desmopressin (Rx)

Brand and Other Names:DDAVP, Stimate, more...Minirin, Noctiva, Nocdurna
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injectable solution (DDAVP)

  • 4mcg/mL

tablet (DDAVP)

  • 0.1mg
  • 0.2mg

nasal spray (DDAVP, DDAVP Rhinal Tube)

  • 0.1mg/mL (5mL): Delivers 10mcg/spray

nasal spray (Stimate)

  • 1.5mg/mL (2.5mL): Delivers 150mcg/spray

preservative-free nasal spray (Noctiva)

  • 0.83 mcg of desmopressin acetate/0.1mL (equivalent to 0.75 mcg desmopressin)
  • 1.66 mcg of desmopressin acetate/0.1mL (equivalent to 1.5 mcg desmopressin)

tablet, sublingual (Nocdurna)

  • 27.7mcg of desmopressin acetate (equivalent to 25 mcg of desmopressin)
  • 55.3mcg of desmopressin acetate (equivalent to 50 mcg of desmopressin)

Diabetes Insipidus

Intranasal (DDAVP)

  • 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
  • 10-40 mcg (0.1-0.4 mL) qDay, either as a single dose or divided into 2 or 3 doses; usual dose is 20 mcg (0.2 mL) qDay in 2 divided doses
  • Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover

PO

  • Initial: 0.05 mg q12hr
  • Effective range: 0.1-1.2 mg divided q8-12hr
  • Observe fluid restriction
  • If switching to PO from intranasal, start PO at least 12 hours after last intranasal dose

IV/SC

  • 2-4 mcg/day divided q12hr or one-tenth the maintenance of intranasal dose

Hemophilia A

IV

  • Indicated for patients with hemophilia A with factor VIII coagulant activity levels greater than 5%
  • 0.3 mcg/kg IV over 15-30 minutes (for pre-op, 30 min before procedure)

Intranasal (Stimate)

  • Indicated for patients with mild to moderate classic von Willebrand disease (Type I) with Factor VIII levels >5%
  • <50 kg: 150 mcg; for pre-op, give 2 hr before procedure
  • >50 kg: 300 mcg; for pre-op, give 2 hr before procedure

Von Willebrand Disease (Type 1)

IV

  • Indicated for patients with mild to moderate classic von Willebrand’s disease (Type I) with factor VIII levels greater than 5%
  • 0.3 mcg/kg IV over 15-30 minutes (for pre-op, 30 min before procedure)

Intranasal (Stimate)

  • Indicated for patients with mild to moderate classic von Willebrand disease (Type I) with Factor VIII levels >5%
  • <50 kg: 150 mcg; for pre-op, give 2 hr before procedure
  • >50 kg: 300 mcg; for pre-op, give 2 hr before procedure

Nocturnal Enuresis

Primary nocturnal enuresis (not intranasal)

0.2 mg PO qHS (up to 0.6 mg/day)

Nocturia

Nocturnal polyuria was defined in clinical trials as nighttime urine production exceeding one-third of 24-hour urine production

Preservative-free nasal spray (Noctiva)

  • Indicated for nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void
  • >50 to <65 years
    • 1 spray of 1.66 mcg in either nostril nightly ~ 30 min before going to bed
  • ≥65 years
    • 0.83 mcg in either nostril nightly ~ 30 min before going to bed; 0.83 mcg dose may have a lower risk of hyponatremia; may be increased to 1 spray of 1.66 mcg after at least 7 days, if needed, provided serum sodium has remained normal

Sublingual tablets (Nocdurna)

  • Indicated for nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void
  • Before starting or resuming, assess the sodium concentration and only start or resume in patients with a normal serum sodium concentration
  • Women: 27.7 mcg SL qDay, 1 hr before bedtime, administered SL without water
  • Men: 55.3 mcg SL qDay, 1 hr before bedtime, administered SL without water
  • Also see Administration and Dosing Consideration

Uremic Bleeding in Acute or Chronic Renal Failure

0.4 mcg/kg IV over 10 minutes  

Dosing Modifications

Renal impairment

  • CrCl <50 mL/min: Contraindicated; has been used unlabeled in acute and chronic renal failure patients experiencing uremic bleeding or prevention of surgical bleeding
  • CrCl ≥50 mL/min: No adjustments necessary

Dosing Considerations

Switching between desmopressin formulations

  • Switching from injection to nasal spray: Administer 10x the amount of desmopressin acetate, rounding down to the nearest 10 mcg
  • Switching from tablets to nasal spray: Individual dose titration is required because intranasal desmopressin is ~10 to 40-fold more potent than oral (tablet) desmopressin

