Included as part of the PRECAUTIONS section.
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 Desmopressin Acetate 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]. 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].
Desmopressin Acetate 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].
Altered Absorption In Patients With Nasal Mucosa
Chronic administration of Desmopressin Acetate 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 Spray in such patients [see
INDICATIONS AND USAGE Â and consider use of other formulations of
desmopressin acetate given by other routes of administration.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (PATIENT INFORMATION and Instructions for Use)
- Inform caregivers for pediatric patients that
administration should be supervised to ensure the patient receives the
- Inform patients that the pump must be primed prior to
first use and again if not used for greater than one week. Inform patients that
the Desmopressin Acetate Nasal Spray bottle delivers 50 sprays of 10 mcg each
following the initial 4 priming pumps.
- Inform patients to discard any solution remaining after
50 sprays since the amount delivered thereafter may be substantially less than
10 mcg of drug.
- Educate patients about the signs and symptoms of
hyponatremia and advise them to contact a healthcare provider if such symptoms
- Discuss downward adjustment of fluid intake and
monitoring of urine output with patients.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Studies with desmopressin acetate have not been performed
to evaluate carcinogenic potential, mutagenic potential, or effects on
Use In Specific Populations
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 1520%,
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 Desmopressin Acetate Nasal Spray and any potential
adverse effects on the breastfed infant from Desmopressin Acetate 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 Desmopressin Acetate 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.
Desmopressin Acetate 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 Spray is not indicated in pediatric patients less than 4 years of age.
Use of Desmopressin Acetate 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].
Clinical studies of Desmopressin Acetate 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, Use In Specific Populations].
Use of Desmopressin Acetate Nasal Spray in geriatric
patients requires careful fluid intake restriction to prevent possible water
intoxication with hyponatremia [see WARNINGS AND PRECAUTIONS].
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
Spray is contraindicated in patients with estimated CLcr by Cockcroft-Gault
equation less than 50 mL/min[see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS].