n of the desmopressin acetate nasal solution 0.01% (nasal spray) dosage [see adverse reactions (6)].

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: desmopressin acetate is not indicated for: treatment of nephrogenic diabetes insipidus (1) treatment of primary nocturnal enuresis (1, 5.1) use in patients with conditions that compromise intranasal route of administration (1, 5.2) use in patients with an impaired level of consciousness (1) use in patients requiring doses less than 10 mcg or doses that are not multiples of 10 mcg (1,3)

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 acetate nasal solution 0.01% (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)]. 5.2 altered absorption in patients with nasal mucosa abnormalities chronic administration of desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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.

once). • discard desmopressin acetate nasal solution 0.01% (nasal spray) after 50 sprays since the amount delivered thereafter may be substantially less than the recommended dosage. 2.2 recommended dosage the use of desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (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. adults 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. pediatric patients • for pediatric patients requiring doses less than 10 mcg, desmopressin acetate nasal solution 0.01% (nasal spray) is not indicated. • for pediatric patients 4 years of age and older, the recommended starting dosage of desmopressin acetate nasal solution 0.01% (nasal spray) 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 been associated with decreased responsiveness with prolonged use, consider increasing the dosage of desmopressin acetate nasal solution 0.01% (nasal spray) if patients demonstrate decreased response over a long period of time. 2.3 switching between desmopressin acetate formulations when switching from the desmopressin acetate injection to desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (nasal spray) individual dose titration is required because intranasal desmopressin is approximately 10 to 40 fold more potent than oral (tablet) desmopressin.

ctions that have been identified in patients administered desmopressin acetate nasal solution 0.01% (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 sun pharmaceutical industries, inc. at 1-800-818-4555 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

n of the desmopressin acetate nasal solution 0.01% (nasal spray) dosage [see adverse reactions (6)].

d 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. data animal data 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/m 2 ). 8.2 lactation risk summary 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 desmopressin acetate nasal solution 0.01% (nasal spray) and any potential adverse effects on the breastfed infant from desmopressin acetate nasal solution 0.01% (nasal spray) or from the underlying maternal condition. data 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 desmopressin acetate nasal solution 0.01% (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. 8.4 pediatric use desmopressin acetate nasal solution 0.01% (nasal spray) is indicated as antidiuretic replacement therapy in the management of central diabetes insipidus in pediatric patients 4 years of age and older. desmopressin acetate nasal solution 0.01% (nasal spray) is not indicated in pediatric patients less than 4 years of age. use of desmopressin acetate nasal solution 0.01% (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)]. 8.5 geriatric use clinical studies of desmopressin acetate nasal solution 0.01% (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 desmopressin acetate nasal solution 0.01% (nasal spray) in geriatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia [see warnings and precautions (5.1)]. 8.6 renal impairment 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. desmopressin acetate nasal solution 0.01% (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)].

e 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/m 2 ).

al 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 populations 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 desmopressin acetate nasal solution 0.01% (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)].

.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)].

y: sun pharmaceutical industries, inc. cranbury, nj 08512 manufactured by: sun pharmaceutical industries ltd. halol-baroda highway, halol-389 350, gujarat, india. iss. 01/2019 pjpi0438c