Sublingual tablets and preservative-free nasal spray

  • Sublingual tab only: Recommended dose for women is lower than for men due to women being more sensitive to the effects of the sublingual tablets and having a higher risk of hyponatremia with the 55.3 mcg dose in clinical trials
  • Before starting treatment
    • Evaluate patient for possible causes for the nocturia, including excessive fluid intake prior to bedtime, and address other treatable causes of nocturia
    • Confirm diagnosis of nocturnal polyuria with a 24-hr urine collection, if not obtained previously
  • Sodium monitoring
    • Ensure serum sodium concentration is normal prior to initiating or resuming treatment Contraindicated in patients with hyponatremia or a history of hyponatremia (see Contraindications)
    • Check serum sodium concentration within the first week and again at 1 month after initiating or resuming therapy
    • Periodically monitor serum sodium during therapy, as clinically appropriate; closely monitor patients ≥65 years and patients at risk of hyponatremia
    • If patient develops hyponatremia, consider temporarily or permanently discontinuing therapy, and institute treatment for hyponatremia, depending on the clinical circumstances, including the duration and severity of the hyponatremia

Limitations of use

  • Stimate: Not to be used in patients with Type IIB von Willebrand's disease since platelet aggregation may be induced
  • Noctiva: Not studied in patients <50 years
  • Nasal spray
    • Treatment of nephrogenic diabetes insipidus or primary nocturnal enuresis
    • Use in patients with conditions that compromise the intranasal route of administration (eg, severe nasal congestion and blockage, nasal mucosa atrophy, severe atrophic rhinitis, recent nasal surgery such as transsphenoidal hypophysectomy)
    • Use in patients with an impaired level of consciousness Use in patients requiring doses <10 mcg or doses that are not multiples of 10 mcg

Dosage Forms & Strengths

injectable solution

  • 4mcg/mL

tablet

  • 0.1mg
  • 0.2mg

nasal spray

  • 0.1mg/mL (5mL): Delivers 10mcg/spray
  • 1.5mg/mL (2.5mL): Delivers 150mcg/spray

Diabetes Insipidus

Nasal spray

  • 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 in patients (>3 months)
  • <3 months: Safety and efficacy not established
  • 3 months-12 years
    • Usual dosage range is 5-30 mcg (0.05-0.3 mL) qDay, either as a single dose or divided into 2 doses
    • About 1/4 to 1/3 of patients can be controlled by a single daily dose of DDAVP administered intranasally
    • Adjust doses separately for appropriate diurnal rhythm of water turnover if administering more than once a day
  • >12 years
    • 10-40 mcg (0.1-0.4 mL) qDay, either as a single dose or divided into 2 or 3 doses; usual dose is 20 mcg (0.2 mL) qDay in 2 divided doses
    • Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover

Nocturnal Enuresis

>6 years: 0.2 mg PO qHS (up to 0.6 mg/day)

Hemophilia A & Von Willebrand Disease

Indicated for patients with hemophilia A or von Willebrand disease (type 1) with Factor VIII coagulant activity levels >5%; will also stop bleeding in patients with episodes of spontaneous or trauma-induced injuries (eg, hemarthroses, intramuscular hematomas, mucosal bleeding)

IV

  • Infants ≥3 months, children, and adolescents
    • 0.3 mcg/kg IV
    • If used preoperatively, administer 30 min before procedure
    • May repeat dose if needed

Intranasal (Stimate)

  • Infants ≥11 months, children, and adolescents
    • <50 kg: 150 mcg intranasally
    • ≥50 kg: 300 mcg intranasally If used preoperatively, administer 2 hr before procedure

Fluid intake should be limited 1 hr prior to dose until the next morning or at least 8 hr after administration

Repeat use determined by clinical symptoms and laboratory values

Dosing Modifications

Renal impairment

  • CrCl <50 mL/min: Contraindicated; has been used unlabeled in acute and chronic renal failure patients experiencing uremic bleeding or prevention of surgical bleeding
  • CrCl ≥50 mL/min: No adjustments necessary

Dosing Considerations

Switching between desmopressin formulations

  • Switching from injection to nasal spray: Administer 10x the amount of desmopressin acetate, rounding down to the nearest 10 mcg
  • Switching from tablets to nasal spray: Individual dose titration is required because intranasal desmopressin is ~10 to 40-fold more potent than oral (tablet) desmopressin

