Desmopressin (injection)

{{DrugProjectFormSinglePage |authorTag=Alberto Plate [1] |genericName=desmopressin acetate |aOrAn=a |drugClass=hemostatic and endocrine-metabolic agent |indicationType=treatment |indication=central diabetes insipidus and primary nocturnal enuresis |adverseReactions=fatigue and rhinitis |blackBoxWarningTitle=TITLE |blackBoxWarningBody=Condition Name: (Content) |fdaLIADAdult=====Central Cranial Diabetes Insipidus====

• Dosage:
  • Injection: 0.5mL - 1.0mL at 4 mcg/mL IV or SC, usually divided in two doses
  • Tablets: 0.05 mcg PO q12h. Total daily dosage should be increased or decreased in the range of 0.1 mg to 1.2 mg divided into two or three daily doses as needed to obtain adequate antidiuresis.
  • Nasal Spray: 0.1 to 0.4 mL daily, either as a single dose or divided into two or three doses.

Hemophilia A with factor VIII Coagulant Activity > 5%

• Dosage
  • Injection: 4 mcg/mL IV at 0.3 mcg/kg of body weight infused in 15-30 minutes. In adults and children weighing more than 10 kg, 50 mL of diluent is recommended; in children weighing 10 kg or less, 10 mL of diluent is recommended.

Von Willebrand's Disease

• Dosage:
  • Injection: 4 mcg/mL IV at 0.3 mcg/kg of body weight infused in 15-30 minutes. In adults and children weighing more than 10 kg, 50 mL of diluent is recommended; in children weighing 10 kg or less, 10 mL of diluent is recommended.

|offLabelAdultGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Desmopressin (patient information) in adult patients. |offLabelAdultNoGuideSupport=====Diagnosis of Cushing's Syndrome====

• Dosage: 5-10 mcg IV has proven ability to stimulate the pituitary-adrenal axis in a set of patients with Cushing's Syndrome, being useful in the differential diagnosis of the given pathology.

Ehlers-Danlos Syndrome

Evidence: profilaxis during labour against bleeding.

Hemorrhage-Uremia

• Dosage: 0.4 microgram/kg IV infusion in patients with chronic renal failure, shortened bleeding time.

Nocturia

• Dosage: 100 mcg (men) and 25 mcg (women) reduces nocturnal voids in 33%.

Urine Concentration Test

• Dosage: 10 mcg intranasally after 12 hours of water depravation concentrated urine in patients as if they were on 24-36 hours of water depravation.

|fdaLIADPed=====Primary Nocturnal Enuresis====

• Dosage:
  • Tablets: (Patients >6 years): Initial dose of 0.2 mg at bedtime. The dose may be titrated up to 0.6 mg to achieve the desired response.

Central Cranial Diabetes Insipidus

• Dosage:
  • Nasal Spray: (Patients 3 months - 12 years old), 0.05 to 0.3 mL daily, either as a single dose or divided into two doses.

Hemophilia A with factor VIII Coagulant Activity > 5%

• Dosage:
  • Injection: 4 mcg/mL IV at 0.3 mcg/kg of body weight infused in 15-30 minutes. In adults and children weighing more than 10 kg, 50 mL of diluent is recommended; in children weighing 10 kg or less, 10 mL of diluent is recommended.

Von Willebrand's Disease

• Dosage:
  • Injection: 4 mcg/mL IV at 0.3 mcg/kg of body weight infused in 15-30 minutes. In adults and children weighing more than 10 kg, 50 mL of diluent is recommended; in children weighing 10 kg or less, 10 mL of diluent is recommended.

|offLabelPedGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Desmopressin (patient information) in pediatric patients. |offLabelPedNoGuideSupport=====Urinary Incontinence====

• Dosage: Desmopressin administered at bedtime at increasing dosages from 10 to 30 mcg with intranasal spray until effective.

Urine Concentration Test

• Dosage: 50 mcg intranasally in children, optimal urine concentration was achieved by 3-5 hours .

|contraindications=Contraindicated in:

*Individuals with known hypersensitivity to desmopressin acetate or to any of the components of DDAVP tablets.

• Patients with moderate to severe ]]renal impairment]] (defined as a creatinine clearance below 50ml/min).
• Patients with hyponatremia

|warnings=*Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with desmopressin acetate. Desmopressin acetate is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required.

• When desmopressin acetate injection is administered to patients who do not have need of antidiuretic hormone for its antidiuretic effect, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia. All patients receiving desmopressin acetate therapy should be observed for the following signs of symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium (hyponatremia), weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest. Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma.
• Desmopressin acetate should not be used to treat patients with Type IIB von Willebrand’s disease since platelet aggregation may be induced.
• Desmopressin acetate should be used with caution in patients with habitual psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.

|clinicalTrials=====Cardiovascular Effects====

• Chest pain: Presented in use of nasal spray.
• Edema: Presented in use of nasal spray.
• Hypotension
• Hypertension
• Increased heart rate
• Myocardial infarction
• Palpitations: Present in use of nasal spray .

Dermatological Effects

• Balanitis: Presented in use of nasal spray.
• Burning pain
• Erythema
• Flushing
  • During intranasal treatment for Hemophilia A and von Willebrand's disease.
  • Presented in use of nasal spray. Although, flushing reduces as the dosis of desmopressin is reduced
• Swelling

Endocrine/Metabolic Effects

• Hyponatremia: present in people with electrolytic imbalance or psycogenic polydipsia in treatment with desmoressin .
  • Associated symptoms: headache, nausea, vomiting, fatigue, depressed reflexes, muscle weakness, weight gain, restlessnes, spasms, cramps, disorientation, [[decreased consciousness] and confusion
  • Associated severe symptoms: seizure, coma, and respiratory arrest .
• Hyposmolality .
• Water intoxication syndrome
  • Risk factors in patients:
    • Previous condition which caused electrolytic imbalance .
      • Cystic Fibrosis
      • Heart Failure
      • Renal Disorders
    • Drugs .
      • NSAIDs
      • Lamotrigine
      • Opioid analgesics
      • SSRIs

Gastrointestinal Effects

• Abdominal cramps: evidenced during Nocturnal Primary Enuresis treatment by desmopressin intranasally
• Abdominal pain
• Indigestion: dyspepsia has been reported during nasal vasopressin use Presented in use of nasal spray.
• Nausea: present during Hemophilia A and von Wilebrand's disease treatment with intranasal vasopressin
• Vomiting: Presented in use of nasal spray.

