Desmopressin Acetate
Desmopressin Acetate Prescribing Information
Desmopressin nasal spray solution is indicated as antidiuretic replacement therapy in the management of central diabetes insipidus in adults and pediatric patients 4 years of age and older.
Desmopressin nasal spray solution is not indicated for:
• Treatment of primary nocturnal enuresis [see],5.1 HyponatremiaExcessive 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 nasal spray solution 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 nasal spray solution 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)].
• 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],5.2 Altered Absorption in Patients with Nasal Mucosa AbnormalitiesChronic administration of desmopressin nasal spray solution 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 nasal spray solution in such patients
[see Indications and Usage (1)]and consider use of other formulations of desmopressin acetate given by other routes of administration.
• 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[see3 DOSAGE FORMS AND STRENGTHSDesmopressin Nasal Spray Solution, USP pump delivers 10 mcg (0.1 mL) of desmopressin acetate per spray.
Desmopressin Nasal Spray Solution, USP is available as a 5 mL bottle with spray pump delivering 50 sprays.
Nasal Spray: 10 mcg per 0.1 mL spray, available in a 5 mL bottle with spray pump delivering 50 sprays
• For intranasal use only ()2.1 Important Administration InstructionsAdminister desmopressin nasal spray solution by intranasal use only. Instruct patients about appropriate fluid restriction during desmopressin nasal spray solution 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 five times (if the spray pump is not used for one week, re-prime the pump by pressing down on the pump once).• Discard desmopressin nasal spray solution after 50 sprays since the amount delivered thereafter may be substantially less than the recommended dosage.
• Instruct patients to prime pump prior to use ()2.1 Important Administration InstructionsAdminister desmopressin nasal spray solution by intranasal use only. Instruct patients about appropriate fluid restriction during desmopressin nasal spray solution 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 five times (if the spray pump is not used for one week, re-prime the pump by pressing down on the pump once).• Discard desmopressin nasal spray solution after 50 sprays since the amount delivered thereafter may be substantially less than the recommended dosage.
• Adults: 10 mcg to 40 mcg daily (either as a single dose or divided into two or three daily doses) ()2.2 Recommended DosageThe use of desmopressin nasal spray solution 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 nasal spray solution 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 nasal spray solution 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.AdultsThe 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 nasal spray solution is not indicated. • For pediatric patients 4 years of age and older, the recommended starting dosage of desmopressin nasal spray solution 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 be associated with decreased responsiveness with prolonged use, consider increasing the dosage of desmopressin nasal spray solution if patients demonstrate decreased response over a long period of time.
• 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 Recommended DosageThe use of desmopressin nasal spray solution 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 nasal spray solution 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 nasal spray solution 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.AdultsThe 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 nasal spray solution is not indicated. • For pediatric patients 4 years of age and older, the recommended starting dosage of desmopressin nasal spray solution 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 be associated with decreased responsiveness with prolonged use, consider increasing the dosage of desmopressin nasal spray solution if patients demonstrate decreased response over a long period of time.
• See the Full Prescribing Information for recommendations for switching between desmopressin acetate formulations ()2.3 Switching Between Desmopressin Acetate FormulationsWhen switching from the desmopressin acetate injection to desmopressin nasal spray solution, administer 10 times the amount of desmopressin acetate, rounding down to the nearest 10 mcg.
When switching from the desmopressin acetate tablets to desmopressin nasal spray solution, individual dose titration is required because intranasal desmopressin is approximately 10 to 40 fold more potent than oral (tablet) desmopressin.
Desmopressin Nasal Spray Solution, USP pump delivers 10 mcg (0.1 mL) of desmopressin acetate per spray.
Desmopressin Nasal Spray Solution, USP is available as a 5 mL bottle with spray pump delivering 50 sprays.
• Pediatric Use:Use requires careful fluid intake restriction to prevent hyponatremia with water intoxication (,5.1 HyponatremiaExcessive 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 nasal spray solution 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 nasal spray solution 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)].)8.4 Pediatric UseDesmopressin nasal spray solution is indicated as antidiuretic replacement therapy in the management of central diabetes insipidus in pediatric patients 4 years of age and older. Desmopressin nasal spray solution is not indicated in pediatric patients less than 4 years of age.
Use of desmopressin nasal spray solution 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)].• Geriatric Use: Carefully monitor renal function; restrict fluid intake to prevent hyponatremia with water intoxication (,5.1 HyponatremiaExcessive 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 nasal spray solution 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 nasal spray solution 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)].)8.5 Geriatric UseClinical studies of desmopressin nasal spray solution 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 nasal spray solution in geriatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia
[see Warnings and Precautions (5.1)].
Desmopressin nasal spray solution is contraindicated in patients with:
• Known hypersensitivity to desmopressin acetate or to any of the components of desmopressin nasal spray solution. Severe allergic reactions and anaphylaxis have been reported[see].6 ADVERSE REACTIONSThe 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: oxybutynin and imipramine
[see Drug Interactions (7.1)].Severe allergic reactions and anaphylaxis
[see Contraindications (4)].Adverse reactions that have been identified in patients administered desmopressin nasal spray solution are headache, nasal congestion, rhinitis, nosebleed, sore throat, cough, upper respiratory infections, nausea, flushing, and mild abdominal cramps
To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.• Renal impairment defined as estimated creatinine clearance (CLcr) by Cockcroft-Gault equation less than 50 mL/min[see.and8.6 Renal ImpairmentDesmopressin 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 nasal spray solution is contraindicated in patients with estimated CLcr by Cockcroft-Gault equation less than 50 mL/min
[see Clinical Pharmacology, Contraindications (4)].]12.3 PharmacokineticsAbsorption: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 PopulationsRenal 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 nasal spray solution). 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)].• Hyponatremia or a history of hyponatremia[see.]5.1 HyponatremiaExcessive 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 nasal spray solution 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 nasal spray solution 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)].
• Hyponatremia:Instruct patients about proper fluid restriction and monitor serum sodium as needed (,2.1 Important Administration InstructionsAdminister desmopressin nasal spray solution by intranasal use only. Instruct patients about appropriate fluid restriction during desmopressin nasal spray solution 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 five times (if the spray pump is not used for one week, re-prime the pump by pressing down on the pump once).• Discard desmopressin nasal spray solution after 50 sprays since the amount delivered thereafter may be substantially less than the recommended dosage.
)5.1 HyponatremiaExcessive 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 nasal spray solution 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 nasal spray solution 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)].• Altered Absorption in Patients with Nasal Mucosa Abnormalities:May occur with chronic administration, and require use of other formulations instead ()5.2 Altered Absorption in Patients with Nasal Mucosa AbnormalitiesChronic administration of desmopressin nasal spray solution 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 nasal spray solution in such patients
[see Indications and Usage (1)]and consider use of other formulations of desmopressin acetate given by other routes of administration.