Sublingual tablets and preservative-free nasal spray

  • Sublingual tab only: Recommended dose for women is lower than for men due to women being more sensitive to the effects of the sublingual tablets and having a higher risk of hyponatremia with the 55.3 mcg dose in clinical trials
  • Before starting treatment
    • Evaluate patient for possible causes for the nocturia, including excessive fluid intake prior to bedtime, and address other treatable causes of nocturia
    • Confirm diagnosis of nocturnal polyuria with a 24-hr urine collection, if not obtained previously
  • Sodium monitoring
    • Ensure serum sodium concentration is normal prior to initiating or resuming treatment Contraindicated in patients with hyponatremia or a history of hyponatremia (see Contraindications)
    • Check serum sodium concentration within the first week and again at 1 month after initiating or resuming therapy
    • Periodically monitor serum sodium during therapy, as clinically appropriate; closely monitor patients ≥65 years and patients at risk of hyponatremia
    • If patient develops hyponatremia, consider temporarily or permanently discontinuing therapy, and institute treatment for hyponatremia, depending on the clinical circumstances, including the duration and severity of the hyponatremia

Limitations of use

  • Stimate: Not to be used in patients with Type IIB von Willebrand's disease since platelet aggregation may be induced
  • Noctiva: Not studied in patients <50 years
  • Nasal spray
    • Treatment of nephrogenic diabetes insipidus or primary nocturnal enuresis
    • Use in patients with conditions that compromise the intranasal route of administration (eg, severe nasal congestion and blockage, nasal mucosa atrophy, severe atrophic rhinitis, recent nasal surgery such as transsphenoidal hypophysectomy)
    • Use in patients with an impaired level of consciousness
    • Use in patients requiring doses <10 mcg or doses that are not multiples of 10 mcg

Nocturia

Nocturnal polyuria was defined in clinical trials as nighttime urine production exceeding one-third of 24-hour urine production

Indicated for treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void; nocturnal polyuria was defined in clinical trials as night-time urine production exceeding one-third of 24-hr urine production

Preservative-free nasal spray (Noctiva)

≥65 years: 0.83 mcg in either nostril ~ 30 min before going to bed; 0.83 mcg dose may have lower risk of hyponatremia; may be increased to 1 spray of 1.66 mcg after at least 7 days, if needed, provided serum sodium has remained normal

Sublingual tablets

A total of 562 subjects 65 years or older were enrolled in the clinical trials, ~48% of the study population

Clinical studies of desmopressin have shown an increased risk of hyponatremia in patients ≥65 years compared to those <65 years

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Interactions

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            Adverse Effects

            >10%

            Nocdurna

            • Dry mouth, men (14%)
            • Dry mouth, women (12%)

            1-10%

            Nocdurna

            • Headache (2-5%)
            • Hyponatremia, men (4%)
            • Headache, men (4%)
            • Hyponatremia, women (3%)
            • Dizziness, men (3%)
            • Dizziness (3%)
            • Epistaxis (2-3%)
            • Headache, women (2%)
            • Dizziness, women (2%)

            Nasal spray

            • Rhinitis (3-8%)
            • Abdominal pain (2%)
            • Asthenia (2%)
            • Chills (2%)
            • Nostril pain (2%)
            • Gastrointestinal disorder (2%)
            • Nausea (2%)
            • Conjunctivitis (2%)
            • Eye edema (2%)
            • Lachrymation disorder (2%)

            Frequency Not Defined

            Abnormal blood pressure (infrequent)

            Increased heart rate

            Increased blood pressure

            Flushing

            Seizure (rare)

            Hyponatremia

            Hyposmolality (rare)

            Water intoxication syndrome

            Thromboembolic disorder

            Allergic reaction (acute)

            Anaphylaxis (rare)

            Noctiva

            • Nasal discomfort
            • Nasal congestion
            • Atrial fibrillation
            • Dizziness
            • Dyuria
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            Warnings

            Black Box Warnings

            Hyponatremia

            • Intranasal preservative-free (Noctiva) and sublingual tablets
              • Hyponatremia may occur; severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death
              • Contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids
              • Ensure serum sodium is normal before starting or resuming therapy; measure serum sodium within 7 days and approximately 1 month after initiating therapy or increasing dose, and periodically during treatment; monitor serum sodium frequently in patients >65 years and patients at increased risk of hyponatremia
              • If hyponatremia occurs, therapy may need to be temporarily or permanently discontinued

