Desmopressin

Registered South African indications:

• Haemophilia A
• Von Willebrand's Disease
• Diabetes insipidus
• Urinary concentration capacity test
• Nocturnal enuresis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe renal impairment (eGFR <19ml/min/1.73m²)
• Habitual polydipsia
• Psychogenic polydipsia
• von Willebrand's Disease Type IIB 
• Alcohol abuse
• Conditions requiring diuretic use
• Hypertension (renal function testing indication)
• Cardiac disease (renal function testing indication)
• Cardiac insufficiency (renal function testing indication; Haemostatic indication)
• Unstable angina pectoris (haemostatic indication)

Cautions

• Pregnancy
• Breastfeeding
• Moderate renal impairment (eGFR ≥20-49ml/min/1.73m²)
• Hepatic impairment
• Conditions characterised by fluid imbalance
• Conditions characterised by electrolyte imbalance
• Risk factors for increased intracranial pressure
• Cardiovascular disease
• Cystic fibrosis
• Oral fluid intake during diagnostic testing
• Repeat dosing for haemostatic indication
• Children younger than 1 year

Forms avail. in SA and covered in this monograph: inj, tab, nas, slt, sol

Haemophilia A - mild, moderate
Von Willebrand's Disease

• IV: 0.3μg/kg as an infusion over 15-30min, 30min prior to surgery

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Dilute dose with 50ml normal saline for infusion

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Do Factor VIII assay before and 20min after infusion to assess patient's response; If Factor VIII coagulant activity is < 5% of normal, desmopressin cannot be relied on for haemostasis

Continue monitoring Factor VIII to gauge efficacy of repeated dosages

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Diagnosis of central diabetes insipidus

• IM/SC: 2μg, as a single dose
• Intranasal (sol, nas): 20μg, as a single dose

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See additional prescribing points for diagnosis of central diabetes insipidus test instructions

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Central diabetes insipidus

• IV/IM/SC: 1-4μg, dly

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Use IV administration only when intranasal administration unsuitable

When switching from intranasal administration to IV administration, IV dosage should be calculated at about 10% of the intranasal dose

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• Intranasal (sol, nas): 10-20μg, 12-24hrly
• Oral (tab): Initial: 0.1mg, 8hrly; Maintenance: 0.1-0.2mg, 8hrly; Max: 1.2mg/24hrs
• Oral (slt): Initial: 60μg, 8hrly; Maintenance: 120-720μg/day, in 2-3 divided doses

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Sublingual tablet: place under the tongue where it dissolves without need for water

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Urinary concentration capacity test

• IM/SC: 2-4μg, as a single dose
• Intranasal (sol, nas): 40μg, as a single dose

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See additional prescribing points for urinary concentration capacity test instructions

See additional prescribing points for administration directions for nasal solution

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Primary nocturnal enuresis

• Oral (tab): Initial: 0.2mg, dly at night; Titrate at intervals of 3 days; Maintenance: 0.2-0.4mg, dly at night; Max: 0.6mg/24hrs
• Oral (slt): Initial: 120μg, dly at night; Titrate at intervals of 3 days; Maintenance: 120-240μg; Max: 360μg/24hrs
• Intranasal (sol, nas): Initial: 10μg, dly at night; Titrate at intervals of at least 1 week; Maintenance: 10-20μg, dly at night; Max: 20μg/24hrs

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Primary nocturnal enuresis: desmopressin can be used for recurrent courses as needed; Treat for 3 months, then taper dosage and stop for 1 week to assess response; If enuresis recurs, restart for a further 3 months

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See additional prescribing points for administration directions for nasal solution

Paed. forms avail. in SA and covered in this monograph: inj, tab, nas, slt, sol

Haemophilia A - mild
Von Willebrand's Disease - type I

• See adult dosage

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Weight > 10kg: Dilute dose with 50ml normal saline for infusion; Weight < 10kg: Dilute dose with 10ml normal saline for infusion

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Do Factor VIII assay before and 20min after infusion to assess patient's response; If Factor-VIII coagulant activity is < 5% of normal, desmopressin cannot be relied on for haemostasis

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Diagnosis of central diabetes insipidus

• See adult dosage

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See additional prescribing points for diagnosis of central diabetes insipidus test instructions

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Central diabetes insipidus

IV: 

• Younger than 1 year: 0.2-0.4μg, 12-24hrly
• Between 1-12 years: 0.4-1.0μg, 12-24hrly
• Older than 12 years: See adult dosage

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Use IV administration only when intranasal administration unsuitable

When switching from intranasal admin to IV admin, IV dosage should be calculated at about 10% of the intranasal dose

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Oral (tab, slt):

• Younger than 4 years: Initial: 0.05mg, 8hrly
• Older than 4 years: See adult dosage

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Monitor closely and individualise dosing to prevent excessive decrease in plasma osmolality, hyponatremia and possible convulsions

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Intranasal (sol, nas):

• Between 3 months and 12 years: 5-30μg/day, in 1-2 divided doses; Max: 30μg/24hrs
• Older than 12 years: See adult dosage

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See additional prescribing points for administration directions for nasal solution

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Urinary concentration capacity test

IM/SC:

• Younger than 1 year: 0.4μg, as a single dose
• Older than 1 year: 1-2μg, as a single dose

Intranasal (sol, nas):

• Younger than 1 year: 10μg, as a single dose
• Older than 1 year: 20μg, as a single dose

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For children it is recommended to use the intranasal preparation for this indication

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See additional prescribing points for urinary concentration capacity test instructions

See additional prescribing points for administration directions for nasal solution

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Primary nocturnal enuresis - short term treatment

Younger than 5 years

• Not indicated for use in children below 5 years

Older than 5 years

• See adult dosage

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When used for primary nocturnal enuresis the fluid intake must be limited and then only to satisfy thirst from 1hr before until 8hrs after administration

Pregnancy

• Caution
• Data on a limited number (n=53) of exposed pregnancies in women with diabetes insipidus indicate rare cases of malformations in children treated during pregnancy. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women. Blood pressure monitoring is recommended due to the increased risk of pre-eclampsia

Breastfeeding

• Caution
• Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 micrograms intranasally) indicate that the amounts of desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis or haemostasis

Renal Impairment

• eGFR ≥50-89ml/min/1.73m²: No dose adjustment recommended
• eGFR ≥20-49ml/min/1.73m²: Caution; dose adjustment recommended  
  Only the intranasal formulations are recommended
  Intranasal (sol, nas): Max: 20μg/24hrs
  Oral and parenteral use should be avoided; except in emergency cases such as head trauma or surgery in the pituitary region
• eGFR <19ml/min/1.73m²: Contraindicated

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Headache
• Aggression
• Emotional disturbances
• Seizures

Gastrointestinal Disorders

• Stomach pain
• Nausea

Endocrine and Metabolic Disorders

• Water retention
• Hyponatraemia

Skin and Subcutaneous Tissue Disorders

• Allergic skin reactions

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions

• Non-steroidal anti-inflammatory drugs
• Agents known to induce syndrome of inappropriate antidiuretic hormone secretion
• Loperamide
• Indomethacin

• Blood pressure (inj)
• Heart rate (inj)
• Electrolytes
• Weight/water balance

Specific cases may require

• Factor-VIII assay
• Urine osmolarity
• Urine output

Dosing in renal impairment

Desmopressin is not contraindicated in patients with central diabetes insipidus who have renal impairment, but dosing needs to be carefully prescribed by a specialist. 

Diagnosis of central diabetes insipidus

Positive diagnosis: Failure to produce concentrated urine after water deprivation, followed by the ability to do so after the administration of desmopressin confirms the diagnosis of central diabetes insipidus; Failure to concentrate after the administration suggests nephrogenic diabetes insipidus

Urinary concentration capacity test

• Adults and children: Patients with normal renal function can be expected to achieve concentrations above 800mOsm/kg in the 5-9hrs following desmopressin dose. It is recommended that the bladder should be emptied at the time of administration. A restricted water intake must be observed.
• Infants normal urine concentration of 600mOsm/kg should be achieved in the 5hr period following administration. Fluid intake at the two meals after admin should be restricted to 50% of the ordinary intake in order to avoid water overload.

Administration directions: Intranasal solution

Performed with a plastic catheter (rhinyle tube). The rhinyle tube has a graduated scale corresponding to 2.5μg, 5μg, 10μg, 15μg and 20μg desmopressin acetate. As the concentration is 100μg/ml, the dose can be varied between 0.025-0.20 ml

If higher doses are needed it is recommended that these be divided into two doses; the one being given in the left nostril and the other in the right

Directions:

1. Take the calibrated part of the rhinyle in one hand and place the fingers of the other hand around the cylindrical part of the closure. Insert the top of the dropper in a downward position into the arrow marked end of the rhinyle and squeeze the dropper until the solution has reached the desired calibration mark (dose is measured from the arrow marked end of the tube to the appropriate calibration).
2. Disconnect the rhinyle from the bottle by withdrawing the bottle quickly downwards.
3. Hold the rhinyle with the fingers approximately 1.5-2 cm from the end and insert into a nostril until the tip of the fingers reach the nostril
4. Put the other end of the rhinyle into the mouth. Hold in breath. Tilt your head back and then blow with a strong puff through the catheter so that the solution reaches the right place in the nasal cavity. Through this procedure, medication is limited to the nasal cavity and the preparation does not pass down into the pharynx

Desmopressin is a synthetic analogue of the natural human hormone vasopressin. Structural changes to desmopressin result in a high antidiuretic activity with low uterotonic and vasopressor effects when compared to natural vasopressin. Desmopressin acts at renal tubular cells to increase water permeability leading to a decreased urine volume and increased urine osmolality. It also increases plasma levels of von Willebrand factor and factor VIII which gives this drug its haemostatic properties.

Tablet sublingual 120μg

• Minirin melt (Ferring) originator

Tablet sublingual 240μg

• Minirin melt (Ferring) originator

Tablet 0.1mg

• DDAVP (Ferring) originator

Tablet 0.2mg

• DDAVP (Ferring) originator

Intranasal solution (per ml) 0.1mg

• DDAVP (Ferring) originator

Injection (per ml) 4μg

• DDAVP (Ferring) originator

Nasal spray (per ml) 0.1mg

• DDAVP (Ferring) originator