Desmopresina

Uses

Desmopresina Acetate sublingual tablet is used for the treatment of-

• Primary Nocturnal Enuresis
• Nocturia and
• Central Diabetes Insipidus

Desmopresina is also used to associated treatment for these conditions: Bleeding, Central Diabetes Insipidus, Nocturia, Nocturnal Polyuria, Polydipsia, Polyuria, Primary Nocturnal Enuresis

How Desmopresina works

Upon binding of desmopressin to V2 receptors in the basolateral membrane of the cells of the distal tubule and collecting ducts of the nephron, adenylyl cyclase is stimulated. The resulting intracellular cascades in the collecting duct lead to increased rate of insertion of water channels, called aquaporins, into the lumenal membrane and enhanced the permeability of the membrane to water .

Dosage

Desmopresina dosage

Treatment of diabetes insipidus: Dosage is individual in diabetes insipidus but the total daily sublingual dose normally lies in the range of 120 micrograms to 720 micrograms. A suitable starting dose in adults and children is 60 micrograms three times daily, administered sublingually. This dosage regimen should then be adjusted in accordance with the patient's response. For the majority of patients, the maintenance dose is 60 micrograms to 120 micrograms sublingually three times daily.

Post-hypophysectomy polyuria/polydipsia: The dose of Desmopresina Acetate Melt should be controlled by measurement of urine osmolality.

Desmopresina Acetate Melt is for sublingual use.

Side Effects

Side-effects include headache, stomach pain and nausea. Isolated cases of allergic skin reactions and more severe general allergic reactions have been reported. Very rare cases of emotional disorders including aggression in children have been reported. Treatment with desmopressin without concomitant reduction of fluid intake may lead to water retention/hyponatraemia with accompanying symptoms of headache, nausea, vomiting, weight gain, decreased serum sodium and in serious cases, convulsions.

Toxicity

Intravenous TDLo in humans is reported to be 0.3 µg/kg/10M . Desmopresina is associated with hyponatremia in case of overdose, which may require temporary or permanent discontinuation of the therapy depending on severity. The effects of hyponatremia include seizure, altered mental status (confusion, drowsiness or continuing headache), cardiac arrhythmias and worsening edema. Other signs of overdose may include oliguria and rapid weight gain due to fluid retention . In case of overdose, reduce the dose or frequency of drug administration, or discontinue use if appropriate. Assessment of serum sodium and initiation of appropriate medical treatment is recommended.

Precaution

Care should be taken with patients who have reduced renal function and/or cardiovascular disease. In chronic renal disease the antidiuretic effect of Desmopresina Acetate Melt would be less than normal. Precautions to prevent fluid overload must be taken in:

• conditions characterised by fluid and/or electrolyte imbalance.
• patients at risk for increased intracranial pressure.

Interaction

Substances which are known to induce SIADH e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia. NSAIDs may induce water retention and/or hyponatraemia. Concomitant treatment with loperamide may result in a 3-fold increase of desmopressin plasma concentrations, which may lead to an increased risk of water retention and/or hyponatraemia. Although not investigated, other drugs slowing intestinal transport might have the same effect. A standardised 27% fat meal significantly decreased the absorption (rate and extent) of a 0.4mg dose of oral desmopressin tablets. Although it did not significantly affect the pharmacodynamic effect (urine production and osmolality), there is the potential for this to occur at lower doses. If a diminution of effect is noted, then the effect of food should be considered before increasing the dose.

Food Interaction

[Minor] Food may decrease the rate and extent of absorption of desmopressin following oral administration.

In 16 healthy, nonsmoking volunteers, administration of a single 400 mcg oral dose of desmopressin concomitantly with a standardized meal (27% fat) resulted in a 52% decrease in the peak plasma concentration (Cmax) of desmopressin and a 43% decrease in systemic exposure (AUC) compared to administration in the fasting state.

The Cmax and AUC were still reduced by 46% and 41%, respectively, when desmopressin was administered 1.5 hours after eating.

Both feeding regimens prolonged the time to reach peak plasma concentration (Tmax) from 1 hour to 1.5 hours.

However, the pharmacodynamic effects of desmopressin were not affected as assessed by urine volume and osmolality for at least 4 hours postdose.

The degree of antidiuresis was similar in the absence of food and when the drug was taken with or 1.5 hours after eating.

These findings would suggest a fairly minor clinical impact of the interaction in most patients, especially since oral desmopressin is intended for administration at bedtime.

Nevertheless, the possibility of food effects should be considered before increasing the dose whenever a diminution of effect is noted.

A significant interaction is not expected to occur with the sublingual formulation, since absorption occurs primarily in the oral mucosa, pharynx, and esophagus.

Desmopresina Hypertension interaction

[Moderate] The use of desmopressin, primarily in parenteral administration and

Therapy with desmopressin, regardless of route of administration, should be administered cautiously in patients with coronary artery insufficiency and

Desmopresina Drug Interaction

Moderate: escitalopram, escitalopramUnknown: aripiprazole, aripiprazole, montelukast, montelukast, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, lisdexamfetamine, lisdexamfetamine, cetirizine, cetirizine

Desmopresina Disease Interaction

Major: renal dysfunction, fluid overload/hyponatremiaModerate: thrombotic events, vascular disease

Volume of Distribution

The distribution volume of orally administered desmopressin is 0.2 – 0.32 l/kg . It is not reported to cross the blood-brain barrier.

Elimination Route

Following nasal spray administration of 0.83 mcg and 1.66 mcg, median time to peak plasma concentrations (Tmax) was 0.25 and 0.75 hour, respectively . The peak plasma concentration was approximately 4.00 (± 3.85) pg/mL and 9.11 (± 6.90) pg/mL, respectively . The bioavailability of 1.5 mg/mL desmopressin administered by the intranasal route was between 3.3 and 4.1% .

The absolute bioavailability of orally administered desmopressin varies between 0.08% and 0.16% where the mean maximum plasma concentration is reached within 2 hours .

Half Life

Following an intranasal dose of 1.66 mcg of desmopressin, the median apparent terminal half-life was 2.8 hours . Terminal half-life significantly increased from 3 hours in normal healthy patients to 9 hours in patients with severe renal impairment . The oral terminal half life of desmopressin ranges from 2 to 3.11 hours .

Elimination Route

Desmopresina is mainly excreted in the urine. About 65% of the amount of desmopressin absorbed after oral administration could be recovered in the urine within 24 hours .

Pregnancy & Breastfeeding use

Pregnancy: 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.

Lactation: 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.

Contraindication

Desmopresina Acetate Melt is contraindicated in cases of cardiac insufficiency and other conditions requiring treatment with diuretic agents. Before prescribing Desmopresina Acetate Melt, the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.

Acute Overdose

An overdose of Desmopresina Acetate Melt leads to a prolonged duration of action with an increased risk of water retention and/or hyponatraemia. Although the treatment of hyponatraemia should be individualised, the following general recommendations can be given. Hyponatraemia is treated by discontinuing the desmopressin treatment, fluid restriction and symptomatic treatment if needed.

Storage Condition

Store in the original package in order to protect from moisture and light.

Innovators Monograph

You find simplified version here Desmopresina