Desmopressin

H01B - Posterior pituitary lobe hormones ATC H01BA02 Protein approved 1978 Oral Parenteral Topical Natural product Black-box warning

JFDA label: Minirin Melt

⚠ Black-Box Warning

Hyponatremia (Noctiva nasal spray):

Mechanism of Action

Synthetic analogue of the antidiuretic hormone arginine vasopressin. In a dose dependent manner, desmopressin increases cyclic adenosine monophosphate (cAMP) in renal tubular cells which increases water permeability resulting in decreased urine volume and increased urine osmolality; increases plasma levels of von Willebrand factor, factor VIII, and t-PA contributing to a shortened activated partial thromboplastin time (aPTT) and bleeding time.

Indications

Approved

Diabetes insipidus
Diabetes insipidus (DDAVP Rhinal tube)
Hemophilia A
Hemophilia A (Stimate; Octostim [Canadian product])
Injection
Intranasal
Nocturia (Nocdurna [Canadian product] only)
Nocturia (Noctiva)
Primary nocturnal enuresis
Tablets
Uremic bleeding (Octostim [Canadian product])
Von Willebrand disease (type 1)
von Willebrand disease (type 1) (Stimate; Octostim [Canadian product])

Off-label

Intracranial hemorrhage associated with certain antiplatelet agents
Surgical bleeding in patients with uremia (prevention)
Uremic bleeding associated with acute or chronic renal failure

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Note: May not be applicable to all available dosage forms Absolute
Known hypersensitivity to desmopressin or any component of the formulations Absolute
concomitant use with loop diuretics or glucocorticoids (inhaled or systemic) Absolute
habitual or psychogenic polydipsia, cardiac insufficiency or other conditions requiring diuretic therapy Absolute
heart failure (NYHA Class II to IV) Absolute
hyponatremia or a history of hyponatremia Absolute
illnesses that may cause fluid or electrolyte imbalance (eg., gastroenteritis, salt-wasting nephropathies, systemic infection) Absolute
moderate to severe renal impairment (CrCl Additional product specific contraindications: Noctiva: Polydipsia Absolute
nephrosis or any other condition associated with impaired water excretion, severe hepatic dysfunction Absolute
primary nocturnal enuresis Absolute
refer to manufacturer labeling for further detail. Type 2B or platelet-type (pseudo) von Willebrand disease Absolute
sodium losing conditions Absolute
syndrome of inappropriate antidiuretic hormone (SIADH) secretion (known or suspected) Absolute
uncontrolled hypertension. Stimate: There are no contraindications listed in the Stimate prescribing information Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (3)

Common Hypertension

Not Known Decreased blood pressure · facial flushing

Nervous system disorders (4)

Common chills · dizziness · Headache · nostril pain

Hepatobiliary disorders (1)

Not Known Increased serum transaminases (transient; associated primarily with tablets)

Gastrointestinal disorders (5)

Common Abdominal pain · gastrointestinal disease · nausea

Not Known Abdominal cramps · sore throat

Musculoskeletal and connective tissue disorders (2)

Common Back pain · weakness

Eye disorders (3)

Common Abnormal lacrimation · conjunctivitis · ocular edema

General disorders and administration site conditions (3)

Not Known Burning sensation at injection site · erythema at injection site · swelling at injection site

Other (1)

Very Common Endocrine & metabolic: Hyponatremia

Respiratory, thoracic and mediastinal disorders (9)

Common bronchitis · epistaxis · nasal congestion · nasal discomfort · nasopharyngitis · Rhinitis · sneezing

