DESMOPRESSIN ACETATE

Desmopressin Acetate Injection USP (desmopressin acetate) 4 mcg/mL is a synthetic analogue of the natural pituitary hormone8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation. It is chemically defined as follows: Mol. Wt. 1183.34 Empirical Formula: C 46 H 64 N 14 O 12 S 2 •C 2 H 4 O 2 •3H 2 O 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate. Desmopressin Acetate Injection USP 4 mcg/mL is provided as a sterile, aqueous solution for injection. Each mL provides: Desmopressin acetate 4 mcg Sodium chloride 9 mg Hydrochloric acid to adjust pH to 4 Desmopressin Structure

Hemophilia A: Desmopressin Acetate Injection 4 mcg/mL is indicated for patients with hemophilia A with factor VIII coagulant activity levels greater than 5%. Desmopressin Acetate Injection will often maintain hemostasis in patients with hemophilia A during surgical procedures and postoperatively when administered 30 minutes prior to scheduled procedure. Desmopressin Acetate Injection will also stop bleeding in hemophilia A patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular hematomas or mucosal bleeding. Desmopressin Acetate Injection is not indicated for the treatment of hemophilia A with factor VIII coagulant activity levels equal to or less than 5%, or for the treatment of hemophilia B, or in patients who have factor VIII antibodies. In certain clinical situations, it may be justified to try Desmopressin Acetate Injection in patients with factor VIII levels between 2% to 5%; however, these patients should be carefully monitored. von Willebrands Disease (Type I): Desmopressin Acetate Injection 4 mcg/mL is indicated for patients with mild to moderate classic von Willebrands disease (Type I) with factor VIII levels greater than 5%. Desmopressin Acetate Injection will often maintain hemostasis in patients with mild to moderate von Willebrands disease during surgical procedures and postoperatively when administered 30 minutes prior to the scheduled procedure. Desmopressin Acetate Injection will usually stop bleeding in mild to moderate von Willebrands patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular hematomas or mucosal bleeding. Those von Willebrands disease patients who are least likely to respond are those with severe homozygous von Willebrands disease with factor VIII coagulant activity and factor VIII von Willebrand factor antigen levels less than 1%. Other patients may respond in a variable fashion depending on the type of molecular defect they have. Bleeding time and factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand factor antigen should be checked during administration of Desmopressin Acetate Injection to ensure that adequate levels are being achieved. Desmopressin Acetate Injection is not indicated for the treatment of severe classic von Willebrands disease (Type I) and when there is evidence of an abnormal molecular form of factor VIII antigen. (See WARNINGS . ) Diabetes Insipidus: Desmopressin Acetate Injection 4 mcg/mL is indicated as antidiuretic replacement therapy in the management of central (cranial) diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Desmopressin Acetate Injection is ineffective for the treatment of nephrogenic diabetes insipidus. Desmopressin Acetate Injection is also available as an intranasal preparation. However, this means of delivery can be compromised by a variety of factors that can make nasal insufflation ineffective or inappropriate. These include poor intranasal absorption, nasal congestion and blockage, nasal discharge, atrophy of nasal mucosa, and severe atrophic rhinitis. Intranasal delivery may be inappropriate where there is an impaired level of consciousness. In addition, cranial surgical procedures, such as transsphenoidal hypophysectomy, create situations where an alternative route of administration is needed as in cases of nasal packing or recovery from surgery.

Hemophilia A and von Willebrand’s Disease (Type I): Desmopressin Acetate Injection 4 mcg/mL is administered as an intravenous infusion at a dose of 0.3 mcg Desmopressin Acetate Injection/kg body weight diluted in sterile physiological saline and infused slowly over 15 to 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. Blood pressure and pulse should be monitored during infusion. If Desmopressin Acetate Injection 4 mcg/mL is used preoperatively, it should be administered 30 minutes prior to the scheduled procedure. The necessity for repeat administration of Desmopressin Acetate Injection or use of any blood products for hemostasis should be determined by laboratory response as well as the clinical condition of the patient. The tendency toward tachyphylaxis (lessening of response) with repeated administration given more frequently than every 48 hours should be considered in treating each patient. Fluid restriction should be observed. (See WARNINGS, PRECAUTIONS , Pediatric Use and Geriatric Use.) Diabetes Insipidus: This formulation is administered subcutaneously or by direct intravenous injection. Desmopressin Acetate Injection 4 mcg/mL dosage must be determined for each patient and adjusted according to the pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. The usual dosage range in adults is 0.5 mL (2.0 mcg) to 1 mL (4.0 mcg) daily, administered intravenously or subcutaneously, usually in two divided doses. The morning and evening doses should be separately adjusted for an adequate diurnal rhythm of water turnover. For patients who have been controlled on intranasal Desmopressin Acetate Injection and who must be switched to the injection form, either because of poor intranasal absorption or because of the need for surgery, the comparable antidiuretic dose of the injection is about one-tenth the intranasal dose. Fluid restriction should be observed. (See WARNINGS, PRECAUTIONS , Pediatric Use and Geriatric Use.) Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Geriatric Use: 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. (See CLINICAL PHARMACOLOGY , Human Pharmacokinetics, CONTRAINDICATIONS , and PRECAUTIONS , Geriatric Use.) Directions for use of One Point Cut (OPC) Ampules for Desmopressin Acetate Injection: 1. Use aseptic technique to clean ampule. Gently tap the top of the ampule to assist the flow of the solution from the upper portion of the ampule to the lower portion. 2. Locate the blue dot on the upper portion of the ampule. Below this dot is a small score on the neck of the ampule. Hold the ampule with the blue dot facing away from you . 3. Cover the vial with an appropriate wipe. Apply pressure to the top and bottom portions of the ampule to snap the ampule open away from you.

Desmopressin Acetate Injection 4 mcg/mL is contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of Desmopressin Acetate Injection 4 mcg/mL. Desmopressin Acetate Injection is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min). Desmopressin Acetate Injection is contraindicated in patients with hyponatremia or a history of hyponatremia.

Infrequently, Desmopressin Acetate Injection has produced transient headache, nausea, mild abdominal cramps and vulval pain. These symptoms disappeared with reduction in dosage. Occasionally, injection of Desmopressin Acetate Injection has produced local erythema, swelling or burning pain. Occasional facial flushing has been reported with the administration of Desmopressin Acetate Injection. Desmopressin Acetate Injection has infrequently produced changes in blood pressure causing either a slight elevation or a transient fall and a compensatory increase in heart rate. Severe allergic reactions including anaphylaxis have been reported rarely with Desmopressin Acetate Injection . See WARNINGS for the possibility of water intoxication and hyponatremia. Post Marketing: There have been rare reports of thrombotic events (acute cerebrovascular thrombosis, acute myocardial infarction) following Desmopressin Acetate Injection in patients predisposed to thrombus formation, and rare reports of hyponatremic convulsions associated with concomitant use with the following medications: oxybutinin and imipramine.