MINIRIN ORAL LYOPHILISATE 240 MCG

Source of information: Drugbank (External Link). Last updated on: 3^rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

1-(3-mercaptopropionic acid)-8-D-arginine-vasopressin | 1-deamino-8-D-arginine vasopressin | 1-desamino-8-D-arginine vasopressin | dDAVP | Desmopresina | Desmopressine | Desmopressinum | Desmopressin |

Description

Desmopressin (dDAVP), a synthetic analogue of 8-arginine vasopressin (ADH), is an antidiuretic peptide drug modified by deamination of 1-cysteine and substitution of 8-L-arginine by 8-D-arginine. ADH is an endogenous pituitary hormone that has a crucial role in the control of the water content in the body. Upon release from the stimulation of increased plasma osmolarity or decreased circulating blood volume, ADH mainly acts on the cells of the distal part of the nephron and the collecting tubules in the kidney [T28]. The hormone interacts with V1, V2 or V3 receptors with differing signal cascade systems. Desmopressin displays enhanced antidiuretic potency, fewer pressor effects due to V2-selective actions, and a prolonged half-life and duration of action compared to endogenous ADH [A31661]. It has been employed clinically since 1972 and is available in various formulations including intranasal solution, intravenous solution, oral tablet and oral lyophilisate [A31662]. Desmopressin is indicated for the treatment of polyuric conditions including primary nocturnal enuresis, nocturia, and diabetes insipidus. It was also newly approved for the treatment of mild classical hemophilia and von Willebrand's disease for minor surgeries. The active ingredient in most formulations is desmopressin acetate. Nocdurna, or desmopressin acetate, was approved by the FDA on June 21st, 2018 for the treatment of nocturia due to nocturnal polyuria in adults. It is available as a sublingual tablet.

Indication

- Indicated for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void (intranasal). - 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 (intranasal/parenteral). - Indicated for patients with hemophilia A with factor VIII coagulant activity levels greater than 5% or mild to moderate classic von Willebrand's Disease (Type I) with factor VIII levels greater than 5% during surgical procedures and postoperatively to maintain hemostasis (parenteral).

Mechanism of Action

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 [T28].

Pharmacodynamics

By mimicking the actions of endogenous ADH, desmopressin acts as a selective agonist of V2 receptors expressed in the renal collecting duct (CD) to increase water re-absorption and reduce urine production. Desmopressin has been shown to be more potent than ADH in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand's disease Type I [L1183]. Desmopressin demonstrates markedly diminished pressor activity. Desmopressin administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection [L1182].

Pharmacokinetics

Absorption:

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 [FDA Label]. The peak plasma concentration was approximately 4.00 (± 3.85) pg/mL and 9.11 (± 6.90) pg/mL, respectively [FDA Label]. The bioavailability of 1.5 mg/mL desmopressin administered by the intranasal route was between 3.3 and 4.1% [L1183]. 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 [L1184].

Distribution:

The distribution volume of orally administered desmopressin is 0.2 – 0.32 l/kg [L1184]. It is not reported to cross the blood-brain barrier.

Metabolism:

In vitro, in human liver microsome preparations, it has been shown that no significant amount of desmopressin is metabolised in the liver and thus human liver metabolism in vivo is not likely to occur [L1184].

Elimination:

Desmopressin 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 [L1184].

Half-life

Following an intranasal dose of 1.66 mcg of desmopressin, the median apparent terminal half-life was 2.8 hours [FDA Label]. Terminal half-life significantly increased from 3 hours in normal healthy patients to 9 hours in patients with severe renal impairm

Clearance

Not Available

Toxicity

Intravenous TDLo in humans is reported to be 0.3 µg/kg/10M [MSDS]. Desmopressin 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 [FDA Label]. 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.