Not Known Cough · upper respiratory tract infection

Dosing

Source: Lexicomp

Diabetes insipidus: Note: Fluid restriction should be observed. Dosing should be individualized to response. IV, SubQ: US labeling: 2 to 4 mcg daily (0.5 to 1 mL) in 2 divided doses or one-tenth (1/10) of the maintenance intranasal dose. Fluid restriction should be observed. IM, IV, SubQ: Canadian labeling (DDAVP Injection only): 1 to 4 mcg (0.25 to 1 mL) once daily or one-tenth (1/10) of the maintenance intranasal dose. Fluid restriction should be observed. Intranasal (100 mcg/mL nasal solution): Usual dose range: 10 to 40 mcg daily (0.1 to 0.4 mL) as a single dose or divided 2 to 3 times daily; adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover. Most adults require 10 mcg (0.1 mL) twice daily. Note: The nasal spray pump can only deliver doses of 10 mcg (0.1 mL) or multiples of 10 mcg (0.1 mL); if doses other than this are needed, the rhinal tube delivery system is preferred. Fluid restriction should be observed. Oral: US labeling: Initial: 0.05 mg twice daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis (range: 0.1 to 1.2 mg divided 2 to 3 times daily). Fluid restriction should be observed. Canadian labeling: Initial: 0.1 mg 3 times daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis (maximum: 1.2 mg/day in 3 divided doses). Fluid restriction should be observed. Sublingual formulation [Canadian product]: DDAVP Melt: Initial: 60 mcg 3 times daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis. Usual maintenance: 120 to 720 mcg equally divided 2 or 3 times daily. Fluid restriction should be observed. Intracranial hemorrhage associated with certain antiplatelet agents (aspirin, clopidogrel, prasugrel, ticlopidine, ticagrelor, cangrelor) (off-label use): IV: 0.4 mcg/kg once (NCS/SCCM [Frontera 2016]). Nocturia: Intranasal: Noctiva: Not at risk for hyponatremia: 1.66 mcg in either nostril ~30 minutes before bedtime. At risk for hyponatremia: Initial: 0.83 mcg in either nostril ~30 minutes before bedtime. After ≥7 days, may increase to 1.66 mcg if needed (provided the serum sodium is within the normal range during treatment with the 0.83 mcg dose). Note: The 0.83 mcg dose did not meet all prespecified efficacy endpoints in clinical trials but may have a lower risk of hyponatremia. Sublingual formulation [Canadian product]: Nocdurna: Females: 25 mcg once daily at bedtime. Fluid intake should be limited 1 hour prior to dose until the next morning, or at least 8 hours after administration. Males: 50 mcg once daily at bedtime; Note: In males ≥65 years, evaluate serum sodium within 4 to 8 days after initiation and at 1 month of treatment; discontinue therapy if sodium falls below normal range. Fluid intake should be limited 1 hour prior to dose until the next morning, or at least 8 hours after administration. Primary nocturnal enuresis: Oral: Initial: 0.2 mg at bedtime; dose

(For additional information see "Desmopressin: Pediatric drug information") Diabetes insipidus: Note: Fluid restriction should be observed in these patients; younger patients more susceptible to plasma osmolality shifts and possible hyponatremia. Dosing should be individualized to response. Parenteral: US labeling: Children ≥12 years and Adolescents: IV, SubQ: Refer to adult dosing. Alternative recommendations (off-label): Infants and Children not be used in this age group; adverse events such as hyponatremia-induced seizures may occur. Dose should be reduced. Some have suggested an initial dosage range of 0.1 to 1 mcg daily in 1 or 2 divided doses (Cheetham 2002). Initiate at low dose and increase as necessary. Closely monitor serum sodium levels and urine output; fluid restriction is recommended. Canadian labeling (DDAVP Injection only): IM, IV, SubQ: Children and Adolescents: 0.4 mcg (0.1 mL) once daily or one-tenth (1/10) of the maintenance intranasal dose. Fluid restriction should be observed. Intranasal (using 100 mcg/mL nasal solution): Infants ≥3 months and Children ≤12 years: Usual dose range: 5 to 30 mcg daily (0.05 to 0.3 mL daily) as a single dose or divided 2 times daily; adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover. Note: The nasal spray pump can only deliver doses of 10 mcg (0.1 mL) or multiples of 10 mcg (0.1 mL); if doses other than this are needed, the rhinal tube delivery system is preferred. Fluid restriction should be observed. Adolescents: Refer to adult dosing. Oral: US labeling: Children ≥4 years and Adolescents: Refer to adult dosing. Canadian labeling: Children: Initial: 0.1 mg 3 times daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis (maximum: 1.2 mg/day in 3 divided doses). Divide daily doses so that the evening dose is 2 times higher than the morning or afternoon dose to ensure adequate antidiuresis during the night. Fluid restriction should be observed. Adolescents: Refer to adult dosing. Sublingual formulation [Canadian product]: DDAVP Melt: Children: Initial: 60 mcg 3 times daily; total daily dose should be increased or decreased as needed to obtain adequate antidiuresis. Usual maintenance: 120 to 720 mcg equally divided 2 to 3 times daily; divide daily doses so that the evening dose is 2 times higher than the morning or afternoon dose to ensure adequate antidiuresis during the night. Fluid restriction should be observed. Adolescents: Refer to adult dosing. Hemophilia A and von Willebrand disease (type 1): IV: Infants ≥3 months, Children, and Adolescents: Refer to adult dosing. Note: Adverse events such as hyponatremia-induced seizures have been reported especially in young children using this dosing regimen (Das 2005; Molnar 2005; Smith 1989; Thumfart 2005; Weinstein 1989). Fluid restriction and careful monitoring of serum sodium levels and urine output are necessary. Intranasal (using high concentration spray [1.5 mg/

Refer to adult dosing. Nocturia: Intranasal: Noctiva: Initial: 0.83 mcg in either nostril ~30 minutes before bedtime. After ≥7 days, may increase to 1.66 mcg, if needed (provided the serum sodium is within the normal range during treatment with the 0.83 mcg dose). Note: The 0.83 mcg dose did not meet all prespecified efficacy endpoints in clinical trials but may have a lower risk of hyponatremia.