            Contraindications

            Hypersensitivity

            Hyponatremia or history of hyponatremia

            Moderate to severe renal impairment (CrCl <50 mL/min)

            Intranasal preservative-free (Noctiva) and sublingual tablets

            • Polydipsia
            • Primary nocturnal enuresis
            • Concomitant use with loop diuretics or systemic or inhaled glucocorticoids
            • Estimated glomerular filtration rate below 50 mL/min/1.73 m²
            • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
            • Uncontrolled hypertension
            • During illnesses that can cause fluid or electrolyte imbalance
            • Noctiva only: New York Heart Association (NYHA) class II-IV congestive heart failure
            • Nocdurna only: Heart failure

            Cautions

            Factor VIII levels <5% or presence of factor VIII antibodies

            Avoid use in Type IIB von Willebrand disease

            Therapeutic effect has not been observed in patients who have been febrile or stressed for several days; monitor for efficacy if necessary

            Use caution in patients with habitual or psychogenic polydipsia (increased risk of hypnatremia)

            Risk of potentially fatal hyponatremia/seizures; may occur with any route of administration

            Anaphylactic reactioins reported (rare) with IV and intranasal administration

            Use alternative route of administration if changes in the nasal mucosa resulting from edema or scarring occurs

            Rapid IV infusions may result in severe hypotension

            Interrupt therapy if patient perform activities associated with increase in water consumption or with acute illness including fever or recurrent vomiting or diarrhea

            Use with caution in patients predisposed to thrombus formation; acute myocardial infarction and cerebrovascular thrombosis reported with desmopressin injection

            Therapy can cause fluid retention, which can worsen underlying conditions that are susceptible to volume status, including congestive heart failure (see Contraindications)

            In children and the elderly adjust fluid intake downward to decrease possibility of water intoxication and hyponatremia

            Nasal spray

            • Chronic administration 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 nasal spray in such patients and consider use of other formulations of desmopressin acetate given by other routes of administration
            • Intranasal DDAVP at high dosage has infrequently produced a slight elevation of blood pressure, which disappeared with a reduced dose; exercise caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease because of possible rise in blood pressure
            • Use with caution in patients predisposed to thrombus formation; acute myocardial infarction and cerebrovascular thrombosis reported with desmopressin injection
            • Noctiva only
              • Before starting or resuming therapy, ensure that serum sodium concentration is normal; consider 0.83-mcg dose as starting dose for patients who may be at risk for hyponatremia
              • Not recommended in patients at risk of increased intracranial pressure or history of urinary retention; monitor volume status in patients with NYHA class I congestive heart failure
              • Discontinue therapy in patients with concurrent nasal conditions that may increase systemic absorption (eg, atrophy of nasal mucosa, acute or chronic rhinitis), because increased absorption may increase risk of hyponatremia; therapy can be resumed when conditions resolve
              • When therapy is administered, fluid intake in the evening and nighttime hours should be moderated to decrease risk of hyponatremia; monitor serum sodium concentration within 7 days and ~1 month of initiating therapy or increasing dose, and periodically thereafter; the frequency of serum sodium monitoring should be based on patient’s risk for hyponatremia

            Hyponatremia

            • Also see Administration, Black Box Warnings, and Dosing Considerations
            • In order to decrease risk of water intoxication with hyponatremia, fluid restriction recommended; careful fluid intake restriction is particularly important in pediatric and geriatric patients because these patients are at greater risk of developing hyponatremia; more frequent monitoring of serum sodium levels 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
            • Nasal spray is not an indicated formulation for treatment of primary nocturnal enuresis due to higher risk of hyponatremia and hyponatremic convulsions with use of nasal spray formulation compared to desmopressin tablets seen in postmarketing reports
            • Signs and 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

            Drug interaction overview

            • Concomitant use of desmopressin sublingual and loop diuretics or systemic or inhaled glucocorticoids is contraindicated because of the risk of severe hyponatremia; may be started or resumed 3 days or 5 half-lives after discontinuing glucocorticoid, whichever is longer
            • Drugs (eg, tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine, opiate analgesics, thiazide diuretics, carbamazepine, lamotrigine, sulfonylureas, particularly chlorpropamide, NSAIDs) may increase the risk of hyponatremia; monitor serum sodium more frequently in patients taking desmopressin concomitantly with these drugs and when doses of these drugs are increased
            • Use of large doses of nasal spray with other vasoconstrictors may require reducing the dose
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            Pregnancy & Lactation

            Pregnancy

            Prolonged experience with desmopressin in pregnant women over several decades, based on 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)

