy in the management of central diabetes insipidus in pediatric patients 4 years of age and older. DDAVP Nasal Spray is not indicated in pediatric patients less than 4 years of age.
Use of DDAVP 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)].
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. 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 DDAVP Nasal Spray in geriatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia [see Warnings and Precautions (5.1)].
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. DDAVP 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)].
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 DDAVP Nasal Spray. There is no known specific antidote for desmopressin acetate.
DDAVP Nasal Spray 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
Empirical formula: C46H64N14O12S2∙C2H4O2∙3H2O
1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate.
DDAVP Nasal Spray is an aqueous solution for intranasal use. Each mL contains:
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.
The use of DDAVP Nasal Spray in patients with central diabetes insipidus reduces urinary output, increases urine osmolality, and decreases plasma osmolality.
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.
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 DDAVP 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)].
DDAVP Nasal Spray is available as a 5 mL bottle containing an aqueous solution with the spray pump delivering 50 sprays of 10 mcg (0.1 mL) (NDC 55566-2500-0).
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)
U.S. Pat. Nos. 5,500,413, 5,596,078, and 5,674,850
Ferring Pharmaceuticals Inc.
Parsippany, NJ 07054 USA
|This Patient Information has been approved by the Food and Drug Administration||09/18|
DDAVP (phonetic spelling)
Nasal Spray, 10 mcg per 0.1 mL
for Intranasal Use Only
|What is DDAVP?|
|DDAVP is a prescription medicine called a vasopressin analog used as an antidiuretic replacement to manage central diabetes insipidus.|
|Who should not use DDAVP?|
|Do not use DDAVP if you:|
|What should I tell my healthcare provider before using DDAVP?
Before using DDAVP, tell your healthcare provider about all your medical conditions including if you:
|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 DDAVP?|
|What are the possible side effects of DDAVP?|
|DDAVP may cause serious side effects including:|
|The most common side effects of DDAVP 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 DDAVP.|
|Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use DDAVP for a condition for which it was not prescribed. Do not give DDAVP 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 DDAVP that is written for health professionals. For more information call 1-888-FERRING (1-888-337-7464).|
|What are the ingredients in DDAVP?|
|Active ingredient: desmopressin acetate|
|Inactive ingredients: benzalkonium chloride solution (50%), sodium chloride, citric acid monohydrate, disodium phosphate dihydrate, purified water|
Nasal Spray, 10 mcg per 0.1 mL
For Intranasal Use Only
Read these instructions before using DDAVP 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 DDAVP Nasal Spray, to make sure the right amount of medicine is used.
The parts of your DDAVP Nasal Spray pump (see Figure A):
Priming your DDAVP Nasal Spray:
Your DDAVP Nasal Spray pump must be primed before you use it for the first time.
Using your DDAVP Nasal Spray:
Step 1. Remove the protective cap.
Step 2. To make sure you get the right dose of medicine tilt your DDAVP Nasal Spray pump so the dip tube inside the bottle draws the medicine up from the deepest part of the medicine inside the bottle (see Figures D and E).
Step 3. Put the spray nozzle tip of your DDAVP Nasal Spray into your nostril and press the spray pump 1 time for 1 dose. (see Figure F). If 2 doses are prescribed, spray each nostril 1 time.
Step 4. Put the protective cap back on the spray nozzle tip when you finish using your DDAVP Nasal Spray.
Keeping track of your Nasal Sprays:
|DDAVP Nasal Spray|
|50-Spray Check-off Chart|
How should I store DDAVP Nasal Spray?
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Ferring Pharmaceuticals Inc.
Parsippany, NJ 07054 USA
desmopressin acetate spray
|Labeler - Ferring Pharmaceuticals Inc. (103722955)|
|Ferring GmbH||328609615||MANUFACTURE(55566-2500) , ANALYSIS(55566-2500) , PACK(55566-2500) , LABEL(55566-2500)|
|Rechon Life Science AB||775207769||MANUFACTURE(55566-2500) , ANALYSIS(55566-2500) , PACK(55566-2500)|
|Ferring International Center SA||481210362||PACK(55566-2500)|
|PolyPeptide Laboratories (Sweden) AB||356580779||API MANUFACTURE(55566-2500) , ANALYSIS(55566-2500)|