Desmopressin

Desmopressin is used for: Diabetes Insipidus, Hemophilia A, Von Willebrand Disease (Type 1), Nocturnal Enuresis, Nocturia, Uremic Bleeding in Acute or Chronic Renal Failure

Diabetes Insipidus 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 10-40 mcg (0.1-0.4 mL) qDay, either as a single dose or divided into 2 or 3 doses; usual dose is 20 mcg (0.2 mL) qDay in 2 divided doses Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover PO Initial: 0.05 mg q12hr Effective range: 0.1-1.2 mg divided q8-12hr Observe fluid restriction If switching to PO from intranasal, start PO at least 12 hours after last intranasal dose IV/SC 2-4 mcg/day divided q12hr or one-tenth the maintenance of intranasal dose Hemophilia A IV Indicated for patients with hemophilia A with factor VIII coagulant activity levels greater than 5% 0.3 mcg/kg IV over 15-30 minutes (for pre-op, 30 min before procedure) Intranasal Indicated for patients with mild to moderate classic von Willebrand disease (Type I) with Factor VIII levels >5% <50 kg: 150 mcg; for pre-op, give 2 hr before procedure >50 kg: 300 mcg; for pre-op, give 2 hr before procedure Von Willebrand Disease (Type 1) IV Indicated for patients with mild to moderate classic von Willebrand’s disease (Type I) with factor VIII levels greater than 5% 0.3 mcg/kg IV over 15-30 minutes (for pre-op, 30 min before procedure) Intranasal Indicated for patients with mild to moderate classic von Willebrand disease (Type I) with Factor VIII levels >5% <50 kg: 150 mcg; for pre-op, give 2 hr before procedure >50 kg: 300 mcg; for pre-op, give 2 hr before procedure Nocturnal Enuresis Primary nocturnal enuresis (not intranasal) 0.2 mg PO qHS (up to 0.6 mg/day) Nocturia Nocturnal polyuria was defined in clinical trials as nighttime urine production exceeding one-third of 24-hour urine production Preservative-free nasal spray Indicated for nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void >50 to <65 years 1 spray of 1.66 mcg in either nostril nightly ~ 30 min before going to bed >65 years 0.83 mcg in either nostril nightly ~ 30 min before going to bed; 0.83 mcg dose may have a lower risk of hyponatremia; may be increased to 1 spray of 1.66 mcg after at least 7 days, if needed, provided serum sodium has remained normal Sublingual tablets Indicated for nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void Before starting or resuming, assess the sodium concentration and only start or resume in patients with a normal serum sodium concentration Women: 27.7 mcg SL qDay, 1 hr before bedtime, administered SL without water Men: 55.3 mcg SL qDay, 1 hr before bedtime, administered SL without water Uremic Bleeding in Acute or Chronic Renal Failure 0.4 mcg/kg IV over 10 minutes

Diabetes Insipidus Nasal spray 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 in patients (>3 months) <3 months: Safety and efficacy not established 3 months-12 years Usual dosage range is 5-30 mcg (0.05-0.3 mL) qDay, either as a single dose or divided into 2 doses About 1/4 to 1/3 of patients can be controlled by a single daily dose of DDAVP administered intranasally Adjust doses separately for appropriate diurnal rhythm of water turnover if administering more than once a day >12 years 10-40 mcg (0.1-0.4 mL) qDay, either as a single dose or divided into 2 or 3 doses; usual dose is 20 mcg (0.2 mL) qDay in 2 divided doses Adjust morning and evening doses separately for an adequate diurnal rhythm of water turnover Nocturnal Enuresis >6 years: 0.2 mg PO qHS (up to 0.6 mg/day) Hemophilia A & Von Willebrand Disease Indicated for patients with hemophilia A or von Willebrand disease (type 1) with Factor VIII coagulant activity levels >5%; will also stop bleeding in patients with episodes of spontaneous or trauma-induced injuries (eg, hemarthroses, intramuscular hematomas, mucosal bleeding) IV Infants >3 months, children, and adolescents 0.3 mcg/kg IV If used preoperatively, administer 30 min before procedure May repeat dose if needed Intranasal Infants >11 months, children, and adolescents <50 kg: 150 mcg intranasally >50 kg: 300 mcg intranasally If used preoperatively, administer 2 hr before procedure Fluid intake should be limited 1 hr prior to dose until the next morning or at least 8 hr after administration Repeat use determined by clinical symptoms and laboratory values

Renal impairment CrCl <50 mL/min: Contraindicated; has been used unlabeled in acute and chronic renal failure patients experiencing uremic bleeding or prevention of surgical bleeding CrCl >50 mL/min: No adjustments necessary

May be taken with or without food. IV infusion: Dilute in 10 mL or 50 mL of NaCl 0.9% inj.

Cardiac insufficiency w/ ongoing diuretic treatment. Patient w/ habitual and psychogenic polydipsia, hyponatraemia or history of hyponatraemia. Moderate to severe renal impairment (CrCl <50 mL/min).

Patient w/ CV disease or cystic fibrosis, coronary artery insufficiency, at risk for increased intracranial pressure, predisposed to thrombus formation. Elderly and childn. Pregnancy and lactation.

Pregnancy Prolonged experience with desmopressin in pregnant women over several decades, based on available published data and case reports, did not identify a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; in addition, in vitro studies with human placenta demonstrate poor placental transfer of desmopressin; no adverse developmental outcomes were observed in animal reproduction studies with administration of desmopressin during organogenesis to pregnant rats and rabbits at doses approximately <1 and 38 times, respectively, the maximum recommended human dose based on body surface area (mg/m²) Not recommended for treatment of nocturia in pregnant women; nocturia is usually related to normal, physiologic changes during pregnancy that do not require treatment Lactation Desmopressin is present in small amounts in human milk and is poorly absorbed orally by infant There is no information on effects of desmopressin on breastfed infant or on milk production; development and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and potential adverse effects on breastfed infant from therapy or from the underlying maternal condition

May enhance antidiuretic effect w/ NSAIDs (e.g. ibuprofen), indometacin, TCAs, chlorpromazine, carbamazepine, SSRIs, opiates, lamotrigine. May reduce antidiuretic effect w/ lithium, epinephrine (large dose), heparin, demeclocycline.

Side effects of Desmopressin : >10% Dry mouth, men (14%) Dry mouth, women (12%) 1-10% Headache (2-5%) Hyponatremia, men (4%) Headache, men (4%) Hyponatremia, women (3%) Dizziness, men (3%) Dizziness (3%) Epistaxis (2-3%) Headache, women (2%) Dizziness, women (2%) Nasal spray Rhinitis (3-8%) Abdominal pain (2%) Asthenia (2%) Chills (2%) Nostril pain (2%) Gastrointestinal disorder (2%) Nausea (2%) Conjunctivitis (2%) Eye edema (2%) Lachrymation disorder (2%) Frequency Not Defined Abnormal blood pressure (infrequent) Increased heart rate Increased blood pressure Flushing Seizure (rare) Hyponatremia Hyposmolality (rare) Water intoxication syndrome Thromboembolic disorder Allergic reaction (acute) Anaphylaxis (rare)

Desmopressin increases cyclic adenosine monophosphate (cAMP) in renal tubular cells which increases water permeability resulting in reduced urine volume and enhanced urine osmolality. It also stimulates factor VII and plasminogen activator activity in the blood, but w/ minimal pressor activity. Onset: Antidiuretic: Approx 60 min (oral); 15-30 min (intranasal).