            Not recommended for treatment of nocturia in pregnant women; nocturia is usually related to normal, physiologic changes during pregnancy that do not require treatment

            Animal data

            • 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
            • No adverse developmental outcomes were observed in animal reproductive and developmental studies following administration of desmopressin acetate during organogenesis to pregnant rats and rabbits, at exposures 92- and 8- times, respectively, the maximum recommended dose in women, based on body surface area

            Lactation

            Desmopressin is present in small amounts in human milk and is poorly absorbed orally by infant

            There is no information on effects of desmopressin on breastfed infant or on milk production; development and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and potential adverse effects on breastfed infant from therapy or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Synthetic analogue of vasopressin with prompt onset and longer, more specific antidiuretic action; desmopressin increases water permeability in renal tubular cells, which in turn decreases urine volume and increases urine osmolality

            Also produces dose-related increase in von Willebrand factor VIII and t-PA levels; this shortens activated partial thromboplastin time (aPTT), as well as bleeding time

            Antidiuretic effects of desmopressin are mediated by stimulation of vasopressin 2 (V2) receptors, thereby increasing water re-absorption in the kidneys, and reducing urine production

            Absorption

            Bioavailability: 3.3-4.1% (Stimate); 3.5% (nasal); 5% (oral; compared to intranasal, 0.16% compared to IV); 0.25 (SL)

            Onset: ADH effect (intranasal), 60 min; hemophilia and von Willebrand disease (IV), 30 min

            Duration: 6-14 hr (intranasal, IV infusion, oral)

            Peak plasma time: 1-5 hr (intranasal); 0.25 hr for 0.83 mcg dose and 0.75 hr for 1.66 mcg dose (preservative-free nasal spray)

            Distribution

            Vd: 26.5 L (IV)

            Metabolism

            Unknown

            Elimination

            Half-life: 3.3-3.5 hr (intranasal); 3 hr (IV, healthy patient); 9 hr (IV, severe renal impairment); 2-3 hr (PO); 2.8 hr (1.66 mcg dose; preservative-free nasal spray): 2.8 hr (SL)

            Excretion (IV): Urine (52%)

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            Administration

            IV Administration

            Dilute appropriate dose in 10 mL NS for children <10 kg or 50 mL NS for adults and children >10 kg

            Infuse slowly over 15-30 min

            Monitor blood pressure and pulse during infusion

            Intranasal Administration

            Only administer intranasally; do not shake bottle

            If dose is missed, do not double dose at next use

            If spray pump is not used for 2 week (DDAVP or Minirin) or 1 week (Stimate), reprime pump by pressing down on the pump once

            Discard after 50 sprays (DDAVP or Minirin) or 25 sprays (Stimate) since the amount delivered thereafter may be substantially less than the recommended dosage

            Ensure that in children administration is under adult supervision in order to control the dose intake

            Intranasal preservative-free (Noctiva)

            • Prime with 5 actuations before initial use; re-prime with 2 actuations if not used for more than 3 days
            • Two sprays of 0.83 mcg are not interchangeable with one spray of 1.66 mcg; nasal spray of 1.66 mcg/0.1 mL bottle for patients who are or will be taking 1.66 mcg dose

            Oral Administration

            Sublingual tablets

            • Place 1 tablet under the tongue 1 hr before bedtime and to empty their bladder immediately prior to bedtime
            • Tablet should remain under the tongue until it dissolves
            • Advise patients to limit fluid intake to a minimum starting 1 hr prior to administration and for 8 hr following administration
            • Avoid caffeine and alcohol before bedtime

            Storage

            Injection: Refrigerate between 2-8°C (36-46°F)

            Sublingual tablets: Store at controlled 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F); keep in original package to protect from moisture and light; use immediately upon opening individual tablet blister

            Intranasal products

            • DDAVP, Minirin
              • Store at controlled room temperature 20-25°C (68-77°F) in upright position
              • Discard after 50 sprays since the amount delivered thereafter per spray may be substantially less than 10 mcg of drug
            • Stimate
              • Store at 25°C (77°F) in upright position
              • Discard after 25 sprays since the amount delivered thereafter per spray may be substantially less
              • Stimate: Discard 6 months after opening
            • Noctiva
              • Before opening, store upright in a refrigerator, 2-8°C (36-46°F); excursion permitted between 0°C and 15°C (32°F and 59°F)
              • After opening, store upright at room temperature 20-25ºC (68-77ºF)
              • Discard 60 days after opening
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            Formulary

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            Tier Description
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