CrCl ≥50 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling. CrCl

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Allergic reactions

Severe allergic reactions have been reported with desmopressin; anaphylactic reactions have only occurred rarely with IV and intranasal administration.

Fluid retention

May cause fluid retention, which can worsen underlying conditions susceptible to volume status. Use with caution in patients with NYHA Class I heart failure; some products are contraindicated in NHYA Class II to IV heart failure or uncontrolled hypertension. Some products are not recommended in patients at risk for increased intracranial pressure of those with a history of urinary retention.

Hyponatremia

Noctiva: Desmopressin can cause hyponatremia. Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death. Desmopressin is 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 concentrations are normal before starting or resuming desmopressin. Measure serum sodium within 7 days and ~1 month after initiating therapy or increasing the dose and periodically during treatment. More frequently monitor serum sodium in patients ≥65 years of age and in patients at increased risk of hyponatremia. If hyponatremia occurs, desmopressin may need to be temporarily or permanently discontinued. Desmopressin use may rarely lead to hyponatremia with associated signs and symptoms (eg, nausea/vomiting, headache, depressed reflexes, disorientation, irritability, muscle weakness/spasms/cramps) and extreme decreases in plasma osmolality, resulting in seizures, coma, respiratory arrest, and death. Other risk factors for hyponatremia with desmopressin use include cystic fibrosis, renal impairment, heart failure, young age, advanced age, inappropriate high fluid intake, a higher than recommended dose, and concomitant use of medications known to either increase thirst or cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid rest

Hypotension

Severe hypotension may occur with rapid IV infusions.

Thrombotic events

Acute cerebrovascular thrombosis and acute myocardial infarction have occurred (rare) with desmopressin injection; use with caution in patients predisposed to thrombus formation. Disease-related concerns:

Cardiovascular disease

Injection and intranasal desmopressin may cause a slight increase or transient decrease in blood pressure, and a compensatory increase in heart rate. Use with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease.

Polydipsia (habitual or psychogenic)

Use with caution in patients with habitual or psychogenic polydipsia. Patients consuming excessive amounts of water are at greater risk of hyponatremia.

Stress states/febrile illness

Lack of therapeutic effect has been observed in patients who have been febrile or stressed for several days; monitor for continued efficacy if indicated.

Primary nocturnal enuresis

When using desmopressin for primary nocturnal enuresis, treatment should be interrupted if the patient experiences an acute illness (eg, fever, recurrent vomiting or diarrhea), vigorous exercise, or any condition associated with an increase in water consumption to prevent hyponatremia.

von Willebrand disease type 2B

Patients with type 2B von Willebrand disease requiring hemostasis should not be treated with desmopressin since may result in platelet aggregation, thrombocytopenia, and possibly thrombosis. Special populations:

Elderly

Fluid intake should be adjusted downward in the elderly to decrease the possibility of water intoxication and hyponatremia.

Pediatric

Fluid intake should be adjusted downward in very young patients to decrease the possibility of water intoxication and hyponatremia. Dosage form specific issues:

Intranasal

Consider alternative route of administration if changes in the nasal mucosa (scarring, edema) occur leading to unreliable absorption. Some patients may demonstrate a change in response after long-term therapy (>6 months) characterized as decreased response or a shorter duration of response. Discontinue in patients with concurrent nasal conditions that may increase systemic absorption of desmopressin (eg, atrophy of nasal mucosa, acute or chronic rhinitis); may resume desmopressin when conditions resolve.

Tablet

Patients should be instructed to restrict fluid intake from 1 hour before to 8 hours after taking desmopressin tablets. Consider alternative route of administration (IV or intranasal) with inadequate therapeutic response at maximum recommended oral doses.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events were not observed in animal reproduction studies. Anecdotal reports suggest congenital anomalies and low birth weight. However, causal relationship has not been established. Desmopressin has been used safely throughout pregnancy for the treatment of diabetes insipidus (Brewster 2005; Schrier 2010). The use of desmopressin is limited for the treatment of von Willebrand disease in pregnant women (NHLBI 2007). Desmopressin is not recommended for nocturia treatment during pregnancy.