Hematologic Effects

• Thrombocytopenia.
• Thrombosis

Hepatic Effects

• Transient increase in AST/SGOT levels

Immunological Effects

• Anaphylaxis
• Hypersensitivity reaction

Neurological Effects

• Asthenia
• Thrombotic cerebrovascular accident,
  • Case report of 7-year old patient, who received desmopressin preoperatively. Partial recovery after some weeks
  • Case report of 7-year old patient who developed an cerebrovascular accident within 48 hours of initiated the therapy for enuresis .
• Dizziness
• Fatigue
• Headache
• Insomnia
• Seizure
• Somnolence
• Vertigo: presented during intranasal treatment with desmopressin for Hemophilia A and von Willebrand's disease .

Ophthalmic effects

• Conjunctivitis
• Eye edema
• Eyes sensitive to light
• Finding of lacrimation
• Itching of eye

Psychiatric Effects

• Agitation.
• Excitability: case report of paranoid behavior in 53-year old patient, treated with vasopressin with medical history of Alzheimer's disease.
• Unusual change in behavior

Respiratory Effects

• Cough
• Cyanosis
• Dyspnea
• Epistaxis
• Nasal congestion
• Pain in throat
• Respiratory failure
• Rhinitis
• Sore nostril
• Upper respiratory infection

Other General Effects

• Warm feeling
• Shivering

|drugInteractions=*Although the pressor activity of desmopressin acetate is very low compared with the antidiuretic activity, use of doses as large as 0.3 mcg/kg of desmopressin acetate with other pressor agents should be done only with careful patient monitoring.

• The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia:
  • Tricyclic antidepressants
  • Selective serotonin re-uptake inhibitors (SSRI's)
  • Chlorpromazine
  • Opiate analgesics
  • NSAIDs
  • Lamotrigine
  • Carbamazepine

|FDAPregCat=B |AUSPregCat=B2 |useInNursing=There have been no controlled studies in nursing mothers. A single study in postpartum women demonstrated a marked change in plasma, but little if any change in assayable desmopressin acetate in breast milk following an intranasal dose of 10 mcg. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when desmopressin acetate is administered to a nursing woman. |useInPed=Use in infants and pediatric patients will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication. Fluid restriction should be discussed with the patient and/or guardian. Desmopressin acetate injection 4 mcg/mL should not be used in infants less than three months of age in the treatment of hemophilia A or von Willebrand’s disease; safety and effectiveness in pediatric patients under 12 years of age with diabetes insipidus have not been established. |useInGeri=Clinical studies of desmopressin acetate injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. |useInRenalImpair=This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Desmopressin acetate is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min). |useInReproPotential=Studies with desmopressin acetate have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility. |administration=*Oral

• IV
• Intranasal

|monitoring=von Willebrand’s Disease: Laboratory tests for assessing patient status include levels of factor VIII coagulant activity, *Factor VIII ristocetin cofactor activity, and factor VIII von Willebrand factor antigen. The skin bleeding time may be helpful in following these patients.

*Diabetes Insipidus: Laboratory tests for monitoring the patient include urine volume and osmolality. In some cases, plasma osmolality may be required.

|overdose=Signs of overdose may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention. In case of overdosage, the dosage should be reduced, frequency of administration decreased, or the drug withdrawn according to the severity of the condition. There is no known specific antidote for desmopressin acetate or desmopressin acetate injection 4 mcg/mL. An oral LD 50 has not been established. An intravenous dose of 2 mg/kg in mice demonstrated no effect. CLOSE

|drugBox=

|PK=Desmopressin acetate is mainly excreted in the urine. A pharmacokinetic study conducted in healthy volunteers and patients with mild, moderate, and severe renal impairment (n=24, 6 subjects in each group) receiving single dose desmopressin acetate (2 mcg) injection demonstrated a difference in desmopressin acetate terminal half-life. Terminal half-life significantly increased from 3 hours in normal healthy patients to 9 hours in patients with severe renal impairment. |howSupplied=*Injection: Desmopressin acetate injection, USP 4 mcg/mL is available as a sterile solution in 10 mL multiple-dose vials, each containing 4 mcg desmopressin acetate, USP per mL.

• Tablets:
  • Flasks containing 100 0.1mcg Desmopressin tablets
  • Flasks containing 100 0.2mcg Desmopressin tablets
• Nasal spray (solution): Desmopressin Nasal Spray Solution USP, 0.01% is available in a 5 mL bottle with a nasal spray pump dispenser with dust cover and patient instruction sheet delivering 50 sprays of 10 mcg

|storage=*Injection: Store refrigerated 2° to 8°C (36° to 46°F). Preserve in tight containers, protected from light.

• Tablets: Store at Controlled Room Temperature 20 to 25°C (68 to 77°F). Avoid exposure to excessive heat or light. This product should be dispensed in a container with a child-resistant cap.
• Nasal spray (solution): Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Store bottle in upright position.

|alcohol=Alcohol-Desmopressin (patient information) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. |brandNames=*DDAVP

• Minirin
• Stimate
• DDAVP Nasal

}}