Lactation

Desmopressin is present in breast milk in small quantities. Analyses of milk from breastfeeding mothers receiving high-dose intranasal desmopressin indicate that the amount of desmopressin transferred to a breastfeeding child are considerably less than that required to influence diuresis. According to the manufacturer, the decision to breastfeed during therapy should take into account the risk of infant exposure, benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring

Clinical pearl	Blood pressure and pulse should be monitored during IV infusion Note: For all indications, fluid intake, urine volume, and signs and symptoms of hyponatremia should be closely monitored especially in high-risk patient subgroups (eg, young children, elderly, patients with heart failure). Diabetes insipidus: Urine specific gravity, plasma and urine osmolality, serum electrolytes Hemophilia A: Factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII antigen levels, aPTT von Willebrand disease: Factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII von Willebrand antigen levels, bleeding time Nocturnal enuresis: Serum electrolytes if used for >7 days Nocturia: Serum sodium concentrations at baseline, within 7 days, ~1 month after initiating/resuming therapy or increasing the dose, and periodically during therapy. More frequent monitoring in patients ≥65 years of age and those at increased risk of hyponatremia. Uremic bleeding: Octostim [Canadian product]): Bleeding time before and 1 hour after IV infusion.

Clinical pearl

Blood pressure and pulse should be monitored during IV infusion Note: For all indications, fluid intake, urine volume, and signs and symptoms of hyponatremia should be closely monitored especially in high-risk patient subgroups (eg, young children, elderly, patients with heart failure). Diabetes insipidus: Urine specific gravity, plasma and urine osmolality, serum electrolytes Hemophilia A: Factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII antigen levels, aPTT von Willebrand disease: Factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII von Willebrand antigen levels, bleeding time Nocturnal enuresis: Serum electrolytes if used for >7 days Nocturia: Serum sodium concentrations at baseline, within 7 days, ~1 month after initiating/resuming therapy or increasing the dose, and periodically during therapy. More frequent monitoring in patients ≥65 years of age and those at increased risk of hyponatremia. Uremic bleeding: Octostim [Canadian product]): Bleeding time before and 1 hour after IV infusion.

Chemistry & Properties

Formula	C46H64N14O12S2
Molecular weight	1069.24 g/mol
IUPAC name	(2S)-N-[(2R)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide
CAS	16679-58-6
PubChem CID	5311065
InChIKey	`NFLWUMRGJYTJIN-PNIOQBSNSA-N`

SMILES

N=C(N)NCCC[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CSSCCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N1)C(=O)NCC(N)=O

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Beclomethasone dipropionate	major
Betamethasone	major
Budesonide	major
Bumetanide	major
Ciclesonide	major
Deflazacort	major
Dexamethasone	major
Etacrynic acid	major
Fludrocortisone	major
Flunisolide	major
Fluticasone	major
Furosemide	major
Hydrocortisone	major
Methylprednisolone	major
Prednisolone	major
Prednisone	major
Torasemide	major
Triamcinolone	major
Alfentanil	moderate
Amitriptyline	moderate
Amoxapine	moderate
Benzhydrocodone	moderate
Bromfenac	moderate
Buprenorphine	moderate
Butorphanol	moderate
Carbamazepine	moderate
Celecoxib	moderate
Chlorpromazine	moderate
Chlorpropamide	moderate
Cisplatin	moderate
Citalopram	moderate
Clofibrate	moderate
Clomipramine	moderate
Codeine	moderate
Cyclophosphamide	moderate
Demeclocycline	moderate
Desipramine	moderate
Desvenlafaxine	moderate
Dextropropoxyphene	moderate
Dezocine	moderate

Showing 40 of 100+.

Registered Products (7)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Nocdurna	Tablet 25 mcg	30 tab	Petra Drug Store	16.370
Minirin	Ampoule 4 mcg/ml	10 ampoule	Petra Drug Store	18.730
Nocdurna	Tablet 50 mcg	30 tab	Petra Drug Store	20.410
Minirin Melt	Tablet 60 mcg	30 tab	Petra Drug Store	21.710
Minirin (DDAVP) N/S	Injection 0.1 mg/ml	5 ml	Petra Drug Store	30.030
Nictur	Solution 360 mcg/1 ml	15 ml	Almutanabbe Drug Store	36.040
Minirin Melt	Tablet 120 mcg	30 tab	Petra Drug Store	41.210